Report on Study of Methods of Execution & Recommendations for Procedures Submitted by: Louisiana Department of Public Safety & Corrections February 18, 2015 House Resolution 142 of the 2014 Regular Legislative Session was enrolled and signed by the Speaker of the House on June 5, 2014 to study and make recommendations relative to the different forms of execution and the methods of execution to determine the best practices for administering the death penalty in the most humane manner. The Secretary of the Louisiana Department of Public Safety and Corrections, James Le Blanc, chaired this work and held an organizational meeting on July 22, 2014 to organize a study committee to conduct this work. At that time, he assigned the following individuals to serve on the committee: Burl Cain, Warden, Louisiana State Penitentiary William Kline, Executive Counsel, DPS&C Legal Department Seth Smith, Chief of Operations, DPS&C Office of Adult Services Stephanie LaMartinere, Assistant Warden, Louisiana State Penitentiary Bruce Dodd, Deputy Warden, Louisiana State Penitentiary James Hilburn, Attorney, Shows Cali & Walsh, LLP Jeff Cody, Attorney, Shows Cali & Walsh, LLP Angela Whittaker, Executive Mgmt Officer, DPS&C Secretary's Office The committee met on the following dates: August 11, 2014: Planning meeting to develop resource and research needs of the group. September 2, 2014: Report and discussion on research findings. October 31, 2014: Report and discussion regarding identifying experts and discussion on additional research compiled. December 4, 2014: Report and discussion regarding research and protocol options and drafting the required written report. January 8, 2015: Review of research and draft report and consensus on recommendations for protocol options. January 22, 2015: Review and approval final report. Study Response to HR 142 of the Louisiana 2014 Regular Legislative Session Page 12 Background: Capital punishment, or the death penalty, is a sentence used in the justice process whereby an offender is put to death as punishment for a crime he/she committed. The death penalty in the United States is a legal sentence and states determine whether the death penalty will be used as a form of punishment for crimes committed within their borders. In Louisiana, the death penalty may be applied in cases involving first degree murder, a violation of La. R.S. 14:30, in circumstances such as: (1) The murder was committed during the commission of or attempt of, a specified felony such as aggravated kidnapping, second degree kidnapping, aggravated escape, aggravated arson, aggravated rape, forcible rape, aggravated burglary, armed robbery, assault by drive-by shooting, first degree robbery, second degree robbery, simple robbery, terrorism, cruelty to juveniles, or second degree cruelty to juveniles. (2) The murder was committed while the defendant was engaged in "ritualistic acts." (3) The murder was committed for pecuniary gain or pursuant to an agreement that the defendant would receive something of value. (4) The defendant caused or directed another to commit murder, or the defendant procured the commission of the offense by payment, promise of payment, or anything of pecuniary value. (5) The defendant has been convicted of, or committed, a prior murder, a felony involving violence, or other serious felony. (6) The capital offense was committed by a person who is incarcerated, has escaped, is on probation, is in jail, or is under a sentence of imprisonment. (7) The defendant was a drug dealer or has prior convictions involving the distribution of a controlled substance. (8) The victim was under the age of 12 years. (9) The victim was 65 years or older. (10) The victim was a fireman, peace officer, or correctional officer engaged in his lawful duties. Study Response to HR 142 of the Louisiana 2014 Regular Legislative Session Page [3 (11) The victim was a witness in a prosecution against the defendant, gave material assistance to the state in any investigation or prosecution of the defendant, or was an eyewitness to a crime alleged to have been committed by the defendant or possessed other material evidence against the defendant. (12) The murder was especially heinous, atrocious, cruel or depraved (or involved torture). Before a jury .may impose the death penalty it must consider whether there were any mitigating circumstances against imposing the death penalty. Louisiana Code of Criminal Procedure Art. 905.5 provides for the following mitigating circumstances: (a) The offender has no significant prior history of criminal activity; (b) The offense was committed while the offender was under the influence of extreme mental or emotional disturbance; (c) The offense was committed while the offender was under the influence or under the domination of another person; (d) The offense was committed under circumstances which the offender reasonably believed to provide a moral justification or extenuation for his conduct; (e) At the time of the offense the capacity of the offender to appreciate the criminality of his conduct or to conform his conduct to the requirements of law was impaired as a result of mental disease or defect or intoxication; (f) The youth of the offender at the time of the offense; (g) The offender was a principal whose participation was relatively minor; (h) Any other relevant mitigating circumstance. Pursuant to La. R.S. 15:569 and 570, every sentence of death executed on or after September 15, 1991, shall be by lethal injection, that is, by the intravenous injection of a substance or substances in a lethal quantity into the body of the offender until such person is dead. Including Louisiana, there are currently 34 states that authorize the death penalty. Most all of these states have adopted lethal injection as the primary means of implementing the death penalty. While 18 of those states have solely authorized lethal injection as the execution method, the rest of the states that impose the death penalty have also set forth alternative methods of execution such as electrocution, lethal gas, hanging, and the use of firing squads. The methods of execution for each such state are set forth in the chart below. Study Response to HR 142 of the Louisiana 2014 Regular Legislative Session Page 14 Research from Other Capital Punishment States: <: 0 ., u Ql ·;: i'ii ..c: Ql ...J State Alabama A rizona Arkansas X X X Colorado X Delaware Georgia X Kansas Kentucky Ql Ql E '" ..c: u "' '" l!) b.O <: ·;;;, <: '" :J: ., ., '" "' :I t:r "' b.O <: ·;: u:: Lethal injection; inmate sentenced on or before 11/15/92 may choose lethal injection or lethal gas Lethal injection, but electrocution if lethal injection declared unconstitutional X X <: 0 ., u <: Ql '" > "' ·.;:; ., '" 0 <: ..c: � - Ql Ql;: 2<( Lethal injection, unless inmate affirmatively selects electrocution X Ql "' ·;: bJ) :I � i'ii c ..c: Ql ...J 500 mg - midazolam hydrochloride; 600 mgrocuronium bromide; 240 milliequivalentspotassium chloride midazlam/ hydromorphone Statute specifies a barbituate preceded by a benzodiazepine Lethal gas or lethal injection may be chosen by inmate; if inmate fails to choose either method, then lethal injection Lethal injection Statute specifies sodium thiopental or equivalent Lethal injection X Lethal injection Lethal injection, unless inmate affirmatively selects electrocution; if both deemed unconstitutional, then any constitutional method Lethal injection X Lethal injection X Lethal injection X X � ..0 X X X Idaho ;:;:; X Florida Indiana u X California Connecticut <: 0 ., :I u 0 � Lethal injection X Lethal injection; inmates sentenced on or before 3/31/98 may choose lethal injection or electrocution Study Response to HR 142 of the Louisiana 2014 Regular Legislative Session Page IS <: 0 :;::; u "' E rti ..<:: .... "' .... State Louisiana X Missouri X Montana X Nebraska X New Hampshire New Mexico North Carolina tl "' jjj � "' .c E "' ..<:: u "' "' 1!1 "" <: ... <: "' J: VI "" ..<:: .... "' .... midazlam/hydromorphone Statute specifies an ultra short-acting barbituate in combination with a paralytic agent Statute specifies an ultrafast-acting barbituate in combination with a chemical paralytic agent Lethal injection Lethal injection X Lethal injection; but may be by hanging if lethal injection deemed "impractical" Statute specifies an ultrashort-acting barbituate in combination with a chemical paralytic agent Lethal injection, but only for crimes committed prior to July 1, 2009; otherwise, capital punishment repealed X X rti 0 :2;<( Lethal gas or lethal injection Lethal injection X Oklahoma QJ;: <: ·;::: u:: X <: 0 :;::; u "' "' ·;:: "" :1 � "' "' > :;::; "' <: � "' Lethal injection Lethal injection X X <: "' "' "C 0 ..<:: .... "' :1 C" X Ohio "C "C X Mississippi Nevada <: 0 :;::; :1 u 0 � Lethal injection X X Lethal injection Lethal injection; but electrocution if lethal injection held unconstitutional; if both lethal injection and electrocution held unconstitutional, then firing squad midazlam/ hydromorphone midazlam/ hydromorphone Study Response to HR 142 of the Louisiana 2014 Regular Legislative Session Page [6 " 0 ;: ·u Q) ·;: iii .<: Q) ...J State " 0 ., ::s u 0 � u Q) ;:u � Q) .<> E "' .<: u "' "' \!) " b.O " "' ·;;, J: , " "' "' , , "' ::s 0" V> "' ·;: u: X Lethal injection Pennsylvania South Carolina X X South Dakota X Tennessee X Texas X Utah X 0 ·;: u "' Q) ·;: b.O ::s � c iii .<: Q) " 0 � .<: - Q) Q).:!:: 2 ·;: ...J Statute specifies an ultrashort-acting barbituate in combination with a chemical paralytic agent and potassium chloride Statute specifies an ultrashort-acting barbituate in combination with chemical paralytic agents Electrocution, but inmate may choose lethal injection; if fails to choose either, then lethal injection; but if convicted prior to date of statute, then electrocution unless chooses letha I injection; if lethal injection held unconstitutional, then electrocution X Lethal injection Lethal injection; but offender, whose capital offense occurred prior to 1/1/99, may choose electrocution; if those methods deemed unconstitutional, then use any constitutional method X X Lethal injection Lethal injection; but firing squad if court determines inmate has a right to this alternative; if lethal injection is held unconstitutional, then firing squad Statute specifies that one of the intravenous injections shall be sodium thipoental or equivalent Study Response to HR 142 of the Louisiana 2014 Regular Legislative Session Page 17 c:: ·.;::;0... QJ ·;: "' .<:: � State Virginia X Washington X Wyoming X c::0 ·�... e tl QJ w QJ � .c "' .<:: u E "'"' (!) bO c:: c::"'.. . :I: "C "C "' C' c:: "' "'QJ tl)".p "C "' > 0 "'c:: "' bO c:: ·;: ... QJ QJ� .s::: ;:;: � :2;<( Inmate may choose lethal injection or electrocution; if refuses to choose, then lethal injection X X X Lethal injection, unless inmate chooses hanging Lethal injection; if lethal injection is held unconstitutional, then lethal gas. * *Wyoming Senate recently approved legislation that allows for the use of a firing squad. Concurrence is pending by the House. Statute specifies an ultra­ short-acting barbituate, alone or in combination with a chemical paralytic agent and potassium chloride It may be noted that the basis for utilizing a particular method of execution is not necessarily uniform among the states that offer more than one execution method. In some states, lethal injection is the primary execution method unless it should be declared unconstitutional, in which case the statute next provides for an alternate method, or a series of alternate methods in the event a successive method should be deemed unconstitutional. In other states, the condemned inmate is actually given a choice between lethal injection and another alternate method of execution. In Louisiana, between 1919 and May 21, 1957, executions were conducted by the local parish law authorities. Prior to August 6, 1941, the penalty in Louisiana was carried out by hanging. The last hanging in Louisiana was on March 7, 1941. Between August 6, 1941 and June 9, 1961, executions were performed by electrocution in the electric chair. Between 1941 and 1957, a portable electric chair was transported from parish to parish in order that the death penalty could be administered in the parish where the crime was committed. After 1957, the State became responsible for administering the death penalty. Prior the reinstatement of capital punishment, the last death in the electric chair was on June 9, 1961. In 1967, there was a rising tide of litigation against the death penalty. Federal courts suspended all executions pending a final decision by the U.S. Supreme Court. In 1972, the U.S. Supreme Court struck down all capital punishment laws as unconstitutional. All individuals under death sentenced at that time were re-sentenced to life in prison. Study Response to HR 142 of the Louisiana 2014 Regular Legislative Session Page 18 Effective October 1, 1976, the new Louisiana death penalty statute was adopted. The state's death penalty law was again revised in 1978, specifying that the sentencing judge must sign the death warrant rather than the governor. Capital punishment was reinstated in Louisiana on June 29, 1979. In 1990, the legislature approved the use of lethal injection for those sentenced after January 1, 1991. In 1991, the legislature provided that every death sentence executed after September 15, 1991 would be by lethal injection. Since the reinstatement of the death penalty in 1979, there have been 28 executions performed, 20 by electrocution and 8 by lethal injection. The last one was on January 7, 2010. The death penalty has risen to the forefront of national headlines recently due to the shortage of drugs historically used in the lethal injection process. States continuing to carry out executions have been forced to obtain drugs from other sources or substitute drugs normally used in the process. The alternatives have provided inmates with new grounds for appeal as they request transparency regarding execution methods. To date, Louisiana has 85 offenders in custody who have been sentenced to death. Study: This study was conducted by reviewing available scientific, technical and safety literature related to various methods of execution. It is not intended to express an opinion about Louisiana's law for administration of capital punishment. Lethal Injection Protocols: Through February 2011, Louisiana had in place a three drug protocol which included 3 gm sodium thiopental, 50 mg pancuronium bromide and 240 meq potassium chloride. In February 2011, after lawsuits, international trade restrictions and raw materials shortages complicated the market for drugs used in executions and the lack of availability of sodium thiopental, a decision was made to modify the three 3 drug protocol to use pentobarbital in lieu of sodium thiopental. This decision was based on experiences in Oklahoma using pentobarbital and the use of it being upheld in the United State District Court in the Western District of Oklahoma. Base on the change, the protocol then called for 1 gm of Pentobarbital, 50 mg pancuronium bromide and 240 meq potassium chloride. In January 2014, the protocol was again updated to provide two options for lethal injection. They are: A) 5 gm of Pentobarbital or B) 10 mg of Midazolam and 40 mg of Hydromorphone Study Response to HR 142 of the Louisiana 2014 Regular Legislative Session Page 19 Recommended Protocols: A. Lethal Injection We are recommending for consideration a lethal injection protocol that calls for the use of a one drug protocol utilizing 5 gm of Pentobarbital injected intravenously (IVP). This protocol has been used in numerous states, including Texas, as a one drug method. The availability of this drug to Departments of Corrections is however severely hampered and there could be issues obtaining a supply of Pentobarbital or any other drug to be used for lethal injection. Drug suppliers have refused to sell drugs to the prison systems for use in executions and other entities have refused to sell to Louisiana DOC. It is this committees understanding that suppliers have threatened providers with no longer supplying the drugs to their businesses if they in turn sell to correctional agencies for the purpose of lethal injection. As a result, suppliers fear the backlash of bad publicity to their businesses if involved in providing the drugs to correctional agencies. This committee also recommends reconsideration of a bill that combines the language from the original and amended versions of House Bill 328 of the 2014 Legislative Session authored by Representative Lopinto. The attached draft legislation (Appendix A) amending LA R.S. 15:569 outlines what is needed to allow for the recommendations within this report and will provide for the confidentiality of information related to the execution of a death sentence. The amended version of the prior bill stated that "The name, address, qualifications, and other identifying information of any person or entity that manufactures, compounds, prescribed, dispenses, supplies or administers the drugs or supplies utilized in an execution shall be confidential, shall not be subject to disclosure, and shall not be admissible as evidence or discoverable in any action of an kind in any court or before any tribunal, board, agency, or person. The same confidentiality and protection shall also apply to any person who participates in an execution or performs any ancillary function related to an execution and shall include information contained in any department records, including electronic records, that would identify any such person." Such legislation would provide some security to those tasked to and involved in carrying out the state's order to execute an individual as punishment for a qualifying crime. It should also be noted that the U.S. Supreme Court will consider in April whether a multi-drug protocol used in recent lethal injections in other states violates the Constitution with regard to cruel and unusual punishment. B. Induced Hypoxia via Nitrogen It is the recommendation of this study group that hypoxia induced by the inhalation of nitrogen be considered for adoption as an alternative method of administering capital punishment in the State of Louisiana. Study Response to HR 142 of the Louisiana 2014 Regular Legislative Session Page 110 It is important to note that the recommendation would induce hypoxia, which is a deficiency of oxygen reaching the tissues of the body. In nitrogen induced hypoxia, there is no buildup of carbon dioxide in the bloodstream so the subject passes out when the blood oxygen falls too low. The research reviewed suggests that this method would be the most humane method and would not result in discomfort or cruel and unusual punishment to the subject. Though the exact protocol and nitrogen delivery device have not been finalized, it has been determined that a Gas Chamber would not be used. Options for the nitrogen delivery device include a mask or a device similar to an oxygen tent house (small clear oxygen tent covering only the head and neck area). Research as to the best method of delivery is ongoing. Oklahoma has recently filed similar legislation to allow for induced hypoxia (refer to Appendix B). Also, you will find attached the Executive Summary (Appendix C) of the research conducted in Oklahoma that supports this method as a humane method which does not require the assistance of licensed medical professionals. We have also attached the documents (Appendix D) which make up the research used in Oklahoma by this committee in developing this recommendation. This method is believed to be simple to administer and nitrogen is readily available. Conclusion: This committee submits this study response to House Resolution 142 of the 2014 Regular Legislative Session to make recommendations to consider relative to the different forms of execution and the methods of execution upon agreement that the above considerations represent the best practices for administering the death penalty in the most humane manner. There are two sides to the debate on the death penalty. Proponents believe that the death penalty reduces crime and provides safe communities, while also honoring the victim and those left behind who grieve a loss. Opponents believe that the cost of capital punishment doesn't justify the outcome, that it does not deter crime, and that there are social injustices that are not addressed that make justice system inequitable. As a whole, this committee takes no stand on either side of this debate, but submits this response based on the request for this study and the research and materials available to the group. We close reminding readers that many are directly impacted by the process of capital punishment: the victim, the victim's friends and family; law enforcement; the judiciary, the prosecutor, the defense attorney, the jurors, the public, the offender, the offender's family, and the staff tasked to carry out the protocol, to name just a few. We understand that the decision to act on these recommendations for consideration is an enormous task before you that cannot be taken lightly. We trust that we have provided the information you needed to consider Louisiana's options. Study Response to HR 142 of the Louisiana 2014 Regular Legislative Session Page Ill Amendment to LSA-R.S. 15:569 Appendix A **Delete current Sections A and B; rewrite statute to read as follows: Section 1. R.S. 15:569 is hereby amended to read as follows: §569. Place for execution of death sentence; manner of execution; confidentiality Every sentence of death executed in this state on or after August 1, 2015, shall be conducted by either of the following methods: (1) Lethal injection, which is the intravenous injection of a substance or substances in a lethal quantity into the body of a person convicted until such person is dead. Execution by lethal injection shall be pennitted in accordance with procedures developed by the department. (2) Induced hypoxia via nitrogen or an ine1t gas, which is the administration of gas in a lethal quantity upon the body of a person convicted until such person is dead. Execution by nitrogen or inert gas shall be pennitted in accordance with procedures developed by the depattment. A. The method of execution shall be chosen by the secretary of the depattment based upon the availability of the depattment to administer the lethal injection or induced hypoxia. B. Every sentence of death imposed in this state shall be executed at the Louisiana State Penitentiary at Angola. Every execution shall be made in a room entirely cut off from view of all except those permitted by law to be in that room. C. No licensed health care professional shall be compelled to administer the lethal injection or induced hypoxia. D. The name, address, qualifications, and other indentifying information of any person or entity that manufactures, compounds, prescribes, dispenses, supplies, or administers the drugs or supplies utilized in an execution shall be confidential, shall not be subject to disclosure, and shall not be admissible as evidence or discoverable in any action of any kind in any court or before any tribunal, board, agency, or person. The same confidentiality and protection shall also apply to any person who participates in an execution or perfonns any ancillary function related to an execution and shall include infom1ation contained in any depattment records, including electronic records, that would identify any such person. E. The provisions of the Administrative Procedure Act, R.S. 49:950, et seq., shall not apply to the procedures and policies conceming the process for implementing a sentence of death. STATE OF OKLAHO! 1 2 3 Appendix B 1st Session of the 55th Legislature By: HOUSE BILL 1879 (2015) Christian 4 5 6 AS INTRODUCED 7 An Act relating to criminal procedure; 8 of inflicting punishment of death; O.S. 2011, Section 1014, amending 22 which relates to the manner providing alternative method for inflicting punishment of 9 death; and providing an effective date. 10 11 12 13 14 15 BE IT ENACTED BY THE PEOPLE OF THE STATE OF OKLAHOMA: SECTION 1. AMENDATORY 22 O.S. 2011, Section 1014, is amended to read as follows: Section 1014. A. The punishment of death shall be carried out 16 by the administration of a lethal quantity of a drug or drugs until 17 death is pronounced by a licensed physician according to accepted 18 standards of medical practice. 19 B. If the execution of the sentence of death as provided in 20 subsection A of this section is held unconstitutional by an 21 appellate court of competent jurisdiction or is otherwise 22 unavailable, 23 nitrogen hypoxia. then the sentence of death shall be carried out by 24 Req. No. 6354 Page 1 1 C. If the execution of the sentence of death as provided in 2 subsection subsections A and B of this section is held 3 unconstitutional by an appellate court of competent jurisdiction or 4 is otherwise unavailable, 5 carried out by electrocution. 6 � D. then the sentence of death shall be If the execution of the sentence of death as provided in 7 subsections A ana� B and C of this section is held unconstitutional 8 by an appellate court of competent jurisdiction or is otherwise 9 unavailable, 10 11 then the sentence of death shall be carried out by firing squad. SECTION 2. This act shall become effective November 1, 2015. 12 13 55-1-6354 GRS 01/20/15 14 15 16 17 18 19 20 21 22 23 24 Req. No. 6354 Page 2 Nitrogen Induced Hypoxia Nitrogen Induced Hypoxia as a Form of Capital Punishment Michael P. Copeland, J.D. Thorn Parr, M.S. Christine Papas, J.D., Ph.D. East Central University Preliminary Draft. Do Not Cite 1 Nitrogen Induced Hypoxia Executive Summary At the request of Oklahoma State Representative Mike Christian, the authors of this study researched the question of whether hypoxia induced by nitrogen gas inhalation could serve as a viable alternative to the current methods of capital punishment authorized under Oklahoma law. As per the above, this study does not express an opinion on the wider question of whether Oklahoma should continue to administer capital punishment in general. The scope of this study is limited to the assumption that capital punishment will continue to be administered in Oklahoma, and given that assumption, analyzing whether hypoxia via nitrogen gas inhalation would be an effective and humane alternative to the current methods of capital punishment practiced in Oklahoma law. This study was conducted by reviewing the scientific, technical, and safety literature related to nitrogen inhalation. The study found that: 1. An execution protocol that induced hypoxia via nitrogen inhalation would be a humane method to carry out a death sentence. 2. Death sentence protocols carried out using nitrogen inhalation would not require the assistance of licensed medical professionals. 3. Death sentences carried out by nitrogen inhalation would be simple to administer. 4. Nitrogen is readily available for purchase and sourcing would not pose a difficulty. 