Fodale Vincenzo, La Monaca Enza
Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, University of Messina, Messina, Italy.
Drug Saf. 2008;31(4):293-303. doi: 10.2165/00002018-200831040-00003.
Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent that is widely used in adults and children for sedation and the induction and maintenance of anaesthesia. Propofol has gained popularity for its rapid onset and rapid recovery even after prolonged use, and for the neuroprotection conferred. However, a review of the literature reveals multiple instances in which prolonged propofol administration (>48 hours) at high doses (>4 mg/kg/h) may cause a rare, but frequently fatal complication known as propofol infusion syndrome (PRIS). PRIS is characterized by metabolic acidosis, rhabdomyolysis of both skeletal and cardiac muscle, arrhythmias (bradycardia, atrial fibrillation, ventricular and supraventricular tachycardia, bundle branch block and asystole), myocardial failure, renal failure, hepatomegaly and death. PRIS has been described as an 'all or none' syndrome with sudden onset and probable death. The literature does not provide evidence of degrees of symptoms, nor of mildness or severity of signs in the clinical course of the syndrome. Recently, a fatal case of PRIS at a low infusion rate (1.9-2.6 mg/kg/h) has been reported. Common laboratory and instrumental findings in PRIS are myoglobinuria, downsloping ST-segment elevation, an increase in plasma creatine kinase, troponin I, potassium, creatinine, azotaemia, malonylcarnitine and C5-acylcarnitine, whereas in the mitochondrial respiratory electron transport chain, the activity of complex IV and cytochrome oxidase ratio is reduced. Propofol should be used with caution for sedation in critically ill children and adults, as well as for long-term anesthesia in otherwise healthy patients, and doses exceeding 4-5 mg/kg/h for long periods (>48 h) should be avoided. If PRIS is suspected, propofol must be stopped immediately and cardiocirculatory stabilization and correction of metabolic acidosis initiated. So, PRIS must be kept in mind as a rare, but highly lethal, complication of propofol use, not necessarily confined to its prolonged use. Furthermore, the safe dosage of propofol may need re-evaluation, and new studies are needed.
丙泊酚（2,6 - 二异丙基苯酚）是一种强效静脉催眠药，广泛用于成人和儿童的镇静以及麻醉诱导和维持。丙泊酚因其起效迅速、即使长期使用后恢复也快以及具有神经保护作用而受到欢迎。然而，文献综述显示，多次出现高剂量（>4毫克/千克/小时）长时间使用丙泊酚（>48小时）可能导致一种罕见但常致命的并发症，称为丙泊酚输注综合征（PRIS）。PRIS的特征是代谢性酸中毒、骨骼肌和心肌横纹肌溶解、心律失常（心动过缓、心房颤动、室性和室上性心动过速、束支传导阻滞和心搏停止）、心肌衰竭、肾衰竭、肝肿大和死亡。PRIS被描述为一种“全或无”的综合征，起病突然且可能导致死亡。文献中没有提供该综合征临床过程中症状程度或体征轻重的证据。最近，有报道称在低输注速率（1.9 - 2.6毫克/千克/小时）下发生了一例致命的PRIS病例。PRIS常见的实验室和仪器检查结果包括肌红蛋白尿、ST段压低、血浆肌酸激酶、肌钙蛋白I、钾、肌酐、氮质血症、丙二酰肉碱和C5 - 酰基肉碱升高，而在线粒体呼吸电子传递链中，复合物IV的活性和细胞色素氧化酶比率降低。在重症儿童和成人中使用丙泊酚进行镇静时应谨慎，在健康患者中进行长期麻醉时也应谨慎，应避免长时间（>48小时）使用超过4 - 5毫克/千克/小时的剂量。如果怀疑发生PRIS，必须立即停止使用丙泊酚，并开始进行心血管循环稳定和代谢性酸中毒的纠正。因此，必须牢记PRIS是丙泊酚使用的一种罕见但高度致命的并发症，不一定局限于长期使用。此外，丙泊酚的安全剂量可能需要重新评估，还需要进行新的研究。
