Clinical death is the medical term for cessation of blood circulation and breathing, the two criteria necessary to sustain the lives of human beings and of many other organisms. It occurs when the heart stops beating in a regular rhythm, a condition called cardiac arrest. The term is also sometimes used in resuscitation research.
Stopped blood circulation has historically proven irreversible in most cases. Prior to the invention of cardiopulmonary resuscitation (CPR), defibrillation, epinephrine injection, and other treatments in the 20th century, the absence of blood circulation (and vital functions related to blood circulation) was historically considered the official definition of death. With the advent of these strategies, cardiac arrest came to be called clinical death rather than simply death, to reflect the possibility of post-arrest resuscitation.
At the onset of clinical death, consciousness is lost within several seconds, and in dogs, measurable brain activity has been measured to stop within 20 to 40 seconds. Irregular gasping may occur during this early time period, and is sometimes mistaken by rescuers as a sign that CPR is not necessary. During clinical death, all tissues and organs in the body steadily accumulate a type of injury called ischemic injury.
Limits of reversal
Most tissues and organs of the body can survive clinical death for considerable periods. Blood circulation can be stopped in the entire body below the heart for at least 30 minutes, with injury to the spinal cord being a limiting factor. Detached limbs may be successfully reattached after 6 hours of no blood circulation at warm temperatures. Bone, tendon, and skin can survive as long as 8 to 12 hours.
The brain, however, appears to accumulate ischemic injury faster than any other organ. Without special treatment after circulation is restarted, full recovery of the brain after more than 3 minutes of clinical death at normal body temperature is rare. Usually brain damage or later brain death results after longer intervals of clinical death even if the heart is restarted and blood circulation is successfully restored. Brain injury is therefore the chief limiting factor for recovery from clinical death.
Although loss of function is almost immediate, there is no specific duration of clinical death at which the non-functioning brain clearly dies. The most vulnerable cells in the brain, CA1 neurons of the hippocampus, are fatally injured by as little as 10 minutes without oxygen. However, the injured cells do not actually die until hours after resuscitation. This delayed death can be prevented in vitro by a simple drug treatment even after 20 minutes without oxygen. In other areas of the brain, viable human neurons have been recovered and grown in culture hours after clinical death. Brain failure after clinical death is now known to be due to a complex series of processes called reperfusion injury that occur after blood circulation has been restored, especially processes that interfere with blood circulation during the recovery period. Control of these processes is the subject of ongoing research.
In 1990, the laboratory of resuscitation pioneer Peter Safar discovered that reducing body temperature by three degrees Celsius after restarting blood circulation could double the time window of recovery from clinical death without brain damage from 5 minutes to 10 minutes. This induced hypothermia technique is beginning to be used in emergency medicine. The combination of mildly reducing body temperature, reducing blood cell concentration, and increasing blood pressure after resuscitation was found especially effective – allowing for recovery of dogs after 12 minutes of clinical death at normal body temperature with practically no brain injury. The addition of a drug treatment protocol has been reported to allow recovery of dogs after 16 minutes of clinical death at normal body temperature with no lasting brain injury. Cooling treatment alone has permitted recovery after 17 minutes of clinical death at normal temperature, but with brain injury.
Under laboratory conditions at normal body temperature, the longest period of clinical death of a cat (after complete circulatory arrest) survived with eventual return of brain function is one hour.
Reduced body temperature, or therapeutic hypothermia, during clinical death slows the rate of injury accumulation, and extends the time period during which clinical death can be survived. The decrease in the rate of injury can be approximated by the Q10 rule, which states that the rate of biochemical reactions decreases by a factor of two for every 10 °C reduction in temperature. As a result, humans can sometimes survive periods of clinical death exceeding one hour at temperatures below 20 °C. The prognosis is improved if clinical death is caused by hypothermia rather than occurring prior to it; in 1999, 29-year-old Swedish woman Anna Bågenholm spent 80 minutes trapped in ice and survived with a near full recovery from a 13.7 °C core body temperature. It is said in emergency medicine that "nobody is dead until they are warm and dead." In animal studies, up to three hours of clinical death can be survived at temperatures near 0 °C.