5. Death sentences carried out by nitrogen inhalation would not depend upon the cooperation of the offender being executed. Accordingly, it is the recommendation of this study that hypoxia induced by the inhalation of nitrogen be offered as an alternative method of administering capital punishment in the State of Oklahoma. The views expressed in this study are solely those of its authors and do not necessarily reflect those of the university at which we are affiliated. Preliminary Draft. Do Not Cite 2 Nitrogen Induced Hypoxia Introduction Nitrogen is an inert gas that at room temperature is colorless, odorless, and tasteless. It is the most common gas in the earth's atmosphere, comprising 78.09% of the air that humans breathe on a regular basis. When combined with the normal 20.95% oxygen found in the atmosphere, nitrogen is completely safe for humans to inhale. However, an environment overly enriched in nitrogen will lack the appropriate level of oxygen necessary for human survival and will thus lead to hypoxia and rapid death. (U.S. Chemical Safety and Hazard Investigation Board, 2003, p.l). Nitrogen hypoxia has been suggested as a means of administering capital punishment in the popular media on previous occasions. For example, inl995 the National Review featured an article by Stuart Creque titled Killing With Kindness: Capital Punishment by Nitrogen Asphyxiation (1995). Creque's article was written in response to a 9th Circuit U.S. District Court decision that California's gas chan1ber was an unconstitutionally cruel and unusual punishment. The article suggested nitrogen could provide a simple and painless alternative to the gas chamber that would require no elaborate medical procedures to administer. The idea of administering capital punishment via nitrogen hypoxia resurfaced more recently in a Tom McNichol Slate magazine mticle titled Death by Nitrogen (2014). The article was inspired by the stay of execution issued by the U.S. Supreme Court for a Missouri man facing execution via lethal injection. Again, the author suggested nitrogen induced hypoxia as a painless alternative to traditional methods of execution, adding that it offered the additional benefits of requiring no medical training to administer and lacked any of the supply issues that exist with lethal injection. Preliminary Draft. Do Not Cite 3 Nitrogen Induced Hypoxia The capital punishment protocols cited that utilize nitrogen to administer a death sentence do not actually rely on the nitrogen itself to bring abont death. Nitrogen simply displaces the oxygen normally found in air and it is the resulting lack of oxygen which causes death. Without oxygen present, inhalation of only 1-2 breaths of pure nitrogen will cause a sudden loss of consciousness and, if no oxygen is provided, eventually death. (European Industrial Gases Association, 2009, p. 3). Since nitrogen has not previously been used for capital punishment there is a lack scientific literature that specifically addresses its pelfonnance for that purpose. However, there have been medical experiments which involved human subjects breathing pure nitrogen until they became unconscious. Beyond those experiments, most of the data related to nitrogen induced hypoxia comes from documented suicides in humans and research in high altitude pilot training. Author's Note: in some cases the lay press will inadvertently refer to hypoxia as asphyxiation. This is technically inaccurate in this context. as asphyxia is the inability to breathe in oxygen and the inability to exhale carbon dioxide. Hypoxia is the pathology related to the inability to intake oxygen even though one may still be able to exhale carbon dioxide. As will be seen later. the ability to exhale carbon dioxide is critical to the proposed method of execution. as it prevents the acidosis normally associated with asphyxiation. Medical Literature The adult brain uses about 15 per cent of the heart's output of oxygenated blood (Graham, 1977, p.l7 0). Hypoxia is the condition of having a lower-than-normal amount of oxygen in the blood. Anoxia is an extreme form of hypoxia in which there is a complete absence of oxygen in the blood (Brierley, 1977 p.l81 ). If the supply of oxygen in the blood is reduced Preliminary Draft. Do Not Cite 4 Nitrogen Induced Hypoxia below a critical level it will result in a rapid loss of consciousness and eventually irreversible brain damage will occur (Graham, 1 977, p.l70). A complete immediate global loss of oxygen to the brain, (a scenario in which no residual oxygen in the lungs or blood is delivered to the brain), will result in a loss of consciousness in eight to ten seconds, and a loss of any electrical output by the brain will occur a few seconds later. The heart may continue to beat for a few minutes even after the brain no longer functions (Brierley, 1 977 p. l82). Ernsting (1 961 ) performed a study on human volunteers that hyperventilated on pure nitrogen gas. The subjects performed the test multiple times, varying the length of time they inhaled the nitrogen. When the subjects inhaled nitrogen for eight-to-ten seconds they reported a dimming of vision. When the period was expanded to fifteen-to-sixteen seconds, the subjects reported some clouding of consciousness and impairment of vision. When the tests were expanded to seventeen-to-twenty seconds, the subjects lost consciousness. There was no reported physical discomfmt associated with inhaling the pure nitrogen. (p. 295) Unlike asphyxiation, hypoxia via the inhalation of nitrogen allows the body to expel the carbon dioxide buildup that is normally associated with the respiratory cycle. This helps prevent a condition known as hypercapnia - an accumulation of carbon dioxide in the blood. The result of this buildup of carbon dioxide is respiratory acidosis - a shifting of the ph levels in the blood to become more acidic. This is the pathology many people associate with suffocating. Some of the symptoms of respiratory acidosis are expected to be present in cases of asphyxiation. but not expected to be present under pure hypoxia are anxiety and headaches, (Merrick Manuel, 2013). Suicide Data Preliminary Draft. Do Not Cite 5 Nitrogen Induced Hypoxia Perhaps one of the greatest testaments to both the humanity of nitrogen induced hypoxia as well as the ease of administration is its rapidly gaining popularity as a self-selected means of suicide. Suicide by hypoxia using an inert gas is the most widely promoted method of human euthanasia by right-to-die advocates (Howard, M.O. et. a!., 20 1 1, P. 6 1). The trend toward using an "exit bag" filled with an inert gas such as nitrogen or helium likely started with a publication of Final Exit: The Practicalities of Se(f'Deliverance and Assisted Suicide for the Dying. The authors of the publication sought to identify methods of death that were swift, simple, painless, failure-proof, inexpensive, non-disfiguring and did not require a physician's assistance or prescription (Howard, M.O. et. a!., 201 1. p 6 1). This method of suicide is indeed simple. It involves a clear plastic bag fitted over the head, two tanks filling the bag with helium via vinyl tubing, and an elastic band at the bottom of the bag to prevent the bag from slipping off the head. The parts needed to create the bag are inexpensive and available locally without prescription (Howard, M.O. et. a!., 20 1 1. p 6 1-62). Reports of deaths observed via this method suggest that it is painless. Jim Chastain, Ph.D. President of the Final Exit Network of Florida described the process this way: In the several events I have observed the person breathes the odorless, tasteless helium deeply about three or four times and then is unconscious. no gagging or gasping. Death follows in 4-5 minutes. A peaceful process. Derek Humphrey, current chair of the Final Exit advisory board is quoted as saying: In the approximate 300 cases which have been reported to me there has never been mention of choking or gagging. When I witnessed the helium death of a friend of mine it could not have been more peaceful (Final Exit, 20 10). However, it should be noted that deviations from the above protocols have not always been as successful. When masks were placed over the face (instead of using bags of helium over Preliminary Draft. Do Not Cite 6 Nitrogen Induced Hypoxia the head) it has been reported some problems have occurred. This is typically a result of the mask not sealing tightly to the face, resulting in a small amount of oxygen being inhaled by the individual. This extends the time to become unconscious and extends the time to death. This may result in purposeless movements by the decedent (Ogden et a!, 2010. p 174- 179). Research on High Altitude Pilot Training A great deal of research on the effects of hypoxia on human beings comes from aerospace medicine. Pilots that t1y at high altitudes are subject to becoming hypoxic if their cabins lose air pressure. Altitude hypoxia has similar effects as the hypoxia one gets from breathing inert gases although it is caused by the inability of the lungs to absorb the oxygen in the air rather than a lack of oxygen in the air. The Federal Aviation Administration (2003, p. 1 1) states: Hypoxia is a lack of sufficient oxygen in the body cells or tissues caused by an inadequate supply of oxygen, inadequate transportation of oxygen, or inability of the body tissues to use oxygen. A common misconception among many pilots who are inexperienced in high-altitude t1ight operations and who have not be exposed to physiological training is that it is possible to recognize the symptoms of hypoxia and to take corrective actions before becoming seriously impaired. While this concept may be appealing in theory, it is both misleading and dangerous for an untrained crew member. Symptoms of hypoxia vary from pilot to pilot, but one of the earliest effects of hypoxia is impairment of judgment. Other symptoms can include one or more of the following: ( l ) Behavioral Changes (e.g. a sense of euphoria). (2) Poor coordination. (3) Discoloration in the fingernails (cyanosis). (4) Sweating. (5) Increased breathing rate, headache, sleepiness, or fatigue (6) Loss or deterioration of vision (7) Light-headedness or dizzy sensations and listlessness. (8) Tingling or warm sensations. Preliminary Draft. Do Not Cite 7 Nitrogen Induced Hypoxia Indeed, hypoxia has caused several airline accidents which are often fatal. The onset of hypoxia is typically so subtle that it is unnoticeable to the subject. The effects of hypoxia are often difficult to recognize. (Federal Aviation Administration. 2014, Ch. 8-1-2 (A) 5) Attempts to train pilots to notice hypoxia are conducted using a hyperbaric chamber to simulate high altitudes. Often a trainee will be asked to remove his or her mask and perform simple tasks. At low levels of hypoxia, trainees typically feel little more than euphoria and a sense of confidence. At higher levels of hypoxia, trainees will quickly become unconscious. Time of useful consciousness at altitudes above 43,000 is 5 seconds (Federal Aviation Administration, 2003, p. 13). Findings Based on the review of the literature related to hypoxia induced by inert gases. this study makes the following findings: 1. An execution protocol that induced hypoxia via nitrogen inhalation would be a humane method to carry out a death sentence. 2. Death sentence protocols carried out using nitrogen inhalation would not require the assistance of licensed medical professionals. 3. Death sentences carried out by nitrogen inhalation would be simple to administer. 4. Nitrogen is readily available for purchase and sourcing would not pose a difficulty. 5. Death sentences carried out by nitrogen inhalation would not depend upon the cooperation of the offender being executed. 6. Use of nitrogen as a method of execution can assure a quick and painless death of the offender Finding 1. An execution protocol that induced hypoxia via nitrogen inhalation would be a humane method to carry out a death sentence. Rationale: Preliminary Draft. Do Not Cite 8 Nitrogen Induced Hypoxia As an inert gas, nitrogen is odorless, colorless, tasteless and undetectable to human beings. It is 78% of the air we breathe on a daily basis, and thus there is little chance that any subject would have an unusual or allergic reaction to the gas itself. Because the subject is able to expel carbon dioxide, the anxiety normally associated with acidosis in asphyxiation would not be present. The literature indicates after breathing pure nitrogen, subjects will experience the following: within eight-to-ten seconds the subjects will experience a dimming of vision, at fifteen-to-sixteen seconds they will experience a clouding of consciousness, and at seventeen-totwenty seconds they will lose consciousness. There is no evidence to indicate any substantial physical discomfort during this process. There is a possibility that subjects will feel euphoria prior to losing consciousness and a slight possibility they will feel a tingling or warm sensation. After the subjects are unconscious, it should be expected some of the subjects will convulse. Most electrochemical brain activity should cease short!y after loss of consciousness, and the heart rate will begin to increase to varying degrees until it stops beating 3 to 4 minutes later. Observed suicides involving inert gas hypoxia are described as peaceful, so long as caution is taken to eliminate the possibility of the subject inadvertently receiving supplemental oxygen during the process. Inert gas hypoxia is considered such a humane and dignified process to achieve death that it is recommended as a preferred method by right-to-die groups. Finding 2. Death sentence protocols carried out using nitrogen inhalation would not require the assistance of licensed medical professionals. Rationale: Preliminary Draft. Do Not Cite 9 Nitrogen Induced Hypoxia The administration of a death sentence via nitrogen hypoxia does not require the use of a complex medical procedure or pharmaceutical products. The process itself, as demonstrated by those who seek euthanasia, requires little more than a hood sufficiently attached to the subject's head and a tank of inert gas to create a hypoxic atmosphere. While a state execution would likely have a more elaborate mechanism to create hypoxia, nothing in the process would require specialized medical knowledge or the use of regulated pharmaceutical products. Accordingly, except for the pronouncement of death, the assistance of licensed medical professionals would not be required to execute this protocol. Finding 3. Death sentences carried out by nitrogen inhalation would be simple to administer. Rationale: When considering a substitute method of capital punishment it is important to consider more than just what happens if everything goes according to protocol. The likelihood of mishaps must also be considered, as well as the consequences that would flow if those mishaps should occur. Because the protocol involved in nitrogen induced hypoxia is so simple, mistakes are unlikely to occur. Oxygen and nitrogen monitors may be placed inside the contained environment to insure the proper mixes of gas are being expelled into the bag and inhaled by the subject. However, the protocol should be careful to prevent the possibility of oxygen entering into the hood, as that can prolong time to unconsciousness and death, as well as increase the possibility of involuntary movements by the subject. Preliminary Draft. Do Not Cite 10 Nitrogen Induced Hypoxia The risks to witnesses are minimal, as any potential leak of the nitrogen would not be harmful in a normal! y ventilated environment. Finding 4. Nitrogen is readily available for purchase and sourcing would not pose a difficulty. Rationale: Nitrogen is utilized harmlessly in many fields within United States industries. Nitrogen is used in welding, hospital and medical facilities, cooking, and used in the preparation of liquid nitrogen cocktails. Nitrogen is used as a process to extend the life of food products such as potato chips. Nitrogen is used in doctor's offices to remove skin tags as well as other procedures. Accordingly, sources of nitrogen to be used for administering a death sentence should be easy to find and readily available for purchase for such purpose. Finding 5. Death sentences carried out by nitrogen inhalation would not depend upon the cooperation of the offender being executed. Rationale: Some forms of capital punishment require the offender to submit or comply to some degree in order to assure an efficient and humane method of execution. With proper protocol and utilizing such devices as a restraint chair, nitrogen inhalation can be administered despite the presence of a non-compliant offender. The use of nitrogen can be used by non-medical personnel and a delivery system can be designed to ensure the execution is carried out without issue. Preliminary Draft. Do Not Cite 11 Nitrogen Induced Hypoxia Conclusion As per the above, it is the recommendation of this study that hypoxia induced by the inhalation of nitrogen be offered as an alternative method of administering capital punishment in the State of Oklahoma. Preliminary Draft. Do Not Cite 12 Nitrogen Induced Hypoxia References Brierley, J.R Experimental hypoxic Brain Damage Journal of Clinical Pathology. 1977, II, 181-187. Creque, S. A (1995). Killing with kindness-capital punishment by nitrogen asphyxiation. Nat/ Rev, 47(17), 51. Ernsting, J. The Effect of Brief Profound Hypoxia upon the Arterial and Venous Oxygen Tensions in Man. J. PhysioL 169, Air Force Inst of Av. Med. 1-23-1963 pp. 292-31 L Federal Aviation Administration, Department of Transportation, (7/24114) - Aeronautical Information ManuaL Retrieved online at: https://www.faa. gov/airtraffic/publications/atpubs/airn/aim080 I .htrnl on 9/14/2014 Federal Aviation Administration, Department of Transportation, (1/2/2003) AC 61-107A­ Operations of Aircraft at Altitudes Above 25,000 Feet MSL And/Or Mach Number (MMO) Greater Than .75 Final Exit Network, The. (March 17,201, 2010lium Deaths Do Not involve Gagging Say Observers. Retrieved on 9114/2014 http://assisted-dying.org/blog/2010/03117/helium-deaths-do­ not-involve-gagging-say-observers/ Graham, D.L Pathology of hypoxic brain damage in man, J, clin. Path., 30, SuppL (Roy. CoiL Path.), 1977, II, 170-180 Hazards of Inert Gases and Oxygen Depletion. IGC Document 44/09/E European Industrial Gases Association. 2009. Hazards of Nitrogen Asphyxiation. No. 2003-10-B, U.S. Chemical Safety and Hazard Investigation Board. June. 2003. Howard, M. 0., Hall, M. T., Edwards, J, D., Vaughn, M. G., Perron. B. E., & Winecker, R. E. (2011). Suicide by asphyxiation due to helium inhalation. The American journal of forensic medicine and pathology, 32(1), 61-70. Humphry, D. (2002). Final exit: the practicalities of seirdeliverance and assisted suicide for the dying. Random House LLC. Merrick Manuel The. (20!3, October) Repertory Acidosis. Retrieved from: http://www.merckmanuals.com/professionallendocrine and metabolic disorders/acid­ base regulation and disorders/respiratory acidosis.htrnl on 9/!4/2014. Preliminary Draft. Do Not Cite 13 Nitrogen Induced Hypoxia McNichol, T. Death by Nitrogen - Slate Magazine.l4 Sep. 2014 http://www .slate.com/articles/news and politics/jurisprudence/20 14/05/death by nitrogen will the new method of execution save the death penaltv.html. 2as Ogden, R.D., Hamilton, W.K., Whitcher, C., (2010 Mar) Assisted suicide by oxygen deprivation with helium at a Swiss right-to-die organisation.J. Med. Ethics: 174-9. Ogden, R. D., & Wooten, R. H. (2002). Asphyxial suicide with helium and a plastic bag. The American journal ojjorensic medicine and pathology, 23(3), 234-237. Preliminary Draft. Do Not Cite 14 Death by nitrogen gas: Will the new method of Sign In Sign Up Appendix D of l l Death by N itrogen: Will This New Method of Execution Save the Death Penalty? Sign In Sign Up JURISPRUDENCE THE LAW, LAWYERS, AND THE COURT. MAY 222014 1 1 :47 AM Death by Nitrogen If lethal injection falls out of favor, death penalty states could turn to a new method: nitrogen gas. Justice Samuel Alita issued an order halting the execution of a Missouri inmate. Photo by Saul Loeb/AFP/Getty l11111gos On Wednesday night, the Supreme Court stopped an execution by lethal injection. The condemned Missouri man, Russell Bucklew, says he has a medical condition, affecting his veins, that would make the injection cause hemorrhaging-and make him feel like he's choking on his own blood. The court took the unusual step of intervening at the last minutes, when every other court had tumed Bucklew down, and also of sending the case back to the lower courts to decide whether to hold a hearing about Bucklew's claim. The Supreme Court ruled in 2008 that Kentucky's three-drug protocol for carrying out lethal injections was constitutional, but there's no question that the method looks grimly suspect in the wake of Clayton Lockett's apparently painful, botched execution in Oklahoma last month. Not so long ago, though, this was the method that represented progress. Hanging. Firing squad. The guillotine. The electric chair. The gas chamber. Lethal injection. Every age seems to feature a new and improved method of capital punishment, blUed as more efficient and humane. The spectacle of Lockett's death, and the Supreme Court's hesitation, shines a spotlight on the latest idea-death by nitrogen. As long as there's a will to kill criminals, someone will come up with an improved form of capital punishment. This new proposed method, known as nitrogen asphyxiation, seals the condemned in an airtight chamber pumped full of nitrogen gas, causing death by a lack of oxygen. Nitrogen gas has yet to be put to the test as a method of capital punishment-no country currently uses it for state�sanctioned executions. But people do die accidentally of nitrogen asphyxiation, and usually never know what hit them. (It's even possible that death by nitrogen gas is mildly euphoric. Deep�sea divers exposed to an excess of nitrogen develop a narcosis, colorfully known as "raptures of the deep,H similar to drunkenness or nitrous oxide inhalation.) Advertisement You can oppose the death penalty and still see the merit in making executions more humane. As Boer Deng and Dahlia Lithwick argued in Slate, opponents of the death penalty inadvertently have made lethal injection less safe, by forcing prison officials into using inferior methods and substandard drug providers. As the states struggle to obtain drugs, such as pentobarbital, for lethal injections because of an export ban by the European Union, lethal injection has been turned from a method of execution into a medical experiment. Proponents say that death by nitrogen, by contrast, adheres to the constitutional prohibition against cruel and unusual punishment. The condemned prisoner would detect no abnormal sensation breathing the odorless, tasteless gas, and would not undergo the painful experience of suffocation, which is caused by a buildup of carbon dioxide in the bloodstream, not by lack of oxygen. In late April, Louisiana Department of Corrections Secretary James LeBlanc suggested to a state legislative committee that Louisiana should look into using nitrogen gas as a new method of execution, since lethal injection has become so contentious. "It's become almost impossible to execute someone," LeBlanc complained to the Louisiana House Administration of Criminal Justice Committee. "Nitrogen is the big thing," LeBlanc told the committee. "It's a painless way to go. But more time needs to be spent [studying] that.� The committee instructed LeBlanc to do some research on the subject and report back. In the meantime, Louisiana has delayed a pending execution. "I'm not taking anything off the table," says state Rep. Joseph P. Lopinto Ill, chairman of the state's Administration of Criminal Justice Committee. "If someone says nitrogen gas is the way to go, then we can debate that and do it if need be." http://www .slate. com/articles/news_and_politics/jurisprudence/20 1 4/05/death_by_nitrogen_... 1/8/201 5 Death by nitrogen gas: Will the new method of execution save the death penalty? Page 2 of 1 1 As long as 32 states have capital punishment on the books, there should be a tess reliably cruel method of execution than lethal injection. "If we're going to take a life, then we should do it in the most humane, civilized manner as Is possible," says Lawrence Gist It, an attorney and professor of business and law at Mount St. Mary's College. "Right now, nitrogen is the best of the available options." Gist, a death penalty opponent, runs a website dedicated to promoting nitrogen asphyxiation for state-sanctioned executions. Polling suggests the public could get behind the idea. In a recent NBC News poll, 1 in 3 people said that if lethal injections are no longer viable, executions should be stopped altogether. But many others were open to alternative methods of putting prisoners to death. About 20 percent opted for the old version of the gas chamber (which traditionally used hydrogen cyanide to kill), 1 8 percent for the electric chair, 12 percent for death by firing squad, and 8 percent for hanging. Nitrogen gas, unlike the lethal drugs that states have relied on, is widely available. The gas is used extensively in industrial settings, from aerospace to oil and gas production "Lethal injection is just fine if you can get the pentobarbital," says Kent Scheidegger, legal director of the Criminal Justice Legal Foundation, a group that favors capital punishment. "But if that's not available, an alternative like nitrogen gas would work." Top Comment I always thought that people who voluntarily went to witness a cyanide gas chamber execution were morons. You have to have a special kind of faith in window caulking. More ... -Pete R Join In In contrast to lethal injection, no medical expertise would be needed to introduce nitrogen gas into a sealed chamber. The gas chamber itself is technology that has been around since the 1 920s. In fact, three states-Arizona, Missouri, and Wyoming-still authorize lethal gas as a method of execution (depending on the choice of the inmate, the date of the execution or sentence or the possibility that lethal injection is held unconstitutional). The last gas chamber execution in the U.S. was in 1999-the method fell out of favor because hydrogen cyanide is a poison causing suffering that lasts 1 0 minutes o r longer. Lethal injection, of course, was supposed to b e painless and better. What i f it's not? That's the question the Supreme Court now finally seems to be returning to. The history of capital punishment suggests that as long as there's a will to kill criminals, someone will come up with an improved way. The new tool in the executioner's bag may turn out to be nitrogen, a better way to carry out a gruesome task. Tom McNichol is a writer in San Francisco. PROMOTED STORIES 5 States that Will Take the Most of Your Paycheck in Income Taxes Monster 5 Easy To Obt�in Jobs That Pay Very Well Exclte Education 1 5 Hot Female Athletes Who Are Only Famous For Their Looks RantSports 4 Surgeries to Avoid AARP Oprah Winfrey's Surprising DNA Test Ancestry This New App is Replacing Human Financial Advisors pcM'''""' MORE FROM SLATE A Conservative Judge Annihilates North Carolina's Ultrasound Requirement Louis C.K. Wrote "'Charlie Hebda" on His Shirt For His Madison Square Garden Show Slate's Favorite Smartphone Apps of 2014 This Puzzle's Simple Design Is Gorgeous and Mind­ Boggling AP Takes Down "Piss Christ'" Image After Complaints About Double Standard Protests Have Achieved Some of America's Greatest Ideals htto://www.slate.com/articles/news and oolitics/iurisorudence/201 4/05/death hv nitro<>Bn 1 /R/?01 'i Page 1 of 6 Killing with kindness - capital punishment by nitrogen asphyxiation alt.suicide.methods Killing with kindness - capital punishment by nitrogen asphyxiation Philbert (too old to reply) 9 years ago http://www .findarticles.com/p/articles/mi_m1 282/is_n 1 7_v47/ai_17374449 Capital punishment needn't be cruel or unusual -- especially if you use nitrogen asphyxiation to put people to sleep. LAST October, Judge Marilyn Hall Patel of the 9th U.S. District Court ruled that execution in California's gas chamber is a form of cruel and unusual punishment, the first ruling ever by a state or federal judge to invalidate a method of execution on Eighth Amendment grounds. She noted that the evidence showed that the condemned man might remain conscious for several minutes, experiencing the emotions of 'anxiety, panic, terror,' as well as 'exquisitely painful muscle spasms' and 'intense visceral pain.' On its face, Judge Patel's ruling applies only to the gas chamber, but every method of execution in current use involves toxic chemicals or physical trauma to induce death -- and every method can go awry. An ideal hanging snaps the condemned man's neck cleanly; a botched one either strangles him slowly or severs the head entirely from the body. A firing squad that misses its mark leaves the condemned man conscious as he bleeds to death. In the electric chair, according to eyewitness accounts, some condemned men have literally been cooked until their flesh was charred and loosened from the bone; some had sparks and flame emanating from their cranial-cap electrodes. Besides society's concern for the condemned man's physical suffering, all of these methods implicitly require an executioner to inflict some degree of trauma upon the condemned. Concern for the executioner's conscience drives such customs as loading one of the guns for a firing squad with a blank cartridge, so that each member of the squad can imagine that his will be the non-lethal shot. And with lethal injection, the executioner's use of skills and procedures normally devoted to life-saving poses ethical questions for medical caregivers. Given these defects, abolitionists will presumably press to have each of these methods declared ' cruel and unusual.' The intended result of these efforts is to make the death penalty unconstitutional in practice, even if it remains constitutional in theory. It is in fact possible to conceive of a method of execution that would cause neither pain nor physical trauma, require no medical procedure (other than pronouncing death), and use no hazardous chemicals. A case of accidental http://alt.suicide.methods.narkive.com/G72bumjnlkilling-with-kindness-capital-punishment-... 1/8/201 5 Killing with kindness - capital punishment by nitrogen asphyxiation Page 2 of6 d eath suggests such a method. Early in the Space Shuttle program, a worker at Kennedy Space Center walked into an external fuel tank (a vessel nearly as big inside as a Boeing 737) to inspect it. He was not aware that it had been purged with pure nitrogen gas to prevent oxygen in the air from corroding its interior. Since nitrogen is the major component of ordinary air, pure nitrogen has no distinctive feel, smell, or taste; the worker had no indication that anything was out of the ordinary. After walking a short distance into the tank, he lost consciousness and collapsed. A co-worker, not realizing that his collapse had an external cause, ran in to aid him and succumbed also. By the time other workers realized what was happening, the two men were dead. More recently, a bizarre accident involving nitrogen killed two people in the Bay Area. They had stolen from a hospital a gas cylinder containing what they thought was laughing gas. However, the cylinder contained not the anaesthetic nitrous oxide but pure nitrogen. When the two men stopped their car to partake of their booty, the nitrogen gas displaced the air in the car, leaving them without oxygen. Had they had any indication of the problem, they could have saved their lives simply by opening the car doors. These deaths were similar in cause to a relatively common drowning accident known as shallow-water blackout, mentioned specifically in certification classes for recreational scuba diving. When a person is skin diving (that is, without scuba gear), his bottom time is limited by how long he can hold his breath. Occasionally, a skin diver will attempt to lengthen the time he can stay under by hyperventilating before a dive. Unfortunately, this can lead to his losing consciousness underwater, sometimes only a few feet before reaching the surface. THE connection between nitrogen asphyxiation and shallow-water blackout lies in human respiratory physiology. When you hold your breath, you begin to develop a powerful urge to breathe. This is caused not by the depletion of oxygen from your body, but by the buildup of carbon dioxide in your bloodstream, which changes the pH of the blood. The ambitious skin diver "blows off most of the carbon dioxide in his bloodstream when he hyperventilates; as a result, he notices the urge to breathe much later than he normally would, at a point when his blood oxygen is dangerously low. If his blood oxygen falls too low before he reaches the surface, he blacks out and drowns. Because the Kennedy Space Center workers continued to exhale carbon dioxide with each breath, neither of them noticed an unusual urge to breathe, even though they were completely deprived of oxygen. Nitrogen asphyxiation is a unique way to die. The victim is not racked by a choking sensation or a burning urge to breathe, because as far as his body 1 /0 /'1 f\ 1 .t: Page 3 of6 Killing with kindness - capital punishment by nitrogen asphyxiation knows, he is breathing normally. Carbon dioxide is not building up in his bloodstream, so he never realizes that anything is wrong, nor does he experience any discomfort; he simply passes out when his blood oxygen falls too low. Nitrogen asphyxiation is therefore a perfect method of execution. It uses a cheap and universally available working medium that requires no special environmental precautions for its storage and disposal. Its first symptom is loss of conscious sensation, a primary goal in a humane execution. It involves no physical trauma, no toxic drugs; the executed man's organs will even be suitable for donation, a factor cited in a recent stay of execution for a Georgia killer. Assuming that the prisoner's guilt has been sufficiently proved, nitrogen asphyxiation is perhaps the most gentle way to deal with him. A condemned man awaiting death by nitrogen asphyxiation would experience no more pain or suffering than he created in his own mind. , Dell Printers i dell.com/Printers . _____, D_ig_gv�r_ ProJe$sional:_Gr9-de_CQlor fnJ!Jl �ellJ�l!s!n��ts. .Print�rs,� nubbins 9 years ago x-no-archive : ye s Maybe even g o out laughing . - nubbi n s - Hey, Sandra Bullock Lied lifecoolbeauty.com/sandra·secret Her Fans Are In Shock. Her Huge Secret > ' Is Finally Exp osed! Philbert 9 years ago Post by nubbins x-no-archive:yes Maybe even go out laughing. - nubbins - You ' re thinking of nitrous oxide aka laughing gas . The article is about nit rogen . nubbins 9 years ago x-no-a rchive : ye s Post by Philbert I Post by nubbins Maybe even go out laughing. http:/Ialt.suicide.methods.narkive. corn!G72bumjnlkilling-with-kindness-capital-punishment-... 