Maclaren Robert, Torian Sterling, Kiser Tyree, Mueller Scott, Reynolds Paul
Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, USA.
Department of Pharmacy, TriStar Centennial Medical Center, Nashville, Tennessee, USA.
J Crit Care Med (Targu Mures). 2023 May 8;9(2):64-72. doi: 10.2478/jccm-2023-0015. eCollection 2023 Apr.
The risk-benefit profile of therapeutic hypothermia is controversial with several randomized controlled trials providing conflicting results.
The purpose of this systematic review and meta-analysis was to determine if therapeutic hypothermia provides beneficial neurologic outcomes relative to adverse effects.
MEDLINE and EMBASE databases were searched for randomized controlled trials of post-cardiac arrest patients comparing therapeutic hypothermia (33 degrees Celsius) to normothermia or the standard of care (36 - 38 degrees Celsius). Data were collected using the Covidence systematic review software. Statistical analysis was performed by Review Manager software. Risk of bias, sensitivity, and heterogeneity were analyzed using the Cochran's Collaboration tool, trial sequential analysis (TSA) software, and I2 statistic respectively.
A total of 1825 studies were screened and 5 studies (n=3614) were included. No significant differences existed between the hypothermia group and normothermia for favorable neurologic outcome (risk ratio [RR] 1.17, 95% confidence interval [CI] 0.97 to 1.41) or all-cause mortality (RR 0.97, 95% CI 0.89 to 1.05). When compared to normothermia, the hypothermia group had greater risk of adverse effects (RR 1.16, 95% CI 1.04 to 1.28), which was driven by the onset of arrhythmias. Subgroup analyses revealed that therapeutic hypothermia provided greater neurologic benefit in trials with a higher percentage of subjects with shockable rhythms (RR 0.73, 95% CI 0.6 to 0.88). Trial sequential analysis revealed statistical futility for therapeutic hypothermia and favorable neurologic outcome, mortality, and adverse effects.
Therapeutic hypothermia does not provide consistent benefit in neurologic outcome or mortality in the general cardiac arrest population. Patients with shockable rhythms may show favorable neurologic outcome with therapeutic hypothermia and further investigation in this population is warranted. Any potential benefit associated with therapeutic hypothermia must be weighed against the increased risk of adverse effects, particularly the onset of arrhythmias.
治疗性低温的风险效益情况存在争议，多项随机对照试验给出了相互矛盾的结果。
本系统评价和荟萃分析的目的是确定治疗性低温相对于不良反应是否能带来有益的神经学转归。
检索MEDLINE和EMBASE数据库，查找关于心脏骤停后患者的随机对照试验，比较治疗性低温（33摄氏度）与正常体温或标准治疗（36 - 38摄氏度）。使用Covidence系统评价软件收集数据。通过Review Manager软件进行统计分析。分别使用Cochran协作工具、试验序贯分析（TSA）软件和I²统计量分析偏倚风险、敏感性和异质性。
共筛选1825项研究，纳入5项研究（n = 3614）。低温治疗组与正常体温组在良好神经学转归（风险比[RR] 1.17，95%置信区间[CI] 0.97至1.41）或全因死亡率（RR 0.97，95% CI 0.89至1.05）方面无显著差异。与正常体温相比，低温治疗组有更大的不良反应风险（RR 1.16，95% CI 1.04至1.28），这是由心律失常的发生导致的。亚组分析显示，在可电击心律患者比例较高的试验中，治疗性低温带来更大的神经学益处（RR 0.73，95% CI 0.6至0.88）。试验序贯分析显示治疗性低温在神经学良好转归、死亡率和不良反应方面无统计学意义。
治疗性低温在一般心脏骤停人群的神经学转归或死亡率方面未提供一致的益处。可电击心律的患者接受治疗性低温可能显示良好的神经学转归，对此人群有必要进行进一步研究。必须权衡治疗性低温带来的任何潜在益处与不良反应风险增加之间的关系，尤其是心律失常的发生。
