Evaluation of efficacy and safety of esketamine combined with remifentanil for analgesia and sedation in patients with severe pneumonia undergoing invasive mechanical ventilation
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摘要: 目的 评价艾司氯胺酮联合瑞芬太尼在重症肺炎有创机械通气患者镇痛镇静中的疗效及安全性。方法 这项单中心的随机对照研究在连云港市第二人民医院重症医学科进行，将纳入患者随机分为研究组(瑞芬太尼联合艾司氯胺酮)和对照组(瑞芬太尼联合丙泊酚)，2组患者行经口气管插管机械通气后均给予镇痛镇静治疗。随访28 d，剔除失访及退出，根据不同临床转归，分为死亡组和生存组。结果 最后纳入统计分析的研究组75例，对照组75例。2组在病死率、ICU住院时间和机械通气时间上均差异无统计学意义(P>0.05)；但是研究组的停药后唤醒时间少于对照组[(27.12±6.87) min vs. (33.89±8.62)min，P < 0.05]，瑞芬太尼总量少于对照组[(23.72±20.05)g vs. (32.31±21.82)g，P < 0.05]。研究组的低血压、呼吸抑制发生率显著低于对照组(20.00% vs. 37.30%，13.30% vs. 28.00%，P < 0.05)，而研究组的谵妄发生率高于对照组(45.30% vs. 28.00%，P < 0.05)。死亡组的年龄显著大于生存组[(73.64±14.81)岁vs. (65.79±15.88)岁，P < 0.05]；死亡组的机械通气时间、停药后唤醒时间以及瑞芬太尼用药总量均显著大于生存组(P < 0.05)；死亡组的低血压、心动过缓、呼吸抑制、反流及谵妄的发生率均显著高于生存组(44.00% vs. 21.00%，46.00% vs. 25.00%，40.00% vs. 11.00%，30.00% vs. 9.00%，50.00% vs. 30.00%，均P < 0.05)。logistic回归显示：停药后唤醒时间，低血压，呼吸抑制，反流是患者死亡的主要危险因素(P < 0.05)。结论 瑞芬太尼联合艾司氯胺酮具有较好的镇痛镇静效果，可减少瑞芬太尼药物使用量，缩短停药后唤醒时间，且未增加不良反应发生风险，可作为重症肺炎机械通气患者镇痛镇静治疗方案的选择之一。Abstract: Objective To evaluate the efficacy and safety of esketamine combined with for analgesia and sedation in patients with severe pneumonia undergoing mechanical ventilation.Methods This single-center randomized controlled trial was conducted in the Department of Critical Care Medicine, the Second People's Hospital of Lianyungang. Patients were randomly divided into study group(remifentanil combined with esketamine, RK group) and control group(remifentanil combined with propofol, RP group). The patients were followed up for 28 days, and the loss to follow-up and withdrawal were excluded. According to different clinical outcomes, the patients were divided into death group and survival group.Results There were 75 cases in the study group and 75 cases in the control group. There were no significant differences in mortality rate, length of ICU stay and mechanical ventilation time between the two groups(P>0.05). However, the wake-up time after drug withdrawal in the study group was less than that in the control group(27.12±6.87 vs. 33.89±8.62, P < 0.05), and the total dose of remifentanil in the study group was less than that in the control group(23.72±20.05 vs. 32.31±21.82, P < 0.05). The incidences of hypotension and respiratory depression in the study group were significantly lower than those in the control group(20.00% vs. 37.30%, 13.30% vs. 28.00%, P < 0.05), while the incidence of delirium in the study group was higher than that in the control group(45.30% vs. 28.00%, P < 0.05). The age of death group was significantly older than that of survival group(73.64±14.81 vs. 65.79±15.88, P < 0.05). The duration of mechanical ventilation, wake-up time after withdrawal and total dose of remifentanil in the death group were significantly than those in the survival group(P < 0.05). The incidences of hypotension, bradycardia, respiratory depression, reflux and delirium in the death group were significantly higher than those in the survival group(44.00% vs. 21.00%, 46.00% vs. 25.00%, 40.00% vs. 11.00%, 30.00% vs. 9.00%, 50.00% vs. 30.00%, P < 0.05). Logistic regression analysis showed that wake-up time after drug withdrawal, hypotension, respiratory depression and reflux were the main risk factors for death in ICU patients with severe pneumonia undergoing mechanical ventilation(P < 0.05).Conclusion Remifentanil combined with esketamine has a better analgesic and sedative effect, reduc the dosage of remifentanil, shorten the wake-up time after withdrawal increas the risk of adverse reactions. Remifentanil combined with esketamine can be used as one of the options of analgesic and sedative treatment for patients with severe pneumonia undergoing mechanical ventilation.
