Deep hypothermic circulatory arrest

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Deep hypothermic circulatory arrest (DHCA) is a surgical technique that involves cooling the body to temperatures below 20°C (68°F), and stopping blood circulation and brain function for up to one hour.[1][2] It is used when blood circulation to the brain must be stopped because of delicate surgery within the brain, or because of surgery on large blood vessels that lead to or from the brain. DHCA is a form of carefully managed clinical death in which heartbeat and all brain activity cease.

At normal body temperature of 37°C only several minutes of stopped blood circulation causes changes within the brain leading to permanent damage after circulation is restored. Reducing body temperature extends the time interval that such stoppage can be survived.[3] At a brain temperature of 14°C , blood circulation can be safely stopped for 30 to 40 minutes.[4] There is an increased incidence of brain injury at times longer than 40 minutes, but sometimes circulatory arrest for up to 60 minutes is used if life-saving surgery requires it.[5][6][7] Infants tolerate longer periods of DHCA than adults.[8]

Applications of DHCA include repairs of the aortic arch, repairs to head and neck great vessels, repair of large cerebral aneurysms, repair of cerebral arteriovenous malformations, pulmonary thromboendarterectomy, and resection of tumors that have invaded the vena cava.[9][10]

Mechanism of brain protection[edit]

Cells require energy to operate membrane ion pumps and other mechanisms of cellular homeostasis. Cold reduces the metabolic rate of cells, which conserves energy stores (ATP) and oxygen needed to produce energy. Cold therefore extends the length of time that cells can maintain homoestasis and avoid damaging hypoxia and anaerobic glycolysis by conserving local resources when blood circulation is stopped and unable to deliver fresh oxygen and glucose to make more energy.[11]

Normally 60% of brain oxygen utilization (CMRO2) consists of energy generation for the neuronal action potentials of brain electrical activity.[12]

A key principle of DHCA is total inactivation of the brain by cooling, as verified by "flatline" isoelectric EEG, also called electrocerebral silence (ECS). Instead of a continuous decrease in activity as the brain is cooled, electrical activity decreases in discontinuous steps. In the human brain, a type of reduced activity called burst suppression occurs at a mean temperature of 24°C, and electrocerebral silence occurs at a mean temperature of 18°C.[13] The achievement of measured electrocerebral silence has been called "a safe and reliable guide" for determining cooling required for individual patients,[14] and verification of electrocerebral silence is required prior to stopping blood circulation to begin a DHCA procedure.[15]

Secondary to conservation of local energy resources by metabolic slowing and brain inactivation, hypothermia also protects the brain from injury by other mechanisms during stopped blood circulation. These include reduction of free radicals and immune-inflammatory processes.[16]

Temperatures used[edit]

Mild hypothermia (28°C to 34°C) and moderate hypothermia (20°C to 28°C) are contraindicated for hypothermic circulatory arrest because 100% and 75% of people respectively will not achieve electrocerebral silence in these temperature ranges.[17] Consequently, safe circulatory arrest times for mild and moderate hypothermia are only 10 and 20 minutes respectively.[18] While moderate hypothermia may be satisfactory for short surgeries, deep hypothermia (14°C to 20°C) affords protection for times of 30 to 40 minutes at the bottom of this temperature range.

Profound hypothermia (< 14 deg°C) usually isn't used clinically. It is a subject of research in animals and human clinical trials. As of 2012, the lowest body temperature ever survived by a human being was 9°C (48°F) as part of a hypothermic circulatory arrest experiment to treat cancer in 1957.[19][20] This temperature was reached without surgery, using external cooling alone. Similar low temperatures are expected to be reached in emergency preservation and resuscitation (EPR) clinical trials described in the Research section of this article.

