Gonzalez Ernest A, Moore Frederick A, Holcomb John B, Miller Charles C, Kozar Rosemary A, Todd S Rob, Cocanour Christine S, Balldin Bjorn C, McKinley Bruce A
Department of Surgery, University of Texas Houston Medical School, Houston, Texas, USA.
J Trauma. 2007 Jan;62(1):112-9. doi: 10.1097/01.ta.0000250497.08101.8b.
Acidosis, hypothermia, and coagulopathy were identified more than 20 years ago as a deadly triad for patients presenting with exsanguinating hemorrhage. This led to fundamental changes in initial management of severely injured patients. Despite major advances, hemorrhage remains a leading cause of early death in trauma patients. Recent studies report most severely injured patients to be coagulopathic at admission, before resuscitation interventions, and that traditional massive transfusion practice grossly underestimates needs. The hypothesis for this study is that our pre-intensive care unit (ICU) massive transfusion (MT) protocol does not adequately correct coagulopathy, and that early uncorrected coagulopathy is predictive of mortality.
Data maintained in our Trauma Research Database were reviewed. Univariate logistic regression analysis was used to analyze the association of early ICU international normalized ratio (INR) and outcomes, including survival.
Ninety-seven of 200 patients admitted during 51 months (ending January 2003) and resuscitated using our standardized ICU shock resuscitation protocol received MT (> or =10 units packed red blood cells [PRBC]) during hospital day 1 (age, 39 +/- 2; ISS, 29 +/- 1; survival, 70%.) All patients required emergency operating room and/or interventional radiology procedures and arrived in the ICU 6.8 +/- 0.3 hours after admission. Coagulopathy, present at hospital admission (pre-ICU INR, 1.8 +/- 0.2), persisted at ICU admission (initial ICU INR, 1.6 +/- 0.1). Pre-ICU resuscitation, 9 +/- 1 L crystalloid fluid, 12 +/- 1 units PRBC, 5 +/- 0.4 units fresh frozen plasma (FFP), was consistent with our MT protocol by which FFP was not given until after 6 units PRBC. ICU resuscitation involved 11 +/- 1 L lactated Ringer's solution (LR) and 10 +/- 1 units PRBC. Mean pH was normal within 8 hours. Mean temperature increased from approximately 35 degrees C to >37 degrees C within 4 hours. In the ICU during resuscitation, patients received 10 +/- 1 units FFP for coagulopathy; the ratio of FFP:PRBC was 1:1. Mean INR decreased to 1.4 +/- 0.03 within 8 hours and remained nearly constant for the remaining 16 hours of ICU resuscitation, indicating moderate coagulopathy. Statistical analysis found severity of coagulopathy (INR) at ICU admission associated with survival outcome (p = 0.02; area under receiver operator curve [ROC] = 0.71.)
These data indicate acidosis and hypothermia to be well managed. Coagulopathy was not corrected in the ICU despite adherence to pre-ICU MT and ICU protocols, likely because of inadequate pre-ICU intervention. More aggressive pre-ICU intervention to correct coagulopathy may be effective in decreasing PRBC requirement during ICU resuscitation, and, because of the association with increased mortality, could improve outcome. We have revised our pre-ICU MT protocol to emphasize early FFP in a FFP:PRBC ratio of 1:1. We think that treatment of coagulopathy can be improved with the development of standardized protocols, both empiric and data driven.
20多年前,酸中毒、体温过低和凝血功能障碍被确认为失血性出血患者的致命三联征。这导致了严重受伤患者初始治疗的根本性改变。尽管取得了重大进展,但出血仍然是创伤患者早期死亡的主要原因。最近的研究报告称,大多数严重受伤患者在入院时、复苏干预之前就存在凝血功能障碍,而且传统的大量输血做法严重低估了需求。本研究的假设是,我们的重症监护病房(ICU)前大量输血(MT)方案不能充分纠正凝血功能障碍,且早期未纠正的凝血功能障碍可预测死亡率。
回顾了我们创伤研究数据库中保存的数据。采用单因素逻辑回归分析来分析早期ICU国际标准化比值(INR)与包括生存在内的结局之间的关联。
在51个月(截至2003年1月)期间入院并采用我们标准化的ICU休克复苏方案进行复苏的200例患者中,有97例在住院第1天接受了MT(≥10单位浓缩红细胞[PRBC])(年龄39±2岁;损伤严重度评分[ISS]29±1;生存率70%)。所有患者均需要急诊手术室和/或介入放射学检查,并在入院后6.8±0.3小时进入ICU。入院时存在凝血功能障碍(ICU前INR为1.8±0.2),在进入ICU时仍持续存在(初始ICU INR为1.6±0.1)。ICU前复苏时,输入9±1升晶体液、12±1单位PRBC、5±0.4单位新鲜冰冻血浆(FFP),这与我们的MT方案一致,即直到输入6单位PRBC后才给予FFP。ICU复苏包括输入11±1升乳酸林格液(LR)和10±1单位PRBC。平均pH值在8小时内恢复正常。平均体温在4小时内从约35℃升至>37℃。在ICU复苏期间,患者因凝血功能障碍接受了10±1单位FFP;FFP与PRBC的比例为1:1。平均INR在8小时内降至1.4±0.03,并在ICU复苏的其余16小时内几乎保持不变,表明存在中度凝血功能障碍。统计分析发现,ICU入院时凝血功能障碍的严重程度(INR)与生存结局相关(p = 0.02;受试者操作特征曲线[ROC]下面积 = 0.71)。
这些数据表明酸中毒和体温过低得到了良好控制。尽管遵循了ICU前MT和ICU方案,但ICU中的凝血功能障碍仍未得到纠正,可能是因为ICU前干预不足。更积极的ICU前干预以纠正凝血功能障碍可能有效减少ICU复苏期间PRBC的需求量,并且由于其与死亡率增加相关,可能改善结局。我们已修订ICU前MT方案,强调以1:1的FFP与PRBC比例早期给予FFP。我们认为,通过制定经验性和数据驱动的标准化方案,可以改善凝血功能障碍的治疗。