BackgroundThe surviving sepsis campaign recommends consideration for extracorporeal membrane oxygenation (ECMO) in refractory septic shock. We aimed to define the benefit threshold of ECMO in pediatric septic shock.MethodsRetrospective binational multicenter cohort study of all ICUs contributing to the Australian and New Zealand Paediatric Intensive Care Registry. We included patients < 16 years admitted to ICU with sepsis and septic shock between 2002 and 2016. Sepsis-specific risk-adjusted models to establish ECMO benefit thresholds with mortality as the primary outcome were performed. Models were based on clinical variables available early after admission to ICU. Multivariate analyses were performed to identify predictors of survival in children treated with ECMO.ResultsFive thousand sixty-two children with sepsis and septic shock met eligibility criteria, of which 80 (1.6%) were treated with veno-arterial ECMO. A model based on 12 clinical variables predicted mortality with an AUROC of 0.879 (95% CI 0.864–0.895). The benefit threshold was calculated as 47.1% predicted risk of mortality. The observed mortality for children treated with ECMO below the threshold was 41.8% (23 deaths), compared to a predicted mortality of 30.0% as per the baseline model (16.5 deaths; standardized mortality rate 1.40, 95% CI 0.89–2.09). Among patients above the benefit threshold, the observed mortality was 52.0% (13 deaths) compared to 68.2% as per the baseline model (16.5 deaths; standardized mortality rate 0.61, 95% CI 0.39–0.92). Multivariable analyses identified lower lactate, the absence of cardiac arrest prior to ECMO, and the central cannulation (OR 0.31, 95% CI 0.10–0.98, p = 0.046) as significant predictors of survival for those treated with VA-ECMO.ConclusionsThis binational study demonstrates that a rapidly available sepsis mortality prediction model can define thresholds for survival benefit in children with septic shock considered for ECMO. Survival on ECMO was associated with central cannulation. Our findings suggest that a fully powered RCT on ECMO in sepsis is unlikely to be feasible.

中文翻译：

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定义脓毒症儿童体外膜肺氧合的获益阈值——一项双边多中心队列研究

背景幸存的脓毒症运动建议在难治性脓毒症休克中考虑体外膜肺氧合 (ECMO)。我们旨在确定 ECMO 在小儿感染性休克中的获益阈值。方法 对澳大利亚和新西兰儿科重症监护登记处做出贡献的所有 ICU 的回顾性双边多中心队列研究。我们纳入了 2002 年至 2016 年因脓毒症和脓毒性休克入住 ICU 的 16 岁以下患者。使用脓毒症特定风险调整模型建立 ECMO 获益阈值，并将死亡率作为主要结果。模型基于入住 ICU 后早期可用的临床变量。进行多变量分析以确定接受 ECMO 治疗的儿童的生存预测因子。结果 562 名脓毒症和感染性休克患儿符合纳入标准，其中 80 名（1.6%）接受了动静脉 ECMO 治疗。基于 12 个临床变量的模型预测死亡率，AUROC 为 0.879（95% CI 0.864–0.895）。收益阈值计算为 47.1% 的预测死亡风险。低于阈值的 ECMO 治疗儿童的观察死亡率为 41.8%（23 例死亡），而根据基线模型的预测死亡率为 30.0%（16.5 例死亡；标准化死亡率 1.40，95% CI 0.89–2.09）。在高于受益阈值的患者中，观察到的死亡率为 52.0%（13 例死亡），而根据基线模型为 68.2%（16.5 例死亡；标准化死亡率 0.61，95% CI 0.39–0.92）。多变量分析确定了较低的乳酸、ECMO 之前没有心脏骤停、和中央插管（OR 0.31，95% CI 0.10–0.98，p = 0.046）作为 VA-ECMO 治疗患者生存的重要预测因子。结论这项双边研究表明，快速可用的败血症死亡率预测模型可以定义生存获益的阈值在考虑进行 ECMO 的感染性休克儿童中。ECMO 的存活率与中央插管有关。我们的研究结果表明，在脓毒症中对 ECMO 进行完全有效的 RCT 不太可能可行。ECMO 的存活率与中央插管有关。我们的研究结果表明，在脓毒症中对 ECMO 进行完全有效的 RCT 不太可能可行。ECMO 的存活率与中央插管有关。我们的研究结果表明，在脓毒症中对 ECMO 进行完全有效的 RCT 不太可能可行。