The purpose of cardiopulmonary resuscitation (CPR) during cardiac arrest is ideally reversal of the clinically dead state by restoration of blood circulation and breathing. However, there is great variation in the effectiveness of CPR for this purpose. Blood pressure is very low during manual CPR, resulting in only a ten-minute average extension of survival. Yet there are cases of patients regaining consciousness during CPR while still in full cardiac arrest. In absence of cerebral function monitoring or frank return to consciousness, the neurological status of patients undergoing CPR is intrinsically uncertain. It is somewhere between the state of clinical death and a normal functioning state.
Patients supported by methods that certainly maintain enough blood circulation and oxygenation for sustaining life during stopped heartbeat and breathing, such as cardiopulmonary bypass, are not customarily considered clinically dead. All parts of the body except the heart and lungs continue to function normally. Clinical death occurs only if machines providing sole circulatory support are turned off, leaving the patient in a state of stopped blood circulation.
Certain surgeries for cerebral aneurysms or aortic arch defects require that blood circulation be stopped while repairs are performed. This deliberate temporary induction of clinical death is called circulatory arrest. It is typically performed by lowering body temperature to between 18 °C and 20 °C (64 and 68 °F) and stopping the heart and lungs. This state is called deep hypothermic circulatory arrest. At such low temperatures most patients can tolerate the clinically dead state for up to 30 minutes without incurring significant brain injury. Longer durations are possible at lower temperatures, but the usefulness of longer procedures has not been established yet.
Death was historically believed to be an event that coincided with the onset of clinical death. It is now understood that death is a series of physical events, not a single one, and determination of permanent death is dependent on other factors beyond simple cessation of breathing and heartbeat.
Clinical death that occurs unexpectedly is treated as a medical emergency. CPR is initiated. In a United States hospital, a Code Blue is declared and Advanced Cardiac Life Support procedures used to attempt to restart a normal heartbeat. This effort continues until either the heart is restarted, or a physician determines that continued efforts are useless and recovery is impossible. If this determination is made, the physician pronounces legal death and resuscitation efforts stop.
If clinical death is expected due to terminal illness or withdrawal of supportive care, often a Do Not Resuscitate (DNR) or "no code" order is in place. This means that no resuscitation efforts are made, and a physician or nurse may pronounce legal death at the onset of clinical death.
A patient with working heart and lungs who is determined to be brain dead can be pronounced legally dead without clinical death occurring. However, some courts have been reluctant to impose such a determination over the religious objections of family members, such as in the Jesse Koochin case. Similar issues were also raised by the case of Mordechai Dov Brody, but the child died before a court could resolve the matter. Conversely, in the case of Marlise Muñoz, a hospital refused to remove a brain dead woman from life support machines for nearly two months, despite her husband's requests, because she was pregnant.
- Kastenbaum, Robert (2006). "Definitions of Death". Encyclopedia of Death and Dying. Retrieved 27 January 2007.
- Lind B, B; Snyder, J; Kampschulte, S; Safar, P; et al. (1975). "A review of total brain ischaemia models in dogs and original experiments on clamping the aorta". Resuscitation. Elsevier. 4 (1): 19–31. doi:10.1016/0300-9572(75)90061-1. PMID 1188189.
- Eisenberg MS, MS (2006). "Incidence and significance of gasping or agonal respirations in cardiac arrest patients". Current Opinion in Critical Care. Elsevier. 12 (3): 189–92. doi:10.1097/01.ccx.0000224862.48087.66. PMID 16672777. S2CID 39042703.
- Hazim J, HJ; Winnerkvist, A; Miller Cc, 3rd; Iliopoulos, DC; Reardon, MJ; Espada, R; Baldwin, JC (1998). "Effect of extended cross-clamp time during thoracoabdominal aortic aneurysm repair". The Annals of Thoracic Surgery. The Society of Thoracic Surgeons. 66 (4): 1204–08. doi:10.1016/S0003-4975(98)00781-4. PMID 9800807. Archived from the original on 2013-01-12. Retrieved 2007-01-09.
