Laboratory of Experimental Surgery and Surgical Research, School of Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
J Surg Res. 2011 Jun 15;168(2):253-61. doi: 10.1016/j.jss.2009.08.020. Epub 2009 Sep 15.
Prolonged sedation with propofol at high doses may lead to fatal multi-organ dysfunction, know as propofol infusion syndrome. We tested the hypothesis that propofol plus remifentanil co-administration attenuates propofol tolerance to its sedative effect and assessed if such an effect has an impact on propofol toxicity in rabbits under prolonged mechanical ventilation.
Eighteen healthy male rabbits were mechanically ventilated and received propofol (group P, n = 6), propofol plus remifentanil (group PR, n = 6), or remifentanil plus sevoflurane (group RS, n = 6) in order to be kept under sedation (group P) or sedation/analgesia (groups PR and RS) for up to 48 h. Initial propofol and remifentanil infusion rates (IRs) were adjusted, if needed, to maintain the desired level of sedation and analgesia, respectively (groups P and PR). In group RS, remifentanil was infused at IRs equivalent to those of group PR. Propofol IRs were recorded, propofol concentrations were measured in the arterial plasma, and blood biochemical parameters and organ histopathology were assessed.
Animals survived for 29-36 h in group P and 22-38 h in group PR (100% mortality rate). Tolerance was developed to propofol's sedative effect. The onset of tolerance was delayed and its magnitude was decreased in group PR compared with group P. Propofol was accumulated in the systemic circulation. Propofol clearance rate was gradually decreased. Arterial lactate, and serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH), bilirubin, cholesterol, triglycerides, and creatine kinase (CK) levels were increased. The heart, lungs, liver, gallbladder, kidneys, urinary bladder, and skeletal muscles were seriously injured in groups P and PR. In group RS, mortality was 0%, while there was only mild injury of the lungs, liver, gallbladder, kidneys, and urinary bladder.
Although propofol tolerance is attenuated in propofol plus remifentanil receiving rabbits under prolonged mechanical ventilation, fatal multi-organ injury occurs resembling human propofol infusion syndrome.
长时间大剂量输注丙泊酚可能导致致命的多器官功能障碍，即丙泊酚输注综合征。我们假设丙泊酚联合瑞芬太尼给药可减轻丙泊酚镇静作用的耐受性，并评估这种效应是否会对长时间机械通气的兔丙泊酚毒性产生影响。
18 只健康雄性兔行机械通气，分别接受丙泊酚（P 组，n = 6）、丙泊酚联合瑞芬太尼（PR 组，n = 6）或瑞芬太尼联合七氟醚（RS 组，n = 6），以维持镇静（P 组）或镇静/镇痛（PR 和 RS 组）状态达 48 h。如果需要，调整初始丙泊酚和瑞芬太尼输注率（IR），以分别维持所需的镇静和镇痛水平（P 和 PR 组）。RS 组以相当于 PR 组的 IR 输注瑞芬太尼。记录丙泊酚 IR，测定动脉血浆中的丙泊酚浓度，并评估血液生化参数和器官组织病理学。
P 组动物存活 29-36 h，PR 组存活 22-38 h（死亡率 100%）。动物对丙泊酚的镇静作用产生了耐受性。与 P 组相比，PR 组丙泊酚镇静作用的耐受性发展延迟，程度降低。丙泊酚在全身循环中蓄积。丙泊酚清除率逐渐降低。动脉血乳酸、血清天冬氨酸转氨酶（AST）、乳酸脱氢酶（LDH）、胆红素、胆固醇、甘油三酯和肌酸激酶（CK）水平升高。P 和 PR 组的心脏、肺、肝、胆囊、肾脏、膀胱和骨骼肌均严重受损。RS 组死亡率为 0%，但肺、肝、胆囊、肾脏和膀胱仅有轻度损伤。
虽然长时间机械通气的兔接受丙泊酚联合瑞芬太尼时丙泊酚耐受性减轻，但仍会发生致命性多器官损伤，类似于人类丙泊酚输注综合征。
