Therapeutic hypothermia versus normothermia in adult patients with traumatic brain injury: a meta-analysis

Abstract

IntroductionMany single-center studies and meta-analyses demonstrate that therapeutic hypothermia (TH), in which the body temperature is maintained at 32–35°C, exerts significant neuroprotection and attenuates secondary intracranial hypertension after traumatic brain injury (TBI). In 2015, two well-designed multi-center, randomized controlled trials were published that did not show favorable outcomes with the use of TH in adult patients with TBI compared to normothermia treatment (NT). Therefore, we performed an updated meta-analysis to assess the effect of TH in adult patients with TBI.MethodsWe reviewed the PubMed, EMbase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang Databases. We included randomized controlled trials that compared TH and NT in adult patients with TBI. Two reviewers assessed the quality of each study and independently collected the data. We performed the meta-analysis using the Cochrane Collaboration’s RevMan 5.3 software.ResultsWe included 18 trials involving 2177 patients with TBI. There was no significant heterogeneity among the studies. TH could not decrease mortality at 3 months post-TBI (RR 0.95; 95 % CI 0.59, 1.55; z = 0.19, P = 0.85) or 6 months post-TBI (RR 0.96; 95 % CI 0.76, 1.23; z = 0.29, P = 0.77). There were no significant differences in unfavorable clinical outcomes when TH was compared to NT at 3 months post-TBI (RR 0.79; 95 % CI 0.56, 1.12; z = 1.31, P = 0.19) or 6 months post-TBI (RR 0.80; 95 % CI 0.63, 1.00; z = 1.92, P = 0.05). TH was associated with a significant increase in pneumonia (RR 1.51; 95 % CI 1.12, 2.03; z = 2.72, P = 0.006) and cardiovascular complications (RR 1.75; 95% CI 1.14, 2.70; z = 2.54, P = 0.01).ConclusionsTherapeutic hypothermia failed to demonstrate a decrease in mortality and unfavorable clinical outcomes at 3 or 6 months post-TBI. Additionally, TH might increase the risk of developing pneumonia and cardiovascular complications.

Therapeutic hypothermia to reduce intracranial pressure after traumatic brain injury: the Eurotherm3235 RCT

“…A previous study found some clinical benefit to TH in TBI, 110 however the Eurotherm3235 Trial 1 was stopped early concerns over participant safety. 1,110 Additionally, a RCT published in 2016 111 showed that strict fever control resulted in similar clinical outcomes as prolonged TH. The most recent systematic reviews 1,112 have also reported conflicting results.…”

“…The most recent systematic reviews 1,112 have also reported conflicting results. 110 A 2016 meta-analysis 111 was unable to demonstrate improved survival and suggested that TH may increase the risk of new pneumonia and cardiovascular complications. Conversely, a large meta-analysis reported a benefit of TH but it was discussed that this benefit may be attributable to the fact that a large number of observational studies were included in this analysis.…”

Src Family Kinase Inhibitors and their Role in the Treatment of Traumatic Brain Injuries

“…In fact, in a study by Andrews et al looking at 387 patients, hypothermia treatment did not result in better outcomes compared to standard care [15]. Not only that, but hypothermia might increase the risk of patients having cardiovascular complications or developing pneumonia [16].…”

Targeted Temperature Management in Traumatic Brain Injury

“…Recent systematic review and metaanalysis of TTM versus normothermia in adult patients with TBI reveals not only no clinical benefit of TTM as compared with normothermia but also increased risk of developing pneumonia and cardiovascular complications associated with TTM [144]. At this moment, application of TTM as routine practice in adult patients with TBI without enrolment into clinical trial is not recommended [145].…”