背景:该快速实践指南(RPG)旨在为成人重症监护病房(ICU)患者接受有创机械通气(iMV)的氯胺酮镇静(单药和辅助)与非氯胺酮镇静剂或常规护理提供循证建议,并确定未来研究的知识空白。
方法:RPG小组由23名跨国多学科小组成员组成,包括患者代表。最新的系统评价和荟萃分析构成了证据基础。分级建议,评估,发展,和评估方法,和证据到决定框架被用来评估证据的确定性,并从证据转向决定/建议。面板提供了关于期望和不期望效果的平衡的输入,证据的确定性,患者的价值观和偏好,成本,资源,股本,可行性,可接受性,和研究重点。
结果:纳入了17项随机临床试验(n=898)和9项观察性研究(n=1934)的数据。关于氯胺酮单药治疗analgo镇静的理想和不良作用存在相当大的不确定性。证据的确定性非常低,并因偏见风险而降级,间接性,和不一致。确定了价值观和偏好的不确定性或可变性。Costs,资源,股本,可接受性被认为是多种多样的。辅助氯胺酮治疗对死亡率(28天内)没有影响(相对风险[RR]0.99;95%置信区间[CI]0.76至1.27;低确定性),并且可能会略微减少iMV持续时间(天)(平均差[MD]-0.05天;95%CI-0.07至-0.03;低确定性),对阿片类药物的累积剂量(mcg/kg/h吗啡当量)的影响不确定(MD-11.6;95%CI-20.4至-2.7;非常低的确定性)。不确定的预期效果(镇静剂和血管加压药的累积剂量)和不良效果(不良事件发生率,谵妄,心律失常,肝毒性,唾液分泌过多,身体约束的使用)也被确定。在患者重要的结果中,重要的不确定性或变异性的可能性导致了既不赞成干预也不赞成比较的平衡效果。成本,资源,公平被认为是多种多样的。
结论:RPG小组提供了两个有条件的建议,并建议(1)当其他analgo镇静剂可用时,不要在iMV危重患者中使用氯胺酮作为单一疗法analgo镇静剂;(2)使用氯胺酮作为非氯胺酮常规镇静剂的辅助药物(例如,阿片类药物,异丙酚,右美托咪定)或继续单独使用非氯胺酮常规镇静剂。大规模试验应提供更多证据。
BACKGROUND: This Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research.
METHODS: The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients\' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities.
RESULTS: Data from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied.
CONCLUSIONS: The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.