Method[edit]

People who are to undergo DHCA surgery are placed on cardiopulmonary bypass (CPB), a procedure that uses an external heart-lung machine that can artificially replace the function of the heart and lungs.[21] A portion of the circulating blood supply is removed and stored for later replacement, with the remaining blood diluted by added fluids with the objective of reducing viscosity and clotting tendencies at cold temperature.[22][23] The remaining diluted blood is cooled by the heart-lung machine until hypothermia causes the heart to stop beating normally, after which the blood pump of the heart-lung machine continues blood circulation through the body. Cardioplegic drugs may be administered to ensure the heart stops beating completely (asystole), which is protective of both the heart and brain when circulation is later stopped.[24] Cooling continues until the brain is also inactivated by cold, and electrocerebral silence (flatline EEG) is attained. The blood pump is then switched off, and the interval of circulatory arrest begins. At this time more blood is drained to reduce residual blood pressure if surgery on a cerebral aneurysm is to be performed.[25]

After surgery is completed during the period of cold circulatory arrest, these steps are reversed. The brain and heart naturally resume activity as warming proceeds. The first activity of the warming heart is sometimes ventricular fibrillation requiring cardioversion to re-establish a normal beating rhythm.[26] Except for the period of complete inactivation just prior to and during the circulatory arrest interval, barbiturate infusion is used to keep the brain in a state of burst suppression for the entirety of the DHCA procedure until emergence from anesthesia.[27] Warming must be done carefully to avoid overshooting normal body temperature. Post-operative hyperthermia is associated with adverse outcomes.[28]

History[edit]

In the 1940s and 1950s, Canadian surgeon Wilfred Bigelow demonstrated in animal models that the length of time the brain could survive stopped blood circulation could be extended from 3 minutes to 10 minutes by cooling to 30°C before circulation was stopped.[29] He found that this time could be extended to 15 to 24 minutes at temperatures below 20°C.[30] He further found that at a temperature of 5°C, groundhogs could endure two hours of stopped blood circulation without ill effects.[31][32] This research was motivated by a desire to stop the heart from beating long enough to do surgery on the heart while it remained still. Since heart-lung machines, also known as cardiopulmonary bypass (CPB), hadn't been invented yet, stopping the heart meant stopping blood circulation to the whole body, including the brain.

The first heart surgery using hypothermia to provide a longer time that blood circulation through the whole body could be safely stopped was performed by F. John Lewis and Mansur Taufic at the University of Minnesota in 1952.[33] In this procedure, the first successful open heart surgery, Lewis repaired an atrial septal defect in a 5-year-old girl during 5 minutes of total circulatory arrest at 28°C. Many similar procedures were performed by Soviet heart surgeon, Eugene Meshalkin, in Novosibirsk during the 1960s.[34] In these procedures, cooling was accomplished externally by applying cold water or melting ice to the surface of the body.

The advent of cardiopulmonary bypass in the United States during the 1950s allowed the heart to be stopped for surgey without having to stop circulation to the rest of the body. Cooling more than a few degrees was no longer needed for heart surgery. Thereafter, the only surgeries that required stopping blood circulation to the whole body ("total circulatory arrest") were surgeries involving blood supply to the brain. The only heart surgeries that continued to require total circulatory arrest were repairs to the aortic arch.

Cardiopulmonary bypass machines were essential to the development of deep hypothermic circulatory arrest (DHCA) in humans.[35] By 1959, it was known from the animal experiments of Bigelow, Andjus and Smith, Gollan, Lewis's colleague, Niazi, and others that temperatures near 0°C could be survived by mammals,[36][37][38] and that colder temperature permitted the brain to survive longer circulatory arrest times, even beyond one hour.[39] Humans had survived cooling to 9°C, and circulatory arrest of 45 minutes, using external cooling only.[40] However, reaching such low temperatures by external cooling was difficult and hazardous. At temperatures below 24°C, the human heart is prone to fibrillation and stopping.[41] This can begin circulatory arrest before the brain has reached a safe temperature. Cardiopulmonary bypass machines allow blood circulation and cooling to continue below the temperature at which the heart stops working. By cooling blood directly, cardiopulmonary bypass also cools people faster than surface cooling, even if the heart is not functioning.