118/2015 Killing with kindness - capital punishment by nitrogen asphyxiation I Page 4 of6 You're thinking of nitrous oxide aka laughing gas. The article is about nitrogen. You are absolutely correct , sir . I was not paying due attention . Gets me in trouble in c l a s s a l l the time . Who would mind i f a doctor diagnosed onychomyco s i s a s cryptorchidism, really? Det a i l s , detai l s . - nubbins 9 years ago d***@hotmail.com Awe s ome articl e . I think you j us t solved the p u z z l e for me . Thank you . 9 years ago Philbert Google nitrogen s u i cide for a l ot o f stuf f . Bas i cal l y people find that euthanising animals works pretty well us ing n i t rogen , plus i t ' s s a fe to use unl e s s i t ' s i n a very high concent ration . Rabb i t s don ' t l i ke nitrogen because they have adaptive traits for living in h ol e s where nit rogen can build u p , On 4 / 6 / 0 6 3 : 2 5 PM , I unlike other anima l s and humans . in article Post by d'**@hotmaif. com Awesome article. I think you just solved the puzzle for me. Thank you. 9 years ago slunky Thanks for finding an a r t i cle on it . I ' ve been saying it for wee ks , and was s tarting to wonder i f I had j u s t imagined it or what . -slunky 9 years ago Cesar Thanks for the great p o s t and it was interest ing and informative . I have concern that when the death penalty i s ruled out as cruel and inhumane , it leaves the potential that the pri sone rs on death row could at some point get release and re-enter society . When p r i s ons be come too ful l , i t can be ruled that a certain amount of p r i s oners be released early . In the years to come , laws could change and s ee a pr i soner sentenced to death instead getting a l i fe sentence of 2 0 years then getting out . O f cour s e , i t would help those that were wrongly convi cted in the f i r s t p l a ce . Jimmy 9 years ago httn ://alt. suicide.methods.narkive com /G7?.hnmin/ki11in "-with-kincln F>«-"RnitR 1-nnni J> )> 5 DOC 44/09 It should be born in mind that when wearing these apparatus, particularly with air filled cylinders, it might sometimes be difficult to enter manholes. Periodic inspection of the correct functioning of the equipment shall be carried out in accordance with local regulations. Users shall be trained and shall practice handling of the equipment regularly. Confined spaces, vessels, etc. Any vessel or confined space where oxygen deficiency is expected and which is connected to a gas source shall be disconnected from such a source: By the removal of a section of pipe; or by inserting a blanking plate before and during the entry period. Reliance on the closure of valves alone might be fatal. A space or vessel should be thoroughly ventilated, and the oxygen content shall be measured periodically before and during entry period. If the atmosphere in such a vessel or space is not breathable, a qualified person shall use breathing equipment. Permission to enter such a space shall be given only after the issue of an entry permit signed by a responsible person. As long as a person is in a vessel or confined space, a watcher shall be present and stationed immediately outside of the confined entrance. He shall have a self-contained breathing apparatus readily available. The person inside the confined space to facilitate rescue shall wear a harness and rope. The duty of the watcher should be clearly defined. A hoist may be necessary to lift an incapacitated person. 6 Emergency Measures In the event of a person having fainted due to oxygen deficiency, he can only be rescued if the rescue personnel are equipped with breathing apparatus enabling them to enter the oxygen deficient space without risk. Remove the patient to the open air and administer oxygen without delay from an automatic resuscitator if available or supply artificial respiration. Guidelines and instructions for resuscitation can be obtained from the European Resuscitation Council (Internet Homepage: www.erc.edu ) Continue until patient revives or advised to stop by qualified medical personnel. . 14 IGC DOC 44/09 Appendix 8 1 : Rescue considerations from normally accessible rooms Planned Rescue Scenario: If work is undertaken on inert gas or cryogenic liquid systems within an enclosed room it is suggested that: • The entrant carries a personal oxygen monitor in addition to any fixed systems as the oxygen concentration may vary within the room if ventilation is absent or inadequate for the leak rate. • The atmosphere within the space is checked before entry • A stand-by watch is posted outside the space, to keep visual and verbal contact with the entrant and to ensure the entrant leaves the room unaided in case of early symptoms of oxygen deficiency • The stand-by watch can raise an alarm by telephone or radio on event of problems • • • The stand-by watch has Self Contained Breathing Apparatus (SCBA) ready so that he can safely enter the enclosed room to go to the assistance of, or to extract the victim if necessary. Unless a plan is in place so that the entrant can be safely removed by the standby-watch alone, then the rescue team should have been warned of the confined space entry work in progress, and be ready with Self Contained Breathing Apparatus (SCBA) and other equipment so that they can safely enter the Confined space to go to the assistance of, or to extract the victim if necessary. Plans have been made to obtain treatmenVassessment from qualified medical personnel for the victim as soon as possible after he is retrieved from the room. If a person is found collapsed in a room where there is a potential inert gas leak I oxygen deficient atmosphere, then the discoverer must assume that his life is at risk entering the same area. He should raise an alarm and call for assistance so that a prepared rescue can be carried out. Unplanned Rescue Scenario: ONLY if the collapsed person can be reached, from outside the room should any consideration be given to extracting the victim from the space and bringing him out to fresh air and medical attention. IF the victim has collapsed as a result of an oxygen deficient atmosphere and been there for any length of time it is very likely that he is dead and the discoverer's life is risked in vain. 15 IGC DOC 44/09 Appendix 82: Rescue considerations from Confined Spaces Planned Rescue Scenario: If work is undertaken within a Confined Space such as a vessel or a difficult access space, with potential inert gas/ oxygen deficient atmosphere, it is essential that: • The atmosphere within the space is made safe, ventilated and checked before entry • The entrant carries a personal oxygen monitor. • If practical the entrant wears a body harness with life line, so that he can be removed from the space by persons outside. A hoist or other mechanical aid may be needed • A stand-by watch is posted outside the space, to keep visual and verbal contact with the entrant and to ensure the entrant exits the Confined Space if symptoms of oxygen deficiency are suspected or observed • The stand-by watch can raise an alarm to call a trained rescue team by telephone or radio on event of problems • • • The rescue team should have been warned of the confined space entry work in progress, and be ready with Self Contained Breathing Apparatus (SCBA) and other equipment so that they can safely enter the Confined space to go to the assistance of, or to extract the victim if necessary. The stand-by watch should never enter the Confined Space. Plans have been made to obtain treatmenVassessment from qualified medical personnel for the victim as soon as possible after he is retrieved from the room. Unplanned Rescue Scenario: All Confined Spaces shall be closed or barricaded to prevent unauthorised access. There should be no possibility for uncontrolled entry into the Confined Space, so the "unplanned rescue" situation should not occur! If however a person is found collapsed in a Confined Space where there is a potential inert gas I oxygen deficient atmosphere, then the discoverer must assume that his life is at risk entering the same area. He must raise an alarm and call for assistance so that a prepared rescue can be carried out. IF the victim has collapsed as a result of an oxygen deficient atmosphere and been there for any length of time it is very likely that he is dead and the discoverer's life is risked in vain. 16 IGC DOC 44/09 Appendix 83: Rescue considerations from pits, trenches Planned Rescue Scenario: If work is undertaken in an excavation, trench, pit, or , , • • • • • • o - �. ,. other open spaces with potential inert gas I oxygen deficient atmosphere, it is strongly recommended that: • The atmosphere within the space is checked before entry The entrant carries a personal oxygen monitor, as the oxygen concentration may vary within the space if there is limited fresh air circulation. A stand-by watch is posted outside the space, to keep visual and verbal contact with the entrant and to ensure the entrant exits the area unaided if symptoms of oxygen deficiency are suspected or observed. The stand-by watch can raise an alarm to call a trained rescue team by telephone or radio on event of problems. The stand-by watch has Self Contained Breathing Apparatus (SCBA) ready IF it is practical for him enter the enclosed room to go to the assistance of, or to extract the victim alone. OR The rescue team should have been warned of the confined space entry work in progress, and be ready with Self Contained Breathing Apparatus (SCBA) and other equipment so that they can safely enter the space to extract the victim if necessary Plans have been made to obtain treatmenUassessment from qualified medical personnel for the victim as soon as possible after he is retrieved from the room. If a person is found collapsed in a trench, pit or other space where there is a potential inert gas leak I oxygen deficient atmosphere, then the discoverer must assume that his life is at risk entering the same area. He should raise an alarm and call for assistance so that a prepared rescue can be carried out. Unplanned Rescue Scenario: IF the victim has collapsed as a result of an oxygen deficient atmosphere and been there for any length of time it is very likely that he is dead and the discoverer's life is risked in vain. In addition it will often require several people to remove a victim from these kinds of spaces. 17 IGC DOC 44/09 Appendix C : Accidents involving oxygen deficiency The following list highlights real accidents recorded by EIGA, some of them very recent. The list illustrates how essential it is to regularly draw the attention of our personnel, as well as that of our customers, to the hazards of inert gases and oxygen deficiency. 1. A new pipeline i n a trench was being proof tested with nitrogen. A charge hand entered the trench to investigate the cause of an audible leak. He was overcome by nitrogen and died. 2. A workman was overcome by lack of oxygen after entering a large storage tank, which had been inerted with nitrogen. Two of his workmates, who went to his aid, without wearing breathing equipment, were also overcome and all three died. 3. A man was overcome on entering a steel tank which had been shut up for several years. The atmosphere inside the tank was no longer capable of supporting life due to removal of oxygen from the air by the rusting of steel. 4. A worker from a contractor company had to carry out welds inside a vessel. The vessel had been under a nitrogen blanket, but was ventilated with air before work started. In order to be on the safe side, the welder was asked to wear a fresh air breathing mask. Unfortunately a fellow worker connected the hose to a nitrogen line and the welder died from asphyxiation. This accident happened because the nitrogen outlet point was not labelled and had a normal air hose connection. 5. Welding work with an argon mixture was performed inside a road tanker. During lunchtime the welding torch was left inside the tank, and as the valve was not properly closed, argon escaped. When the welder re-entered the tank, he lost consciousness, but was rescued in time. Equipment that is connected to a gas source, except air, must never be left inside confined spaces during lunch breaks, etc. Merely closing the valves is not a guarantee against an escape of gas. If any work with inert gas is carried out in vessels, etc. take care with adequate ventilation or the use of proper breathing equipment. 6. A driver of a small-scale liquid nitrogen delivery service vehicle was making a delivery. He connected his transfer hose to the customer-installed tank, which was situated in a semi­ basement. After he had started to fill, one of the customer's employees told him that a cloud of vapour was forming around the tank. The driver stopped the filling operation and returned to the area of the tank to investigate. On reaching the bottom of the stairs, he collapsed, but fortunately he was seen by one of the customer's staff that managed to put on breathing apparatus, go in and drag the man to safety. The driver fully recovered. Unknown to the driver, the bursting disc of the storage tank had failed prior to the start of his fill and as soon as he started filling, nitrogen escaped in the vicinity of the storage tank. The oxygen deficient atmosphere overcame him when he went down to investigate without wearing his portable oxygen monitor, which would have warned him of the oxygen deficiency. The installation had been condemned and was no longer being used. Not only was the tank situated in a semi­ basement, but the relief device was also not piped to a safe area. 7. During a routine overhaul of an air separation plant, a maintenance technician had the task of changing the filter element on a liquid oxygen filter. The plant was shut down and a work permit was issued each day for each element of work. In spite of these precautions, the technician collapsed when he inadvertently worked on the filter after it had been purged with nitrogen. The fitter collapsed apparently asphyxiated by nitrogen. All efforts to revive him failed. 18 IGC DOC 44/09 8. At a cryogenic application, the equipment pressure relief valve located on the equipment inside the building opened because the pressure in the storage tank outside increased above the setting of the equipment pressure relief valve. Personnel about to enter the room the next morning were warned by the frosted appearance and did not enter. 9. A customer was supplied with 2 low temperature-grinding machines, which were located in the same area in the factory. The customer installed a joint nitrogen extraction system between the two machines. One machine was switched off for cleaning while the other machine was left running. One of the operators who had entered the unit for cleaning fell unconscious and was asphyxiated before help arrived. The linked extraction system had allowed exhausted nitrogen from the operating machine to flow into the unit to be cleaned. 1 0 . A driver was fatally asphyxiated during commissioning of a nitrogen customer station. The customer station tank was located in a pit that was not recognized as a confined space by the design team, distribution operation team or the driver. The driver was sent to do the commissioning by himself. During the commissioning the driver made a mistake in opening the liquid supply line valve, instead of the gas vent valve, for purging and cool down of the tank. It is believed he did not immediately notice the valving error partially due to a modified manifold that allowed gas to vent from an uncapped drain in the liquid supply line. When the driver opened the valve gas started venting as would normally occur except from the wrong location. Once he noticed that liquid rather than gas venting, he went into the pit to correct the valving error. At this point he walked into a nitrogen rich/oxygen deficient atmosphere. 1 1 . A group of workers were routinely working at the in-feed end of a tunnel freezer. As the temperature of the tunnel was approaching the desired set point, a new operator noticed that there was a cloud of N2 gas coming out at exit end of the freezer. He suddenly increased the speed of the scroll fan in order to remove the gas from exit to product entrance. The exhaust and scroll fans were running on manual mode. As a result, the N2 cloud moved to product entrance and five workers who were working around the loading table passed out. Fortunately, there were no serious injuries and all of them returned to work after taking a rest. 12. On an ASU still in commissioning phase three painters from a sub-subcontractor were working on a ladder to complete external painting works on nitrogen/water tower. To complete the painting of top tower section a wooden plank was put across the exhaust section to atmosphere. ·One painter climbed on the plank, surrounded by the nitrogen stream, and fell off inside the tower. The two other painters rushed from the ladder to the plank to rescue their team mate. Both collapsed into the tower as well. The three painters died before they could be rescued. 13. An experienced contractor was used to purge a natural gas pipeline, 0.5m diameter 10 km long, with nitrogen before start-up. When one contractor employee and two customer employees entered the remotely located chamber, they were asphyxiated and later found dead in the chamber. Two blind flanges were leaking and the oxygen monitor was not used. 3 14. A customer nitrogen tank, volume 1 0 m , on a PSA plant was to be inspected by the competent body. The inspector entered the tank and lost consciousness immediately. Two persons from the gas company participating in the inspection managed to bring the inspector out without entering the tank. The inspector recovered. 15. A liquid C02 tank was installed. The tank should be purged with air but mistakenly the hose was connected to nitrogen. The tank manhole was situated 4 m above ground. For reasons unknown, a contract employee brought a ladder, entered the tank and was asphyxiated. Previously that morning employees had been told not to enter the tank before the atmosphere was officially checked. 16. Employee stepped into a control cubicle where the instrument air was temporarily replaced with N2 during shutdown. The green light outside the door was on indicating safe atmosphere. As soon as he stepped into the cubicle his personal 02 monitor alarmed indicating 18% 02 or less. After exiting safely he opened the door and when 02 level was OK, checked the fan. The ventilation fan was not running. The light was wrongly wired. 19 IGC DOC 44/09 1 7. The perlite in a storage tank under erection had to be emptied by a contractor company, familiar with this job. During this work one of the workers fell down in the perlite, depth approximately 3m, and was asphyxiated. 1 8 . During the cleaning and painting maintenance of the internal and external surfaces of a water tank, one operator suffered anoxia due to nitrogen being used to purge the vessel instead of air. Two employees tried to rescue the victim and fainted. These two operators were rescued and transported to hospital for intensive care however the original operator died. 1 9. During the installation of a new LIN phase separator on LIN pipe work at a customer site, a technician went into the roof space. His personal oxygen-monitoring device began to alarm immediately, indicating low oxygen levels. The technician left the roof space immediately and informed the customer. Later in the same week, the customer owned food-freezing machinery was operating, and a project engineer measured concentrations far below 19% in the production room. He left the room, asked all subcontractors to stop work and leave the room, and informed the customer. Investigation showed that the customer had not connected the exhaust dueling to the food-freezing machine that they owned and installed. The exhaust pipes ended in the attic space, not being extended to the atmosphere. Customer had "bridged" the alarm/trip output so LIN supply would not be shut off by low 02 concentrations. 20. An experienced site employee wanted to take some photographs to add to a report concerning production problems relating to problems with leaks in the argon condenser. In the control room he asked a Contractor to accompany him to take photographs of equipment in the cold box. One hour later the two men were found unconscious in a manhole access to the cold box. Emergency authorities were called and declared the two men dead. 21 . Two people on a customer's site were asphyxiated and died whilst attempting to unblock a pipe, using Argon gas in a confined space. The use of Argon gas in this application is not authorised. The incident took place in a sump 2 metres below ground level, which is used to drain water from a 22. An air compressor that provided instrument air to an acetylene plant and for breathing air failed. A back-up nitrogen supply from a liquid cylinder was connected to the piping system to replace the function of the air compressor. An operator put on a full respiratory face mask to load Calcium Carbide into the hopper and inhaled nitrogen. He died. 20 IGC DOC 44/09 Appendix D: Hazard of inert gases sign DAN G E R O F D EATH Potenti a l Asphyxiati ng Atmosphere 21 SaiBIV Bulletin U.S. Chemical Safety and Hazard Investigation Board HAZARDS OF NITROGEN AsPHYXIATION �E inadvertent use of nitrogen rather I ntroduction than breatl:ring-air delivery very year people are killed by breatl:ring , alr' that contains too litt:le j hazard of asphyxiation, though many people assume thatnitrogenis not harmful. However, nitrogen is safe to breathe only when mixed with tire appropriate amount o en: nitrogen also presents cryogenic of iljg and high-pressure hazards. These two gases. cannot be dete<;ted by the sense of smeU: . A nitrogen- . enriched environillent, which depletes oxygen, can be detected onlywith special instruments. 1f the concentration of nitrogenis boo high (and · oxygen too low), the body becomes oxygen deprived and a.SphyxiaHon occurs. Safety Bulletin is pub­ attention to the continuing hazards of nitrogen asphyxiation.' Commercial • Good practices and awareness One of the most important of nitrogen asphyxiation an inerting agent to improve of hazards minimize the risk (Figure 1). commercial uses of nitrogen is as safety. Nitrogen is inert under Nitrogen is widely used com­ Many incidents reviewed by CSB most conditions (i.e., it does not keep material free of con­ knowledge of the hazard or It is often used to keep material mercially. It is often used to taminants (such as oxygen) that may corrode equipment, present a fire hazard, or be toxic. • • Uses of N itrogen lished to bring additional • systems. This bulletin focuses only on the oxygen. Because 78 Percent ?f the air we breathe is nitrogen gas, This No. 2003- 1 0-B I June 2003 Nitrogen asphyxiation hazards in industry resulted in 80 deaths from 1992 to 2002. These incidents occurred in a variety of facilities, including industrial plants, laboratories, and medical facilities; almost half involved contractors. were caused by inadequate * Figure I . Sign warning of nitrogen hazard. react with or affect other material). free of contaminants, including oxygen- which can corrode equipment or present a fire and explosion hazard when in contact with flammable liquids or combustible solids. In such cases, a flow of nitrogen is maintained in a vessel to keep oxygen out. Nitrogen is also used to purge air from equipment prior to introducing material, or to purge flammable or toxic material prior to opening equipment for maintenance. In 1998, the U.S. Chemical Safety Board (CSB) investigated a nitrogen asphyxiation incident that occurred in Hahnville, Louisiana. As part of that investigation, CSB reviewed the prevalence of asphyxiation incidents. 1 in industrial and commercial settings where a nitrogen-enriched environment may present a hazard, such as when using supplied air or working in or around spaces that are confined, 2 precautions must be taken to ensure that sufficient oxygen is provided to personnel. i� serious and immediate effects, including unconsciousness after only one or two breaths. The exposed person has no warning and cannot sense that the oxygen level is too low. Nitrogen is safe to The Occupational Safety and Health Administration (OSHA) requires employers to maintain workplace oxygen at levels between 19.5 and 23.5 percent. As shown in the table on page 3, the human body is adversely affected by lower concentrations. breathe only when m ixed with the appropriate amount of oxygen. Effects of Oxygen­ As the oxygen concentration falls below 16 percent, the brain sends commands to the breathing control center, causing the victim to Deficient Atmosphere Nitrogen is not a "poison" in the traditional sense. It presents a hazard when it displaces oxygen, making the atmosphere hazardous to humans. Breathing an oxygen­ deficient atmosphere can have iiE- In industrial and commercial settings � i n the atmosphere. information. Safety Bulletins differ ' : from CSB Investigation Reports in , that they do not comprehensively : review all the causes of an incident. i U.S. Chemical Safety and Hazard ' · Investigation Board Office of Investigations and Safety 2 1 75 K Street NW. Suite 400 Washington, DC 20037- 1 848 202-26 1 -7600 Programs www. chemsafety.gov ·. oxygen. Statistics on Nitrogen Asphyxiation From reported data for the United States, CSB identified 85 nitrogen asphyxiation incidents that occurred in the workplace between 1992 and 2002. In these incidents, 80 people were killed and 50 were injured. 2 Industries and Activities there is sufficient oxygen , Case studies provide supporting hazard when it displaces enriched environment taken to ensure that managing chemical process hazards. Nitrogen . . . presents a Profile of Affected . . . precautions must be ; CSB Safety Bulletins offer advisory i� where a nitrogen­ may present a hazard, .; information on good practices for resuscitated, he or she risks cardiac arrest. breathe faster and deeper. As the oxygen level continues to decrease, full recovery is less certain. An atmosphere of only 4 to 6 percent oxygen causes the victim to fall into a coma in less than 40 seconds. Oxygen must be administered within minutes to offer a chance of survival. Even when a victim is rescued and Of the 85 incidents reported, 62 percent occurred in chemical plants and refineries, food processing and storage facilities, metal and manufacturing operations, and other industrial, maritime, and manufacturing sites, including nuclear plants. Approximately 13 percent of the incidents involved maintenance 2 Data sources for the CSB review include regulatory agencies, media reports, technical publications, and contacts with safety personnel; however, only those incidents that were reported and accessible are represented. Although the summary data reported above are not all-inclusive, the numbers dearly indicate that nitrogen asphyxiation presents a serious hazard in the workplace. Statistical analysis is based on available, limited information. 3 Effects of Oxygen Deficiency on the Human Body Atmospheric Oxygen Concentration (%) . , . 1 30 workplace fatalities and injuries occurred from breathing Possible Results 20.9 Normal nitrogen-enriched air. 1 9.0 Some unnoticeable adverse physiological effects Over 60 percent of these 1 6.0 _I ncreased pulse and breathing rate, impaired th-inking and attention, reduced _c�ordinatiOn . victims were working in 14.0 1 2.5 :, Abnor-mal fatigue upon exertion; ef!1otional upset,_;; . . �aulty coordination, poor judg�e!lt ' Very poor judgment and c o�d_inadOn, im aired . respiration that may cause per�a:ne-nt 'he!art damage, nausea, and vomiting . - .. P � · <10 SOURCE: Inability to move, loss of consciousriess; _ convulsions, death Compressed Gas Association, 200 I . CSB identified 85 nitrogen asphyxiation incidents that occurred in the workplace between 1 992 and 2002 . . . 