Gibson Jeffrey B, Maxwell Robert A, Schweitzer John B, Fabian Timothy C, Proctor Kenneth G
Department of Surgery, University of Tennessee Health Science Center, Memphis 38163, USA.
Shock. 2002 Mar;17(3):234-44. doi: 10.1097/00024382-200203000-00013.
The original purpose of this study was to compare initial resuscitation of hemorrhagic hypotension after traumatic brain injury (TBI) with saline and shed blood. Based on those results, the protocol was modified and saline was compared to a blood substitute, diaspirin cross-linked hemoglobin (DCLHb). Two series of experiments were performed in anesthetized and mechanically ventilated (FiO2 = 0.4) pigs (35-45 kg). In Series 1, fluid percussion TBI (6-8 ATM) was followed by a 30% hemorrhage. At 120 min post-TBI, initial resuscitation consisted of either shed blood (n = 7) or a bolus of 3x shed blood volume as saline (n = 13). Saline supplements were then administered to all pigs to maintain a systolic arterial blood pressure (SAP) of >100 mmHg and a heart rate (HR) of <110 beats/min. In Series 2, TBI (4-5 ATM) was followed by a 35% hemorrhage. At 60 min post-TBI, initial resuscitation consisted of either 500 mL of DCLHb (n = 6) or 500 mL of saline (n = 5). This was followed by saline supplements to all pigs to maintain a SAP of >100 mmHg and a HR of <110 beats/min. In Series 1, most systemic markers of resuscitation (e.g., SAP, HR, cardiac output, filling pressures, lactate, etc.) were normalized, but there were 0/7 vs. 5/13 deaths within 5 h (P = 0.058) with blood vs. saline. At constant arterial O2 saturation (SaO2), mixed venous O2 saturation (SvO2), cerebral perfusion pressure (CPP), and cerebral venous O2 saturation (ScvO2) were all higher, intracranial pressure (ICP) was lower, and CO2 reactivity was preserved with blood vs. saline (all P < 0.05). In Series 2, SAP, ICP, CPP, and lactate were higher with DCLHb vs. saline (all P< 0.05). Cardiac output was lower even though filling pressure was markedly elevated with DCLHb vs. saline (both P< 0.05). Neither SvO2 nor cerebrovascular CO2 reactivity were improved, and ScvO2 was lower with DCLHb vs. saline (P < 0.05). All survived at least 72 h with neuropathologic changes that included sub-arachnoid hemorrhage, midline cerebellar necrosis, and diffuse axonal injury. These changes were similar with DCLHb vs. saline. Thus, whole blood was more effective than saline for resuscitation of TBI, whereas DCLHb was no more, and according to many variables, less effective than saline resuscitation. These experimental results are comparable to those in a recent multicenter trial using DCLHb for the treatment of severe traumatic shock. Further investigations in similar experimental models might provide some plausible explanations why DCLHb unexpectedly increased mortality in patients.
本研究的最初目的是比较用生理盐水和自体失血对创伤性脑损伤（TBI）后出血性低血压进行初始复苏的效果。基于这些结果，研究方案进行了修改，将生理盐水与一种血液替代品二阿司匹林交联血红蛋白（DCLHb）进行比较。在麻醉并机械通气（FiO2 = 0.4）的猪（35 - 45 kg）身上进行了两组实验。在第1组实验中，先进行液体冲击性脑损伤（6 - 8个大气压），随后失血30%。在脑损伤后120分钟，初始复苏采用自体失血（n = 7）或3倍自体失血体积的生理盐水推注（n = 13）。然后给所有猪补充生理盐水，以维持收缩压（SAP）>100 mmHg和心率（HR）<110次/分钟。在第2组实验中，先进行脑损伤（4 - 5个大气压），随后失血35%。在脑损伤后60分钟，初始复苏采用500 mL DCLHb（n = 6）或500 mL生理盐水（n = 5）。随后给所有猪补充生理盐水，以维持收缩压>100 mmHg和心率<110次/分钟。在第1组实验中，大多数复苏的全身指标（如收缩压、心率、心输出量、充盈压、乳酸等）都恢复正常，但在5小时内，用血液复苏与用生理盐水复苏的死亡率分别为0/7和5/13（P = 0.058）。在动脉血氧饱和度（SaO2）恒定的情况下，与生理盐水相比，用血液复苏时混合静脉血氧饱和度（SvO2）、脑灌注压（CPP）和脑静脉血氧饱和度（ScvO2）均更高，颅内压（ICP）更低，且二氧化碳反应性得以保留（所有P < 0.05）。在第2组实验中，与生理盐水相比，使用DCLHb时收缩压、颅内压、脑灌注压和乳酸水平更高（所有P< 0.05）。尽管与生理盐水相比，使用DCLHb时充盈压明显升高，但心输出量更低（两者P< 0.05）。SvO2和脑血管二氧化碳反应性均未改善，与生理盐水相比，使用DCLHb时ScvO2更低（P < 0.05）。所有猪至少存活72小时，神经病理学改变包括蛛网膜下腔出血、小脑中线坏死和弥漫性轴索损伤。这些改变在使用DCLHb和生理盐水时相似。因此，对于创伤性脑损伤的复苏，全血比生理盐水更有效，而DCLHb并不比生理盐水更有效，并且根据许多变量，其效果比生理盐水复苏更差。这些实验结果与最近一项使用DCLHb治疗严重创伤性休克的多中心试验结果相当。在类似实验模型中的进一步研究可能会对DCLHb意外增加患者死亡率的原因提供一些合理的解释。
