Division of General Surgery and Trauma, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15213, USA.
J Trauma Acute Care Surg. 2012 Aug;73(2):358-64; discussion 364. doi: 10.1097/TA.0b013e31825889ba.
Controversy surrounds the optimal ratios of blood (packed red blood cell [PRBC]), plasma (fresh frozen plasma [FFP]) and platelet (PLT) use for patients requiring massive transfusion (MT) owing to possible survival bias in previous studies. We sought to characterize mortality during the first 24 hours while controlling for time varying effects of transfusion to minimize survival bias.
Data were obtained from a multicenter prospective cohort study of adults with blunt injury and hemorrhagic shock. MT was defined as 10 U of PRBC or more over 24 hours. High FFP/PRBC (≥1:1.5) and PLT/PRBC (≥1:9) ratios at 6, 12, and 24 hours were compared with low ratio groups. Cox proportional hazards regression was used to determine the independent association of high versus low ratios with mortality at 6, 12, and 24 hours while controlling for important confounders. Cox proportional hazards regression was repeated with FFP/PRBC and PLT/PRBC ratios analyzed as time-dependent covariates to account for fluctuation over time. Mortality for more than 24 hours was treated as survival.
In the MT cohort (n = 604), initial base deficit, lactate, and international normalized ratio were similar across high and low ratio groups. High 6-hour FFP/PRBC and PLT/PRBC ratios were independently associated with a reduction in mortality risk at 6, 12, and 24 hours (hazard ratio [HR] range, 0.20-0.41, p < 0.05). These findings were consistent for 12-hour and 24-hour ratios. When analyzed as time-dependent covariates, a high FFP/PRBC ratio was associated with a 68% (HR, 0.32; 95% confidence interval [CI], 0.12-0.87, p = 0.03) reduction in 24-hour mortality, and a high PLT/PRBC ratio was associated with a 96% (HR, 0.04; 95% CI, 0.01-0.94, p = 0.04) reduction in 24-hour mortality. Subgroup analysis revealed that a high 1:1 ratio (≥1:1.5) had a significant 24-hour survival benefit relative to a high 1:2 (1:1.51-1:2.50) ratio group at both 6 hours (HR, 0.19; 95% CI, 0.03-0.86, p = 0.03) and 24 hours (HR, 0.25; 95% CI, 0.06-0.95, p = 0.04), suggesting a dose-response relationship. A high FFP/PRBC or PLT/PRBC ratio was not associated with development of multiple-organ failure, nosocomial infection, or adult respiratory distress syndrome in a 28-day Cox proportional hazards regression.
Despite similar degrees of early shock and coagulopathy, high FFP/PRBC and PLT/PRBC ratios are associated with a survival benefit as early as 6 hours and throughout the first 24 hours, even when time-dependent fluctuations of component transfusion are accounted for. This suggests that the observed mortality benefit associated with high component transfusion ratios is unlikely owing to survivor bias and that early attainment of high transfusion ratios may significantly lower the risk of mortality in MT patients.
由于先前研究中可能存在生存偏差，对于需要大量输血（MT）的患者，血液（浓缩红细胞[PRBC]）、血浆（新鲜冷冻血浆[FFP]）和血小板（PLT）的最佳使用比例存在争议。我们旨在控制输血时变效应的同时，在 24 小时内描述死亡率，以尽量减少生存偏差。
数据来自多中心前瞻性成人钝性损伤和出血性休克队列研究。MT 定义为 24 小时内输注 10 U 以上 PRBC。在 6、12 和 24 小时时比较高 FFP/PRBC（≥1:1.5）和 PLT/PRBC（≥1:9）比值与低比值组。使用 Cox 比例风险回归来确定高比值与 6、12 和 24 小时死亡率的独立关联，同时控制重要混杂因素。使用 Cox 比例风险回归重复 FFP/PRBC 和 PLT/PRBC 比值分析作为时间依赖性协变量，以解释随时间的波动。超过 24 小时的死亡率被视为存活。
在 MT 队列（n=604）中，高和低比值组的初始基础缺陷、乳酸和国际标准化比值相似。高 6 小时 FFP/PRBC 和 PLT/PRBC 比值与 6、12 和 24 小时的死亡率降低风险独立相关（风险比[HR]范围，0.20-0.41，p<0.05）。12 小时和 24 小时比值的结果一致。当作为时间依赖性协变量进行分析时，高 FFP/PRBC 比值与 24 小时死亡率降低 68%（HR，0.32；95%置信区间[CI]，0.12-0.87，p=0.03）相关，高 PLT/PRBC 比值与 24 小时死亡率降低 96%（HR，0.04；95%CI，0.01-0.94，p=0.04）相关。亚组分析显示，与高 1:2（1:1.51-1:2.50）比值组相比，高 1:1 比值（≥1:1.5）在 6 小时（HR，0.19；95%CI，0.03-0.86，p=0.03）和 24 小时（HR，0.25；95%CI，0.06-0.95，p=0.04）时均具有显著的 24 小时存活获益，表明存在剂量反应关系。在 28 天 Cox 比例风险回归中，高 FFP/PRBC 或 PLT/PRBC 比值与多器官衰竭、医院获得性感染或成人呼吸窘迫综合征的发展无关。
尽管早期休克和凝血障碍的程度相似，但高 FFP/PRBC 和 PLT/PRBC 比值与 6 小时内和整个 24 小时内的存活获益相关，即使考虑到成分输血的时变波动也是如此。这表明与高成分输血比值相关的观察到的死亡率获益不太可能归因于生存偏差，并且早期达到高输血比值可能显著降低 MT 患者的死亡率风险。