80 identified as being in manu­ facturing facilities - account for about 14 percent of the incidents. The remainder of the incidents occurred in laboratories and miscellaneous industries, such as medical and transportation. people were killed and 50 The data show that employees and were injured. contractors alike are victims of asphyxiation. Of the 85 incidents reviewed, 42 involved contractors, activities, such as railcar and tank including construction workers; truck cleaning, painting, maintenance, and repair. These Of the 85 incidents "maintenance"' because incident reviewed, 42 involved informalion on the type of contractors, including industrial setting; they could have construction workers; occurred at manufacturing sites, these 42 incidents which would increase the 62 percent estimate above. account for over 60 Likewise, trenches and percent of the fatalities. manholes -not specifically space . these 42 incidents account for over 60 percent of the fatalities. Causal Information From the CSB data, a combined total of 130 workplace fatalities and injuries occurred from breathing nitrogen-enriched air. Over 60 percent of these victims were working in or next to a confined space.3.4 One characteristic of a confined space is its capability to contain an atmosphere that may be totally different from outside air. Confined spaces in manufacturing sites typically include equipment such as reactors, vessels, tanks, and boilers. Other such spaces are railcars, trenches, and areas accessible by manholes. incidents are categorized as reports do not include enough or next to a confined "Next to a confined space" means that a person's breathing zone is affected by the atmosphere emanating from the space. The person may be standing in the immediate area but not actually in the space. 3 4According to OSHA, a confined space can be entered to perform work, has limited means of egress, and is not designed for continuous employee occupancy. A "permit-required confined space" includes a space that contains or has the potential to contain a serious safety or health hazard, such as a hazardous atmosphere. 4 Failure to Detect Oxygen­ Deficient Atmosphere flush equipment prior to entry. In either situation, inadequate The data provide examples of workers inadvertently using knowledge of the hazard and nitrogen instead of air because of failure to detect additional interchangeable couplings on lines deficient (nitrogen-enriched) nitrogen resuited in a fatal and poor or nonexistent labeling. atmosphere was a significant concentration of gas. Failure to detect an oxygen­ factor in several incidents. In one incident, a worker In the data evaluated for this When fatalities and injuries involved circumstances where occurred in "open areas" unexpected and undetected. One . . . the hazard of worker was killed, and a colleague study, 67 of the 85 incidents personnel were in or around a confined area- such as a railcar, room, process vessel, or tank (Figure 2)- and nitrogen was initially present in high levels or mistakenly used nitrogen instead asphyxiation was not expected and personnel later collected in the area. These were typically caught off incidents accounted for fatalities and 33 injuries. In each guard. failed to detect elevated levels of Mix-Up of N itrogen and 62 of the 67 incidents, personnel nitrogen and take appropriate precautions. When fatalities and injuries occurred in open areas" II (including areas with ventilation, laboratories, buildings, and outside in the vicinity of equipment), the hazard of asphyxiation Breathing Air Confusing nitrogen gas with air and problems with breathing-air of air to purge a confined space. An inert atmosphere was also died while attempting rescue. In another case, workers inadvertently connected the hose for their breathing-air respirator to a pure nitrogen line. In one incident, a worker mistakenly used nitrogen instead of air to purge a confined space . _ . In delivery systems accounted for 12 another case, workers of the 85 incidents, and approxi­ inadvertently connected mately 20 percent of fatalities. the hose for their breathing-air respirator to a pure nitrogen line. was not expected and personnel were typically caught off guard. In Fatalities and Injuries During Attempted Rescue some cases, One of the most difficult issues personnel concerning hazardous atmosphere unknowingly emergencies is the human instinct created a to aid someone in distress. nitrogen­ Approximately enriched fatalities from the CSB data were atmosphere by mistakenly using nitrogen instead of air to 10 percent of due to attempts to rescue injured persons in confined spaces. 5 ¥ Approximately I 0 percent of fatalities from the CSB data were due to attem pts to rescue injured persons in confined spaces. Asphyxiation Hazards Outside Industry and Effect on General Public Asphyxiation hazards may also be present outside industry, especially among people who use breathing air, such as firefighters, divers, and medical patients. Statistics on these types of incidents are difficult to collect and are not included in this bulletin, though one such case is summarized below. Selected Case Studies Failure to Recognize Asphyxiation Hazards Near Confined Spaces Employee Dies After Partially Entering a Nitrogen-Purged Tank Two coworkers and the victim were cleaning filters in a hydrogen purifying tank. The tank was partly purged with nitrogen to remove internal dust particles. The victim used a lift to access the external area of the upper tank, which was fitted with a manway. As he leaned into the tank opening, his coworkers noticed that he was not responding to their communication. They found the victim unconscious, and he later died as a result of oxygen deficiency. Employee Overcome While Testing Atmosphere An operator was conducting a flammable gas test on a tower feedline that discharged into a low-pressure flare gas header. The test was required for a hot work permit to take flash photos. The chief operator issued a work perrnit that required a supplied­ air respirator. Two contractor pipefitters wore respirators and removed the safety valve. The operator, however, wore no respiratory protection. After climbing the scaffold, he was overcome by nitrogen gas from the open flare line before he could complete atmospheric sampling. The operator backed away, turned, and slumped to his knees. He was disoriented and briefly lost consciousness. An investi­ gation concluded that the incident was due to elevated levels of nitrogen gas that had inadvertently entered the flare system. Inadequate Monitoring of Atmosphere Contractor Asphyxiated Inside Tank Car White mineral oil in a tank car at an oil refinery was offloaded by injecting nitrogen gas into the car. An employee of a rallcar cleaning company was asphyxiated while cleaning the nitrogen-filled tank car. Corrupt Breathing Air Supply Two Laborers/Painting Contractors Asphyxiated Two painting contractors were abrasive-blasting tubes inside a boiler at a chemical plant. They each wore supplied-air respirators connected to a 12-pack cluster of compressed air cylinders. Another subcontractor monitored the work outside the confined space. Work proceeded normally throughout the night shift; however, at 3:00 am, the attendant got no response after repeatedly sounding the air horn. When another contractor employee was sent into the boiler to assess the situation, he found the two men lying on opposite ends of the scaffolding. When the plant health, safety, and environmental department tested the compressed air 12-pack, they found that it contained less than 5 percent oxygen. The "air" had been manufactured with too low a 6 concentration of oxygen. (Note: A splitter diverted one part of the This fatal incident prompted gas stream to the air hammer and OSHA to issue a safety alert on the the other part to the airline res­ batch of breathing air.) pirator. Once the respirator was Mix-Ups Between pure nitrogen and was Nitrogen and Air asphyxiated. Good Practices for Safe Handling of in place, the worker breathed Three Employees Asphyxiated in Coating Tank The atmosphere inside a coating tank was tested and ventilated the day before work was to be performed. On the following day, a contractor entered the tank to clean it and collapsed. Two plant employees entered to attempt rescue, but they were also overcome. The tank had been ventilated with what was thought to be com­ pressed air but was actually nitrogen. The atmosphere was not tested prior to beginning work. All three men were asphyxiated. Employee Killed by Overexposure to Pure Nitrogen N itrogen Four Killed and Six Injured in Implement Warning Nursing Home Systems and Continuous Atmospheric Monitoring A nursing home routinely ordered large pure oxygen of Enclosures compressed gas cylinders for The atmosphere in a confined residents with respiratory system diseases. The supplier mistakenly space or small enclosed area may delivered one cyIinder of pure be unfit for breathing prior to nitrogen with three cylinders of entry, or it may change over time, oxygen; a nursing home depending on the type of maintenance employee equipment or work being mistakenly accepted the nitrogen performed. Recognizing this tank. hazard, good practice calls for continuous monitoring of a Another maintenance employee took confined space to detect oxygen­ this cylinder, which had a deficient, toxic, or explosive nitrogen label partially covering atmospheres. The entire confined an oxygen label, to connect it to space should be monitored- not the oxygen supply system. The just the entry portal. tank was fitted with nitrogen­ compatible couplings. The employee removed a fitting from A contractor planned to use an air­ powered hammer to chip residue an empty oxygen cylinder and from a furnace in an aluminum the nitrogen tank to the oxygen foundry. He wore an airline system. Four deaths and six used it as an adapter to connect "� The atmosphere in a confined space or small enclosed area may be respirator. Of two compressed gas injuries occurred as a resnlt of unfit for breathing prior lines with fittings, one was labeled pure nitrogen being delivered to "natural gas" and the other had an the patients. to entry, or it may old paper tag attached with " air" change over time . . . handwritten on it. However, this line actually contained pure nitrogen. Warning and protection systems include flashing lights, audible alarms, and auto-locking entryways to prevent access. Such devices, if properly installed and 7 maintained, warn workers of Personnel should be trained on or legs. The attendant and rescue hazardous abnospheres. Personal how to properly respond and personnel should be available at monitors can measure oxygen evacuate in the event of failure of all times. Rescuers must have an concentration and give an audible the system. effective system to communicate or vibration alarm for low oxygen with personnel inside enclosures. concentrations. '� I mplement System for No one should enter a dangerous Safe Rescue of Workers abnosphere without proper Rescue may be necessary in the Good practice calls for event of continuous monitoring, continuous monitoring ventilation failure, or another of a confined space to emergency condition. The ability to immediately retrieve detect oxygen­ immobilized workers is a critical deficient, toxic, or component of confined space entry explosive atmospheres. preplanning. Ensure Ventilation With ¥ continuous forced draft Because the abnosphere of a fresh-air ventilation confined space or small/ enclosed before the job begins course of work, it is essential to The last measure of defense requires personnel to actually enter the confined area to retrieve the victim. This approach should be used only when personnel are appropriately trained, have donned rescue equipment, and have dependable breathing air. Approximately 10 percent of It is essential to maintain Fresh Air area often changes dming the personal protective equipment. through to completion. fatalities from the survey data occurred to personnel attempting rescue. These deaths could have been prevented if a reliable retrieval system was in place. Such a system would also prevent many entry worker fatalities maintain continuous forced draft because it provides for quickly fresh-air ventilation before the job removing the worker from a begins through to completion. Areas with the potential to contain elevated levels of nitrogen gas should be continuously ventilated prior to and dming the course of the job. Ventilation is also required in One method is to attach a body dangerous abnosphere to a safe harness and lifeline to personnel one. entering confined areas. This procedure also benefits potential Ensure Uninterrupted rescuers because they do not have Flow and Integrity of to enter the confined area to retrieve the victim. However, Breathing Air when a worker enters a pipeline, nitrogen may leak or vent. in a Breathing air must be supplied some furnaces, ducts, or other when workers enter environments narrow-diameter confined spaces, where oxygen is or may become were simply working close to the pulling on a line attached to a deficient. Workers may use either body harness may cause the a self-contained breathing rooms and chambers into which few of the study cases, people who nitrogen-containing confined space, room, or enclosure were asphyxiated. Systems must be in place to properly design, evaluate, and maintain ventilation systems. A warning system will alert workers of a dangerous abnosphere. person to bunch up and become apparatus (SCBA) or an airline stuck inside. respirator, which consists of a long Depending on the situation, wristlets or anklets attached to a hose connecting a breathing air supply to the respirator or hood. lifeline and a retrieval mechanism Because a worker using an airline allow the confined space attendant respirator does not control the to pull the person out by the arms 8 Breathing air m ust be and dedicated to breathing-air systems. The compressor should supplied when workers have a moisture trap, an oil trap, enter environments and a carbon monoxide sensor and where oxygen is or may become deficient. alarm. When breathing air is manufactured by mixing nitrogen and oxygen, the pressure of the cylinders during filling must be known to ensure that the correct source of supply, air may amounts are mixed. The final suddenly or inadvertently be product must be tested to ensure interrupted. For example, a power its integrity. failure may stop an air compressor, the air supply may Prevent Inadvertent Mix­ simply run out, or the supply hose Up of Nitrogen and may become twisted or obstructed (e.g., by a vehicle). When supplied air is used, facility management Breathing Air To prevent interchanging com­ systems must protect against pressed nitrogen with compressed interruption of airflow and industrial grade air or compressed provide alternate sources of power breathing-quality air, specific for the compressors. A comprehensive management system includes the following: • • industrial grade air, and breathing-quality air have distinct, Continuous monitoring of air incompatible fittings that cannot supply. be cross-connected. Routine inspection and replacement of supplied-air • fittings should be used for each cylinder. Cylinders for nitrogen, Personnel should Restriction of vehicular traffic in understand that the the area of supply hoses. fittings are intended to should carry a small backup cylinder (escape pack) - attached be incompatible to ensure safety. to a different supplied-air system-with enough breathing air to last 5 to 10 minutes. Breathing air is manufactured either by purifying and compressing air or by mixing nitrogen and oxygen to the appropriate ratio. A breathing-air compressor and its hoses should be specifically manufactured for which gas is contained inside. Color coding also helps to identify systems. Develop and I mplement Comprehensive Training hoses. When using supplied air, a worker fittings are additional reminders of Programs The good practices for safe handiing of nitrogen, described above, are effective only if personnel are trained on the importance of the following: • Use of ventilation systems, retrieval systems, and atmospheric monitoring Personnel should understand that equipment-both how to use the fittings are intended to be them and how to determine incompatible to ensure safety. when they are not working Cylinders should be clearly properly. labeled; typical cylinders are shown in Figure 3. Labels on piping systems, compressors, and • Dangers of nitrogen-enriched atmospheres and the systems to 9 prevent interchanging breathing • air and nitrogen. Implementing good hazard communication, which includes safe handling of air and nitrogen delivery systems. • American National Standards procedures for entry into Society of Safety Engineers confined spaces, such as (ASSE), 2003. Safeti; permits, providing an attendant, Requirementsfor Confined Spaces, monitoring, ventilating, rescue, Z117.1-2003. ANSI/ ASSE, 2003. Criteria for Precautions when working Accepted Practices in Safehj, around equipment that may Health, and Environmental contain elevated levels of Training, Z490.1-2001. The reason for special fittings on compressed gas cylinders. • Information Institute (ANSI)/ American nitrogen. • Additional Mandatory safety practices and and contractor oversight. • References and Proper use of air supply ANSI, 2002. Standards on Signage and Labeling, Z535 Series. Compressed Gas Association, Inc., 2002. Standard for Compressed equipment. Training should cover new and revised procedures for confined space entry, and establish proficiency. Contractors as well as employees should be trained. Contractors as well as employees should be trained. 1996. Field Guidelines for Temporan; Ventilation of Confined Spaces, American Industrial Hygiene Association (AIHA) . Kletz, Trevor, 1995. What Went Wrong? Case Histories of Process Plant Disasters, Gulf Publishing Company. Institution of Chemical Engineers (!ChernE), 2003. Acddent Data Base, she@iciune.org.uk. Martin, Lawrence, 1997. "Effects of Gas Pressure at Depth: Nitrogen Narcosis, CO and C02 Toxicity, Oxygen Toxicity, and 'Shallow-Water' Blackout," Scuba Diving Explained, PhysiolOgJJ and Medical Aspects of Scuba Diving, Best Publishing Inlet Connections, V-1, lOth Company. edition. 2001. SafehJ Bulletin, Oxygen­ Deficient Atmospheres, SB-2, 4th edition. Compressed Gas Association, Inc., ;� Booher, and Stephanie Carter, Gas Cylinder Valve Outlet and Compressed Gas Association, Inc., measurements for employee Harris, Michael K., Lindsay E. McManus, Neil, 1999. SafehJ and Health in Confined Spaces, Lewis Publishers/ CRC Press. National Institute for Occupational Safety and Health (NIOSH), 2002. "State FACE Inves­ 1999. Handbook of Compressed tigations of Fatal Confined­ Gases, 4th edition, Kluwer Space Incidents," Traumatic Academic Publishers. Federal Aviation Administration (FAA), 2003. NASA Physiolog>; Training, www.faa.gov/ avr/ cmo/ coa/PH-TR.htmi. Finkel, Martin H., 2000. Guidelines for Hot Work in Confined Spaces; Recommended Practices for Industrial Hygienists and Safeti; Professionals, ASSE. Occupational Injun;, www. cdc.gov/niosh/ face, Oct­ Nov 2002. Occupational Safety and Health Administration (OSHA), 2003. Safeti; and Health Topics: Confined Spaces, www.osha.gov/ SLTC/ confinedspaces/ index.htmi. 10 OSHA, 2002. Accident Investigation Safety Engineering, 2002. Daily U.S. Air Force, 2003. Hypoxia, .bainet.com/mfwright/ Summan; Index Page, Incident Alert Archives, www www.osha.gov, Oct-Nov 2002. www.safteng.net, Oct-Nov 2002. hypoxia.html. OSHA, 1994. "Permit-Required Confined Spaces," Federal The Bureau of National Affairs, inc. (BNA), 1998. U.S. Chemical Safety and Hazard Occupational investigation Board (USCSB), Register, 29 CFR 1910.146, May SafetlJ and Health Reporter, Vol. 2002. Incident Data Base, 1994. 27, No. www.csb.gov, Oct-Nov 2002. Rekus, jolm F., 1994. Complete 46, April 22, 1998. BNA, 1996. Occupational Safetl; and Confined Spaces Handbook, Lewis Health Reporter, Vol. 25, No. 47, Publishers/ CRC Press. May 1, 1996. The U.S. Chemical Safety and Hazard Investigation Board (CSB) is an independent Federal agency whose mission is to ensure the safety of workers, the public, and the environment by investigating and preventing chemical incidents. CSB is a scientific investigative organization; it is not an enforcement or regulatory body. Established by the Clean Air Act Amendments of 1 990, CSB is responsible for determining the root and contributing causes of accidents, issuing safety recommendations, studying chemical safety issues, and evaluating the effectiveness of other government agencies involved in chemical safety. No part of the conclusions, findings, or recommendations of CSB relating to any chemical incident may be admitted as evidence or used in any action or suit for damages arising out of any matter mentioned in an investigation report (see 42 U.S.C. § 741 2(r)(6)(G)). CSB makes public its actions and decisions through investigation reports, summary reports, safety bulletins, safety recommendations, case studies, incident digests, special technical publications, and statistical reviews. More information about CSB may be found at www.chemsafety.gov. obtained by contacting: CSB investigation reports may be purchased from: U.S. Chemical Safety and Hazard Investigation Board 5285 Port Royal Road Information about available publications may be National Technical Information Service Office of Prevention, Outreach, and Policy 2 1 75 K Street NW. Suite 400 Washington, DC 20037- 1 848 (202) 26 1 -7600 Springfield, VA 22 1 6 1 (800) 553-NTIS or (703) 487-4600 Email: info@ntis.fedworld.gov For international orders, see: www.ntis.gov/support/cooperat.htm. Salus Populi Est Lex Suprema People's Safety is the Highest Law J. clin. Path., 30, Suppl. (Roy. Coli. Path.), 11, 181-187 Experimental hypoxic brain damage J. B. BRIERLEY From the Medical Research Council Laboratories, Carshalton, Surrey The maJority of hypoxic episodes that result in histologically proven damage in the human brain cannot be adequately defined in physiological tenns. They are usually accidents so that basic information such as the precise duration of a cardiac arrest or the blood pressure and heart rate during a period of severe hypotension is very rarely available. In such cases, neuropathological descriptions, however ex­ haustive, may well explain the final neuropsychiatric status of the patient but can at best indicate only tentatively the nature of the episode itself. The experimental approach is justified if it can indicate whether damage of a particular type in neurones and in white matter is or is not a direct consequence of a particular hypoxic stress adequately delineated in physiological terms. At the outset it must be recalled that the energy for the normal functioning of the central nervous system is derived from the oxidative metabolism of glucose. A deficiency of oxygen or glucose will impair function and if severe and protracted enough will lead to irreversible brain damage. Interruption of the oxygen supply produces the most rapid impairment of brain function. Thus consciousness is lost about 10 sec after circulatory arrest. Abrupt anoxia exemplified by inhalation of an inert gas or sudden decompression to an altitude above 50 000 ft leads to loss of consciousness after a slightlylonger interval (17-20 sec). This rapid loss of consciousness in instances of profound hypoxia may well be responsible for the widely held view that enduring brain damage may begin soon after consciousness is lost. Types of hypoxia Before considering the relationships between the known neuropathological patterns in the human brain that are ascribed to hypoxia and their apparent counterparts in the brains of experimental animals, it will be useful to classify the several types of hypoxia. However, it will be shown that there is no justifica­ tion for the assumption that each type of hypoxia can, per se, give rise to brain damage. The original classification of Barcroft (1925) must be modified in the light of subsequent information from human and experimental animals sources as foUows : 1 ISCHAEMIC Blood flow is arrested in the brain as a whole or in the territory of a single artery. OLIGAEMIC A reduction in blood flow in the brain as a whole or within the territory of a single artery may occur as a result of a greatly reduced cardiac output or major systemic hypotension from any cause. 2 3 ANOXIC The arterial OXYgen tension is 0 mm Hg. It occurs if inert gases are inhaled, if there is total obstruction of the upper respiratory tract or in the event of sudden exposure to an altitude greater than 50 000 ft (the combined tensions of water vapour and carbon dioxide within the pulmonary alveoli then exceed the ambient pressure and no OXYgen can enter the lungs). 4 HYPOXIC There is some reduction in a p02 short of anoxaemia. This occurs in chronic pulmonary disease and in congestive heart disease; when the inspired OXYgen is diluted by an inert gas (as in some anaesthetic accidents) and also in exposures to altitudes less than 50 000 ft. 5 ANAEMIC There is some reduction in the amount of circulating haemoglobin available for combination with oxygen. It can occur after severe haemorrhage, in severe hypochromic anaemia but the commonest apparent cause of anaemic brain damage is carbon monoxide intoxication. 6 HtSTOTOXlC This implies the poisoning of oxidative enzymes within neuronal mitochondria. Cyanide and azide are examples. 7 HYPOGLYCABMIA A deficiency of the principal substrate, glucose, ]Mr 181 J. B. Brierley 182 se can also give rise to ischaemic cell change even if primate are sharp reminders that such 'models' can­ the level of arterial oxygenation is normal. not provide two of the most important factors in the The previous contributors to this section of the aetiology of 'stroke' in man. These are some impair­ Symposium have defined the nature and time course ment in cardiac function (leading to some reduction of ischaemic cell change and have pointed out that it is the principal neuronal response to an types of in cerebral blood How) and some degree of occlusive vascular disease. These factors, singly or together, hypoxia in the brains of rodents as well as in those of account for the extension of the infarct into the primates including man. In this survey of the brain damage attributable to hypoxia in all its forms, only the patterns of distribution of ischaemic cell change centrum semi-ovate and even into the whole of the anatomical cortical territory. It follows, that in the will be considered with emphasis on the contributions from experimental studies. human brain, ischaemic necrosis in some portion of an arterial territory can seldom be explained satisfactorily without careful examination of the 1 Ischaemic myocardium, the coronary arteries and the major Arrest of circulation within a single brain artery leads to a loss of consciousness in eight to 10 sec and results in an infarct which can range in size from the the EEG is isoelectric a few seconds later. Respira­ arteries of the neck and brain. Overall or global arrest of the brain circulation 'total territory' in an anatomical sense to a small tion fails at about the same time while the heart may volume of tissue close to the point of arterial occlusion. Where the cortex of cerebrum or cerebel­ lum is concerned the extent of infarction is deter· mined by the level of systemic blood pressure at and after the instant of occlusion and, in particular, by the functional efficiency of the leptomeningeal ves· sels that anastomose with the cortical branches of neighbouring arteries. If these anastomotic systems and the major arteries in the neck and the circle of Willis are normal, the cortical infarct will be small. If continue to beat for a matter of minutes. Neuro· pathological descriptions of the consequences of circulatory arrest (including 35 personal cases) pro­ vide the best examples of the involvement of the 'selectively vulnerable' regions of the brain in hypoxia. Frequently, little of the cerebral cortex is normal but damage is usually greater in the posterior half of each cerebral hemispltere, in the floors of sulci rather than over the crests of gyri and in the one or both are the site of occlusive vascular disease, and fourth. Certain portions of the hippocampus third, fifth and sixth layers rather than in the second the infarct will be larger. (zones h.1-Sommer sector-and h.3-5,--endfolium) It must be borne in mind that the basal ganglia and the internal capsule, in particular, are supplied by are vulnerable as are the Purkinje cells of the cerebellum. Many sensory nuclei in the brain stem end-arteries (penetrating organglionic branches ofthe are vulnerable in the infant and young child (Ranck and Windle, 1959; Brierley, 1965, 1976). Where circulatory arrest has been studied in the experimental animal, it is important to recognize that earlier studies were concerned to define the major cerebral arteries). Occlusion of an arterial trunk proximal to the ganglionic branches produces an infarct in these deeply placed regions of grey and white matter even in the healthy experimental primate. Evidently the retrograde How of blood from leptomeningeal anastomoses into the arterial stem may never enter all its ganglionic branches or, if it does so, it may be too little and too late to avert irreversible tissue damage. Thus, for example, maximum period of arrest of the cerebral circulation beyond which some degree of irreversible brain damage would occur. Attempts to define such a 'threshold' have been reviewed by Hoff et a/ (1945), Meyer (1963) and Brierley (1 976). The general division of the middle cerebral artery close to its origin from the internal carotid artery in the baboon conclusion from these studies has been stated by Schneider (1963) as follows : 'A complete revival leaves the sensory and motor cortex intact and without neurological or histological damage cannot cortical infarction is confined to some portion of the insula. A variable hemiparesis involves only the contralateral face and upper limb and its neuro­ pathological basis has been shown to Jie entirely within white matter, ie, in the genu and supra­ lentiform portions of the internal capsule, where after a survival of three years there is a sharply circum· scribed cystic infarct (Symon and Brierley, 1976). The limited neurological deficit and the small, deeply placed infarct that follow division of the middle cerebral artery in a healthy experimental be brought about after a complete stop of brain circulation of more than four to five min duration'. In contrast to the experiments summarized above, certain recent studies have attempted to define a much greater period of circulatory arrest after which there can be some evidence of recovery in at least a neurophysiologicalsenseandhistologicalexamination can show that some parts of the brain are normal. Thus Rossmann and Sato (1970) claimed that •. . . unequivocal signs of neuronal recovery can be detected after complete ischaemia of more than one 183 Experimental hypoxic brain damage hour's duration'. Hirsch eta/ (1975) failed to confirm these results and attributed 'recovery' after such protracted ischaemia in the experimentsofHossmann and Sato (1970 and subsequent studies) to the pro­ tective effects of anaesthesia and the progressive fall in temperature that must occur in the isolated head during such periods of time. It must be emphasized that experimental studies of the effects of circulatory arrest (or any other form of hypoxia) on the brain, whether directed towards the definition of a 'threshold' for a particular hypoxic stress or to the capacity for recovery after an extended period of the same stress, have clinical relevance only if spontaneous respiration has been resumed in the unmedicated animal, and detailed neurological assesm s ents, together with serial recordings of the EEG, have been made during an adequate period of survival. All these are essential for a meaningful appraisal of'recovery'. Finally, after in�vivo perfusion�fixation of the brain, neuro­ pathological examination of the brain must be comprehensive. Unfortunately clinico-pathological studies according to such standards have not yet been reported in support of the claim that 'recovery' of the central nervous system can occur after periods of circulatory arrest far in excess of those hitherto accepted as 'critical' where the inception of minimal brain damage is concerned. 