Amer Marwa, Maghrabi Khalid, Bawazeer Mohammed, Alshaikh Kamel, Shaban Mohammad, Rizwan Muhammad, Amin Rashid, De Vol Edward, Baali Mawadah, Altewerki Malak, Bano Mehreen, Alkhaldi Fawziah, Alenazi Sanaa, Hijazi Mohammed
Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Center, (MBC # 11), PO Box 3354, Riyadh, 11211, Kingdom of Saudi Arabia.
College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
J Intensive Care. 2021 Aug 30;9(1):54. doi: 10.1186/s40560-021-00569-1.
Ketamine has been shown to decrease sedative requirements in intensive care unit (ICU). Randomized trials are limited on patient-centered outcomes. We designed this pilot trial to evaluate the feasibility of a large randomized controlled trial (RCT) testing the effect of ketamine as an adjunct analgosedative compared with standard of care alone as a control group (CG) in critically ill patients with mechanical ventilation (MV). We also provided preliminary evidence on clinically relevant outcomes to plan a larger trial.
Pilot, active-controlled, open-label RCT was conducted at medical, surgical, and transplant ICUs at a large tertiary and quaternary care medical institution (King Faisal Specialist Hospital and Research Center, Saudi Arabia). The study included adult patients who were intubated within 24 h, expected to require MV for the next calendar day, and had institutional pain and sedation protocol initiated. Patients were randomized in a 1:1 ratio to adjunct ketamine infusion 1-2 μg/kg/min for 48 h or CG alone.
Of 437 patients screened from September 2019 through November 2020, 83 (18.9%) patients were included (43 in CG and 40 in ketamine) and 352 (80.5%) were excluded. Average enrollment rate was 3-4 patients/month. Consent and protocol adherence rates were adequate (89.24% and 76%, respectively). Demographics were balanced between groups. Median MV duration was 7 (interquartile range [IQR] 3-9.25 days) in ketamine and 5 (IQR 2-8 days) in CG. Median VFDs was 19 (IQR 0-24.75 days) in ketamine and 19 (IQR 0-24 days) in the CG (p = 0.70). More patients attained goal Richmond Agitation-Sedation Scale at 24 and 48 h in ketamine (67.5% and 73.5%, respectively) compared with CG (52.4% and 66.7%, respectively). Sedatives and vasopressors cumulative use, and hemodynamic changes were similar. ICU length-of-stay was 12.5 (IQR 6-21.2 days) in ketamine, compared with 12 (IQR 5.5-23 days) in CG. No serious adverse events were observed in either group.
Ketamine as an adjunct analgosedative agent appeared to be feasible and safe with no negative impact on outcomes, including hemodynamics. This pilot RCT identified areas of improvement in study protocol before conducting a large, adequately powered, multicenter RCT which is likely justified to investigate ketamine association with patient-centered outcomes further. Trial registration ClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020.
已证明氯胺酮可降低重症监护病房（ICU）的镇静需求。关于以患者为中心的结局的随机试验有限。我们设计了这项试点试验，以评估一项大型随机对照试验（RCT）的可行性，该试验测试氯胺酮作为辅助镇痛镇静剂与仅作为对照组（CG）的标准治疗相比，对机械通气（MV）的重症患者的效果。我们还提供了关于临床相关结局的初步证据，以规划一项更大规模的试验。
在一家大型三级和四级医疗保健机构（沙特阿拉伯费萨尔国王专科医院和研究中心）的内科、外科和移植ICU进行了试点、活性对照、开放标签的RCT。该研究纳入了在24小时内插管、预计次日需要MV且已启动机构疼痛和镇静方案的成年患者。患者按1:1的比例随机分为接受1 - 2μg/kg/min氯胺酮输注48小时或仅接受CG的组。
在2019年9月至2020年11月筛选的437例患者中，83例（18.9%）患者被纳入（CG组43例，氯胺酮组40例），352例（80.5%）被排除。平均入组率为每月3 - 4例患者。同意率和方案依从率足够（分别为89.24%和76%）。两组间人口统计学特征均衡。氯胺酮组的MV持续时间中位数为7天（四分位间距[IQR] 3 - 9.25天），CG组为5天（IQR 2 - 8天）。氯胺酮组的VFDs中位数为19天（IQR 0 - 24.75天），CG组为19天（IQR 0 - 24天）（p = 0.70）。与CG组（分别为52.4%和66.7%）相比，氯胺酮组在24小时和48小时达到目标里士满躁动 - 镇静量表的患者更多（分别为67.5%和73.5%）。镇静剂和血管加压药的累积使用以及血流动力学变化相似。氯胺酮组的ICU住院时间为12.5天（IQR 6 - 21.2天），CG组为12天（IQR 5.5 - 23天）。两组均未观察到严重不良事件。
氯胺酮作为辅助镇痛镇静剂似乎是可行且安全的，对包括血流动力学在内的结局没有负面影响。这项试点RCT确定了在进行一项大型、有足够效力的多中心RCT之前研究方案中需要改进的方面，进一步研究氯胺酮与以患者为中心的结局之间的关联可能是合理的。试验注册ClinicalTrials.gov：NCT04075006。于2019年8月30日注册。当前对照试验：ISRCTN14730035。于2020年2月3日注册。
