Dynamic impact of transfusion ratios on outcomes in severely injured patients: Targeted machine learning analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios randomized clinical trial.
Dynamic impact of transfusion ratios on outcomes in severely injured patients: Targeted machine learning analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios randomized clinical trial.
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DOI：
10.1097/ta.0000000000002819
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发表时间：
2020-09
期刊：
影响因子：
--
通讯作者：
Hubbard A
中科院分区：
文献类型：
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作者：
Nguyen M;Pirracchio R;Kornblith LZ;Callcut R;Fox EE;Wade CE;Schreiber M;Holcomb JB;Coyle J;Cohen M;Hubbard A
治疗创伤后出血的大量输血方案是基于预定义的血液制品输血比例，然后根据患者的临床进展进行目标导向输血。然而，目前尚不清楚这些输血比例如何影响患者在受伤后的预后。Pragmatic，Randomized Optimal Platelet and Plasma Ratio（PROPPR）是一项在北美12个I级创伤中心进行的III期随机对照试验。从2012年到2013年，680名严重受伤的患者需要大量输血。我们使用半参数机器学习技术和因果推理方法来增强PROPPR的意向治疗分析，估计输血率和结局之间的动态关系：入院后前24小时内不同时间点的死亡率和止血率。在意向治疗分析中，1：1：1组的死亡率有下降的趋势，但无统计学意义。对于止血时间超过2小时的患者，1：1：1比例与止血概率较高相关，从第4小时开始具有统计学显著性。在符合方案的实际输血率分析中，在连续4个时间间隔内，未发现实际输血率与死亡率之间存在显著相关性。当比较同时接受高血浆：PRBC和高血小板：PRBC比值的患者组与两者比值均较低的患者组时，在入院后3小时内实现止血的相对风险为2.49（95% CI = 1.19-5.22），表明较高的血浆和血小板输注比例对止血具有显著的有益影响。我们的研究结果表明，输血比例对止血的影响是动态的。总体而言，输血比例对死亡率无显著影响。然而，在入院后3小时内尚未实现止血的受试者中，接受血小板和血浆相对于红细胞的较高比例可加速止血。
Massive transfusion protocols to treat post-injury hemorrhage are based on pre-defined blood product transfusion ratios followed by goal-directed transfusion based on patient’s clinical evolution. However, it remains unclear how these transfusion ratios impact patient outcomes over time from injury. The Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) is a phase 3, randomized controlled trial, across 12 level-I trauma centers in North America. From 2012 to 2013, 680 severely injured patients required massive transfusion. We used semi-parametric machine learning techniques and causal inference methods to augment the intent-to-treat analysis of PROPPR, estimating the dynamic relationship between transfusion ratios and outcomes: mortality and hemostasis at different time-points during the first 24 hours after admission. In the intention-to-treat analysis, the 1:1:1 group tended to have decreased mortality, but with no statistical significance. For patients in whom hemostasis took longer than 2 hours, the 1:1:1 ratio was associated with a higher probability of hemostasis, statistically significant from the 4th hour on. In the per-protocol, actual-transfusion-ratios-received analysis, during four successive time intervals, no significant association was found between the actual ratios and mortality. When comparing patient groups who received both high plasma:PRBC and high platelet:PRBC ratios to the group of low ratios in both, the relative risk of achieving hemostasis was 2.49 (95% CI = 1.19–5.22) during the 3rd hour after admission, suggesting a significant beneficial impact of higher transfusion ratios of plasma and platelets on hemostasis. Our results suggest that the impact of transfusion ratios on hemostasis is dynamic. Overall, the transfusion ratios had no significant impact on mortality over time. However, receiving higher ratios of platelets and plasma relative to red blood cells hastens hemostasis in subjects who have yet to achieve hemostasis within 3 hours after hospital admission.