2 Oligaemlc hypoxia A reduction of blood flow in a single artery of the human brain is usually due to a combination of systemic hypotension and occlusive disease in the vessel itself. If flow is sufficiently impaired the out­ cow will be an infarct involving grey and white matter. Such a local reduction in flow can only be inferred ifthrombosis and embolism can be excluded. There are, as yet, no experimental models of this particular situation. Global oligaemia implies some reduction in the overall flow of blood through the brain. Experi­ mental studies in the Rhesus monkey have shown that, if arterial oxygenation remains normal, cerebral perfusion pressure (mean arterial blood pressure - venous sinus pressure) must be reduced to 25 mm Hg for at least 15 min before brain damage is produced (Brierley et a/, 1969; Meldrum and Brierley, 1969). However, it was only possible to damage the brain if the profound hypotension was continued beyond the point of apnoea when mechanical ventilation was required in order to maintain a normal arterial oxygen tension. These experiments clearly demonstrated that in the healthy spontaneously breathing primate, global oligaemia per se is unlikely to lead to brain damage if respiration does not fail. In these monkeys, typical ischaemic neuronal alterations were not evenly distributed in the cerebral cortex but were restricted to the arterial boundary zones of the cortex of the cerebrum and also of the cerebellum. They were variable in the basal ganglia. The pysiological basis of lesions along arterial boundary zones has been discussed by Zillch and Behrend (1961) and by Meldrum and Brierley (1971). When perfusion pres­ sure falls below 45-50 mm Hg the capacity of the vascular bed to maintain a constant cerebral blood flow (autoregulation) is lost (there is then maximum vasodilatation) and flow becomes directly dependent upon perfusion pressure. The reduction in flow is greatest in the vessels most remote from the arterial stem, ie, at the boundary of each arterial territory. In the clinical situation, a reduction in brain perfusion pressure while arterial oxygenation remains normal is virtually confined to the technique ofhypotensive anaesthesia with controlled ventilation and then only when perfusion pressure through the brain is lowered by excessive head-up tilt (Brierley and Cooper, 1962). The two additional factors that may result in brain damage after a period ofrelatively moderate hypotension are some degree of hypoxaemia and some element of occlusive disease in the extra- and/or intracranial arteries. The fre­ quency of these two factors in addition to the reduction in brain blood flow due to the initial systemic hypotension is largely responsible for the fact that ischaemic damage along arterial boundary zones of the cortex of cerebrum and cerebellum is the commonest neuropathological outcome of hypoxia in all its forms. It is important to appreciate that no experimental model permitting the introduction and control of oligaemla, hypoxaemia and partial vascular occlusion is yet available. Previous contributors to this section of the Symposium have emphasized that this 'boundary zone' pattern of brain damage can only be identified if blocks for histological examination are selected with an awareness of the anatomical distribution of the cortical arteries of cerebrum and cerebellum. 3 Anoxic Anoxia, induced by breathing pure nitrogen, has been studied in human volunteers by Gastaut et al (1961) and Emsting (1963). After a few seconds the EEG shows low voltage activity at 11 to 13 cjs and consciousness is lost at 17 to 20 sec. In experimental animals, longer periods of nitrogen breathing lead, after an initial hyperventilation, to slowing of respiration, bradycardia and a falling blood pres­ sure. Apnoea occurs at about the third minute while blood pressure is still appreciable (5-20 mm Hg) at 184 the fifth minute (Swann and Brucer, 1949). In the Rhesus monkey, the responses to nitrogen breathing are similar and if mechanical ventilation is begun soon after the 'last breath', the blood pressure rises, spontaneous respiration is resumed and the EEG, previously isoelectric, returns to normal. Subsequent neuropathological examination reveals no brain damage (Brierley and Meldrum, unpublished observations). Evidently the period of anoxaemia and of secondary circulatory impairment is too brief to lead to ischaemic neuronal alterations so that it must be concluded that pure anoxic anoxia cannot produce brain damage. 4 Hypoxic In spontaneously breathing experimental animals, including primates, the minimal level of arterial oxygen tension that does not lead to early apnoea and cardiac failure is about 20 mm Hg. At this level the cerebral vascular bed is fully dilated, the cerebral A-Y oxygen difference is reduced (due to reduced oxygen consumption and increased blood flow) but the EEG is normal. This precarious state can be dis­ turbed by a slight fall in perfusion pressure and the immediate decline in the EEG is evidence of some reduction in cerebral blood flow. This may occur as a consequence of a period of cardiac arrhythmia. A progressive fall in heart rate and blood pressure together with slowing of respiration herald the cardio-respiratory crisis that sets the limit to the period during which the organism can tolerate this level of hypoxia. Where the circulatory failure is concerned the final bradycardia and falling blood pressure may not be a direct effect of hypoxia on the myocardium but a consequence of the stimulation of chemoreceptors in the carotid bodies or brain stem (Cross et a/, 1963). As blood pressure continues to fall respiration ceases and the EEG becomes iso­ electric at about the same time. Adequate resuscita­ tion commenced soon after the 'last breath� can, as after anoxic anoxia, allow the heart to recover, spontaneous respiration to be resumed and the EEG to return to normaL Brain damage is rarely seen and only when there has been a prolonged period of car­ diac impairment and an even longer period of iso­ electric EEG (Brierley, Prior, Calverley, and Brown­ unpublished results). Brain damage in such animals consists of ischaemic neuronal alterations along the arterial boundary zones of the cerebrum and cerebellum and sometimes in the basal ganglia. This pattern of damage� indistinguishable from that seen after oligaemic hypoxia, underlines the fact that systemic hypoxaemia can only bring about brain damage through the medium of a secondary reduc­ tion in perfusion pressure. J. B. Brierley In the human subject exposed to hypoxia not severe enough to bring about failure of respiration and the heart, the initial increase in cerebral blood flow may be so restricted by occlusive vascular disease in the arteries of the brain and/or neck that ischaemic brain damage may ensue. 5 Anaemic There is no convmcmg evidence that a simple reduction in circulating haemoglobin due to severe hypochromic anaemia (iron-deficient or haemolytic) or to haemorrhage can result in brain damage. Carbon monoxide intoxication remains the sole example of anaemic hypoxia (due to the formation of stable carboxyhaemoglobin) that can be associated with ischaemic cell change and also with damage in white matter. The pathology in the human brain has been reviewed by Meyer (1963), Lapresle and Fardeau (1966) and Brierley (1976). Ischaemic alterations may be seen in the vulnerable regions of the cortex of cerebrum and cerebellum and of the hippocampus. Necrosis in the globus pallidus is not invariable (Meyer, 1928; Lapresle and Fardeau, 1967) and damage in white matter varies con­ siderably. The presence of some element of perfusion failure in the genesis of, at least, the cortical damage was suggested by the report of Poursines et a/ (1956). A woman, aged 33 years, Jived 26 days after attempted suicide with illuminating gas. In her brain, laminar necrosis was distributed along arterial boundary zones but information concerning respiratory and cardiac functions early in the survival period was lacking. The case of Neubuerger and Clarke (1945), dying 13 days after carbon monoxide poisoAing, exhibited patchy myocardial infarction suggesting a direct effect ofcarbon monoxide on the myocardium. Among experimental studies, that of Lewey and Drabkin (1944) in the dog was important because, after intermittent exposures to carbon monoxide for up to 1 1 weeks the electrocardiograms were abnormal and the brain damage was considered to be similar to that seen in man but was not described in detail. Further details of electrocardiographic abnormalities were presented by Ehrich et a/ (1944). Recently Ginsberg et a/ (1974) exposed 1 9 Rhesus monkeys to 0·2 or 0·3 per cent carbon monoxide for 60 to 325 min with a carboxyhaemoglobin level of 72 to 77 per cent throughout. Cardiac arrhythmias and some degree of hypotension were common but the EEG was oniy intermittently isoeiectric. Grey matter damage (globus pallidus and hippocampus) was seen in less than a fifth of the brains while white matter was abnormal in the majority. Apparently the degree of intoxication was not sufficient to produce the 185 Experimental hypoxic brain damage more extensive grey matter damage so often seen in the human brain. Further confirmation of a direct effect of carbon monoxide on the heart was provided by Hodjati et a/ (1976) who irrigated the cerebral circulation of one dog from one carotid artecy of a donor animal. A mean carboxyhaemoglobin level of 52 per cent in the donor animal led to bradycardia, hypotension and its death in 10 to 15 min. All the recipients survived. change was restricted to the striatum of a single animal. In the latter there had been a period of bradycardia, hypotension and raised central venous pressure. It was concluded that in the lightly anaesthetized and spontaneously breathing Rhesus monkey, as in the rat, there is no evidence for the entity of hypoxic neuronal damage of purely histotoxic type. 7 Hypoglyeaemla 6 Histotoxic Cyanide, the best known cause of histotoxic hypoxia, acts by inhibiting cytochrome oxidase in mito­ chondria while the oxygen tension and content of arterial blood remain normal. The few human cases with delayed death and evidence of brain damage have been reviewed by Brierley (1976). There was loss of neurones in cerebral cortex and cerebellum and a single case showed haemorrhagic necrosis in each globus pallidus. Hyperaemia and haemorrhages occurred in white matter. Numerous experimental studies have suggested that cyanide, in any form and administered by any route, can damage neurones and myelin sheaths. In the first experimental stndy (Meyer, 1933) sub­ cutaneous injections of potassium cyanide in dogs and rabbits produced typical ischaemic alterations in cerebral cortex, globus pallidus, hippocampus and cerebellum. White matter damage was most marked in the corpus callosum. Subsequent stndies were more concerned with white matter damage because of its apparent similarity to the plaques of multiple sclerosis. However, the report of Levine and Stypulkowski (1959) was noteworthy because it sug­ gested that grey matter damage in the rat brain after the administration of cyanide was largely due to concomitant ischaemia and hypoxic hypoxia. Brierley et a/ (1976) gave sodium cyanide to rats by intravenous infusion. There was full physiological monitoring in an anaesthetized group and restricted monitoring in the unanaesthetized remainder. White matter, particularly the corpus callosum, was damaged in six of 19 animals and grey matter additionally in only one. In the latter animal bradycardia, epileptic seizures and hypotension were particularly marked and it was concluded that the neuronal damage was brought about through the medium of the secondary effects of cyanide on the circulation. In a recent study in M mulatta (Brierley et a/, 1977) sodium cyanide was given by intravenous infusion. The effects of the infusion on respiration, heart rate, blood pressure, blood gases and the EEG were monitored in the lightly anaesthetized animals. Brain damage was seen in four of 1 1 animals. It involved white matter in all four but ischaemic cell Hypoglycaemic damage in the human brain is usually associated with irreversible coma and Meyer (1963) stated that the neuropathological findings '. . . closely resemble those which occur in other types of anoxia'. Most of the selectively vulnerable regions may be involved but with a tendency to spare the globus pallidus and cerebellum. Although hypo­ glycaemic coma may be associated with cardio­ vascular disturbances and epileptic seizures the ability of hypoglycaemia per se to produce ischaemic damage in physiologically monitored experimental primates has been demonstrated only recently. Kairn and Myers (1971) and Myers and Kahn (1971) studied the long-term effects of insulin­ induced hypoglycaemia in Rhesus monkeys. Blood glucose fell to 20 mg/100 ml after one and a half to threeh and was maintained at this level for four to 10 h with normal blood oxygenation. In seven of 11 animals there was neuronal loss with a gliomesodcr­ mal reaction in striatum, cerebral cortex and hippocampus. In order to define the earliest neuronal alterations due to insulin-induced hypoglycaemia, lightly anaesthetized Rhesus monkeys received insulin intravenously while EEG, EKG, heart and respira­ tory rates were recorded and blood -aas tensions, pH and glucose content were measured at intervals (Meldrum et a/, 1971). When blood glucose was below 20 mg/1 00 ml for more than two h and the brains were fixed by perfusion, typical ischaemic cell change (from the stage of microvacuolation) was seen in the cortex and occasionally in striatum, hippocampus and cerebellum. Thus a major deficiency in substrate alone can produce the same type of neuronal damage as a deficiency of oxygen. Conclusion It will be evident from this briefreview that ischaemic cell change is the cytopathological common denomi­ nator in all types of hypoxia. Nevertheless there is no pattern of its distribution specific for each categocy with the exception of circulatocy arrest (global ischaemia) and pure hypoglycaemia after both of which ischaemic neuronal alterations may occur J. B. Brierley 186 uniformly within the 'selectively vulnerable' regions of the brain. In the remaining categories of hypoxia, ie, oligaemic, anoxic, hypoxic, histotoxic and probably anaemic (carbon monoxide), an initially pure hypoxic stress in the intact and spontaneously breathing animal gives rise, sooner or later, to terminal secondary impairments of respiration and particularly of circulation. In the healthy experi­ mental animal, however, it is only rarely that the associated period of reduced cerebral blood flow is long enough to cause brain damage but not too long to preclude recovery. In such instances, brain damage consists of a concentration of ischaemic cell change along the arterial boundary zones. Experimental studies have shown that the terminal hypoxic cardio-respiratory deterioration or crisis consists of a slowing of respiration to the point of apnoea with a fall in blood pressure and in heart rate (but the heart may continue to beat long after the 'last breath'). There is a more or less parallel decline in EEG background activity and an isoelectric state is reached at about the time of the 'last breath'. There is no evidence to suggest that systemic hypoxia of any type can lead to brain damage unless the EEG has been isoelectric for an appreciable period. In the paralyzed and mechanically ventilated animal exposed to systemic hypoxia, initial hyperventilation as well as the 'last breath' cannot occur and the duration of hypoxia may be considerably prolonged. For this reason 'thresholds' for brain damage defined in such preparations must be applied with considerable caution to the spontaneously breathing experimental animal and to man. There is now ample evidence to show that in the intact healthy, and spontaneously breathing animal tolerance to hypoxia is limited by the respiratory and circulatory systems and not by the intrinsic energy reserves of the brain itself. If effective resuscitation is begun soon after the 'last breath' the EEG will return and the brain will be undamaged. Thus a depression of central nervous system function up to and some time after the 'last breath' and the appear­ ance of transiently isoelectric EEG need have no structural consequences. The relative frequency of all degrees of ischaemic damage in the human brain after hypoxic episodes does not, however, necessarily imply a greater susceptibility of the brain itself. The existence of a single type of hypoxia in human patients is rare. It should be stressed that several types of hypoxia, each constituting a relatively mild stress can, in combi­ nation, produce brain damage. The additional factors most probably responsible for the increased extent and frequency of brain damage in man are twofold. Preexisting cardiac disease will impair the capacity to maintain a high level of blood flow through a cerebral vascular bed initially fully dilated by hypoxia. It will also impair the rapid restoration of normal cerebral blood flow after any terminal cardio-respiratory crisis. Secondly, preexisting occlu­ sive disease in the arteries of brain and neck and any impairment of the normal reactivity of the smaller cerebral vessels will further reduce cerebral blood flow during and after hypoxia. In conclusion, experiments in physiologically monitored, spontaneously breathing animals can show that hypoxia gives rise to an integrated series of responses in the respiratory and circulatory systems and in the nervous system itself. Initially these serve to maintain brain function and respiration in particular. Ultimately these compensatory cardio­ respiratory responses may fail. Experiments have also shown that where the human brain is concerned the commonest cause of damage must be sought in some failure of brain perfusion. The author is greatly indebted to Dr Pamela F. 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Cross-circulation experiments in dogs discerning the target organ of carbon monoxide intoxication. (Abstract.) British Journal of Surgery, 63, 655. Hoff, E. C., Grenell, R. G., and Fulton, J. F. (1945). Histo­ pathology of the central nervous system after exposure to high altitudes, hypoglycemia and other conditions associa­ ted with central anoxia. Medicine (Baltimore), 24, 161-217. Rossmann, K. A. and Sato, K, (1 970). Recovery of neuro­ nal function after prolonged cerebral ischemia Science, 168, 375-376. Kahn, K. J., and Myers, R. E. (1971). Insulin-induced hypoglycaemia in the non-human primate. I. Clinical consequences. In Brain Hypoxi-:t, edited by J. B. Brierley and B.S. Meldrum, pp. 185-194. (Clinics in Developmental Medicine 39/40, Spastics International Medical Publica­ tions). Heinemann, London. Lapresle, J., and Fardeau, M. ( 1966}. Les leuco-encCphalo­ pathies de l'intoxication oxycarboneC. Etude de seize observations anatomo-cliniques. Acta Neuroparhologica, 6, 327-348. Lapresle, J., and Fardeau, M. (1 967). The central nervous system and carbon monoxide poisoning. If. Anatomical study of brain lesions following intoxication with carbon monoxide (22 cases). Progress in Brain Research, 24, 3 1 -74. Levine, S., and Stypulkowski, W. (1959). Effect of ischemia on cyanide encephalopathy. Neurology (Minneapolis), 9, 407-4 1 1 . Lewey, F. H., and Drabkin, D. L. (1944). Experimental chronic carbon monoxide poisoning of dogs. Americ3n Journal of Medical Science, 208, 502-51 1 . Meldrum, B. S., and Brierley, J. B . (1969). Brain damage in the Rhesus monkey resulting from profound arterial hypo­ tension. II. Changes in the spontaneous and evoked electrical activity of the neocortex. Brain Research, 13, 101- Meldrum, B. S., and Brierley, J. B. (1971). Circulatory factors and cerebral boundary zone lesions. In Brain Hypoxia, edited by J. B. Brierley and B. S. Meldrum, pp. 20-33. 1 1 8. 187 (Clinics in Developmental Medicine 39/40. Spastics International Medical Publications). Heinemann, London. Meldrum, B. S., Horton, R. W., and Brierley, 1. B. (1971). Insulin-induced hypoglycaemia in the primate: relationship between physiological changes and neuropathology. I n Brain Hypoxia, edited b y J . B . Brierley and B. S. Meldrum, pp. 207�224. (Clinics in Developmental Medicine 39/40. Spastics International Medical Publications). Heinemann, London. Meyer, A. (1 928). Ober das Verhalten des Hemisph!lrenmarks bei der menschlichen Kohlenoxydvergiftung. Zeitschriftfiir die gesamte Neurologie und Psychiarrie, 112, 172-186. M�yer, A. (1933). Experimentelle Vergiftungsstudien. III. Uber Gehirnveriinderungen bei experimenteller Blau­ sliurevergiftung. Zeitschrift /iir die gesamte Neurologie und Psychiatrie, 143, 333-348. , Meyer, A. (1963). Anoxic poisons and the problems of anoxia and selective vulnerability. In Greenfield's Neuropathology 2nd edn, edited by W. Blackwood et at., pp. 237-261 Arnold, London. Myers, R. E., and Kahn, K. J. (1971). Insulin-induced hypoglycemia in the non-human primate. II. Long-term neuropath�logical consequences. In Brain Hypoxia, edited by J. B. Bnerley and B. S. Meldrum, pp. 195-206. (Clinics in Developmental Medicine 39/40. Spastics International Medical Publications). Heinemann, London. Neubuerger, K. T., and Clarke, E. R. (1945). Subacute carbon monoxide poisoning with cerebral myelinopathy and multiple myocardial necroses. Rocky Mountain Medlca/ Journal, 42, 29-35 and 196. Poursines, Y., Alliez, J., and Toga, M. (1956). Etude des lc!:sions corticales d'un cas d'intoxication oxycarbonCe. ReYue Neurologique, 94, 73 1-735. Ranck, J. B. Jr., and Windle, W. F. (1959). Brain damage in the monkey, Macaca mulatto, by asphyxia neonatorum. Experimental Neurology, 1, 1 30-154. Schneider, M. (1 963). Critical blood pressure in the cerebral circulation. In Selective Vulnerability of the Brain in Hypoxaemia, edited by J. P. Schade and W. M. McMenemey, pp. 7-20. Blackwell, Oxford. Swann, H. G., and Brucer, M. (1 949). The cardiorespiratory and biochemical events during rapid anoxic death. I. Fulminating anoxia. Texas Reports on Biology and : Medicine, 1, 5 l l -538. Symon, L., and Brierley, J. B. (1 976). Morphological changes in cerebral blood vessels in chronic ischemic infarction: How correlation obtained by the hydrogen clearance method. In The Cerebral Vessel Wall, edited by J. Cerv6s­ Navarro, et a/., pp. 165·174. Raven Press, New York. ZUlch, K. J., and Behrend, R. C. H. (1961). The pathogenesis and topography of anoxia, hypoxia and ischemia of the brain in man. In Cerebral Anoxia and the Electroencephalo­ gram, edited by H. Gastaut and J. S. Meyer, pp. 144-163. Thomas, Springfield, Illinois. J. Physi<>l. (1963), 169, pp. 292-311 292 With 9 texl·foJur.. Printed in Great Britain THE EFFECT O F BRIEF PROFOUND HYPOXIA UPON THE ARTERIAL AND VENOUS OXYGEN TENSIONS IN MAN BY J. ERNSTING From the Royal Air Force Institute of Aviation Medicine, Farnborough, Hants. (Received 23 January 1963) The partial pressure of oxygen in the alveolar gas may be reduced either by decreasing the total pressure of the environment or by replacing the oxygen normally present in the inspired air by an inert gas. The severe anoxia induced by rapid decompression from 565 to 155 mm Hg absolute, whilst breathing air, may be terminated by the delivery of 100% oxygen to the respiratory tract. The effects of such brief profound anoxia upon the alveolar and arterial gas tensions and upon the central nervous system have been studied extensively (Ernsting & McHardy, 1963; Ernsting, Gedye & McHardy, 1960; Ernsting, 1962). The effect of the resultant severe but short-lived arterial hypoxaemia upon the supply of oxygen to various organs of the body is of considerable interest. The oxygen content of the venous blood flowing from a region reflects the balance between the supply of oxygen to it and its metabolic oxygen consumption. Continuous measurements of the oxygen content of the venous blood flowing from several regions have been made in subjects exposed to brief but profound hypoxia. In the experiments described in this paper a short period of over­ ventilation, nitrogen being used as the inspired gas, was employed in place of rapid decompression to induce hypoxia. This method allowed more extensive observations to be made than were considered practical in a decompression chamber. METHODS Induction of hypoxia. Three healthy men, aged from 33 to 38 years, were used. The sub­ ject lay on a couch and breathed through a valve box, to the inlet of which two taps were connected in series. The side arm of the tap next to the box wa.a open to the atmosphere. One arm of the second tap was connected to a demand valve which was supplied with nitrogen, whilst the other arm was connected to a second demand valve supplied with oxygen. Before the experiment was started the hoses between the two demand regulators and the second tap were purged with the gas delivered by the corresponding regulator. The dead space between the two taps was purged with nitrogen to ensure that 100 % nitrogen was delivered directly the first tap was operated. During each rest period the first tap was positioned so that the subject breathed air. Nitrogen was administered by instructing the subject to expire maximally at the end of a normaJ. expiration, and at this instant the first tap was turned so that the subject breathed from the demand valve which supplied nitrogen. - 293 BRIEF PROFOUND HYPOXIA During the period of breathing nitrogen the subject was instructed to breathe as deeply as possible at a rate of about 20 breaths per minute. Mter 7-20 sec over.ventila.tion with nitrogen the first tap was returned to its original position so that air was breathed again. At the same time the subject was told to cease over-breathing. Respired ga8 tensions. The partial pressures of oxygen and carbon dioxide in the gas passing the subject's lips were recorded continuously in all the experiments by means of a respiratory maas spectrometer (Fowler & Hugh-Jones, 1957). Preliminary studies showed that the output of the instrument was linearly related to the partial pressure of each of these gases. The delay between a. sudden change of partial pressure of either at the sampling tip and the beginning of the response of the recording pen motor was 0·2 sec and 90% of the total response occurred in a further 0·1 sec. Calibrations employing gas mixtures of known composition were performed at intervals throughout each experiment. Over a. 30 min period no significant change occurred in the sensitivity of the instrument. The pulmonary ventilation was recorded in some of the experiments by collecting the expired gas in a Blood sampling. In separate experiments blood was sampled continuously from various recording Tissot spirometer. sites in the cardiovascular system. Blood was obtained from the brachial artery and the femoral vein through a. Courna.nd needle introduced into the vessel after local analgesia had been produced with 2 % lignocaine. A catheter was introduced into the right side of the heart through a. large-bore needle which had been inserted into a. vein in the antecubital fossa. The position of the catheter was determined during its introduction by recording the ced until its tip lay in the pulmonary artery, Blood flowing through the internal jugular pressure at the tip by means of a strain-gauge pressure transducer. The catheter was advan­ which had been exposed through an incision in the right antecubital fossa. This catheter was vein was sampled by means of a radio-opaque catheter which was introduced into a. vein advanced under direct fluoroscopic control with the subject's head held against his left shoulder. The catheter entered the right internal jugular vein and was placed so that its end lay above the level of the tip of the right mastoid process. When in place, the patency of the Cournand needle or the intravascular catheter was maintained when sampling was not in progress by a flow of sterile physiological saline (NaCl 0·9 g/100 ml.), approximately 2 ml.jmin containing heparin (200 i.u./100 mi.}. Recording of blood oxygen saturation and pH. The blood from the intravascular needle or catheter flowed through a tubular cuvette oximeter (Fig. 1) and was then diluted 1 : 10 with neutral physiological saline to which heparin had been added (Sherwood-Jones, Robinson & Cooke, 1960). The diluted suspension of blood was then passed through a microfl.ow-gla.ss­ electrode-.