In 1959, using cardiopulmony bypass (CPB), Barnes Woodhall and colleagues at Duke Medical Center performed the first brain surgery using DHCA, a tumor resection, at a brain temperature of 11°C and esophageal temperature of 4°C.[42] This was quickly followed by use of DHCA by Alfred Uihlein and other surgeons for treatment of large cerebral aneurysms, another neurosurgical procedure, for which DHCA is still used today.[43] In 1963, Christiaan Barnard and Velva Schrire were the first to use DHCA to repair an aortic aneurysm, cooling the patient to 10°C.[44] Randall B. Griepp, in 1975, is generally credited with demonstrating DHCA as a safe and practical approach for aortic arch surgery.[45][46]

Research[edit]

One of the anticipated medical uses of long circulatory arrest times, or so-called clinical suspended animation, is treatment of traumatic injury. In 1984 CPR pioneer Peter Safar and U.S. Army surgeon Ronald Bellamy proposed suspended animation by hypothermic circulatory arrest as a way of saving people who had exsanguinated from traumatic injuries to the trunk of the body.[47] Exsanguination is blood loss severe enough to cause death. Until the 1980s, it had been thought impossible to resuscitate victims whose heart stopped because of blood loss, resulting in these victims being declared dead when cardiac resuscitation failed. Traditional treatments such as CPR and fluid replacement or blood transfusion are not effective when cardiac arrest has already occurred and bleeding remains uncontrolled.[48] Safar and Bellamy proposed flushing cold solution through blood vessels of victims of deadly bleeding, and leaving them in a state of cold circulatory arrest with the heart stopped until the cause of bleeding could be surgically repaired to allow later resuscitation. In preclinical studies at the University of Pittsburgh during the 1990s, the process was called deep hypothermia for preservation and resuscitation, and then suspended animation for delayed resuscitation.[49]

The process of cooling victims of fatal bleeding for surgical repair and later resuscitation was finally called Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR-CAT), or EPR.[50][51][52][53] It is presently undergoing human clinical trials.[54] In the trials, victims who suffer clinical death of less than five minutes duration from blood loss are being cooled from normal body temperature of 37°C to less than 10°C by pumping a large quantity of ice-cold saline into the largest blood vessel of the body (aorta). By remaining in circulatory arrest at temperatures below 10°C (50 °F), it is believed that surgeons have one[55] to two hours[56][57] to fix injuries before circulation must be restarted. Surgeons involved with this research have said that EPR changes the definition of death for victims of this type of trauma.[58]

See also[edit]

References[edit]

