Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest

Background: Cardiac arrest with widespread cerebral ischemia frequently leads to severe neurologic impairment. We studied whether mild systemic hypothermia increases the rate of neurologic recovery after resuscitation from cardiac arrest due to ventricular fibrillation. Methods: In this multicenter trial with blinded assessment of the outcome, patients who had been resuscitated after cardiac arrest due to ventricular fibrillation were randomly assigned to undergo therapeutic hypothermia (target temperature, 32°C to 34°C, measured in the bladder) over a period of 24 hours or to receive standard treatment with normothermia. The primary end point was a favorable neurologic outcome within six months after cardiac arrest; secondary end points were mortality within six months and the rate of complications within seven days. Results: Seventy-five of the 136 patients in the hypothermia group for whom data were available (55 percent) had a favorable neurologic outcome (cerebral-performance category, 1 [good recovery] or 2 [moderate disability]), as compared with 54 of 137 (39 percent) in the normothermia group (risk ratio, 1.40; 95 percent confidence interval, 1.08 to 1.81). Mortality at six months was 41 percent in the hypothermia group (56 of 137 patients died), as compared with 55 percent in the normothermia group (76 of 138 patients; risk ratio, 0.74; 95 percent confidence interval, 0.58 to 0.95). The complication rate did not differ significantly between the two groups. Conclusions: In patients who have been successfully resuscitated after cardiac arrest due to ventricular fibrillation, therapeutic mild hypothermia increased the rate of a favorable neurologic outcome and reduced mortality.

Alan D. Lopez | Joseph S. Salama | Stephen S. Lim | R. Malekzadeh | Kara Estep | L. Dandona | R. Dandona | V. Feigin | T. Vos | C. Murray | M. Forouzanfar | M. Naghavi | J. Silverberg | A. Banerjee | S. Hay | B. Duncan | Y. Khang | J. Singh | C. Abbafati | K. H. Abate | M. Ahmed | A. Alkerwi | Rajaa Al-Raddadi | E. Weiderpass | E. Amini | J. Ärnlöv | H. Asayesh | A. Barać | D. Bennett | J. Carrero | S. Dharmaratne | A. Esteghamati | João Fernandes | Thomas Fürst | Philimon N. Gona | N. Hafezi-Nejad | F. Islami | A. Kasaeian | S. Katikireddi | A. Kengne | Y. Khader | Y. Kim | Y. Kinfu | S. Kosen | B. K. Defo | Xiaofeng Liang | R. Lozano | A. Majeed | D. Malta | M. Mazidi | C. McAlinden | G. Mensah | E. Mirrakhimov | A. Mokdad | M. Moradi-Lakeh | U. Mueller | F. Ogbo | M. Owolabi | G. Patton | M. Qorbani | Anwar Rafay | R. Rai | M. Reitsma | S. Safiri | J. Salomon | J. Sanabria | I. Santos | B. Sartorius | M. Sawhney | A. Schutte | S. Sepanlou | R. Shiri | I. Shiue | P. Sur | R. Tabarés-Seisdedos | A. Terkawi | M. Tonelli | R. Topor-Madry | S. Tyrovolas | K. Ukwaja | O. Uthman | T. Vasankari | S. Vollset | A. Werdecker | R. Westerman | Y. Yano | N. Yonemoto | Z. Zaidi | Z. M. Zenebe | B. Zipkin | A. Amare | B. Eshrati | T. Gebrehiwot | A. Goto | C. Kesavachandran | J. Khubchandani | A. S. Beyene | S. Biadgilign | S. Biryukov | D. Boneya | R. Kamal | L. Marczak | H. Mezgebe | C. Obermeyer | F. Pourmalek | C. Ranabhat | Nikolas Reinig | S. Swaminathan | J. Thakur | V. Vlassov | S. Sheikhbahaei | H. Larson | S. Damtew | Desalegn Tadese Mengiste | H. Shore | Fentaw Tadese | B. Tedla | R. Anjana | E. Bjertness | S. Mcgarvey | Gert B. M. Mensink | Tiffany Ku | Min-Jeong Shin | Leslie Cornaby | A. Amberbir | S. Amrock | M. Leinsalu | S. Stranges | J. Schmidhuber | A. Amegah | G. Yonga | Audra L Gold | T. Habtewold | Joshua Wesana | Ashkan Mohammad H. Marissa Patrick Kara Alex Laurie Ali H Afshin Forouzanfar Reitsma Sur Estep Lee M | Alex Lee | Estifanos Baye | Masako Horino Berger | P. Cecílio | Kokeb Tesfamariam Hadush | Patrick Liu | Jean Jacques N. Noubian | Moretza Shamsizadeh | D. A. Santos Silva | B. Tegegne | Liliana G. Ciobanu | Ismael Campos-Nonato | Kelly M. Cercy | A. Afshin | Z. Al‐Aly | Masoud Vaezghasemi | G. Kumar | M. Schmidt | Daniel H. Kim | K. T. Hadush

[1]  M. Eisenberg,et al.  Cardiac resuscitation [3] , 2001 .

[2]  H S Levin,et al.  Lack of effect of induction of hypothermia after acute brain injury. , 2001, The New England journal of medicine.

[3]  C. Callaway,et al.  Delayed, spontaneous hypothermia reduces neuronal damage after asphyxial cardiac arrest in rats , 2000, Critical care medicine.

