From the Department of Anesthesiology, University of Utah, Salt Lake City, Utah.
Anesth Analg. 2020 May;130(5):1320-1330. doi: 10.1213/ANE.0000000000004654.
The need to reduce the dose of intravenous anesthetic in the setting of hemorrhagic shock is a well-established clinical dogma. Considered collectively,; the body of information concerning the behavior of intravenous anesthetics during hemorrhagic shock, drawn from animal and human data, confirms that clinical dogma and informs the rational selection and administration of intravenous anesthetics in the setting of hemorrhagic shock. The physiologic changes during hemorrhagic shock can alter pharmacokinetics and pharmacodynamics of intravenous anesthetics. Decreased size of the central compartment and central clearance caused by shock physiology lead to an altered dose-concentration relationship. For most agents and adjuncts, shock leads to substantially higher concentrations and increased effect. The notable exception is etomidate, which has relatively unchanged pharmacokinetics during shock. Increased concentrations lead to increased primary effect as well as increased side effects, notably cardiovascular effects. Pharmacokinetic changes are essentially reversed for all agents by fluid resuscitation. Propofol is unique among agents in that, in addition to the pharmacokinetic changes, it exhibits increased potency during shock. The pharmacodynamic changes of propofol persist despite fluid resuscitation. The persistence of these pharmacodynamic changes during shock is unlikely to be due to increased endogenous opiates, but is most likely due to increased fraction of unbound propofol. The stage of shock also appears to influence the pharmacologic changes. The changes are more rapid and pronounced as shock physiology progresses to the uncompensated stage. Although scant, human data corroborate the findings of animal studies. Both the animal and human data inform the rational selection and administration of intravenous anesthetics in the setting of hemorrhagic shock. The well-entrenched clinical dogma that etomidate is a preferred induction agent in patients experiencing hemorrhagic shock is firmly supported by the evidence. Propofol is a poor choice for induction or maintenance of anesthesia in severely bleeding patients, even with resuscitation; this can include emergent trauma cases or scheduled cases that routinely have mild or moderate blood loss.
在失血性休克的情况下减少静脉麻醉剂剂量的需求是一个既定的临床教条。从动物和人类数据中得出的关于静脉麻醉剂在失血性休克期间行为的信息,共同证实了这一临床教条,并为失血性休克时静脉麻醉剂的合理选择和应用提供了依据。失血性休克期间的生理变化会改变静脉麻醉剂的药代动力学和药效动力学。休克生理引起的中央隔室和中央清除率减小会导致剂量-浓度关系改变。对于大多数药物和辅助药物,休克会导致浓度显著升高和作用增强。唯一的例外是依托咪酯,它在休克期间的药代动力学相对不变。浓度增加会导致主要作用增强以及副作用增加,特别是心血管作用。所有药物的药代动力学变化在液体复苏后基本得到逆转。丙泊酚在药物中是独特的,除了药代动力学变化外,它在休克期间表现出增强的效力。丙泊酚的药效学变化在液体复苏后仍然存在。这些药效学变化在休克期间持续存在的原因不太可能是内源性阿片类物质增加,而是很可能是由于未结合丙泊酚的比例增加。休克的阶段似乎也会影响药理变化。随着休克生理学进展到代偿不全阶段,这些变化会更快、更明显。尽管数据很少,但人体数据证实了动物研究的发现。动物和人体数据共同为失血性休克时静脉麻醉剂的合理选择和应用提供了依据。依托咪酯是失血性休克患者首选诱导剂的既定临床教条得到了证据的有力支持。即使进行了复苏,丙泊酚也不是严重出血患者麻醉诱导或维持的理想选择,包括紧急创伤病例或常规轻度或中度失血的择期病例。