- Replantation at eMedicine
- Safar P, P (1986). "Cerebral resuscitation after cardiac arrest: a review". Circulation. Lippincott Williams & Wilkins. 74 (6 Pt 2): IV138–53. PMID 3536160.
- Safar P, P (1988). "Resuscitation from clinical death: pathophysiologic limits and therapeutic potentials". Critical Care Medicine. Lippincott Williams & Wilkins. 16 (10): 923–41. doi:10.1097/00003246-198810000-00003. PMID 3048894. S2CID 25384932.
- Kirino T, T (2000). "Delayed neuronal death". Neuropathology. 20: S95–97. doi:10.1046/j.1440-1789.2000.00306.x. PMID 11037198. S2CID 651613.
- Popovic R, R; Liniger, R; Bickler, PE (2000). "Anesthetics and mild hypothermia similarly prevent hippocampal neuron death in an in vitro model of cerebral ischemia". Anesthesiology. Lippincott Williams & Wilkins. 92 (5): 1343–49. doi:10.1097/00000542-200005000-00024. PMID 10781280. S2CID 18553131.
- Kim SU, SU; Warren, KG; Kalia, M; et al. (1979). "Tissue culture of adult human neurons". Neuroscience Letters. Elsevier Scientific Publishers Ireland. 11 (2): 137–41. doi:10.1016/0304-3940(79)90116-2. PMID 313541. S2CID 42264136.
- Crippen, David. "Brain Failure and Brain Death: Introduction". ACS Surgery Online, Critical Care, April 2005. Archived from the original on 11 October 2007. Retrieved 9 January 2007.
- Holzer M, Behringer W, M; Behringer, W (2005). "Therapeutic hypothermia after cardiac arrest". Current Opinion in Anesthesiology. Lippincott Williams & Wilkins. 18 (2): 163–68. doi:10.1097/01.aco.0000162835.33474.a9. PMID 16534333. S2CID 6675084.
- Davis, Robert (11 December 2006). "To treat cardiac arrest, doctors cool the body". USA Today. Retrieved 7 January 2007.
- Leonov Y, Y; Sterz, F; Safar, P; Radovsky, A; Oku, K; Tisherman, S; Stezoski, SW; et al. (1990). "Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs". Journal of Cerebral Blood Flow and Metabolism. Nature Pub. Group. 10 (1): 57–70. doi:10.1038/jcbfm.1990.8. PMID 2298837.
- Safar P, P; Xiao, F; Radovsky, A; Tanigawa, K; Ebmeyer, U; Bircher, N; Alexander, H; Stezoski, SW; et al. (1996). "Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion". Stroke. Lippincott Williams & Wilkins. 27 (1): 105–13. doi:10.1161/01.STR.27.1.105. PMID 8553385.
- Lemler J, J; Harris, SB; Platt, C; Huffman, TM; et al. (2004). "The arrest of biological time as a bridge to engineered negligible senescence". Annals of the New York Academy of Sciences. New York Academy of Sciences. 1019 (1): 559–63. Bibcode:2004NYASA1019..559L. doi:10.1196/annals.1297.104. PMID 15247086. S2CID 27635898.
- Leonov Y, Y; Sterz, F; Safar, P; Radovsky, A; et al. (1990). "Moderate hypothermia after cardiac arrest of 17 minutes in dogs. Effect on cerebral and cardiac outcome". Stroke. Lippincott Williams & Wilkins. 21 (11): 1600–06. doi:10.1161/01.STR.21.11.1600. PMID 2237954.
- Hossmann KA, KA; Sato, K; et al. (1970). "Recovery of Neuronal Function after Prolonged Cerebral Ischemia". Science. American Association for the Advancement of Science. 168 (3929): 375–76. Bibcode:1970Sci...168..375H. doi:10.1126/science.168.3929.375. PMID 4908037. S2CID 39147135.
- Hossmann KA, KA; Schmidt-Kastner, R; Grosse Ophoff, B; et al. (1987). "Recovery of integrative central nervous function after one hour global cerebro-circulatory arrest in normothermic cat". Journal of the Neurological Sciences. Elsevier. 77 (2–3): 305–20. doi:10.1016/0022-510X(87)90130-4. PMID 3819770. S2CID 11822788.