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Key words:
- severe pneumonia /
- mechanical ventilation /
- analgesia and sedation /
- esketamine /
- remifentanil
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表 1 研究组与对照组一般资料比较
X±S，M(Q1，Q3) 一般资料 对照组(n=75) 研究组(n=75) t/Z/χ2 P 男性/例 51 44 1.407 0.309 年龄/岁 67.00±16.61 69.81±15.17 -1.083 0.281 APACHEⅡ评分/分 27.24±7.93 26.91±7.80 0.259 0.796 最高体温/℃ 38.67±0.71 38.50±0.77 1.428 0.155 白细胞计数/(×109/L) 12.00(8.50，14.80) 12.60(9.50，16.10) 1.041 0.298 血小板计数/(×109/L) 155.00(129.00，203.00) 161.00(117.00，218.00) 0.506 0.613 血红蛋白/(g/L) 102.10±22.99 102.91±23.03 -0.216 0.829 降钙素原/(ng/mL) 0.59(0.14，4.28) 0.51(0.18，2.91) 0.271 0.787 白蛋白/(g/L) 28.27±6.34 29.69±6.70 -1.334 0.184 心率/(次/min) 100.12±28.21 100.16±28.67 -0.009 0.993 呼吸频率/(次/min) 24.31±8.22 24.24±8.87 0.048 0.962 
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表 2 研究组与对照组病死率及不良反应比较
X±S 项目 对照组(RP)(n=75) 研究组(RK)(n=75) t/χ2 P 死亡/例(%) 26(34.67) 24(32.00) 0.120 0.863 ICU住院时间/d 12.32±9.88 9.79±7.01 1.811 0.072 机械通气时间/h 178.40±100.66 159.55±94.54 1.182 0.239 停药后唤醒时间/min 33.89±8.62 27.12±6.87 5.322 0.001 瑞芬太尼总量/g 32.31±21.82 23.72±20.05 2.501 0.013 高血压/例(%) 10(13.30) 19(25.30) 3.463 0.097 低血压/例(%) 28(37.30) 15(20.00) 5.510 0.030 心动过速/例(%) 16(21.30) 18(24.00) 0.152 0.846 心动过缓/例(%) 29(38.70) 19(25.30) 3.064 0.115 呼吸抑制/例(%) 21(28.00) 10(13.30) 4.920 0.043 呕吐/例(%) 8(10.70) 6(8.00) 0.315 0.780 反流/例(%) 15(20.00) 9(12.00) 1.786 0.265 便秘/例(%) 15(20.00) 13(17.30) 0.176 0.834 谵妄/例(%) 21(28.00) 34(45.30) 4.852 0.042
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表 3 生存组与死亡组临床资料比较
X±S，M(Q1，Q3) 项目 生存组(n=100) 死亡组(n=50) t/Z/χ2 P 男性/例(%) 61(61.00) 34(68.00) 0.703 0.474 年龄/岁 65.79±15.88 73.64±14.81 -2.918 0.004 最高体温/℃ 38.51±0.69 38.73±0.82 -1.703 0.091 白细胞计数/(×109/L) 11.65(8.70，15.00) 13.20(9.48，16.55) 1.609 0.108 血小板计数/(×109/L) 157.00(126.00，206.00) 186.50(126.50，227.25) 0.833 0.405 血红蛋白/(g/L) 101.31±24.63 104.88±19.14 -0.898 0.371 降钙素原/(ng/mL) 0.41(0.14，1.86) 0.78(0.30，5.13) 1.920 0.055 白蛋白/(g/L) 28.92±6.66 29.09±6.36 -0.152 0.879 ICU住院时间/d 11.39±9.37 10.38±6.98 0.674 0.501 机械通气时间/h 126.50(90.00，212.50) 195.50(112.50，273.00) 2.887 0.004 停药后唤醒时间/min 29.00(23.00，33.00) 35.50(28.00，41.00) 4.282 < 0.001 瑞芬太尼总量/g 20.00(10.00，35.75) 28.00(14.00，45.00) 2.128 0.033 高血压/例(%) 22(22.00) 7(14.00) 1.368 0.280 低血压/例(%) 21(21.00) 22(44.00) 8.623 0.004 心动过速/例(%) 25(25.00) 9(18.00) 0.932 0.410 心动过缓/例(%) 25(25.00) 23(46.00) 6.756 0.015 呼吸抑制/例(%) 11(11.00) 20(40.00) 17.098 < 0.001 呕吐/例(%) 8(8.00) 6(12.00) 0.630 0.552 反流/例(%) 9(9.00) 15(30.00) 10.938 0.002 便秘/例(%) 17(17.00) 11(22.00) 0.549 0.508 谵妄/例(%) 30(30.00) 25(50.00) 5.742 0.020
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表 4 变量赋值表
变量 赋值情况 预后(Y) 生存=0, 死亡=1 研究分组(X1) 对照组=0, 研究组=1 年龄≥72.00岁(X2) 否=0, 是=1 机械通气时间≥135.50 h(X3) 否=0, 是=1 停药后唤醒时间≥31.00 min(X4) 否=0, 是=1 瑞芬太尼总量≥22.00 g(X5) 否=0, 是=1 低血压(X6) 否=0, 是=1 心动过缓(X7) 否=0, 是=1 呼吸抑制(X8) 否=0, 是=1 反流(X9) 否=0, 是=1 谵妄(X10) 否=0, 是=1
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表 5 logistic回归分析不良结局发生危险因素
自变量 β SE Waldχ2 P OR 95%CI 研究分组 -0.808 0.503 2.578 0.108 0.446 0.166~1.195 年龄 0.840 0.448 3.508 0.061 2.316 0.962~5.578 机械通气时间 -0.526 0.552 0.907 0.341 0.591 0.200~1.745 停药后唤醒时 1.673 0.550 9.246 0.002 5.330 1.813~15.674 瑞芬太尼总量 0.869 0.482 3.243 0.072 2.383 0.926~6.133 低血压 1.499 0.504 8.838 0.003 4.479 1.667~12.037 心动过缓 0.575 0.479 1.441 0.230 1.776 0.695~4.539 呼吸抑制 1.624 0.550 8.729 0.003 5.074 1.728~14.905 反流 1.290 0.582 4.909 0.027 3.632 1.161~11.368 谵妄 0.584 0.471 1.537 0.215 1.793 0.712~4.512
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