[4]  K. Kanmatsuse,et al.  Cardiopulmonary cerebral resuscitation using emergency cardiopulmonary bypass, coronary reperfusion therapy and mild hypothermia in patients with cardiac arrest outside the hospital. , 2000, Journal of the American College of Cardiology.

[5]  A. Buchan,et al.  Indefatigable CA1 Sector Neuroprotection with Mild Hypothermia Induced 6 Hours after Severe Forebrain Ischemia in Rats , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  J. Zhang,et al.  What's the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes. , 1998, JAMA.

[7]  Y. Yanagawa,et al.  Preliminary clinical outcome study of mild resuscitative hypothermia after out-of-hospital cardiopulmonary arrest. , 1998, Resuscitation.

[8]  H. Wellens,et al.  Out-of-hospital cardiac arrest in the 1990's: a population-based study in the Maastricht area on incidence, characteristics and survival. , 1997, Journal of the American College of Cardiology.

[9]  M. Horne,et al.  Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. , 1997, Annals of emergency medicine.

[10]  D. Stein,et al.  Mild hypothermia: therapeutic window after experimental cerebral ischemia. , 1996, Neurosurgery.

[11]  R. J. Hayes,et al.  Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. , 1995, JAMA.

[12]  P. Safar,et al.  Delay in cooling negates the beneficial effect of mild resuscitative cerebral hypothermia after cardiac arrest in dogs: A prospective, randomized study , 1993, Critical care medicine.

[13]  T. Wieloch,et al.  Hypothermia ameliorates neuronal survival when induced 2 hours after ischaemia in the rat. , 1992, Acta physiologica Scandinavica.

[14]  R. Green,et al.  Cerebral blood flow and metabolism in hypothermic circulatory arrest. , 1992, The Annals of thoracic surgery.

[15]  P. Safar,et al.  Beneficial Effect of Mild Hypothermia and Detrimental Effect of Deep Hypothermia After Cardiac Arrest in Dogs , 1992, Stroke.

[16]  P. Safar,et al.  Multifocal cerebral blood flow by Xe-CT and global cerebral metabolism after prolonged cardiac arrest in dogs. Reperfusion with open-chest CPR or cardiopulmonary bypass. , 1992, Resuscitation.

[17]  Andrew M. Johanos A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest. , 1991, The New England journal of medicine.

[18]  P. Safar,et al.  Mild hypothermia cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs , 1991, Critical care medicine.

[19]  P. Safar,et al.  Moderate hypothermia after cardiac arrest of 17 minutes in dogs. Effect on cerebral and cardiac outcome. , 1990, Stroke.

[20]  P. Safar,et al.  Mild Cerebral Hypothermia during and after Cardiac Arrest Improves Neurologic Outcome in Dogs , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  M D Ginsberg,et al.  Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain. , 1989, Stroke.

[22]  A. Macneil Cardiopulmonary Cerebral Resuscitation: Basic and Advanced Cardiac and Trauma Life Support: An Introduction to Resuscitation Medicine , 1989 .

[23]  L. D'alecy,et al.  Protection from cerebral ischemia by brain cooling without reduced lactate accumulation in dogs. , 1989, Stroke.

[24]  K. Welch,et al.  The Metabolic Effects of Mild Hypothermia on Global Cerebral Ischemia and Recirculation in the Cat: Comparison to Normothermia and Hyperthermia , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  V. Negovsky Postresuscitation disease , 1988, Critical care medicine.

[26]  R. Dempsey,et al.  Moderate hypothermia reduces postischemic edema development and leukotriene production. , 1987, Neurosurgery.

[27]  B. Jennett,et al.  ASSESSMENT OF OUTCOME AFTER SEVERE BRAIN DAMAGE A Practical Scale , 1975, The Lancet.

[28]  A. P. Sanders,et al.  The effect profound hypothermia on preservation of cerebral ATP content during circulatory arrest. , 1968, The Journal of thoracic and cardiovascular surgery.

[29]  M Fryczkowski,et al.  [Use of hypothermia after cardiac arrest]. , 1966, Wiadomosci lekarskie.

[30]  P. Safar,et al.  Lightning stroke. Report of a case with recovery after cardiac massage and prolonged artificial respiration. , 1961, The New England journal of medicine.

[31]  F C SPENCER,et al.  The clinical use of hypothermia following cardiac arrest. , 1959, Annals of surgery.

[32]  Williams Gr,et al.  The clinical use of hypothermia following cardiac arrest. , 1958 .

[33]  A. H. Hegnauer,et al.  Oxygen consumption and cardiac output in the hypothermic dog. , 1954, The American journal of physiology.

[34]  Joakim Bjorkdahl Mild resuscitative hypothermia to improve neurological outcome after cardiac arrest: A clinical feasibility trial.: , 2000 .

[35]  P. Safar,et al.  Improved cerebral resuscitation from cardiac arrest in dogs with mild hypothermia plus blood flow promotion. , 1996, Stroke.

[36]  Igor Sartori,et al.  Empirical Evidence of Bias. Dimensions of Methodological Quality Associated with Estimates of Treatment Effects in Controlled Trials , 1996 .

[37]  J. Cuzick A Wilcoxon-type test for trend. , 1985, Statistics in medicine.

[38]  B Jennett,et al.  Assessment of outcome after severe brain damage. , 1975, Lancet.