  1. ^ Rosenthal, Elisabeth (13 November 1990). "At Surgery's Frontier: Suspended Animation". The New York Times. Retrieved 14 April 2016. 
  2. ^ Fong, Kevin (27 September 2010). "Surgeons use cold to suspend life". BBC News. Retrieved 14 April 2016. 
  3. ^ Conolly S, Arrowsmith JE, Klein AA (July 2010). "Deep hypothermic circulatory arrest". Contintinuing Education in Anaesthesia Critical Care & Pain. 10 (5): 138–142. doi:10.1093/bjaceaccp/mkq024. 
  4. ^ Yan DY; et al. (March 2013). "Consensus on hypothermia in aortic arch surgery". Annals of Cardiothoracic Surgery. 2 (2): 163–168. doi:10.3978/j.issn.2225-319X.2013.03.03. PMC 3741830Freely accessible. PMID 23977577. HCA at 14 °C is also reported to provide at least 30-40 minutes of safe HCA time. 
  5. ^ Conolly S, Arrowsmith JE, Klein AA (July 2010). "Deep hypothermic circulatory arrest". Contintinuing Education in Anaesthesia Critical Care & Pain. 10 (5): 138–142. doi:10.1093/bjaceaccp/mkq024. Most patients tolerate 30 min of DHCA without significant neurological dysfunction, but when this is extended to longer than 40 min, there is a marked increase in the incidence of brain injury. Above 60 min, the majority of patients will suffer irreversible brain injury, although there are still a small number of patients who can tolerate this. 
  6. ^ "Cerebral ischemia: deep hypothermia". Open Anesthesia. Retrieved 14 April 2016. 45 to 60 minutes is upper limit of safe time period. 
  7. ^ Rosenthal, Elisabeth (13 November 1990). "At Surgery's Frontier: Suspended Animation". The New York Times. Retrieved 14 April 2016. At a body temperature of 60 degrees, almost 40 degrees below normal, the brain can survive an hour without blood flow. 
  8. ^ Conolly S, Arrowsmith JE, Klein AA (July 2010). "Deep hypothermic circulatory arrest". Contintinuing Education in Anaesthesia Critical Care & Pain. 10 (5): 138–142. doi:10.1093/bjaceaccp/mkq024. Longer periods of DHCA are tolerated in neonates and infants compared with adults. 
  9. ^ Anton JM, Kanchuger M. "Anesthetic Management for Deep Hypothermic Circulatory Arrest" (PDF). Society of Cardiovascular Anesthesiologists. Retrieved 14 April 2016. DHCA is used for open heart procedures where the ability to perfuse the brain through the head vessels is not possible with standard proximal aorta cannulation. Repairs of the aortic arch, congenital repairs involving the aortic arch, repairs to the head and neck great vessels, or neurosurgical and pulmonary endarterectomies may require DHCA. Inability to clamp the distal arch, secondary to severe aortic atheromas, may also require DHCA to minimize stroke risk. 
  10. ^ Conolly S, Arrowsmith JE, Klein AA (July 2010). "Deep hypothermic circulatory arrest". Contintinuing Education in Anaesthesia Critical Care & Pain. 10 (5): 138–142. doi:10.1093/bjaceaccp/mkq024. 
  11. ^ Ziganshin BA, Elefteriades JA (May 2013). "Deep hypothermic circulatory arrest". Annals of Cardiothoracic Surgery. 2 (3): 303–315. doi:10.3978/j.issn.2225-319X.2013.01.05. PMC 3741856Freely accessible. PMID 23977599. 
  12. ^ Grocott HP. "Update on Techniques for Neuroprotection during Hypothermic Arrest" (PDF). Society of Cardiovascular Anesthesiologists. Retrieved 14 April 2016. approximately 60% of CMRO2 is utilized for neuronal function (with the remainder being required for cellular integrity) 
  13. ^ Stecker MM; et al. (January 2001). "Deep hypothermic circulatory arrest: I. Effects of cooling on electroencephalogram and evoked potentials". The Annals of Cardiothoracic Surgery. 71 (1): 14–21. doi:10.1016/S0003-4975(00)01592-7. PMID 11216734. 
  14. ^ Mizrahi EM; et al. (January 1989). "Hypothermic-induced electrocerebral silence, prolonged circulatory arrest, and cerebral protection during cardiovascular surgery". Electroencephalogr Clin Neurophysiol. 72 (1): 81–85. doi:10.1016/0013-4694(89)90033-3. PMID 2464479. These data suggest that ECS is a safe and reliable guide for determining the appropriate level of hypothermia during cardiovascular procedures. 