- Walpoth BH, BH; Locher, T; Leupi, F; Schüpbach, P; Mühlemann, W; Althaus, U; et al. (1990). "Accidental deep hypothermia with cardiopulmonary arrest: extracorporeal blood rewarming in 11 patients". European Journal of Cardio-Thoracic Surgery. Elsevier Science. 4 (7): 390–93. doi:10.1016/1010-7940(90)90048-5. PMID 2397132.
- "Skier revived from clinical death". BBC News. 18 January 2000. Retrieved 9 January 2007.
- Haneda K, K; Thomas, R; Sands, MP; Breazeale, DG; Dillard, DH; et al. (1986). "Whole body protection during three hours of total circulatory arrest: an experimental study". Cryobiology. Academic Press. 23 (6): 483–94. doi:10.1016/0011-2240(86)90057-X. PMID 3802887.
- Behringer W, Safar P, W; Safar, P; Wu, X; Kentner, R; Radovsky, A; Kochanek, PM; Dixon, CE; Tisherman, SA; et al. (2003). "Survival without brain damage after clinical death of 60–120 mins in dogs using suspended animation by profound hypothermia". Critical Care Medicine. Lippincott Williams & Wilkins. 31 (5): 1592–93. doi:10.1097/01.CCM.0000063450.73967.40. PMID 12771628. S2CID 12947736.
- Chandra NC, NC; Tsitlik, JE; Halperin, HR; Guerci, AD; Weisfeldt, ML; et al. (1990). "Observations of hemodynamics during human cardiopulmonary resuscitation". Critical Care Medicine. Lippincott Williams & Wilkins. 18 (9): 929–34. doi:10.1097/00003246-199009000-00005. PMID 2394116.
- Cummins RO, RO; Eisenberg, MS; Hallstrom, AP; Litwin, PE; et al. (1985). "Survival of out-of-hospital cardiac arrest with early initiation of cardiopulmonary resuscitation". The American Journal of Emergency Medicine. W B Saunders. 3 (2): 114–19. doi:10.1016/0735-6757(85)90032-4. PMID 3970766.
- Lewinter JR, JR; Carden, DL; Nowak, RM; Enriquez, E; Martin, GB; et al. (1989). "CPR-dependent consciousness: evidence for cardiac compression causing forward flow". Annals of Emergency Medicine. Mosby. 18 (10): 1111–15. doi:10.1016/S0196-0644(89)80942-4. PMID 2802288.
- Conolly, S; Arrowsmith, JE; Klein, AA (2010). "Deep hypothermic circulatory arrest". Continuing Education in Anaesthesia, Critical Care & Pain. 10 (5): 138–42. doi:10.1093/bjaceaccp/mkq024.
- Greenberg, Mark S (15 February 2010). Handbook of Neurosurgery. Thieme. p. 1063. ISBN 978-1-60406-326-4. Retrieved 18 November 2012.
- Bellamy, R; Safar, P; Tisherman, S. A.; Basford, R; Bruttig, S. P.; Capone, A; Dubick, M. A.; Ernster, L; Hattler Jr, B. G.; Hochachka, P; Klain, M; Kochanek, P. M.; Kofke, W. A.; Lancaster, J. R.; McGowan Jr, F. X.; Oeltgen, P. R.; Severinghaus, J. W.; Taylor, M. J.; Zar, H (1996). "Suspended animation for delayed resuscitation". Critical Care Medicine. 24 (2 Suppl): S24–47. doi:10.1097/00003246-199602000-00046. PMID 8608704.
- Appel, JM. Defining Death: When Physicians and Families Differ" Journal of Medical Ethics Fall 2005
- "Brain-dead NYC boy at center of care controversy dies – USAToday.com". usatoday.com. 16 November 2008. Retrieved November 17, 2008.
- "Texas judge: Remove brain-dead woman from ventilator, other machines". CNN. January 24, 2014.