Therapeutic Whole-Body Hypothermia Reduces Death in Severe Traumatic Brain Injury if the Cooling Index Is Sufficiently High: Meta-Analyses of the Effect of Single Cooling Parameters and Their Integrated Measure

Abstract

Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the deaths of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure interstudy homogeneity. We extracted data on TBI severity, body temperature, death, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but interstudy heterogeneity was high. On the contrary, by meta-analysis of randomized clinical trials that were homogenous with regard to statistical, clinical designs, and precisely reported the cooling protocol, we showed decreased odds ratio for death in therapeutic hypothermia compared with no cooling. As independent factors, milder and longer cooling, and rewarming at <0.25°C/h were associated with better outcome. Therapeutic hypothermia was beneficial only if the cooling index (measure of combination of cooling parameters) was sufficiently high. We conclude that high methodological and statistical interstudy heterogeneity could underlie the contradictory results obtained in previous studies. By analyzing methodologically homogenous studies, we show that cooling improves the outcome of severe TBI, and this beneficial effect depends on certain cooling parameters and on their integrated measure, the cooling index.

Effect of Early Sustained Prophylactic Hypothermia on Neurologic Outcomes Among Patients With Severe Traumatic Brain Injury

“…Multiple studies and meta-analyses have reported benefit for prophylactic hypothermia as a potential neuroprotectant after traumatic brain injury. 7,8,[21][22][23][24][25][26][27][28][29][30][31] Three higher-quality multicenter randomized trials of prophylactic hypothermia demonstrated no benefit, but these had methodological limitations and 2 stopped prematurely (≤50% projected sample size). [13][14][15] The most recent meta-analysis of prophylactic hypothermia after severe traumatic brain injury 8 suggested that early prophylactic hypothermia may be most beneficial when Data are presented as n/N (%) unless otherwise indicated and are presented for the intention-to-treat population.…”

“…The study design accounted for limitations of previous trials of prophylactic hypothermia. 7,8,16,32 The protocol included early induction and maintenance of hypothermia for at least 72 hours, followed by individually titrated rewarming. The time from injury to initiating hypothermia was short (median, 1.8 hours).…”

Bidirectional Relationship Between Reduced Blood pH and Acute Pancreatitis: A Translational Study of Their Noxious Combination

“…Our meta-analysis was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (Moher et al, 2009 ) (Supplementary Table 1 ), similarly as in our recent study (Olah et al, 2018 ). The analysis was based on the Patients, Intervention (or indicator), Comparison, Outcome (PICO) model: in patients with AP, we aimed to assess the predictive role of the change in pH status (as assessed by blood pH, bicarbonate concentration, base excess, or base deficit) on disease severity (indicated by clinical scores), length of hospital stay (LOS), and mortality ratio.…”

Effect of Hypothermia in the Emergency Department on the Outcome of Trauma Patients: A Cross-Sectional Analysis

“…In this study, although the injury severity had been adjusted in PSM to estimate the effect of hypothermia on mortality, it should be noted that, with the continuous variable of body temperatures being turned into a binary categorical data, the cut-off value selected for a definition of hypothermia (i.e., body temperatures of <36 °C in this study) may present a bias or even a false negative finding in the outcome measurement. For example, a much lower temperature (e.g., 32 °C or less) may even present a survival advantage for the trauma patients, as evidenced by a decreased odds ratio for death in the therapeutic hypothermia [20,21,22]. Furthermore, Reynolds et al reported that a temperature of <34 °C in hemorrhagic patients requiring massive transfusion was associated with a two-fold increased risk of mortality [11].…”