Wagner B K, O'Hara D A
Department of Pharmacy Practice, Rutgers University, College of Pharmacy, Piscataway, New Jersey, USA.
Clin Pharmacokinet. 1997 Dec;33(6):426-53. doi: 10.2165/00003088-199733060-00003.
The pharmacokinetics and pharmacodynamics of sedatives and analgesics are significantly altered in the critically ill. These changes may account for the large differences in drug dosage requirements compared with other patient populations. Drugs that in other settings may be considered short-acting often have significantly altered onset and duration of action in critically ill patients, necessitating a change in dosage. Of the benzodiazepines, lorazepam is the drug whose parameters are the least likely to be altered in critical illness. The presence of active metabolites with other benzodiazepines complicates their use during periods of prolonged use. Similarly, the presence of active metabolites of morphine and pethidine (meperidine) warrants caution in patients with renal insufficiency. The fewer cardiovascular effects seen with high-potency opioids, such as fentanyl and sufentanil, increase their usefulness in haemodynamically compromised patients. The pharmacodynamics of propofol are not significantly altered in the critically ill. Ketamine should be used with a benzodiazepine to prevent the emergence of psychomimetic reactions. Lower sedative doses of benzodiazepines and anaesthetics may not provide reliable amnesia. Barbiturates and propofol probably do not induce hyperalgesia and lack intrinsic analgesic activity. The antipsychotic agent haloperidol has a calming effect on patients and administration to the point of sedation is generally not necessary. Combinations of sedatives and analgesics are synergistic in producing sedation. The costs of sedation and analgesia are very variable and closely linked to the pharmacokinetics and pharmacodynamics of the drug. Monitoring of sedation and analgesia is difficult in uncooperative patients in the intensive care unit. In the future, specific monitoring tools may assist clinicians in the regulation of infusions of sedative and analgesic agents.
在危重症患者中，镇静剂和镇痛药的药代动力学和药效动力学发生显著改变。与其他患者群体相比，这些变化可能是药物剂量需求存在巨大差异的原因。在其他情况下可能被视为短效的药物，在危重症患者中其起效时间和作用持续时间常常发生显著改变，因此需要调整剂量。在苯二氮䓬类药物中，劳拉西泮是其参数在危重症中最不易改变的药物。其他苯二氮䓬类药物存在活性代谢产物，这使其在长期使用期间的应用变得复杂。同样，吗啡和哌替啶（度冷丁）的活性代谢产物的存在，使得肾功能不全患者使用时需谨慎。强效阿片类药物，如芬太尼和舒芬太尼，较少出现心血管效应，这增加了它们在血流动力学不稳定患者中的实用性。丙泊酚的药效动力学在危重症患者中无显著改变。氯胺酮应与苯二氮䓬类药物合用，以防止出现拟精神反应。较低剂量的苯二氮䓬类镇静剂和麻醉剂可能无法提供可靠的遗忘效果。巴比妥类药物和丙泊酚可能不会诱发痛觉过敏，且缺乏内在镇痛活性。抗精神病药物氟哌啶醇对患者有镇静作用，一般无需给予至镇静状态。镇静剂和镇痛药联合使用在产生镇静作用方面具有协同效应。镇静和镇痛的费用差异很大，且与药物的药代动力学和药效动力学密切相关。在重症监护病房中，对不合作的患者进行镇静和镇痛监测很困难。未来，特定的监测工具可能会帮助临床医生调整镇静剂和镇痛药的输注。