-!$. ' -J' · -� L· -�-� �·20L-�� �g_ �� O l_�� 0 5 10 15 25 30 35 40 �5 50 Time from start of nitrogen breathing (sec:) Fig. 9. Effect of over·ventilation with nitrogen upon the oxygen tension of the aystemio arterial (�). femoral venous ( + ), internal jugular (D) and pulmonary .arterial {0) blood. Each point represents the mean of the values obtained from three subjects. The pattern of the reduction of the oxygen saturation of the venous blood produced by the period of nitrogen breathing varies markedly with the site of sampling (Fig. 5). The oxygen content of the jugular venous blood was the first to change and it exhibited the greatest reduction and the most rapid recovery. In contrast the oxygen saturation of the femoral venous blood started to fall last, was reduced by the smallest amount and recovered the most slowly. Mixed venous blood showed changes which BRIEF PROFOUND H YPOXIA 305 were intermediate between those of the jugular and femoral venous bloods. The maximal fall of the oxygen saturation of the femoral venous blood was half that which occurred in the blood sampled from the pul­ monary artery, whilst the maximal reduction of the oxygen content of the jugular blood was more than twice the latter. The changes of the oxygen tension of the blood sampled from these venous sites have been calculated from the measured values of oxygen saturation and pH and the mean curves are presented in Fig. 9, together with the mean curve for the arterial oxygen tension. It is apparent that during the period of severe hypoxia the oxygen tension of the blood flowing from the lower limbs, the brain and the whole body was greater than that of the arterial blood flowing into these regions. Cardiovascular effects of profound hypoxia The limited measurements made in this study demonstrate that the period of over-ventilation with nitrogen produced significant changes in the cardiovascular system. The control experiments in which the subject over-breathed with air make it possible to distinguish two phases in the cardiovascular response. First, during the period in which the pulmonary ventilation was increased there was a moderate rise of heart rate and the arterial pressure and calf blood flow were raised (Fig. 7). Immediately the over-ventilation ceased the arterial pressure and calf blood flow returned to their resting values. These changes occurred when either air or nitrogen was breathed. When the over-breathing was performed with nitrogen the rise of heart rate persisted for considerably longer and there was a secon­ dary increase of arterial pressure and calf blood flow. These secondary changes were absent when air was substituted for nitrogen and were due, therefore, to the severe hypoxia induced by the nitrogen. Throughout each experiment the calf blood flow was directly proportional to the mean systemic arterial pressure. Thus the observed changes of calf blood flow were a result of the concomitant changes of arterial pressure. The secondary changes which occurred after over-ventilation with nitrogen were probably the result of an increase of cardiac output and of systemic arteriolar con­ striction which were produced reflexly by chemoreceptor stimulation. It is apparent that the arterioles of the calf did not contribute to this vaso­ constriction, and the most probable sites for the increase of peripheral resistance were the splanchnic and cutaneous circulations. The rise of the oxygen saturation of the jugular venous blood above the control value when air breathing was restored (Fig. 5) suggests that there was an increase of the over-all cerebral blood flow at this time. In the steady state moderate arterial hypoxaemia, even when accompanied by hypo­ capnia, is known to produce a dilatation of the cerebral vessels (Kety & 306 J. ERNSTING Schmidt, 1948). The rate at which the cerebral vasodilatation develops when arterial hypoxaemia is induced suddenly is not known, but the present experiments suggest that the cerebral vessels respond to a fall of arterial oxygen tension within 20 sec. Pulmorw,ry gas exchange in profound hypoxia The arterial oxygen-tension values derived in this study demonstrated that during over-ventilation with nitrogen the oxygen tension of the arterial blood was significantly greater than that of the alveolar gas. The time for which this state existed was only 7-8 sec, although during this period the rates of change of alveolar and arterial oxygen tensions were relatively slow. Furthermore, this length of time is large relative to the average transit time of 0·73 sec (Roughton, 1945; Roughton & Forster, 1957) for a red cell through the pulmonary capillaries lining ventilated alveoli. It would appear, therefore, that the observed difference between systemic arterial and alveolar oxygen tensions cannot be accounted for on the basis of the short period for which the condition existed. Such a difference could be produced by the presence of either a shunt of venous blood into the systemic arterial tree or a higher tension of oxygen in the blood leaving the pulmonary capillaries than in the alveolar gas. Mixed venous blood flowing into the systemic arterial tree without having transversed the capillaries of ventilated alveoli would raise the oxygen tension of the systemic arterial blood above that of the alveolar gas. The effect of the normal quantity of venous admixture upon the arterial oxygen tension would be insignificant, because of the relative steepness of the blood-oxygen dissociation curve over the range concerned here. If, however, the proportion of the cardiac output perfusing ventilated alveoli was reduced during nitrogen breathing, this effect could become significant. In order for this mechanism to account for the total observed oxygen­ tension gradient the venous-arterial shunt would have to amount to at least half of the total cardiac output. There is at present no evidence in favour of such a degree of shunting during severe hypoxia. It would appear probable, therefore, that the tension of oxygen in the blood leaving the pulmonary capillaries is considerably greater than that in the alveolar gas during over-ventilation with nitrogen. Since no measurements were made of the rate of gaseous exchange during the period of over-ventilation with nitrogen it is impossible to examine quantitatively the factors affecting the exchange of oxygen between the pulmonary capillary blood and the alveolar gas. It is of value, however, to compare the effects of over-ventilation with nitrogen with those produced by moderate hypoxia in the steady state. Thus, Lilienthal, Riley, Proemmel & Franke (1946) found that at an alveolar BRIEF PROFOUND HYPOXIA 307 oxygen tension of 46 mm Hg at rest the difference between the tensions of oxygen in the alveolar gas and the systemic arterial blood amounted to 9·1 mm Hg. They calculated that under these circumstances the oxygen tension of the mixed venous blood was 19 mm Hg less than that of the alveolar gas and that the oxygen tension of the blood leaving the pul­ monary capillaries was about 8 mm Hg less than that of the alveolar gas. Although in the nitrogen over-ventilation experiments the oxygen tension gradient between the alveolar gas and the mixed venous blood was reversed, it was of the same order as that which existed in the experiments performed by Lilienthal et al. (1946). Furthermore, the mean difference between the oxygen tensions of the arterial blood and the alveolar gas obtained in the present study, which amounted to l l mm Hg, was only slightly greater than that found in moderate hypoxia by Lilienthal et al. (1946). The arterial-alveolar oxygen-tension difference observed in nitro­ gen over-ventilation experiments was probably due, therefore, to a mechanism analogous to that which was deduced by Lilienthal et al. (1946) to be responsible for the existence of an alveolar to end-pulmonary capil­ lary blood-oxygen tension difference in moderate hypoxia. The limited rate at which oxygen was transferred from chemical combination in the pulmonary blood into the alveolar gas under the circumstances which existed in the nitrogen-breathing experiments gave rise to a large oxygen­ tension difference between the blood leaving the pulmonary capillaries and the alveolar gas. Exchange of oxygen between blood and peripheral tissues in profound hypoxia The reduction in the rate at which oxygen is carried to a part caused by a short period of arterial hypoxaemia depends upon the degree and duration of the desaturation of the arterial blood and the arterial flow to the part. In the resting state the total blood flow to the brain is over twice that to the lower limbs. Thus in the present experiments the deficit of the oxygen supply to the brain was twice that to the lower limbs. The effect of such a deficit in the oxygen supply to a region upon the oxygen content of the blood flowing from it will be determined in part by the relation between the magnitude and nature of its oxygen store and its metabolic oxygen consumption. Where the available oxygen store is small in relation to the oxygen uptake, the venous oxygen saturation will be reduced to a greater extent than when the store is large in relation to the oxygen consumption. Quantitatively the most important oxygen store is that contained by the blood, and the greater proportion of this resides in the small and large veins. Muscle possesses in addition a specific oxygen storage mechanism in the form of oxymyoglobin. The amount of oxygen stored in this manner in man is, however, relatively small (Drabkin, 1950) J. ERNSTING 308 and the oxygen tension in muscle must be reduced below 10 mm Hg before a significant proportion of the oxygen held in this form is liberated (Hill, 1936). Finally, all tissues contain oxygen in simple physical solution, although quantitatively this store is relatively small. The brain, in contrast to the lower limbs and the body as a whole, has a high arterial inflow, a high oxygen consumption and a small oxygen store. For a specified tran­ sient arterial hypoxaemia all these factors tend to produce a greater fall of the oxygen saturation in the jugular blood than in the blood flowing from the lower limbs. The pattern of the fall of the saturation of venous blood caused by a transient arterial hypoxaemia will be modified by changes of blood flow into the region and of the capacity of its vascular bed. In the present experiments there were transient changes of calf blood flow during and after the period of hypoxaemia. There was also evidence which suggested that the cerebral blood flow changed, although no direct measurements of this quantity were made. If an increase of blood flow occurred during the period of hypoxaemia, the deficit of the oxygen supply would have been increased. If, however, the increase of blood flow did not occur until the arterial oxygen saturation was rising, it would have produced a more rapid recovery of the venous oxygen saturation, or even a rise to above the e.ontrol value. Although no direct measurements of the capacity of the vessels of the calf were made, it was noted that the volume of this region was decreased by the period of over-ventilation with nitrogen. Eckstein, Hamilton & McCammond (1958) have shown that the reflex reduction of the distensibility of the capacity vessels produced by over-ventilation is in part due to the hypocapnia and in part a result of the intrathoracic pressure changes associated with the over-ventilation. Such a reduction of the blood content of the calf would have tended to increase the venous desaturation produced by the arterial hypoxaemia. During the period of over-ventilation with nitrogen, the oxygen tension of the arterial blood was reduced to 20-30 mm Hg below that of the venous blood normally flowing from the regions studied. Thus the oxygen tension of the arterial blood during this period was lower than the mean capillary oxygen tension (Barcroft, 1938) which existed before nitrogen breathing was commenced. Furthermore, during the period of profound hypoxaemia the oxygen tension of the blood flowing from the regions under investiga­ tion was greater than that of the arterial blood perfusing them. Although the oxygen content of the blood leaving the tissue capillaries was probably raised by admixture with the blood already present in the venules and veins of the part, it is apparent that during the period of severe hypoxaemia the oxygen tension of the capillary blood was markedly reduced. Thus the diffusion of oxygen into the various tissues from the blood flowing through BRIEF PROFOUND HYPOXIA 309 them was severely reduced by the period of hypoxia. Indeed, in some areas, especially those with a relatively high capillary blood flow, the capillary oxygen tension may have been reduced below that of the sur­ rounding tissues, so that oxygen actually diffused into the blood as it flowed through them. Thus direct measurements of the oxygen tension of the grey matter of the cerebral cortex in animals breathing air have given values of the order of 18-25 mm Hg (Cater, Garattini, Marina & Silver, 1962), whilst in the present experiments the arterial oxygen tension was reduced to about 17 mm Hg. The effect of a given reduction of the rate at which oxygen diffuses into a tissue upon the cellular oxygen tension will depend upon the relation between the cellular oxygen consumption and the extravascular oxygen store. There is considerable evidence that the cellular oxidative enzyme systems will continue to function normally until the local oxygen tension is reduced to below 5 mm Hg (Keilin, 1930). Thus the cellular metabolic oxygen uptakewill probablyremain unchanged until severe hypoxia is induced. In the brain, where the only extravascular oxygen store is oxygen dissolved in tissue fluid, and the metabolic oxygen uptake is high, sudden arterial hypoxaemia will produce a very rapid fall of the cellular oxygen tension. In the present series of experimente it was found that unconsciousness ensued if over-ventilation with nitrogen was continued for longer than 17 sec. A more rapid fall of arterial oxygen tension can be produced by sudden reduction of the environmental pressure to below 140 mm Hg whilst air is breathed. Thus in one series of experiments in which the arterial oxygen tension was reduced to below 20 mm Hg in about 1 sec, unconsciousness ensued 8 sec after the induction of arterial hypoxaemia (Ernsting et al. 1960). The delay between a sudden occlusion of the cerebral circulation and loss of consciousness in man also amounts to between 7 and 8 sec (Rossen, Kabat & Anderson, 1943). Thus the time which elapses between a sudden reduction of the arterial oxygen tension to below 20 mm Hg and the onset of unconsciousness is very similar to the interval which occurs between sudden occlusion of the cerebral circulation and loss of consciousness. Kety (1950) has calculated that at any one moment the tota,l oxygen content of the brain and of the cerebral capillary blood is about 7 mi. Thus at the normal level of cerebral oxygen consumption the oxygen tension of the brain following cessation of the supply of this sub . stance would be reduced to zero in about 8 sec. These results suggest that when unconsciousness supervenes following the sudden induction of severe cerebral hypoxia the cellular oxygen tension in many regions of the brain will be virtually zero. This conclusion is in close agreement with the results of ca,lculations ma,de by Thews (1962) with respect to hypoxia of slow onset. His calculations suggest that when the arterial oxygen tension is 310 J. ERNSTING reduced to the level which produces unconsciousness, the oxygen tension of the neurones which are furthest from their vascular supply will be of the order of 2-4 mm Hg. SUMMARY l. Brief profound hypoxia was induced by voluntary over-ventilation whilst breathing nitrogen. Unconsciousness ensued when this procedure was performed for longer than 16 sec. Voluntary over-ventilation with nitrogen for 16 sec reduced the end-tidal oxygen tension to below I 0 mm Hg for 8 sec. 2. Continuous recordings were made of the systemic arterial oxygen saturation and pH during 16 sec of nitrogen over-ventilation. The cal­ culated minimal arterial oxygen tension was 16 mm Hg. There was there­ fore a reversal of the normal alveolar-arterial oxygen tension Y,. J. R. (1960). Anoxia subsequent to rapid decompression. Flying Peraonml Research Committee Report, No. 1141. London: Air Ministry. ERNSTING, J. & McHARDY, G. J. R. (1960). Brief anoxia. following rapid decompression from 560 to 150 mm Hg. J. Phyoiol. 153, 73P. ERNSTING, J. & McHAlmY, G. J. R. (1963). The oxygen saturation a.nd pH of the arterial blood during brief profound anoxia. induced by rapid decompression from 560 to 140 mm Hg. In 0uNmNGRAM, D. J. C. a.nd LLoYD, B. B., The- Regulation of Human Respiration. Oxford: Blackwell. BRIEF PROFOUND HYPOXIA 311 and research. Brit. med. J. i, 1205-1211. Hl::L,L R. (1936). Oxygen dissociation curves of muscle haemoglobin, Proc. Roy. Soc. B, 130, 472--483. FoWLER, K . T. & HuGH-JoNEs, P . (1957). Mass spectrometry applied to clinical practice KEILIN, D. (1939}. Cytochrome and intra-cellular oxidase, Proc. Roy. Soc. B, 106, 418-444. Amer. J. Med. 8, 205-217. KETY, S. S. (1950). Circulation and metabolism of the hwna.n brain in health and disease. KETY, S. S. & ScHMIDT, C. F. (1948). The effects of altered arterial tensions of carbon dioxide and oxygen on cerebral blood :flow and cerebral oxygen consumption of normal young men. J. clin. Invest. 27, 484.--492. D. D. & FR..untE, R. E. (1946). An experi­ mental analysis in man of the oxygen pressure gradient from alveolar air to arterial blood during rest and exercise at sea level and at altitude. Amer. J. Phyaiol. 147, 199-216. LILIENTHAL, J. L., RILEY, R. L., PRoEM::MEL, LUFT, U. C., CLA.MANN, H. G. & ADLER, H. F. (1949). Alveolargases in rapiddecompressions to high altitudes. J. appl. Phyaiol, 2, 37-48. RAHN, H. (1963). Lessons from breath holding. In CuNNINGHAM, The Regulation of human respiration. Oxford : Blackwell. in man. Arch. Neural. Psychiat., Chicago, 50, 510-528. D. J. C. and LLOYD, B. B. RosSEN, R., KABAT, H. & ANDERSON, J. P. (1943). Acute arrest of the cerebral circulation capillary and its relation to the rate of CO uptake and elimination in man. Amer. J. RouGHTON, F. J. W. (1945). The average time spent by the blood in the human lung • Physiol. 143, 621-633. RouGHTON, F. J. W. & FoRSTER, R. E. (1957). Relative importance of diffus.ion and chemical reaction rates in determining rate of exchange of gases in the human lung, with special reference to true diffusing capacity of pulmonary membrane and volume of blood in the lung capillaries. J. appl. Phylliol. 11, 290-302. A device for the con­ tinuous measurement and recording of intravascular pH. Lancet, 278, 1329. SHERWOOD-JONES, E., ROBINSON, J. S. & Cooxx, W. H. (1960). THEws, G. (1962). Implications of the physiology and pathology of oxygen diffusion at the capillary level. In McMENEMEY, W. H. & SCHADE, J. P. Selective Vulnerability of t� WRI'l'NEY, R. J. (1953). The measurement of volume changes in human limbs. J. Physiol. 121, 1-27. Brain in Hypoxaemia. Oxford : Blackwell. J. c/in. Path., 30, Suppl. (Roy. Coli. Path.), 11, 170-180 Pathology of hypoxic brain damage in man D . I . GRAHAM From the University Department of Neuropathology, Institute of Neurological Sciences, Southern General Hospital, Glasgow The energy requirements of the brain demand amongst other things adequate supplies of oxygen and glucose. These are provided by the functions of respiration and circulation. Neurons are particularly susceptible to hypoxia since they have an obligative, aerobic, glycolytic metabolism. The adult brain receives about 15 per cent of the cardiac output, or as expressed in terms of blood flow, about 45 ml/ 100 g/minute in the adult and about twice as much in children (Mcilwain, 1966). The respiratory quotient of the brain is almost unity and glucose is the principal source of energy by oxygenation. If the supply of oxygen or glucose is reduced helow a critical level consciousness is lost after a few seconds and irreversible brain damage may occur if the 'hypoxia' is more prolonged. until the CPP falls to less than 25 mm Hg (Brierley et a/, 1969). The energy state of the brain may also he severely reduced in the presence of normal supplies of oxygen and glucose by substances which poison the oxi­ dative enzymes of nerve cells. These considerations form the basis of the various categories of brain hypoxia (Brierley, 1976; Adams, 1976). Categories of brain hypoxia 1 STAGNANT (a) lschaemic is due to local or generalized arrest of blood supply ; (b) oligaemic is due to local or generalized reduction in blood supply. 2 Physiology The supply of oxygen to the brain depends on the cerebral blood flow (CBF) and the oxygen content of the blood. Cerebral blood flow in turn depends on the cerebral perfusion pressure (CPP) which is defined as the difference between the mean systemic arterial pressure (SAP) and the cerebral venous blood pressure. Blood flow to the brain shows a remarkable capacity for remaining constant, only hypercapnia, hypoxia and extreme hypotension affecting it to any marked extent. The preservation of CBF in response to changes in arterial blood pressure is brought about by autoregulation which can be defined as the 'maintenance of a relatively constant blood flow in the face of changes in perfu­ sion pressure' (Harper, 1972). The mechanism of this autoregulation is still uncertain but it appears to he lost or at least severely impaired in a wide range of acute conditions producing brain damage (Bruce et a/, 1973; Harper et a/, 1975). Thus there are many situations in which cerebral autoregulation may be impaired before an episode of hypoxia. The level of CPP at which brain damage is produced is not known in man but in the presence of normal auto­ regulation the critical level of SAP is about 50 mm Hg (Harper, 1972). In primates with a normal PaOz, it would appear that brain damage does not occur ANOXIC A N D HYPOXIC (a) Anoxic, an absence of oxygen in the lungs which leads to tissue anoxia; (b) hypoxic, a reduced oxygen tension in the lungs which leads to tissue hypoxia. 3 ANAEMIC Anaemic is where there is insufficient haemoglobin in the blood to carry the oxygen in chemical com­ bination. 4 HISTOTOXIC Histotoxic is due to poisoning of neuronal respiratory enzymes. 5 HYPOGLYCAEMIC Hypoglycaemic is due to a deficiency of the substrate glucose. 6 FEBRILE CONVULSIONS A N D STATUS EPILEPTICUS Hypoxic brain damage Hypoxic brain damage may occur in any situation where there is an inadequate supply of oxygen or glucose to nerve cells. It is therefore a potential hazard to any patient subjected to general anaes­ thesia, a severe episode of hypotension, cardiac arrest, status epilepticus, carbon monoxide or 170 171 Pathology of hypoxic brain damage in man barbiturate intoxication and hypoglycaemic coma. The eventual degree of clinical recovery will be determined by whether or not satisfactory resuscita­ tion can be achieved before permanent brain damage ensues. Crises of this kind are not uncommon in clinical practice but the central question as to •what duration of anoxia or ischaemia defines the watershed between recovery of the tissue and extensive perma­ nent injury?' has not been critically defined in man (Plum, 1973). Reasons for this include the Jack of precise physiological data about a patient's cardio­ vascular and respiratory status at the time of a crisis since the immediate priority is resuscitation, and the inadequate neuropathological examination of the brains from fatal cases. Postmortem examination of patients with severe hypoxic brain damage is usually carried out under warrant by the forensic pathologist who often feels obliged to slice the unfixed brain in the mortuary. Under these conditions it is impossible to recognize recent hypoxic brain damage up to and including frank cerebral infarction even when subsequent histological examination shows severe and extensive neuronal necrosis. When the brain has been properly dissected after adequate fixation (up to three weeks' immersion in buffered 10 per cent formal saline) an infarct of about 1 8 to 24 hours' duration may just be recognizable but even an experienced neuro­ pathologist may fail to identify extensive diffuse hypoxic brain damage if it is less than some three to four days' duration (figs I and 2). The extent and severity of hypoxic brain damage can be identified and its distribution analysed only by the micro­ scopical examination of many large, bilateral and representative sections of the brain.! It is, however, often possible to establish that a patient has suffered hypoxic brain damage on the basis of a more restricted histological examination provided that the pathologist knows that certain parts of the brain are selectively vulnerable and is familiar with the cyto­ logical and histological appearances of ischaemic nerve cell change. The identification of ischaemic cell change is made difficult in the human brain because of the frequent occurrence of histological artefact. The commonest artefacts are 'dark cells', 'hydropic cells' and 'perineuronal and perivascular spaces' (Cammer­ meyer, 1961). They are due partly to postmortem handling and to the slow penetration of fixative. Studies in experimental primates and in selected human material haveshown that there is an identifiable process, namely ischaemic cell change, which is the neuropathological common denominator in all types of hypoxia. The earliest histological stage of recent hypoxic neuronal damage in experi1Jlental animals in per- survived 48 hours after cardiac arrest. There are no macroscopic abnormalities. Fig 1 Coronal section of brain from patient who Fig 2 Same patient as in figure I. Note subtotal ('laminar') necrosis of the third, fifth and sixth cortical layers with relative sparing of the second andfourth /ayers (darker staining). Cresyl violet. X 4. fusion-fixed material is microvacuolation (Brown and Brierley, 1966; Brierley et a/, 1971a and b; Meldrum and Brierley, 1973). This rather subtle histological change is difficult to identify in human material so that perhaps the earliest incontrovertible evidence in man of hypoxic brain damage is the second stage, ie, ischaemic cell change. The cell body and nucleus are shrunken and become tri� angular in shape. The cytoplasm, which usually still contains microvacuoles, stains intensely with eosin and from bright blue to dark mauve with the very useful Luxol fast blue/cresyl violet technique (Adams and Miller, 1970); the nucleus stains intensely with basic aniline dyes. The succeeding stage of ischaemic cell change with incrustations is characterized by D. I. Graham 172 Fig 3 Fig 3 Bottom: normal cortex. H and E Fig 4 x 500. Top: Ischaemic cell change, The nerve cells are small and triangular and contain hyperchromatic nuclei (arrows). The cytoplasm is intensely eosinophilic. There is also some disintegration of the neuropil. H and E x 500. Top inset: Ischaemic cell change with incrustations. Note the granules on the surface of the cell. H and E X 500. nuclei (arrows). Cresyl violet. x 500. Fig 4 Homogenizing cell change. Note the Purkinje cells with swollen homogeneous cytoplasm and hyperchromatic further shrinkage of the nerve cell cytoplasm and the development of small, relatively dense granules lying on or close to the surface of the nerve cell (fig 3). Finally the neuron undergoes homogenizing cell change when the cytoplasm becomes progressively paler and homogeneous and the nucleus smaller. This type of change is most commonly seen in the Purkinje cells (fig 4) of the cerebellum. The time course of ischaemic cell change is relatively constant for neurons according to their size and site so that the interval between a hypoxic episode and death if between two and 1 8 to 24 hours can be assessed with reasonable accuracy. If the patient survives for more than 24 to 36 hours more advanced changes occur in neurons, and early reactive changes appear in astrocytes, microglia and endothelial cells. After a few days the dead nerve cells disappear and reactive changes become more intense, including the forma� tion of lipid phagocytes, even though the latter may not appear if damage is restricted to neuronal necrosis. When survival is for more than a week or so the damaged tissue becomes rarefied due to loss of myelin and there is a reactive gliosis. Collagen and reticulin fibres are also laid own, the whole appearing as a glio-mesodermal reaction. The differing susceptibility ofnerve cells to hypoxia has been known for many years. According to Jacob (1963), 'in general the nerve cells are the most sensitive followed by oligodendroglia and astrocytes while the microglia and the cellular elements of the vessels are the least vulnerable'. Recent work suggests that local metabolic rather than vascular factors largely determine the pattern of selective vulnerability (Brierley, 1976). Pathology of hypoxic brain damage in man 173 1 STAGNANT HYPOXIC BR A I N D A MA G E This is divided into two main types, viz, ischaemic and oligaemic. Ischaemic If the blood flow through an artery is arrested, eg by thrombus or an embolus, an infarct will develop within part or the whole of the distribution of the occluded vessel. The earliest macroscopic change is swelling of the infarct and its edges may be just discernible in the fixed brain within 12 to 18 hours. The lesion may be 'haemorrhagic' or 'anaemic' (fig 5) and at an early stage there is irregular, blotchy pallor of the affected cortex (fig 6). A sharp Fig 5 Coronal section of brain from patient who survived three days after sudden stroke. There is a large recent swollen infarct in territories of left middle and anterior cerebral arteries. Part of the injGrct is 'anaemic' and part is 'haemorrhagic'. Note the asymmetry of the lateral ventricles, the displacement of the midline structures to the right, the supracallosal hernia to the right (black arrow) and deep grooving (white arrows) along the line ofbilateral tentorial herniae. Fig 7 Recent infarction in white matter. There is