Segredo V, Caldwell J E, Matthay M A, Sharma M L, Gruenke L D, Miller R D
Department of Anesthesia, University of California, San Francisco 94143-0648.
N Engl J Med. 1992 Aug 20;327(8):524-8. doi: 10.1056/NEJM199208203270804.
The muscle relaxant vecuronium is sometimes administered to facilitate mechanical ventilation. Neuromuscular paralysis lasting up to seven days may occur after the termination of long-term administration (i.e., more than two days) of vecuronium in critically ill patients. We investigated the role of clinical factors and plasma concentrations of vecuronium and its metabolite in causing this prolonged neuromuscular blockade.
We studied 16 critically ill adult patients (8 women and 8 men) who had received vecuronium to facilitate mechanical ventilation for at least two consecutive days. Clinical factors and plasma concentrations of vecuronium and 3-desacetylvecuronium, the active metabolite of vecuronium, were compared in patients with and without prolonged neuromuscular blockade. In addition, we performed detailed pharmacokinetic studies in the patients without prolonged neuromuscular blockade.
Seven of the 16 patients had prolonged neuromuscular blockade, lasting from six hours to more than seven days, after the termination of vecuronium therapy. These seven patients, six of whom were women, had higher plasma magnesium concentrations and lower arterial blood pH values than the nine patients without prolonged neuromuscular blockade. They also had higher plasma concentrations of 3-desacetylvecuronium and a higher frequency of renal failure (seven of seven patients vs. four of nine patients, P less than 0.03). In the patients without prolonged neuromuscular blockade, the mean (+/- SD) plasma clearance, elimination half-life, and volume of distribution of vecuronium were 2.5 +/- 1.0 ml per kilogram of body weight per minute, 299 +/- 154 minutes, and 1.1 +/- 0.6 liters per kilogram, respectively.
Prolonged neuromuscular blockade after the termination of long-term treatment with vecuronium is associated with metabolic acidosis, elevated plasma magnesium concentrations, female sex, and probably more important, the presence of renal failure and high plasma concentrations of 3-desacetylvecuronium.
肌肉松弛剂维库溴铵有时用于辅助机械通气。在重症患者中长期（即超过两天）使用维库溴铵后，停药后可能会出现长达七天的神经肌肉麻痹。我们研究了临床因素以及维库溴铵及其代谢产物的血浆浓度在导致这种延长的神经肌肉阻滞中的作用。
我们研究了16名接受维库溴铵辅助机械通气至少连续两天的成年重症患者（8名女性和8名男性）。比较了有和没有延长神经肌肉阻滞的患者的临床因素以及维库溴铵及其活性代谢产物3-去乙酰维库溴铵的血浆浓度。此外，我们对没有延长神经肌肉阻滞的患者进行了详细的药代动力学研究。
16名患者中有7名在维库溴铵治疗结束后出现了延长的神经肌肉阻滞，持续时间从6小时到超过7天。这7名患者中有6名是女性，与9名没有延长神经肌肉阻滞的患者相比，她们的血浆镁浓度更高，动脉血pH值更低。她们的3-去乙酰维库溴铵血浆浓度也更高，肾衰竭发生率更高（7名患者中的7名 vs. 9名患者中的4名，P<0.03）。在没有延长神经肌肉阻滞的患者中，维库溴铵的平均（±标准差）血浆清除率、消除半衰期和分布容积分别为每分钟每千克体重2.5±1.0毫升、299±154分钟和每千克1.1±0.6升。
长期使用维库溴铵治疗结束后出现的延长的神经肌肉阻滞与代谢性酸中毒、血浆镁浓度升高、女性性别有关，可能更重要的是，与肾衰竭的存在以及3-去乙酰维库溴铵的高血浆浓度有关。
