Jun Hyun Kim, Ádám Nagy1,2,3, Alessandro Putzu4, Alessandro Belletti1, Giuseppe Biondi-Zoccai5,6, Valery V Likhvantsev7,8, Andrey G Yavorovskiy9, Giovanni Landoni1,2. 1. Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy. 2. Vita-Salute San Raffaele University, Milan, Italy. 3. Károly Rácz School of PhD Studies, Semmelweis University, Budapest, Hungary. 4. Division of Anesthesiology, Department of Anesthesiology, Pharmacology, Intensive Care, and Emergency Medicine, Geneva University Hospital, Geneva, Switzerland. 5. Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. 6. Mediterranea Cardiocentro, Napoli, Italy. 7. V. Negovsky Reanimatology Research Institute, Moscow, Russia. 8. Intensive Care Department, Moscow Regional Research and Clinical Institute, Moscow, Russia. 9. Anesthesiology and Intensive Care Department, Sechenov First Moscow State Medical University, Moscow, Russia.
Abstract
OBJECTIVES: To investigate the effect of the application of therapeutic hypothermia (32-35°C) on survival and major clinical endpoints in critically ill patients. DATA SOURCES: We searched online database and clinical trial registries dated up to April 30, 2019, and references of relevant studies. STUDY SELECTION: Low risk of bias randomized trials which compared hypothermia applied for at least 24 hours and conventional therapy in critically ill patients were included. We excluded trials investigating therapeutic hypothermia in indications already supported by international guidelines (adult cardiac arrest and hypoxic-ischemic encephalopathy of newborns) or intraoperative hypothermia. DATA EXTRACTION: Titles and abstracts were reviewed independently by two authors. If the articles seemed eligible, full-text articles were reviewed, and data were abstracted using a structured template. DATA SYNTHESIS: Our search retained 14 low risk of bias randomized trials (2,670 patients) performed in three different settings: traumatic brain injury, serious infections, and stroke. Therapeutic hypothermia was associated with an increase in mortality at longest follow-up available (432/1,375 [31%] vs 330/1,295 [25%]; risk ratio, 1.24; 95% CI, 1.10-1.39; p = 0.0004; I = 0%). Pooled results showed no difference of good neurologic outcome among survivors between the two treatment arms (493/1,142 [43%] vs 486/1,067 [46%]; risk ratio, 1.04; 95% CI, 0.97-1.12; p = 0.27; I = 1%). Arrhythmias were significantly increased among patients undergoing therapeutic hypothermia. We found no difference between groups in pneumonia, serious infections, any infection, hemorrhage, renal failure, deep vein thrombosis, and uncontrollable intracranial hypertension. CONCLUSIONS: High-quality randomized evidence indicates that therapeutic hypothermia is associated with higher mortality and no difference in good neurologic outcome compared with normothermia in critically ill patients. Although there still might be a possibility that therapeutic hypothermia is beneficial in a specific setting, routine application of therapeutic hypothermia would better be avoided outside the settings indicated by international guidelines (adult cardiac arrest and hypoxic-ischemic encephalopathy of newborns).
OBJECTIVES: To investigate the effect of the application of therapeutic hypothermia (32-35°C) on survival and major clinical endpoints in critically illpatients. DATA SOURCES: We searched online database and clinical trial registries dated up to April 30, 2019, and references of relevant studies. STUDY SELECTION: Low risk of bias randomized trials which compared hypothermia applied for at least 24 hours and conventional therapy in critically illpatients were included. We excluded trials investigating therapeutic hypothermia in indications already supported by international guidelines (adult cardiac arrest and hypoxic-ischemic encephalopathy of newborns) or intraoperative hypothermia. DATA EXTRACTION: Titles and abstracts were reviewed independently by two authors. If the articles seemed eligible, full-text articles were reviewed, and data were abstracted using a structured template. DATA SYNTHESIS: Our search retained 14 low risk of bias randomized trials (2,670 patients) performed in three different settings: traumatic brain injury, serious infections, and stroke. Therapeutic hypothermia was associated with an increase in mortality at longest follow-up available (432/1,375 [31%] vs 330/1,295 [25%]; risk ratio, 1.24; 95% CI, 1.10-1.39; p = 0.0004; I = 0%). Pooled results showed no difference of good neurologic outcome among survivors between the two treatment arms (493/1,142 [43%] vs 486/1,067 [46%]; risk ratio, 1.04; 95% CI, 0.97-1.12; p = 0.27; I = 1%). Arrhythmias were significantly increased among patients undergoing therapeutic hypothermia. We found no difference between groups in pneumonia, serious infections, any infection, hemorrhage, renal failure, deep vein thrombosis, and uncontrollable intracranial hypertension. CONCLUSIONS: High-quality randomized evidence indicates that therapeutic hypothermia is associated with higher mortality and no difference in good neurologic outcome compared with normothermia in critically illpatients. Although there still might be a possibility that therapeutic hypothermia is beneficial in a specific setting, routine application of therapeutic hypothermia would better be avoided outside the settings indicated by international guidelines (adult cardiac arrest and hypoxic-ischemic encephalopathy of newborns).