a sharply defined border between the abnormal (pale) and normal white matter. H and E x 40. Fig 6 Recent infarction in cerebral cortex. There is irregular pallor (infarction) of staining of the affected areas. H and E x 15·6. and often very irregular line of demarcation between normal and abnormal myelin also appears early, the abnormal myelin staining palely (fig 7). A large infarct may swell sufficiently to constitute a space� occupying mass within 24 to 48 hours (Adams, 1966) resulting in tentorial herniation with secondary distortion of the mid-brain and infarction in the medial occipital (calcarine) cortex. The necrotic tissue is ultimately removed and replaced by a rather shrunken and cystic gliomesodermal scar. A generalized arrest of blood flow to the brain is most commonly the result of cardiac arrest. This is usually a complication of some surgical procedure under general anaesthesia. Milstein (1956) estimated that about 300 deaths in the United Kingdom were caused by cardiac arrest related to surgery but by 1970 the number of such deaths had dropped to 100 D. I. Graham 174 Fig Sa Normal right Ammon's horn to compare with figure 8b. Fig Sb Right Ammon's horn. Necrosis in the Sommer Fig 9a Normal right Ammon's horn. To compare with figure 9b. The arrows delineate the Sommer sector. Cresyl violet. x 9. Fig 9b Right Ammon's horn showing recent selective neuronal necrosis of Sommer sector (between arrows) and in endfolium. Cresy/ violet. X 9. sector is seen macroscopically. per annum in England and Wales (Wylie, 1975), the the brain, apart from a variable degree of swelling, difference in mortality being attributed to better may appear normal externally and on section even . after adequate fixation. Within 36 to 48 hours it is methods of resuscitation. If cardiac arrest is of abrupt onset and occurs in sometimes possible to identify laminar or patchy a patient at normal body temperature, complete discolouration in the depths of sulci, particularly in clinical recovery is unlikely if the period of arrest is the posterior halves ofthe brain and selective necrosis more than five to seven minutes (Brierley, 1 972). A in the Sommer sector of the Ammon's horn (fig Sa short period of cardiac arrest combined with periods and b). Microscopy reveals diffuse neuronal necrosis of reduced cerebral perfusion pressure before or after with a characteristic pattern of selective vulnerability. the arrest may be as important as the duration of Ischaemic damage is commonly greater within sulci complete arrest (Miller and Myers, 1972) and may than at the crests of gyri and is maximal in the third, lead to accentuation of the ischaemic damage in the fifth and sixth layers of the parietal and occipital lobes (fig 2). In the Ammon's horn the Sommer arterial boundary zones (Brierley, 1976). If death occurs within 24 to 36 hours of the arrest, sector and endfolium are the most vulnerable (fig 9a Pathology of hypoxic brain damage in man and b). These changes are sometimes associated with necrosis of the baso-lateral portion of the amyg­ daloid nucleus. The pattern of damage in the basal ganglia is less constant and tends to be most frequent in the outer halves of the head and body of the caudate nucleus, and in the outer half of the putamen. Damage in the globus pallidus may occur in all types of hypoxia but is especially common in carbon monoxide intoxication. Primary hypoxic damage in the thalamus is most common in the anterior, dorsa­ medial and ventro-lateral nuclei. In the cerebellum there is characteristically diffuse necrosis of Purkinje cells. Damage to the brain stem nuclei tends to be more severe in infants and young children than in adults. Patients with severe diffuse brain damage due to cardiac arrest rarely survive for more than a few days (Bell and Hodgson, 1974) but occasionally they may remain alive in a persistent vegetative state for up to six months or longer (Brierley et a/, 1971; Jennett and Plum, 1972). With increasing survival, the necrotic tissue is replaced by a glio­ mesodermal scar. When this occurs there may be an appreciable reduction in the weight of the brain and evidence of atrophy of both the cortical gyri and cerebellar folia. In coronal slices ventricular enlarge­ ment may be considerable. Whereas the cortex of the parietal and occipital lobes will be reduced to a thin band of discoloured tissue, often with a line of cleavage between it and the underlying white matter, that .of the frontal and temporal lobes may appear essentially normal. While the parahippocampal gyri are usually normal, the hippocampi may show the features of Ammon's horn sclerosis. Even when Fig 10 Coronal section of brain from patient who survived for four years in a persistent vegetative state after cardiac arrest. The cortex is greatly narrowed and there is gross essentially symmetrical enlargement of the ventricles. The Ammon's horns and the thalami are also small. 175 cortical necrosis is severe and survival is for only a few weeks the thalami may appear grossly normal. Eventually evidence of retrograde degeneration will be seen in the corresponding thalamic association nuclei (fig 1 0). 0/igaemic Because of autoregulation a moderate fall in cerebral perfusion pressure does not lead to a reduction in cerebral blood flow. However, when vasodilatation is maximal, autoregulation ceases and the cerebral blood flow will fall parallel to the perfusion pressure. Oligaemic brain damage due to systemic arterial hypotension confonns to one of three patterns (Adams et a!, 1966), of which the first two types are the most common. 1 Ischaemic damage is concentrated along the boundary zones between the arterial territories of the cerebral cortex and in the cerebellum (fig 11). If the lesions are large and of several days' duration they can be recognized macroscopically provided that the brain is cut in the coronal plane (fig 12a). They vary in size from foci of necrosis in the cortex to large, wedge-shaped lesions extending from the cortex almost to the angle of the lateral ventricle. In the cortex, damage is most frequent and most severe in �) �� - - PICA Fig 11 , Diagram to show arterial boundary zones in cerebral and cerebellar hemispheres. The right cerebral hemisphere is shown at three levels, viz, I frontal, 2 mid-temporal and 3 occipital. Each boundary zone is sti'ppled. ACA anterior cerebral artery, MCA middle cerebral artery, PCA posterior cerebral artery, SCA superior cerebellar artery and PICA posterior inferior cerebellar artery. = = = = = = = = 176 D. I. Graham Fig 12a Coronal section of brain from patient who sur.ivedfor 17 days after a myocardial infarct. Note focally haemorrhagic infar.cts (arrows) in the boundary zones between the anterior and middle cerebral arterial territories, and between the middle andposterior cerebral arterial territories. Compare distribution of lesions with figure 11. Fig 12b Same case as illustrated in figure 12a. Slices of cerebellar hemispheres to show duskily haemorrhagic infarcts at dorsal angle ofeach hemiSphere, ie, in the boundary zones between the superior andposterior lnfer�'or cerebellar arterial territories. Compare with figure 11. Fig J2a Fig J2b the parieto-occipital regions, ie, in the common boundary zone between the territories of the anterior, middle and posterior cerebral arteries : it decreases towards the frontal pole along the intraparietal and the superior frontal sulci, ie, between the anterior and middle cerebral arterial territories, and towards the temporal pole along the inferior temporal gyrus, ie, between the middle and posterior cerebral arterial territories. The lesions are usually asymmetrical and may be unilateral, the pattern of ischaemic damage often being determined by atheroma and variations in the calibre of the vessels forming the circle of Willis. In the cerebellum the boundary zone between the territories of the superior and posterior inferior cerebellar arteries lies just beneath the dorsal angle of each hemisphere (fig 12b). There is variable involvement of the basal ganglia particularly in the head of the caudate nucleus and the upper part of the putamen. The Ammon's hom and brain stem are usually not involved. While infarction in the cortical boundary zones may occur in the absence of ischae· mic lesions in the basal ganglia and cerebellum the converse is not common. On the basis of clinical evidence (Adams et a/, 1966; Adams, 1974) and experimental studies on primates (Brierley et a/, 1969) this type of brain damage appears to be caused by a major and abrupt episode of hypotension followed by a rapid return to a normal blood pressure. It is often seen after a conscious patient has collapsedas aresult of asudden reduction in cardiac output, viz, due to ischaemic heart disease, and it may occur in the anaesthetized subject during dental or neurosurgical procedures, particularly in the sitting position (Brierley, 1970). More recently it has been described following the use of methylmethacrylic bone cement (Adams et a/, Pathology of hypoxic brain damage in man 1972), in patients undergoing emergency treatment with antihypertensive agents (Graham, 1975) and in patients dying from blunt head injury (Graham eta/, 1975). Because of the precipitate decrease in arterial pressure there is a transient failure of autoregulation and a severe reduction in CBF in the regions most removed from the parent arterial stems, ie, the boundary zones. 2 Ischaemic damage is generalized in the cortex of the cerebrum and cerebellum, is minor or absent in the hippocampi and is often severe in the thalami. The number of reported cases is small (Brierley and Cooper, 1962; Adams et a/, 1966) but it would seem that this type of damage appears to be associated with hypotension of a relatively slow onset but of long duration. 3 Ischaemic damage is generalized in the cortex of the cerebrum and cerebellum but with variable accentuation along the arterial boundary zones. The hippocampi are usually spared and there is patchy damage in the basal ganglia. This type of damage appears to be associated with the abrupt onset of hypotension which is responsible for the accentuation of damage within the boundary zones followed by a sustained period of less severe hypotension which causes the diffuse damage. 177 Fig 13 Carbon monoxide poisoning. There is infarction of the superior pole of the globus pallidus (arrow). Celloidin section-myelin stain. x 1 ·6. These terms imply that the blood leaving the lungs is either devoid of or has a greatly reduced oxygen content. Hypoxaemia of this severity will occur if there is obstruction of the air passages, after the inhalation of inert gases and in aviation accidents producing decompression. Even though it is still widely believed that brain damage can result from a simple reduction in the oxygen content of arterial blood, there is a lack of critical physiological data about cases purporting to show a correlation between neurological dysfunction and brain damage ascribed to the hypoxaemia. Indeed there is good experi­ mental evidence in Rhesus monkeys and in baboons (Brierley, 1972) that the severity of the hypoxia required to produce brain damage also produces myocardial depression and a reduction in cardiac output. Thus, Brierley concluded that hypoxic hypoxia can produce brain damage only through the medium of a secondary depression of the myo­ cardium, the pattern of damage being similar to that of oligaemic hypoxic brain damage as described above. and psychiatric symptoms that can be regarded as the specific consequences of such poisoning since similar symptoms and signs may be encountered after cardiac arrest, hypoglycaemia, etc. When death occurs within a few hours after poisoning, the organs display the pink/red colour characteristic of carboxyhaemoglobin. When sur­ vival is for 36 to 48 hours, the brain shows evidence of congestion, and petechiae are frequently seen in the white matter and the corpus callosum. Although there is a particular predilection for infarction of the globus pallidus in carbon monoxide poisoning (fig 13), there is also neuronal necrosis in other selectively vulnerable regions such as the Ammon's hom and the cerebral and cerebellar cortex. Changes in the white matter are a common and often conspicuous neuropathological consequence of carbon monoxide poisoning. Damage to whitt: matter tends to occur, particularly in patients who develop delayed signs of intoxication after a period of relative normality following acute poisoning. Recent experimental work in the Rhesus monkey (Ginsberg et a/, 1974) has underlined the importance of systemic circulatory factors in the production of brain damage, the concentration of damage in the white matter possibly being due to a combination of a toxic effect of carbon monoxide together with a moderate reduction in blood flow and perhaps an additional acidosis. 3 4 2 ANOXIC AND HYPOXIC BRAIN D AM AG E ANAEMIC BRAIN D AM AGE This occurs classically in carbon monoxide poison­ ing. The neurological complications of carbon monoxide poisoning are many (Garland and Pearce, 1967) but there is not a combination of neurological HISTOTOXIC BRAIN D A M A G E The histotoxic effects of the cyanide ion and sodium azide are due to the inhibition of cytochrome oxidase. In acute intoxication death ensues rapidly from respiratory failure. In such cases the brain shows D. I. Graham 178 hyperaemia and multiple petechial haemorrhages. In longer surviving cases necrosis bas been identified in the lentiform nucleus and in the cortex of the cerebrum and cerebellum (Brierley, 1976). Experi­ mental studies have now shown that brain damage produced by either cyanide (Brierley, 1975) or azide (Mettler and Sax, 1972) cannot be attributed to histotoxic hypoxia alone but results from their secondary effects on respiration and circulation. 5 HYPOGLYCAEMIC B RAIN D AMA G E 'J Hypoglycaemia in man may lead to permanent brain damage. It may be due to an excess of insulin given either for the treatment of diabetes mellitus or psychosis and in rare instances of islet cell tumour of the pancreas and in examples of idiopathic hypoglycaemia in infants (Brierley, 1 976). In cases of short survival the brain may appear normal. There may be atrophy of the cortex and hippocampi and enlargement of the ventricular system in cases surviving for a number of weeks. Microscopy shows that the brain damage is very similar in type and distribution to that seen in ischaemic hypoxic brain damage, ie, nerve cell Joss and a glio-mesodermal reaction in the striatum, the cortex and the hippocampus, except that there is often relative sparing of the Purkinje cells in the cerebellum. Studies of hypoglycaemia in experimental animals have shown that ischaemic cell change is the principal neuropathological consequence of uncomplicated hypoglycaemia (Meldrum et a/, 1971 ; Brierley et a/, 1971a and b) and in longer surviving animals there is nerve ceJl loss and a variable gUo-mesodermal reaction in the striatum, the cerebral cortex and the hippocampus (Kahn and Myers, 1971). These experiments show that the blood glucose level must fall to about I mmol/1 (20 mgfl 00 ml) if uncompli­ cated hypoglycaemia is to produce brain damage though a higher level of blood sugar may produ� similar damage if complicated by some hypotension, hypoxaemia or epileptic activity. It is therefore quite possible that if a patient has been in hypoglycaemic coma for some time, both oJigaemic and hypoxic factors may have contributed to the brain damage. A different type of neuropathological change has been described in the human infant as a consequence of hypoglycaemia (Anderson et a/, 1967). Neuronal changes were generalized and included chromato­ lysis with cytoplasmic vacuolation in some and fragmentation of nuclear chromatin in others. It has, however, been suggested that these appearances could be attributed to autolysis (Brierley, 1976). 6 FEBRILE C O N V U L S I O N S AND STATUS EPILEPTICUS Status epilepticus may be defined broadly as aconvul- Fig 14 Status epilepticus. Celloidin section of right temporal lobe from a child who died in coma five days after a series of convulsions. Note widespread neuronal necrosis in cortex and Ammon's horn. There is also some 11erve eel/ loss in the thalamus. Cresyl violet. X ]·8. sive episode lasting over an hour without an interve­ ning period of consciousness (Corsellisand Meldrum, 1976). It has long been recognized as a serious danger to life at any age but it offers a special threat in childhood. The basic neuropathology is that of severe and diffuse ischaemic damage of stagnant hypoxic type in which there is widespread necrosis of the cortex, Ammon's horn, basal ganglia, thalamus, cerebellum and parts of the brain stem (fig 14). Thus status epilepticus, particularly in children, constitutes a medical emergency. Fortu­ nately many patients make an uneventful recovery but some have a permanent intellectual or neuro­ logical deficit caused by hypoxic brain damage. Experimental studies in subhuman primate (Meldrum and Horton, 1973; Meldrum and Brierley, 1973; Meldrum eta/, 1973) have emphasized that several factors may contribute to the brain damage, eg, arterial hypotension and hyperpyrexia. Evidence of an impaired neuronal energy metabolism was also found due to a combination of excessive neuronal activity and accumulative effects of second­ ary changes such as hypoxia, hypoglycaemia, hypotension, etc. Conclusions Hypoxic brain damage may occur in diverse clinical situations where there is an inadequate supply of oxygen or glucose to nerve cells. Many patients who experience an episode of severe hypoxia die within a few hours when the pathologist will not be able to Pathology of hypoxic brain damage in man identify any macroscopic abnormalities in the brain. If the patient survives for more than a few hours, however, varying degrees of damage are easily identified, particularly if the brain has been properly dissected after adequate fixation. The identification of early hypoxic brain damage is made difficult in the human brain because of histo­ logical artefact. The earliest clearly identifiable structural damage is selective neuronal necrosis as shown by ischaemic nerve cell change with incrusta­ tion formation. If the hypoxic insult is more severe then frank infarction may occur. In each instance the necrotic tissue is replaced by a glio-mesodermal reaction. The distribution of hypoxic damage is most easily assessed in large representative sections of the brain. It is not usually feasible for the general pathologist to undertake a comprehensive neuropathological analysis in every case of suspected hypoxic brain damage. Fortunately, however, it is possible to establish that a patient has experienced an episode of hypoxia sufficiently severe to produce widespread hypoxic damage by the histological examination of bilateral small blocks from the 'selectively vulnerable areas', namely, the arterial boundary zones, the Ammon's horns, the thalamus and the cerebellum. My thanks to Professor J. H. 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Control of the cerebral circulation. In Scientific Foundations ofNeurology, edited by M. Critchley, J. L. O'Leary and B. Jennett, pp. 235-243. Heinemann, London. 180 Harper, A. M., Jennett, W. B., Miller, J. D., and Rowan, I. 0. Eds. (1975). Blood Flow and Metabolism in the Brain: Proceedings of the Seventh International Symposium on Cerebral Blood Flow and Metabolism, Aviemore, Churchill Livingstone, Edinburgh. Jacob, H. (1963). CNS tissue and cellular pathology in hypox.aemic states. In Selective Vulnerabllity of the Brain in Hypoxaemia, edited by J. P. Schade and W. H. McMenemey, pp. 153�163. Blackwell, Oxford. Jennett, B., and Plum, F. (1972). Persistent vegetative state after brain damage: a syndrome in search of a name. Lancet, I, 734-737, Kahn, K. J., and Myers, R. E. (1971). Insulin-induced hypoglycaemia in the non-human prjmate. I. Clinical consequences. In Brain Hypoxia, edited by I. B. Brierley and B.S. Meldrum, pp. 185-194. (Clinics in Developmental Medicine, no. 39/40). Spastics International Medical Publications and Heinemann, London. Mcilwain, H. (1966). Biochemistry and the Central Nervous System, 3rd ed. Churchill, London. Meldrum, B. S., and Brierley, J. B. (1973). Prolonged epileptic seizures in primates: ischemic cell change and its relation to ictal physiological events. Archives ofNeurology, 28, 10-17. Meldrum, B. S., and Horton, R. W. (1973). Physiology of status epilepticus in primates. Archives of Neurology, 28, 1-9. D, I. Graham Meldrum, B. S., Horton, R. W., and Brierley, J. B. (1971). Insulin-induced hypoglycaemia in the primate: relationship between physiological changes and neuropathology. In Brain Hypoxia, edited by J. B. Brierley and B.S. Meldrum, pp, 207-224. (Clinics in Developmental Medicine, no. 39/40). Spastics International Medical Publications and Heinemann, London. Meldrum, B. S., Vigouroux, R. A., and Brierley, J. B. (1973). Systemic factors and epileptic brain damage. Archives of Neurology,29, 82-87. Mettler, F. A., and Sax, D. S. (1972). Cerebellar cortical degeneration due to acute azide poisoning. Brain, 95, 505516. Miller, J. R., and Myers, R. E. (1972). Neuropathology of systemic circulatory arrest in adult monkeys. Neurology, 22, 888-904. Milstein, B. B. (1956). Cardiac arrest and resuscitation. Annals of the Royal College of Surgeons of England, 19, 6987. Plum, F. (1973). The clinical problem : how much anoxia­ ischemia damages the brain ? Archives of Neurology, 29, 359-360. Wylie, W. D. (1975). "There, but for the Grace of God . . .". AmJa[�- ofthe Royal College ofSurgeons ofEngland, 56, 171180. MERCI< MANUALS > SEE ALL MERCK MANUALS Merck Manual > Health Care Professionals Acid-Base Regulation and Disorders > Endocrine and Metabolic Disorders > Respi ratory Acidosis Respiratory acidosis is primary increase in Pco2 with or without compensatory increase in HC03-; pH is usually low but may be near normal. Cause is a decrease in respiratory rate, volume (hypoventifation), or both due to CNS, pulmonary, or iatrogenic conditions. Respiratory acidosis can be acute or chronic; the chronic form is asymptomatic, but the acute, or worsening, form causes headache, confusion, and drowsiness. Signs include tremor, myoclonic Respiratory Acidosis: Acid-Base Regulation and Disorders: Merck Manual Professional Page 2 of2 Treatment • Adequate ventilation • NaHC03 almost always contraindicated Treatment is provision of adequate ventilation by either endotracheal intubation or noninvasive positive pressure ventilation (for specific indications and procedures, see Resoiratorv Failure and Mechanical Ventilation) . Adequate ventilation is all that is needed to correct respiratory acidosis, although chronic hypercapnia generally must be corrected slowly (eg, over several hours or more), because too-rapid Pco2 lowering can cause a posthypercapnic "overshoot" alkalosis when the underlying compensatory hyperbicarbonatemia becomes unmasked; the abrupt rise in CNS pH that results can lead to seizures and death. Any K+ and Cl- deficits are corrected. NaHC03 is almost always contraindicated, because HC03- can be converted to Pco2 in serum but crosses the blood-brain barrier slowly, thus increasing serum pH without affecting CNS pH. One exception may be in cases of severe bronchospasm, in which HC03- may improve responsiveness of bronchial smooth muscle to [3-agonists. Key Poi nts • Respiratory acidosis involves a decrease in respiratory rate and/or volume (hypoventilation) . • Common causes include impaired respiratory drive (eg, due to toxins, CNS disease), and airflow obstruction (eg, due to asthma, COPD, sleep apnea, airway edema) . • Recognize chronic hypoventilation by the presence of metabolic compensation (elevated HC03-) and clinical signs of tolerance (less somnolence and confusion than expected for the degree of hypercarbia) . • Treat the cause and provide adequate ventilation, using tracheal intubation or noninvasive positive pressure ventilation as needed. Last full review/revision February 2013 by James L. Lewis, Ill, MD Content last modified October 201 3 Audio Copyright Permissions Figures Photographs Sidebars Tables Videos © 2010·2014 Merck Sharp & Oehme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station. N.J., U.S.A. Privacy Terms of Use 1 /0/"11"\1 � ' - < ORIGINAL ARTICLE Su icide By Asphyxiation Due to Helium Inhalation Matthew 0. Howard, PhD, * Martin T. Hall, PhD, t Jeffrey D. Edwards, MSW, * Michael G. Vaughn, PhD,/ Brian E. Perron, PhD,§ and Ruth E. Winecker, PhD1f Abstract: Suicide by asphyxiation using helium is the most widely promoted method of "self�deliverance" by right-to-die advocates. However, little is known about persons committing such suicides or the circumstances and manner in which they are completed. Prior reports of suicides by asphyxia­ tion involving helium were reviewed and deaths determined by the North asphyxial suicides occurring between January I, 2000 and December 3 1 , Carolina Office of the Chief Medical Examiner to be helium-associated 2008 were included i n a new case series examined i n this article. The 1 0 asphyxial suicides involving helium identified i n North Carolina tended to 4 1 . 1 :::!:: 1 1 .6). In 6 of 10 cases, decedents suffered from occur almost exclusively in non-Hispanic, white men who were relatively young (M age = significant psychiatric dysfunction; in 3 of these 6 cases, psychiatric disor­ ders were present comorbidly with substance abuse. In none these cases were decedents suffering from terminal illness. Most persons committing suicide with helium were free ofterminal illness but suffered from psychiatric and/or substance use disorders. Key Words: asphyxia, helium, suicide, right-to-life effective suicide method to the masses. The book was a commercial success, appearing on the New York Times bestseller list and selling more than 1.5 million copies in the decade following its publication. ln 2007, Final Exit was named one of the 25 most influential books of the past quarter-century by book critics and editors of USA Today.3 Concerns that suicides in nonterminally ill depressed persons might follow exposure to methods elucidated in Final Exit were soon raised,4 and dramatic increases in plastic bag asphyxial sui­ cides were observed in New York City5 and the United States6 in the year following publication of Final Exit. Investigators concluded that "most persons exposed to Final Exit were not terminally ill and had used it as a suicide manual . . . (and that) it is likely that a psychiatric disorder would have been diagnosed in most of these people."s {p. tS09) Efforts by NuTech and others to develop a more effective suicide method and widely disseminate it to the public have contin­ ued to the present. In 2000, a supplement to Final Exit was published (Am J Forensic Med Pathol 2010;XX: 000-000) that presented the first description of helium-assisted plastic bag asphyxiation. 