  15. ^ "Cerebral ischemia: deep hypothermia". Open Anesthesia. Retrieved 14 April 2016. Verify isoelectric brain prior to stopping circulation. 
  16. ^ Ziganshin BA, Elefteriades JA (May 2013). "Deep hypothermic circulatory arrest". Annals of Cardiothoracic Surgery. 2 (3): 303–315. doi:10.3978/j.issn.2225-319X.2013.01.05. PMC 3741856Freely accessible. PMID 23977599. 
  17. ^ Yan DY; et al. (March 2013). "Consensus on hypothermia in aortic arch surgery". Annals of Cardiothoracic Surgery. 2 (2): 163–168. doi:10.3978/j.issn.2225-319X.2013.03.03. PMC 3741830Freely accessible. PMID 23977577. At 28 °C, 99-100% of patients have not achieved ECS, while at 20.1 °C, 75-98% of patients have not achieved ECS. 
  18. ^ Yan DY; et al. (March 2013). "Consensus on hypothermia in aortic arch surgery". Annals of Cardiothoracic Surgery. 2 (2): 163–168. doi:10.3978/j.issn.2225-319X.2013.03.03. PMC 3741830Freely accessible. PMID 23977577. Moderate HCA between 20.1-28 °C only affords approximately 10-20 minutes of safe HCA time. 
  19. ^ Brown DJ, Brugger H, Boyd J, Paal P (November 2012). "Accidental Hypothermia" (PDF). The New England Journal of Medicine. 367 (20): 1930–1938. doi:10.1056/NEJMra1114208. PMID 23150960. The lowest reported core body temperatures in patients with full neurologic recovery are slightly less than 14°C (57°F) in a case of accidental hypothermia(40) and 9°C (48°F) in a case of induced hypothermia.(58)... 58. Niazi SA, Lewis FJ. Profound hypothermia in man: report of a case. Ann Surg 1958;147:264-6. 
  20. ^ Niazi SA, Lewis FJ (February 1958). "Profound hypothermia in man; report of a case" (PDF). Annals of Surgery. 147 (2): 264–266. doi:10.1097/00000658-195802000-00019. PMC 1450560Freely accessible. PMID 13498651. In a 51-year-old woman widespread, metastatic ovarian carcinoma was treated by body cooling to a rectal temperature of 9° C. (48° F.). This low temperature was reached, as planned, during cardiac standstill which lasted for one hour, yet the immediate recovery was complete. 
  21. ^ "Deep Hypothermic Circulatory Arrest, How it is Performed". Kaiser Permanente. Retrieved 18 April 2016. 
  22. ^ Young WL; et al. (February 2002). "Anesthetic Management of Deep Hypothermic Circulatory Arrest for Cerebral Aneurysm Clipping". Anesthesiology. 96 (2): 497–503. doi:10.1097/00000542-200202000-00038. PMID 11818785. During craniotomy and dural opening, platelet-rich plasma and red blood cells can be harvested for postbypass reinfusion to aid in the return of normal coagulation status. Euvolemia is maintained by replacing the amount of blood withdrawn with an equal volume of albumin. 
  23. ^ Conolly S, Arrowsmith JE, Klein AA (July 2010). "Deep hypothermic circulatory arrest". Contintinuing Education in Anaesthesia Critical Care & Pain. 10 (5): 138–142. doi:10.1093/bjaceaccp/mkq024. During hypothermia, the combination of increased plasma viscosity, erythrocyte rigidity, and progressive vasoconstriction leads to impairment of the microcirculation. Haemodilution, typically to a haematocrit of 20%, is thought to improve flow in the microcirculation. 
  24. ^ "Cerebral protection and resuscitation". CNS Clinic - Jordan - Amman. Retrieved 16 April 2016. Spontaneous atrial fibrillation may occur below 30°C, and continuous ventricular fibrillation frequently occurs below 28°C. To prevent myocardial ischemic injury, persistent ventricular fibrillation should be terminated by the administration of potassium chloride (KCl), 20 to 60 mEq. 
  25. ^ Young WL; et al. (February 2002). "Anesthetic Management of Deep Hypothermic Circulatory Arrest for Cerebral Aneurysm Clipping". Anesthesiology. 96 (2): 497–503. doi:10.1097/00000542-200202000-00038. PMID 11818785. When the brain temperature reaches 15°C, the circulation is arrested and blood is drained through the venous cannula until the cerebral vasculature appears relaxed. 
  26. ^ Young WL; et al. (February 2002). "Anesthetic Management of Deep Hypothermic Circulatory Arrest for Cerebral Aneurysm Clipping". Anesthesiology. 96 (2): 497–503. doi:10.1097/00000542-200202000-00038. PMID 11818785. Spontaneous cardiac rhythm usually reappears between 20 and 26°C. If present, ventricular fibrillation may be electrically cardioverted. 
