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中华卫生应急电子杂志 ›› 2022, Vol. 08 ›› Issue (01) : 6 -13. doi: 10.3877/cma.j.issn.2095-9133.2022.01.002

论著

不同负荷剂量苯磺酸瑞马唑仑对ICU机械通气患者镇静效果及循环系统的影响
詹维强1, 许明1, 史新格1, 徐先伟2, 芦乙滨1,†()   
  1. 1. 464000　河南信阳，郑州大学附属信阳医院（信阳市中心医院）重症医学科
    2. 443005　湖北宜昌，宜昌人福药业有限责任公司
  • 收稿日期:2021-11-09 出版日期:2022-02-18
  • 通信作者: 芦乙滨
  • 基金资助:
    中华国际医学交流基金(Z-2017-24-2028-37)

Sedative effects of different loading doses of remimazolam on mechanical ventilation of patients in intensive care unit

Weiqiang Zhan1, Ming Xu1, Xinge Shi1, Xianwei Xu2, Yibin Lu1,†()   

  1. 1. Department of Intensive Care Medicine, Xinyang Hospital Affiliated to Zhengzhou University, Xinyang 464000, China
    2. Yichang Humanwell Pharmaceutical Co., Ltd. Yichang 443005, China
  • Received:2021-11-09 Published:2022-02-18
  • Corresponding author: Yibin Lu
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引用本文：

詹维强, 许明, 史新格, 徐先伟, 芦乙滨. 不同负荷剂量苯磺酸瑞马唑仑对ICU机械通气患者镇静效果及循环系统的影响[J/OL]. 中华卫生应急电子杂志, 2022, 08(01): 6-13.

Weiqiang Zhan, Ming Xu, Xinge Shi, Xianwei Xu, Yibin Lu. Sedative effects of different loading doses of remimazolam on mechanical ventilation of patients in intensive care unit[J/OL]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2022, 08(01): 6-13.

目的

对比研究不同剂量苯磺酸瑞马唑仑对重症监护病房(ICU)机械通气患者的镇静效果及循环系统的影响。

方法

采用前瞻性观察性研究方法，选择在2021年1月至2021年9月郑州大学附属信阳医院(信阳市中心医院)重症医学科收治的需要镇静并且满足纳入及排除标准的机械通气患者作为研究对象。随机分为A、B、C三组，先分别给予舒芬太尼预镇痛，镇痛目标为重症监护疼痛观察工具(CPOT)评分<2分，然后分别给予负荷量苯磺酸瑞马唑仑0.10 mg/kg、0.15 mg/kg、0.20 mg/kg在10 min内匀速泵入，再以0.05~0.5 mg·kg-1·h-1静脉泵入维持。根据Richmond躁动-镇静评分(RASS)标准，维持目标的镇静深度-2~0级。对比三组患者用药前(T0)，用药后5 min(T1)、10 min(T2)、15 min(T3)、45 min(T4)、90 min(T5)、180 min(T6)RASS评分、心率(HR)、平均动脉压(MAP)、呼吸频率(RR)、氧合指数(OI)变化，比较呼吸循环系统不良事件(呼吸系统：呼吸抑制；循环系统：低血压、心动过缓)的发生率。

结果

最终纳入98名患者随机分为A、B、C三组。三组患者在性别、年龄、身高、体重、急性生理与慢性健康评分(APACHEⅡ)等一般资料及用药前呼吸和血流动力学指标比较差异均无统计学意义。在T2时A、B、C组镇静有效率(RASS≤1分)分别为67.7%(21例)、87.9%(29例)、100%(34例)，对比差异有统计学意义(χ2＝14.25，P<0.01)；三组镇静不足(RASS≥2分)发生率分别为32.3%(10例)、12.1%(4例)、0%(0例)，对比差异有统计学意义(P<0.01)；三组镇静过深(RASS≤-3分)的发生率分别为3.2%(1例)、15.2%(5例)、47.1%(16例)，对比差异有统计学意义(χ2＝18.99，P<0.01)；在维持剂量时期(T4、T6)三组约有46.9%(46例)患者维持剂量低于0.1 mg·kg-1·h-1；34.7%(34例)的患者维持剂量在0.1~0.2 mg·kg-1·h-1；18.4%(18例)的患者维持剂量高于0.2 mg·kg-1·h-1。HR下降幅度(T2 vs T0)分别为13.8%、19.6%、29.7%，T3时三组患者HR仍有下降。组间分析提示A组vs B组(T2、T3)、A组vs C组(T1、T2、T3)、B组vs C组(T2、T3)差异均有统计学意义(P<0.05)。三组患者给药后MAP的均值也呈现逐渐下降趋势，完全泵入负荷剂量苯磺酸瑞马唑仑后(T2 vs T0)MAP下降幅度分别为12.9%、14.4%、22.8%。组间分析提示与C组比较，A组(T1、T2)和B组(T2)差异均有统计学意义(P<0.05)。给药后虽然RR均值和OI均值均有变化，但是仅在T2时A组同C组RR差异有统计学意义(P<0.05)，其余时间点RR差异无统计学意义；三组患者在T1~T6时OI差异无统计学意义(P>0.05)。

结论

在ICU机械通气患者镇静中给于0.15 mg/kg负荷量在10 min泵入可达到较为理想的镇静效果。对于部分RASS评分≥3分的患者可以适当增加负荷剂量。短期内大剂量泵入苯磺酸瑞马唑仑可导致患者呼吸及循环系统不良事件发生率增加，因此在ICU患者镇静中应避免高负荷量快速泵入。

关键词: 镇静, 重症监护, 机械通气, 瑞马唑仑
Objective

To explore the sedative effect of different loading doses of remimazolam on patients with mechanical ventilation in intensive care unit (ICU) and its influence on respiratory and circulatory system.

