Köppel C, Pohle S, Müller C
Medical Intensive Care Unit, Universitätsklinikum Rudolf Virchow, Standort Charlottenburg, Freie Universität Berlin, Germany.
Eur J Drug Metab Pharmacokinet. 1993 Oct-Dec;18(4):327-31. doi: 10.1007/BF03190181.
Changes in liver perfusion may have a substantial influence on the pharmacokinetics of drugs with flow-controlled metabolism. This may have important implications for drug dosage in patients in an intensive care unit (ICU). The hepatic D-sorbitol plasma clearance has been suggested as a non-invasive test for evaluating functional liver plasma flow, which is in reasonable agreement with the direct blood measurement. However, its determination requires D-sorbitol infusion for 3 h or administration of a D-sorbitol bolus and withdrawal of blood specimens every 3-5 min. Since both variants are impractical in the ICU setting, a bolus/infusion technique was tested. A combined technique applying a bolus (0.85 mg/kg) and steady-state infusion (0.0014 mg/kg/min) of D-sorbitol was tested in 10 ICU patients without hepatic disease (group 1) and in 10 ICU patients with liver disease (group 2). Steady-state plasma levels (+/- 9%, P < 0.05) could be achieved within 60 min in all patients. The modified D-sorbitol clearance method requires a bolus and an infusion of D-sorbitol and withdrawal of a single blood specimen after 60 min. The lowest values of functional liver plasma flow were determined in patients with decompensated liver cirrhosis, acute fatty degeneration of the liver or Budd-Chiari syndrome. The method for routine determination of functional hepatic plasma perfusion proved to be rapid, safe and non-invasive in ICU patients. Hepatic D-sorbitol clearance may be especially useful for assessing the functional aspect of liver perfusion.
肝脏灌注的变化可能对具有血流控制代谢的药物的药代动力学产生重大影响。这可能对重症监护病房(ICU)患者的药物剂量具有重要意义。肝D-山梨醇血浆清除率已被建议作为评估功能性肝血浆流量的非侵入性检测方法,这与直接血液测量结果合理一致。然而,其测定需要输注D-山梨醇3小时或给予D-山梨醇推注并每隔3 - 5分钟采集血样。由于这两种方法在ICU环境中都不实用,因此对一种推注/输注技术进行了测试。在10名无肝病的ICU患者(第1组)和10名有肝病的ICU患者(第2组)中测试了一种联合技术,该技术应用D-山梨醇推注(0.85 mg/kg)和稳态输注(0.0014 mg/kg/min)。所有患者均可在60分钟内达到稳态血浆水平(±9%,P < 0.05)。改良的D-山梨醇清除率方法需要推注和输注D-山梨醇,并在60分钟后采集一份血样。在失代偿性肝硬化、急性肝脂肪变性或布加综合征患者中测定到功能性肝血浆流量的最低值。在ICU患者中,常规测定功能性肝血浆灌注的方法被证明是快速、安全且非侵入性的。肝D-山梨醇清除率对于评估肝脏灌注的功能方面可能特别有用。