  27. ^ Young WL; et al. (February 2002). "Anesthetic Management of Deep Hypothermic Circulatory Arrest for Cerebral Aneurysm Clipping". Anesthesiology. 96 (2): 497–503. doi:10.1097/00000542-200202000-00038. PMID 11818785. During the period just before CPB, thiopental or propofol is titrated in small (50–100 mg) doses to achieve burst-suppression pattern on the raw EEG signal. A continuous infusion is established to maintain the EEG pattern during normothermia. Once cooling begins, the infusion is left constant at the normothermic rate. Alpha-stat PaCO2 management is used. During circulatory arrest, the drug infusion used for EEG burst-suppression is interrupted and then restarted at the same rate during rewarming. 
  28. ^ Conolly S, Arrowsmith JE, Klein AA (July 2010). "Deep hypothermic circulatory arrest". Contintinuing Education in Anaesthesia Critical Care & Pain. 10 (5): 138–142. doi:10.1093/bjaceaccp/mkq024. Excessively rapid rewarming with perfusion temperatures >37°C may induce cerebral ischaemia secondary to an imbalance between oxygen supply and demand. Similarly, cerebral hyperthermia should be avoided as this may exacerbate neurological injury and increase the risk of adverse neurological outcomes. 
  29. ^ Conolly S, Arrowsmith JE, Klein AA (July 2010). "Deep hypothermic circulatory arrest". Contintinuing Education in Anaesthesia Critical Care & Pain. 10 (5): 138–142. doi:10.1093/bjaceaccp/mkq024. In pioneering experiments conducted in the 1940s and 1950s, Bigelow demonstrated that at 30°C, the ‘safe’ period of cerebral ischaemia could be increased from 3 to 10 min—time enough for expeditious surgery. 
  30. ^ Rimmer L, Fok M, Bashir M (Aug 2014). "The History of Deep Hypothermic Circulatory Arrest in Thoracic Aortic Surgery". Aorta. 2 (4): 129–134. doi:10.12945/j.aorta.2014.13-049. PMC 4682724Freely accessible. PMID 26798730. The team performed further research on Macacus Rhesus monkeys, once again using cooling blankets, this time to below 20°C; 11 of 12 monkeys cooled to temperatures between 16 and 19°C survived between 15 and 24 minutes. 
  31. ^ Rimmer L, Fok M, Bashir M (Aug 2014). "The History of Deep Hypothermic Circulatory Arrest in Thoracic Aortic Surgery". Aorta. 2 (4): 129–134. doi:10.12945/j.aorta.2014.13-049. PMC 4682724Freely accessible. PMID 26798730. Bigelow et al. used groundhogs cooled below 5°C (as in their natural hibernating state), operated, and successfully revived 5 of 6 animals. 
  32. ^ Gravlee, Glenn P; Davis, Richard F; Hammon, John; Kussman, Barry (2015). Cardiopulmonary Bypass and Mechanical Support: Principles and Practice. LWW. Bigelow and colleagues continued to study hypothermia and hibernation and learned that a groundhog could be cooled to a body temperature of 5°C and be revived. This temperature allowed circulatory arrest with a cardiotomy procedure lasting 2 hours without ill effects. 
  33. ^ Rimmer L, Fok M, Bashir M (Aug 2014). "The History of Deep Hypothermic Circulatory Arrest in Thoracic Aortic Surgery". Aorta. 2 (4): 129–134. doi:10.12945/j.aorta.2014.13-049. PMC 4682724Freely accessible. PMID 26798730. 
  34. ^ Ziganshin BA, Elefteriades JA (May 2013). "Deep hypothermic circulatory arrest". Annals of Cardiothoracic Surgery. 2 (3): 303–315. doi:10.3978/j.issn.2225-319X.2013.01.05. PMC 3741856Freely accessible. PMID 23977599. In the 1960s, a young, intelligent, and creative Soviet cardiac surgeon - Professor Eugene N. Meshalkin, who worked in the city Novosibirsk, in central Siberia - started using hypothermia to make possible the treatment of ventricular septal defect and atrioventricular canal. It is reported that he even approached tetralogy of Fallot and implanted prosthetic mitral and aortic valves under intervals of arrest with hypothermia. 