7 Advocates emphasized the enhanced lethality of this approach, reduction in time required for death to occur to less than 5 minutes, and elimination of the need for a sedative prescription. P Proponents of the method also noted that materials needed to controversy regarding the appropriateness of suicide as a response to findings are typically nonspecific) or toxicological analysis (because ublication, in 1991, of the right-to-die manifesto and suicide complete such suicides are readily accessible and that asphyxiation "how-to" guide, Final Exit: The Practicalities of Self-Deliver­ ance and Assisted Suicide for the Dying,1 raised a maelstrom of due to helium inhalation is often undetected by autopsy (where terminal or "hopeless" physical illness and exposed divisions within the right-to-die movement itself. In the 1990s, many right-to-die suicides are likely to remain undetected in cases where the helium special sampling and assay methods are required). Thus, such advocates were engaged in public education as to the purported delivery apparatus and plastic bag are removed before the death assisted suicide? At the same time, other elements of this move­ death by helium-assisted asphyxiation. Modifications of the helium Group, were developing technologies to "empower people to die on step-by-step demonstration of the method is available for pur­ virtues of advanced directives, living wills, and legalized physician­ scene is examined and no other information is available implicating ment, including the Self-Deliverance New Technology (NuTech) method were published in 20028 and 2009,9 a DVD including a their own terms by controlling the timing and manner of their own death."2 (p. S) NuTech members, including Derek Humphry, author of on the internet. A schematic of the helium delivery apparatus is chase, 10 and instructional videos depicting the method are accessible Final Exit, sought to identify multiple suicide methods that were presented in Figure 1.9 group also considered it vital that the method be simple, leave little table lethality of helium-assisted suicide, we endeavored to better swift, painless, failure-proof, inexpensive, and nondisfiguring. The or no indication that the death was unnatural in nature, and not Given the recent development, broad dissemination, and no­ understand characteristics of suicides by this method. First, we require a physician's assistance or prescription.2 reviewed findings of extant studies examining suicides by asphyx­ specific endorsement of the plastic bag asphyxiation method, pub­ the largest series of these suicides heretofore examined. Results of With its detailed descriptions of diverse suicide methods and lication of Final Exit brought an easily understood and generally iation due to helium inhalation. Second, we report new findings from this investigation may lead to improved identification of helium­ assisted suicides by medical examiners, enhanced screening and prevention efforts on the part of physicians and other professionals Manuscript received January 19, 2010; accepted March 3, 2010. From the *School of Social Work, University of North Carolina at Chapel Hill; tDepartment of Behavioral Medicine, School of Medicine, University of Kentucky; tSchool of Public Health, Saint Louis University; §Department of Psychiatry, School of Medicine, University of Michigan; and 'i[North Carolina Office of the Chief Medical Examiner. Supported by NIH grants DA15929, DA15556, DA021405 (M.O.H.) and DA007304 (M.T.H.). Correspondence: Matthew 0. Howard, Frank Daniels Distinguished Professor, Tate-Tumer-Kuralt Building, 325 Pittsboro, CB 3550, Chapel HiU, NC 27599-3550. E-mail: mohoward@email.unc.edu. Copyright 0 2010 by Lippincott Williams & Wilkins ISSN' 0!95-7910/l0/0000-000! DOl: 10.1 097/PAF.Ob013e3 181ed7a2d Am j Forensic Med Patho/ • Volume XX, Number X, XXX 20 1 0 treating individuals at risk for suicide, and shed new light on unintended deleterious consequences of widespread dissemination of detailed suicide methods to the general public. MATERIALS AND METHODS The current report presents findings from 2 related studies. The first is a review of published investigations of suicides by asphyxiation due to helium inhalation. The second is a case series of suicides by asphyxiation due to helium inhalation occurring in North Carolina between 2000 (the year in which the method was first described) and December 3 1 , 2008. www.amjforensicmedicine.com 1 1 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Howard et al Am I Forensic Med Patho/ • Volume XX, Number X, XXX 201 0 fled cases. Only the first reported case (ie, 2001) was not subjected to toxicological testing for helium. Specimens from suspected he­ lium asphyxiation cases autopsied at the NCOCME are collected in 20 mL headspace vials. In some cases, given that one central laboratory conducts testing for all medical examiner cases in the state, blood samples are delivered to the NCOCME in standard collection vials. Immediately upon arrival, 5 mL of blood from the standard autopsy vial is transferred to a headspace vial for later analysis. Medical records associated with these deaths were manu­ ally reviewed and abstracted including the OCME Report of Inves­ tigation, State of North Carolina Death Certificate, Report of Au­ topsy, Toxicology Report, Case Encounter Fonn, Pathologist's Notes, and Supplemental Report of Cause of Death. On January 5, 2010, the University of North Carolina Institutional Review Board detennined that the reported research does not require Institutional Review Board approval under pertinent federal regulations. Char­ acteristics of the 1 0 cases identified are presented in Table 2. RESULTS Review of Published Cases The first death attributed to suicide by asphyxiation due to helium inhalation reported in the medical literature occurred in September 2000, 1 1 shortly after the description of the method was published. Several investigators asserted that suicides by the helium method had not been seen in their localities prior to publication of the 2000 Supplement to Final Exit. 1 1 • 12•15·16 The 14 decedents whose cases were presented in the 6 published reports ranged in age from 19 to 8 1 (M age = 50.0, SD FIGURE 1 . Schematic of plastic bag asphyxiation suicide us­ ing helium gas in final exit. Reprinted with permission from Final Exit: The Practicalities of Self-deliverance and Assisted Sui­ cide for the Dying.9 (pA) Identification of Published Reports A broad search of the general medical literature was under­ taken for any relevant reports addressing suicide by asphyxiation due to helium inhalation. This process entailed searching the 21.8, median = = 48.5). Between these extremes, decedents were approximately evenly divided between those in their 20s, 30s, 40s, 60s, and 70s. Medical and psychiatric histories were scant or entirely unreported for some cases, but revealed a history of depression, prior suicide attempt(s), paranoid schizophrenia, or some combina­ tion thereof in 4 (25.6%) cases. In 4 (25.6%) additional cases, psychiatric dysfunction may have contributed to the suicide, given that 3 of these decedents were detennined to be in good health (ages 49, 49, and 76) and one mentioned the recent death of his wife as a reason for his suicide in a note left at the death scene. In 5 other cases (including 4 decedents in their 20s or 30s), no medical or psychiatric histories were reported. A tenninal disease process was PubMed database for the period January 1 , 1957 to November I , present in only 2 of 14 (14.3%) cases. In 2 (14.3%) additional cases records were identified as follows: 6 English-language case stud­ iesu-16 and a Danish-language case study.17 A search of EMBASE health problems" were possible contributing factors. Medical disor­ 2009 using the search phrase "suicide and helium." Seven pertinent November 1, 2009 identified the same 7 reports. The 6 English­ using the identical approach for the period January 1, 1988 to language reports relevant to this review were published between 2002 and 2007 and present a total of 1 4 cases.u-16 The Danish involving men ages 7 1 and 78, "failing health" and "unspecified ders were not implicated in 1 0 of 14 (71 .4%) suicides. In all reported cases, routine toxicological testing did not reveal the presence of helium and manner and cause of death determinations relied heavily on death scene investigations. Autopsy findings tended to be absent or nonspecific in the 12 cases that study included a synoptic abstract in English indicating that the involved an autopsy. a plastic bag and helium using a "new and highly lethal tech­ (28.6%) right-to-die literature was found at the death scene. entirety of published research on helium-assisted suicide and are cases involved use of a mask; 4 of these cases were reported in 2002 decedent was a 35-year-old man who had committed suicide with nique."17 The case reports included in this review constitute the presented in Table 1 . Identification of Suicides by Asphyxiation Due to Helium Inhalation in North Carolina All deaths determined by the North Carolina Office of the In 8 cases (57.1 %), a suicide note was found, and in 4 cases A number of helium delivery devices were employed. Five or 2003, before plastic bag asphyxiation (without use of a mask) became preferred by advocates of the helium method.8 Character­ istics of the plastic tubing used, use of rubber bands and Velcro employed, and use of multiple plastic bags in 1 case were consistent straps to secure plastic bags to the neck, types of helium canisters Chief Medical Examiner (NCOCME) to be asphyxial suicides due to with published descriptions of helium-assisted suicide.8 cember 3 1 , 2008, were included in this study. These suicides were Characteristics of Suicides by Asphyxiation due to Helium Inhalation in North Carolina helium inhalation that occurred between January 1 , 2000 and De­ identified through a search of the manner and cause of death fields of the electronic records maintained by the NCOCME. The presence of helium was confirmed by toxicological testing in 9 of 1 0 identi- 2 I www .amjforensicmedicine.com Asphyxial suicides in North Carolina involving helium inha­ lation tended to occur almost exclusively in non-Hispanic, white © 2010 Lippincott Williams & Willdns Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 0 @ '� 0 � � - 0 t-o 0 ·� .a :::r � @ c u :J "9. 8 ::+ "' " -· � � ;; TABLE Autltors/Date/ (2002), Somh Ogden and Wooten Carolina11 � w. � Gilson et al. Tucson, Arizona12 (2003) Woman, 60, white, Qo Gilson et al. � " :r (2003) (1) u 0. c (2003), Jndiana13 Gallagher et al. 0 g :J 0 over head. Next to body was Final Exit, Final Exit videotape, and Spring death scene that decedent's psychoactive substances carcinoma with antedated carcinoma diagnosis. refillable industrial tank of Hemlock society newsletter were found on a skin color was unremarkable were negative. related eye helium. Clear plastic tube led nearby coffee table. and no external signs of involvement and from plastic bag to helium diplopia. Death tank valve. ur Ill ro r;· ::J � c:!: 3 0 "' c. (1) o: � (ii" u .... 0 "' " ::J 3 0 =r. 0" "' ft 0. 9/2000 and 2; man, 49 occurred Cases I and woman, 48, who were common-law 3 78; wife, 76 and 4: husband, Case 5; tnan, 8 1 6: man, 71 7: man, 25 Woman, 19, well- nourished � a "' 3 g. � No specific information presented; decedents were reportedly in good health. Motivation for suicide unclear. Husband reportedly in "failing over their heads, which were master bedroom in their residence. Couples' secured by elastic straps attorney had called police after receiving a mailed around their necks. Both decedents were wearing (2007) Freiburg, Gennany1"' Man, 23 medications and poisoning were observed. Each decedent had 3 plastic bags Couple found lying supioe by police on floor of decompositional changes. Unremarkable for both decedents. External exams unremarkt�ble. Negative for ethanol, filter cartridge-style masks notes were found close to bodies. Notes referring Internal e1tams not perfonned medications, and illicit "good health" other than a attached to heliwn tanks with to the Hemlock society were found in apartment. per family's wishes. drugs for both decedents. recent minor elective surgery. plastic tubing. No other right-to-die materials fowtd. Advanced squamous cell carcinoma Plastic bag over head with of throat, cnchectic. Found by daughter in bed. Fantily unable to provide plastic tube running from infonnation as to whether "right-to-die" literature inside plastic bag to helium or suicide note were found at death scene. Not clear that an autopsy was conducted. Plastic bag over head secured Found e1tpired in chair in living room of home by with elastic band and Velcro police. A suicide note found, but no right-to-die death of his wife as principal strap at neck. Plastic tube literature. reasons for his suicide. from helium tank connected Extemal exam unremarkable To1ticology tests not except for decomposition. performed due to decomposition. to the mask in5ide plastic bag. motivation for suicide unclear. Plastic bag over head with negative, but it was not were assayed. health problems and the recent Medical history unknown; Blood and urine tests were clear what substances tank. Decedent mentioned unspecified Found dead in empty bathtub of his apartment by plastic tube running from landlord. Right-to-die literature and suicide note helium tank to bag with tube were not found. (\' :s:: " a S' Q.. " < Unremarkable except for decompositional changes. 1: 0 "' >< 3 suicide note. No right-to-die materials found. Couple found dead in bed by neighbor. Suicide iil "' � r;· • Remarkable only for early health" and "depressed"; wife in (234 mgfdL) in :?< z c: 3 0" � :r- >< >< >< N 0 0 � Remarkable only for ethanol decomposition fluid. passing through a sink where wann water was running. History ofptior tiUicide attempts (number ami nature not Dc..-edent wore air filter gas Decedent found supine in backseat of car with Conjunctival petechial Routine to�icology mask coated with a substance helium tank on floor and valve between knees. hemorrhages bilaterally. Nares unremarkable. Presents a described). No description of similar to correction fluid. A Many signed suicide notes and a page from the and oral cavity contained method by which medical history. Had searched heliwn tank obtained fium a "Church of Euthanasia" website entitled "How to frothy white edema fluid. R specimens can be methods of suicide on the local 5upply company was kill yourself' were left in an envelope on the hUJg internet a\lachcd via dear plastic driver's scat. A hand�written map to a local Lungs congested with severe for the presence of tubing to the mask. Duct tape general store was also found in the envelope with pulmonary edema. No evidence helium. sealed mask to skin of face Auwaertcr et al. Blood/urine tests for depression/suicide allempt ;:;; · � 2000 Does not appear an autopsy was adenoid cystic Case (1) 0. Decedent discovered on living room floor of home Toxicology Findings conducted. II was noted at Case 0 � Found with sw·gical mask over Autopsy Findings with suicide note and copy of her will. The book (continued) :J Ill c ..... :::r His101y of depression and a prior Death Scene face and clear plastic bag Tucson, Arizona � c Helium-Delivery Apparatus suicide attempt. Unclear whether Cases (/) Medical/Psychiatric History suffering from manicd. a;· 3 � Chanlcterlstlcs of Decedent Location � � 3 1 . Published Case Reports of Suicides by Asphyxia Due to Helium Inhalation � Ro ),. covering nose and mouth. No infonnation presented. A helium gas canister was = 670 g; L lung = 620 g. a list including tubing, mask and duct tape. A oftrawna, injury, or Jetter was f01.md in decedent's residence Cltp!anation for death other describing where her body was located. than helium inhalation. Decedent was found dead in "lying" position in Nonspecific findings included "an collected and analyzed "'" "' ,. � -13 � c;· BAC of 0.9 mglg; Routine tests revealed a connected to a plastic bag unidentified location. A nearly empty bottle of aqueous swelling of the brain with polypropylene tubing. tequila, blister pack of travel sickness medication, and of the lungs and an acute diphenhydramine in hcan The bag was over the and pack of Ibuprofen tablets were found. hyperemia of the kidneys." No serum decedent's head and affixed evidence of severe illness or urine to neck with a rubber band. injury. (0.81 J.tg/mL) and (2.2 J.tg/mL). Ibuprofen found in urine and gastric content. A positive test for helium by novel assay method was reported. r;· � (Conti1zued) "' "' " "' 0 :J: "' g- 3 � 5" :;,. Q Q g. "' ' Howard et a! 4 www.amjforensicmedicine.com Am f Forensic Med Potho/ • Volume XX, Number X, XXX 201 0 © 2010 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article i s prohibited. Am j Forensic Med Pathol • Volume XX, Number X, XXX 2010 Suicide by Asphyxiation Due ta Helium Inhalation . � £ g), " " '6 � � = � � " 0 ;:. 0 � B ;:. 0 � = < ., 0 0 'I' 0 0 0 N ;,; .so 1 1 � B = • 0 0 " 0 @' .M " "' -"' �� .il z • 0 e B .<:: t 0 z £ c 0 .., "' '" .<:: c E .2 Qj I " " '0 c 0 .., "' .8 } "- .:0: £ /;) '0 ·o ·:; "' 0 v .., � ·.:: tl ::: "' .<:: u N UJ .... "' � © 2010 Lippincott Williams & Wilkins www.amjforensicmedicine.com 5 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. g � _ � :::!� tCj" � � ]. @ Q TABLE 2. � of Death 2005 r @ '0 :::J (') ;:;· Characteristics of Decedent Man, 34, unmarried, � Toxicology Exam MedicaUPsychiatric History History of alcohol Helium-Delivery Apparatus Had clear plastic bag over head with ;;:+ Sll rt' tubing connecting it to a helium a car parked in the yard of vascular congestion; atherosclerotic coronary aortic blood samples tank. A velcro closure secured the a relative's house. A artery disease, focal, mild to moderate. R were positive for treatment for both bag around neck. picture of his girlfriend was lung: 960 g; L lung 820 g. Lungs heavy and ethanol (70 mgldL) and found on dashboard. congested. Lung sections revealed areas of heliunt, respectively. atelectasis, pulmonary edema, and collections Ethanol was listed as a car and taking Zololl. 3 Woman, 60, never (/)' Decedent had clear plastic bag over medical or psychiatric head with 1'2 inch plastic tubing Hispanic), 12 yr of history information auached to helium tank in back education 3 Obese (5'9", 303 lbs). No married white (non- Qo <::: < 2007 Man, 4 1 , married (but recently separated from 0 g. 0- stayed Leucrs to different 430 g; L lung: 400 g); decomposition. people and "a very organized" Sectioned lungs showed vascular congestion Elevated BAC may on right lower leg. left secure bag to neck. The plastic suicide note were found in with patchy intra-alveolar edema. No have been partially or lower leg and Jell am1. tubing was taped to lower margin car Note referred to pgs. No acute precipitants of of plastic bag. 132-137 . in Final Exit 3rd edition wl1ich describe Previously disabled in motor "Return to Sender due to Suicide." Clear blue plastic bag covered head Found expired at home sitting A 13.0 mL subclavian blood sample was Black tubing was connected at one suicide note left. negative for ethanol, Hispanic), 14 yr of reportedly depressed due to end to the inside of bag and at the education recent separntion from wife other end to a 65lb helium tank and pending sale of home. used to fill balloons for parties. but positive for helium. white (non-Hispanic) History of alcohol and drug Clear plastic bag was found over Found sitting in chair in parent's home. Patient was capillaries in lower legs bilaterally were sample was negative Decedent has been very helium tank into the plastic bag. pulseless and not breathlng. observed at death scene. for ethanol and positive Had purchased these materials at Tite book Final Exit was � report. Family noted a local hardware store. The helium lying open and face doWil history of social, medical tank was from a party store on the bed. A suicide note and emotional problems. balloon-filling kit. was left describing how � (if �8 a :::t (") � § �c., Rt> :J"' ::::::. :::r C"' ::::· Was taking Coumadin, severely depressed the Clonidine, Aspirin, decedent had felt and Verapamil, Atenolol, and apologizing for the suicide. Man, 56, married, white (non-Hispanic), 12 yr of education History of depression and substance abuse. Decedent had a bag over his head Found in car in garage at • < Q. >< z :?< No autopsy. 18.0 mL subclavian blood sample was positive for helium tank positioned on car running and exhaust piped helium and negative for into the vehicle. A suicide ethanol. Carbon note was found. monoxide detected at <5.0% saturation. . OTC indicates over-the-counter; BAC, blood alcohol COI\CL'!tlration; EKG. electrocardiOgram. 2. m home by wife with car passenger scat. S:. 3 with a tube attached to it and to a � -· �· c., for helium. Lovastatin. 2008 Q "\:: 19.0 mL subclavian blood head. Two black tubes led from 0 �- No autopsy, but blue nail beds and burst abuse and diabetes. depressed per family's N ';:; � Oxycontin, and VicoditL Man, 45, never married, )::. :S:: antidepressants, Neurontin, 2007 3 a('\" Wife reported that decedent @ 0. No autopsy. and back injuries. Was (f � 0 totally due to decomposition. was taking prescnbed Q -· (I) evidence of acute trawna. in chair in basement. No .{g < >< X N 0 """"' 0 Howard et al suffocations in the year final exit was published. Am J Psychia/1)'. 1994; 1 5 1 : ! 8 !3-!8!4. 7. Humphry D. Supplement to Final Exit: The Latest How�to and Why of Euthanasia/Hastened Death. Junction City, OR: Norris Lane and ERGO; 2000. 8. Humphry D. Final Exit: ne Practicalities ofSe!f.Deliverance and Assisted Suicide for the Dying. 3rd ed. New York, NY: Delta; 2002. 9. Humphry D. Final Exit: ne Practicalities of Sel.fdeliverance and Assisted Suicide for the Dying. 3rd ed. Addendum. Junction City, OR: ERGO; 2009. 10. Humphry D. Final Exit on DVD: The Art ofSelf-deliverance From a Terminal Illness. Junction City, OR: ERGO; 2006. ISBN: 978-0-9768283-0-3. 1 1 . Ogden RD, Wooten RH. Asphyxial suicide with helium and a plastic bag. Am J Forensic Med ?athol. 2002;23:234-237. 12. Gilson T, Parks BO, Porterfield CM. Suicide with inert gases: Addendum to Final Exit. Am J Forensic Med Patlwl. 2003;24:306-308. 13. Gallagher KE, Smith OM, Mellen PF. Suicidal asphyxiation by using pure helium gas: case report, review, and discussion of the influence of the internet. Am J Forensic Med ?athol. 2003;24:361-363. 14. Auwaeter V, Perdekamp MG, Kempf J, et a!. Toxicological analysis after asphyxial suicide with helium and a plastic bag. Forensic Sci Int. 2007; 1 70: !39-!4!. 15. Grassberger M, Kmuskopf A. Suicidal asphyxiation with helium: Report of three cases. Wien Klin Wochenschr. 2007; 1 1 9:323-325. 16. Schon CA, Ketterer T. Asphyxial suicide by inhalation of helium inside a plastic bag. Am J Forensic Med ?athol. 2007;28:364-367. Am j Forensic Med Patho/ • Volume XX, Number X, XXX 2010 20. Ward D. Helium in an "exit bag" new choice for suicide: at least 19 people in B.C. have used method since 1999. Vancouver Sun. December 8, 2007. 2 1 . Lam A. Asian Americans' rising suicide rates-three students take their lives. New American Media. August 13, 2009. 22. Bowers P. Final exit: compassion or assisted suicide? Time. March 2, 2009. 23. Disposable helium tank for sale at Amazon.com. Available at: http://wwsw. amazon.com/BuyCostumes�Disposable-Helium-Tank/dp/BOOOWR8QQG/ ref=pd_sbs_hpc_3. Accessed November 6, 2009. 24. Poklis JL, Garside D, Gaffney�Kraft M, et a\. A qualitative method for the detection of helium in postmortem blood and tissues. In: Proceedings from the Society of Forensic Toxicologists; October 17-21, 2005; Nashville, TN. 25. Lubell KM:, Swahn MH, Crosby AE, eta\. Methods of suicide among persons aged 10-19 years-United States, 1992-2001. MMWR Morb Mortal Weekly Rep. 2004;53:471-474. 26. Lubell KM, Kegler SR, Crosby AE, et a\. Suicide trends among youths and young adults aged 1 0 -24 years-United States, 1990-2004. MMWR Morb Mortal Weekly Rep. 2007;56:905-908. 27. HuG, Wilcox HC, Wissow L, eta\. Midlife-suicide: an increasing problem in U. S.Whites, 1999-2005. Am J Prev Med. 2008;35:589-593. 28. Barber C. Trends and rates in methods of suicide: United States, 1985-2004. Harvard Injury Control Research Center (cbarber@hsph.harvard.edu). Report based on data from the Web�based Injury Statistics and Reporting System (WISQARS), National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, U.S. Vital Statistics. Available at: http:// www.cdc.gov/ncipc/wisqars. 17. Bamung SK, Feddersen C. Suicide by inhaling helium inside a plastic bag[In Danish]. Ugeskr Laeger. 2004;166:3506-3507. 29. Gould MS, Marrocco FA, Kleinman MS, eta\. Evaluating iatrogenic risk of youth suicide screening programs: a randomized controlled trial. JAMA. 2005;293: 1 635-1 643. 19. Tyson AS. Military investigates West Point suicides. Washington Post. January 30, 2009. 30. American Psychiatric Association.Practice guidelines for the assessment and treatment of patients with suicidal behaviors. In: Practice Guidelines for the Treatment of Psychiatric Disorders Compendium. 2nd ed. Arlington, VA: American Psychiatric Association; 2004:835-1027. 18. Recupero PR, Harms SE, Noble JM. Googling suicide: suicide information on the internet. J Clin Psychiatry. 2008;69:878-888. 8 1 1/1/WW.amjforensicmedicine.com © 2010 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Am j Forensic Med Patho/ • Volume XX, Number X, XXX 201 0 men who were relatively young (M age, 4 1 . 1 ; SD, 1 1 .6; range, Suicide by Asphyxiation Due to Helium lnhalotion Of particular concern, are recent national reports of notable significant psychiatric dysfunction; in 3 of these 6 cases, psychiatric increases in the prevalence of suicide due to suffocation (a category ciated with injuries suffered in a motor vehicle accident, and observed in respondents of widely varying ages, including adoles­ 21-60; median, 40.0). In 6 of 10 cases, decedents suffered from problems were present comorbidly with substance abuse. Medical histories identified chronic pain, disability, and chronic pain asso� diabetes (with probable coronary artery disease in 3 decedents). One decedent was found with electrocardiogram leads attached to her body, but autopsy and toxicological findings were negative for potential explanations for the death other than helium-assisted sui­ cide. In none of the 1 0 cases were decedents suffering from terminal illness. Helium delivery devices were consistent with those recom­ mended in Final Exit (eg, use of T-valves, 2 helium tanks, Velcro and other neck fasteners), and all were associated with use of a plastic bag rather than mask.8 In 5 cases, a suicide note was found; in 2 cases, a will was left; in 1 case, insurance papers were left; and in 2 cases, right-to-die materials were found. Autopsies were performed in a majority of cases and typically that includes deaths by plastic bag asphyxiation with or without helium assistance as well as hanging and strangulation) since the 1990s and especially since 2000.25-27 Such increases have been cents, and both genders. Observers have noted that the reasons for these increases are poorly understood, that declining rates of suicide observed in the 1990s have been largely reversed, and that recent increases in suicides due to suffocation account for most of the recent overall increases in rates of suicide.28 It is possible that greater awareness of the plastic bag asphyxiation method and the enhanced lethality of the method when used with helium may account for the significant increases in suicides due to suffocation reported since 2000. Given the national growth in adolescent, young adult, and adult suffocation suicides since 2000,25•26 and relatively young age, psychiatric dysfunction, and absence of tenninal illness character­ istic of many identified cases, it is possible that many persons revealed evidence of pulmonary vascular congestion and mild cere­ committing suicide by the helium method are neither hopelessly nor uting causes of death in 1 case each. author of Final Exit cautions readers to be certain they are hopelessly ill, and not just depressed and to talk to their doctor,8 bral edema. Ethanol and diphenhydramine were considered contrib­ , DISCUSSION Despite reports identifying a plethora of prosuicide internet sites providing detailed instructions in methods of suicide including helium-assisted asphyxiation, 18 media accounts of helium-assisted suicides, 1 9-2 1 and the recent arrests afFinal Exit Network members for allegedly assisting in asphyxial suicides involving helium,22 scientific investigations of such suicides are largely absent from the medical literature. This dearth of information is unfortunate given the tragic consequences of such acts and because it is possible that suicides by the helium method are underestimated and increasingly common for reasons described later in the text. The methods by which helium-assisted suicides are carried out have been carefully detailed and widely publicized and the approach is promoted as simple, painless, and quick.8 Materials needed for helium-assisted suicides are easily obtained and inexpen­ sive. One well-known internet vendor currently sells disposable helium tanks for less than $50, and reports that customers who bought helium tanks also often bought the book Final Exit.23 Unless there is a high index of suspicion for helium involvement in a death, the death may be erroneously attributed to natural causes or under­ lying illness because standard toxicological assays are unlikely to 6 detect helium and autopsy findings are generally nonspecifi.c. 14• 1 Standard toxicological assays using GC/MS employ helium as the terminally ill, but rather psychiatrically disordered. Although the depressive illness and substance dependency often impair the very capacities required to make these assessments and undertake these actions. Prospective studies are needed to better understand the prev­ alence, incidence, predictors, and characteristics of asphyxial sui­ cides due to helium inhalation. It is important to learn more about decedents' medical and psychiatric histories and the circumstances in which depressed and/or suicidal persons encounter descriptions of the helium method (eg, internet demonstrations of the process). At present, professionals working with persons at risk for suicide should routinely assess whether patients have read or viewed in­ structional materials describing specific methods of suicide such as helium-assisted plastic bag asphyxiation. Inquiries of this nature do not increase subsequent risk for suicide and can provide critically important information to guide appropriate preventative actions where indicated.29•30 Medical examiners should also increase their index of suspicion for suicides by asphyxiation associated with helium inhalation. Medical ethicists and the general public may also want to carefully weigh the unintended adverse consequences of widely disseminated suicide methods likely to appeal to some depressed persons (irrespective of their physical health status or age) against the putative benefits associated with making these methods more widely known and available. ACKNOWLEDGMENTS carrier gas and therefore cannot detect helium unless another gas The authors thank P. Barnes, Administrative Services Man­ (eg, nitrogen) is substituted for the helium. Auwaeter et al14 and Gallagher et al13 developed useful methods of collecting, preserv­ ing, and analyzing gas samples taken from decedents' for qualitative detection of helium. In all North Carolina cases, helium-delivery ager, and other staff of the North Carolina Office of the Chief Medical Examinerfor their assistance. devices were found at the death scene, and toxicological testing was conducted in 9 of 1 0 cases. However, it is possible that an unknown number of such suicides went undetected, if and when helium­ delivery devices and plastic bags were removed from the death scene prior to investigation. The author of Final Exit states that a person may choose to leave right-to-die materials to be found to make an ethical statement that they are committing "rational sui­ cide" or, conversely, make plans to have the helium delivery apparatus and plastic bag removed following their death if they prefer to keep the suicidal nature of the death concealed.8 Toxico­ logical testing for helium has been conducted at the NCOCME in suspected cases since 2003 by a novel testing procedure using a dual cell thermal conductivity detector.24 © 2010 Lippincott Williams & Wilkins 2. REFERENCES Final Exit: The Practicalities of Self-Deliverance and Assisted Suicide for the Dying. New York, NY: Delta; 1991. COte R. In Search ofGentle Death: A BriefHistory ofthe NuTech Group. Mt 1. Humphry D. Pleasant, SC: Corinthian; 2008. 3. The most memorable books ofthe last 25 years: 25 books that leave a legacy. April 9, 2007. Available at: http:/Jwww.usatoday.com/life/top25-books.htm. Accessed November 6, 2009. 4. Sacks lv1H, Kemperman I. Final exit as a manual for suicide in depressed patients. Am J Psychiatry. 1992;149:842. 5. Marzuk PM, TardiffK, Hirsch CS, et aL Increase in suicide by asphyxiation in New York City after the publication of final exit. N Eng[ J Med. 6. Marzuk PM, Tardiff K. Leon AC. Increase in fatal suicidal poisonings and 1993;329: 1508-1 510. wvvw.amjforensicmedicine.com [ 7 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.