  35. ^ Rimmer L, Fok M, Bashir M (Aug 2014). "The History of Deep Hypothermic Circulatory Arrest in Thoracic Aortic Surgery". Aorta. 2 (4): 129–134. doi:10.12945/j.aorta.2014.13-049. PMC 4682724Freely accessible. PMID 26798730. In these early experiments, a common theme was to avoid ventricular fibrillation or at least to correct it as soon as it developed. We must remember this, as in the current era of cardiopulmonary bypass, we are immune to the impact of ventricular fibrillation, which is expected as part-and-parcel of deep hypothermia. 
  36. ^ Woodhall B, Sealy WC, Hall KD, Floyd WL (July 1960). "Craniotomy Under Conditions of Quinidine-Protected Cardioplegia and Profound Hypothermia" (PDF). Annals of Surgery. 152 (1): 37–44. doi:10.1097/00000658-196007000-00006. PMC 1613605Freely accessible. PMID 13845854. Laboratory animals (mice, rats, hamsters, dogs and monkeys) have been cooled to levels of 10 to -5° C. with encouraging survival rates. 
  37. ^ Rimmer L, Fok M, Bashir M (Aug 2014). "The History of Deep Hypothermic Circulatory Arrest in Thoracic Aortic Surgery". Aorta. 2 (4): 129–134. doi:10.12945/j.aorta.2014.13-049. PMC 4682724Freely accessible. PMID 26798730. A physiologist named Frank Gollan worked in the 1950s using hypothermia and an oxygenator of his own invention, and presented his work in 1955. Gollan made an important step in that his bubble oxygenator included a heat exchange device, whereby he could induce hypothermia as well as carry out rewarming. He was able to achieve measured core temperatures of 4°C and published revival of the animals. 
  38. ^ Cooper KE (March 1959). "Physiology of Hypothermia". British Journal of Anaesthesia. 31 (3): 96–105. doi:10.1093/bja/31.3.96. PMID 13638444. Following the publication of work by Andjus in 1951, in which adult rats had been resuscitated after cooling to 1°C, a good deal of attention has been paid to methods of body cooling down to near freezing.... More recently, larger mammals have been cooled to body temperatures between 10° and 0°C. Niazi and Lewis (1957) have cooled dogs and monkeys to these temperatures and successfully resuscitated them. 
  39. ^ Niazi SA, Lewis FJ (February 1958). "Profound hypothermia in man; report of a case" (PDF). Annals of Surgery. 147 (2): 264–266. doi:10.1097/00000658-195802000-00019. PMC 1450560Freely accessible. PMID 13498651. It is evident that a number of homeothermic animals, including man, can tolerate cooling to body temperatures near freezing-temperatures attained regularly by true hibernators. Unlike the hibernators, however, the warm-blooded animals are brought through the lower temperature ranges in a state of cardiac standstill which may usually last up to two and one half hours, though as long as four hours has been tolerated in the rat (one hour in the patient reported here). 
  40. ^ Niazi SA, Lewis FJ (February 1958). "Profound hypothermia in man; report of a case" (PDF). Annals of Surgery. 147 (2): 264–266. doi:10.1097/00000658-195802000-00019. PMC 1450560Freely accessible. PMID 13498651. 
  41. ^ Woodhall B, Sealy WC, Hall KD, Floyd WL (July 1960). "Craniotomy Under Conditions of Quinidine-Protected Cardioplegia and Profound Hypothermia" (PDF). Annals of Surgery. 152 (1): 37–44. doi:10.1097/00000658-196007000-00006. PMC 1613605Freely accessible. PMID 13845854. Fay abandoned attempts to induce hypothermic levels below 24°C because of "fibrillation and cardiac failure" and reported 11 deaths due to sudden cardiac failure among 19 deaths in 169 episodes of general body refrigeration in 124 patients. 
  42. ^ Woodhall B, Sealy WC, Hall KD, Floyd WL (July 1960). "Craniotomy Under Conditions of Quinidine-Protected Cardioplegia and Profound Hypothermia" (PDF). Annals of Surgery. 152 (1): 37–44. doi:10.1097/00000658-196007000-00006. PMC 1613605Freely accessible. PMID 13845854. 
  43. ^ Rothoeri RD, Brawanski A (June 2006). "The history and present status of deep hypothermia and circulatory arrest in cerebrovascular surgery" (PDF). Neurosurg Focus. 20 (6): 1–5. doi:10.3171/foc.2006.20.6.5. PMID 16819813. 
  44. ^ Rimmer L, Fok M, Bashir M (Aug 2014). "The History of Deep Hypothermic Circulatory Arrest in Thoracic Aortic Surgery". Aorta. 2 (4): 129–134. doi:10.12945/j.aorta.2014.13-049. PMC 4682724Freely accessible. PMID 26798730. 
  45. ^ Conolly S, Arrowsmith JE, Klein AA (July 2010). "Deep hypothermic circulatory arrest". Contintinuing Education in Anaesthesia Critical Care & Pain. 10 (5): 138–142. doi:10.1093/bjaceaccp/mkq024. Although reports of the use of CPB-induced hypothermia and DHCA to facilitate aortic arch surgery appeared in the 1960s, it was Griepp, in 1975, who demonstrated that the technique offered a practical and safe approach for aortic arch surgery. 
  46. ^ Rimmer L, Fok M, Bashir M (Aug 2014). "The History of Deep Hypothermic Circulatory Arrest in Thoracic Aortic Surgery". Aorta. 2 (4): 129–134. doi:10.12945/j.aorta.2014.13-049. PMC 4682724Freely accessible. PMID 26798730. 
  47. ^ Tisherman, Samuel; Sterz, Fritz (2007). Therapeutic Hypothermia. Springer US. p. 160. In 1984, U.S. Army surgeon Ronald Bellamy and anesthesiologist Peter Safar met and discussed the pathophysiology of rapid death in combat casualties killed in action. Similar patters have been observed in civilian victims of penetrating truncal injuries. Until the 1980s it had been thought impossible to resucitate victims of truncal internal exsanguination to cardiac arrest, which occurs over a few minutes, because the surgery required for stopping the hemorrhage cannot be performed rapidly enough in the field. Bellamy and Safar recommended research into a new approach: "suspended animation" for preservation of the organism until hemostasis, followed by delayed resuscitation. Pharmacologic and hypothermic preservation potentials seemed worth exploring. 
  48. ^ Alam HB; Pusateri AE; Kindzelski A; et al. (October 2012). "Hypothermia and hemostasis in severe trauma: A new crossroads workshop report" (PDF). The Journal of Trauma and Acute Care Surgery. 73 (4): 809–817. doi:10.1097/TA.0b013e318265d1b8. PMID 23026915. 
  49. ^ Kochanek P (June 2007). "Emergency Preservation and Resuscitation: Beyond CPR" (PDF). Society of Critical Care Medicine. Retrieved 20 April 2016. This concept, first described in the literature by Samuel Tisherman, MD, FCCM, from the University of Pittsburgh (Tisherman et al. J Trauma. 1990;30:836), was called deep hypothermia for preservation and resuscitation. In further studies, the process was called suspended animation for delayed resuscitation and eventually emergency preservation for resuscitation. 
  50. ^ Kutcher ME, Forsythe RM, Tisherman SA (Oct 2015). "Emergency preservation and resuscitation for cardiac arrest from trauma". International Journal of Surgery. doi:10.1016/j.ijsu.2015.10.014. PMID 26497780. 
  51. ^ Thomson, Helen (26 March 2014). "Gunshot victims to be suspended between life and death". New Scientist. Retrieved 20 April 2016. 
  52. ^ Wendling, Patrice (March 2010). "Trauma Study Tests Hypothermia's Limits". American College of Emergency Physicians News. Retrieved 20 April 2016. 
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  56. ^ Alam HB; Pusateri AE; Kindzelski A; et al. (October 2012). "Hypothermia and hemostasis in severe trauma: A new crossroads workshop report" (PDF). The Journal of Trauma and Acute Care Surgery. 73 (4): 809–817. doi:10.1097/TA.0b013e318265d1b8. PMID 23026915. When hemorrhage has progressed to cardiac arrest, induction of profound hypothermia can (1) maintain viability of critical organs (including brain) during prolonged periods (up to 120 minutes) of no (or very low) flow, (2) attenuate reperfusion injury, and (3) improve survival and decrease organ dysfunction. 
  57. ^ Thomson, Helen (26 March 2014). "Gunshot victims to be suspended between life and death". New Scientist. Retrieved 20 April 2016. The patient will be disconnected from all machinery and taken to an operating room where surgeons have up to 2 hours to fix the injury. 
  58. ^ Thomson, Helen (26 March 2014). "Gunshot victims to be suspended between life and death". New Scientist. Retrieved 20 April 2016. After we did those experiments, the definition of ‘dead’ changed," says Rhee. "Every day at work I declare people dead. They have no signs of life, no heartbeat, no brain activity. I sign a piece of paper knowing in my heart that they are not actually dead.