Methods

A prospective observation was conducted. From January 2021 to September 2021, the patients with mechanical ventilation who needed sedation and met the inclusion and exclusion criteria were enrolled in ICU of Xinyang Central Hospital. They were randomly divided into three groups: A, B and C. Sufentanil was given pre-analgesia; the analgesic target was critical-care pain observation tool (CPOT) score<2. Then, the loading doses of remimazolam (0.10 mg/kg, 0.15 mg/kg, 0.20 mg/kg)was pumped at a constant speed within 10 minutes, followed by 0.05-0.5 mg·kg-1·h-1 was given intravenously. According to Richmond restlessness-sedation score (RASS), the sedation depth of the target was maintained at -2 to 0 point. The RASS score, heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), and respiratory rate were compared among the three groups at different times before administration (T0) and 5 min(T1), 10 min(T2), 15 min(T3), 45 min(T4), 90 min(T5), 180 min(T6) after administration. Adverse events of respiratory and circulatory system (respiratory depression; hypotension and bradycardia) were recorded.

Results

Totally 98 patients were involved in this study. There was no significant difference in general data such as gender, age, height, weight, acute physiology and chronic health score (APACHEⅡ), respiratory and hemodynamic indexes before medication between three groups. The sedative effective rate (RASS≤1 point) of groups A, B and C in T2 time was 67.7%(21 cases), 87.9%(29 cases) and 100%(34 cases), respectively, and the difference was statistically significant (χ2=14.25, P<0.01). The incidence of sedation insufficiency (RASS ≥2 points) in the three groups was 32.3%(10 cases), 12.1%(4 cases) and 0%(0 cases), respectively, and the difference was statistically significant (P<0.01). The incidence of deep sedation (RASS ≤ -3 points) in the three groups was 3.2%(1 cases), 15.2%(5 cases) and 47.1%(16 cases) respectively, and the difference was statistically significant (χ2=18.99, P<0.01). In the maintenance dose period (T4, T6), about 46.9%(46 cases) patients in the three groups had the maintenance dose lower than 0.1 mg·kg-1·h-1, about 34.7%(34 cases) patients was 0.1~ 0.2 mg·kg-1·h-1, about 18.4%(18 cases) patients was higher than 0.2 mg·kg-1·h-1. HR decreased by 13.8%, 19.6% and 29.7% respectively (T2 vs T0), and HR of the three groups still decreased at 15 min(T3) after administration. Inter-group analysis showed that there were significant differences among groups A and B (T2, T3), groups A and C (T1, T2, T3) and groups B and C (T2, T3) (P<0.05). The mean value of MAP in the three groups also showed a gradual downward trend after administration, and the decrease ranges of MAP were 12.9%, 14.4% and 22.8% respectively after fully pumping the loading dose of remimazolam (T2 compared to T0). Inter-group analysis showed that there were significant differences between group A (T1, T2) and group B (T2) compared with group C (P<0.05). Although the mean RR and mean OI changed after administration, the RR of group C and group A was statistically different only at T2 time (P<0.05), but there was no statistical difference at other time points. There was no significant difference in OI between the three groups at T1~T6 (P>0.05).

Conclusion

In the sedation of ICU patients with mechanical ventilation, the optimal loading dose is 0.15 mg/kg. For some patients with RASS score ≥3, the loading dose can be appropriately increased. High loading dose of remimazolam pumped rapidly should be avoided, which can increase the incidence of adverse events of respiratory and circulatory system.

Key words: Sedation, Intensive care, Mechanical ventilation, Remimazolam
表1 三组患者的患者的基线和临床特征[例(±s)]
组别 例数 年龄(岁) 性别(男/女) 身高(cm) 体重(kg) APACHEⅡ评分(分)
A组 31 59.81±12.35 18/13 165.58±9 75.1±11.41 15.74±6.18
B组 33 62.64±9.95 21/12 168.48±9.82 72.03±8.22 17.27±5.81
C组 34 58.38±12.73 17/16 166.59±10.29 71.35±11.37 18.15±4.81
F/χ2值   1.13 0.78 0.74 1.17 1.52
P值   >0.05 >0.05 >0.05 >0.05 >0.05
表2 不同镇静方案的三组重症患者T0~T6各时间点RASS评分、HR、MAP、RR、脉搏血氧饱和度、OI比较[(±s)或M(QL，QU)]
组别 指标 T0 T1 T2 T3 T4 T5 T6
A组 RASS评分 2(2，3) 1(1，2.5) 0(-0.5，2) -1(-1.5，0) -2(-2，-1) -2(-2，-2) -2(-2，-1)
B组   2(2，3) 1(0，2) 0(-2，1) -1(-2，0) -2(-2，-1) -2(-2，-1) -1(-2，-1)
C组   2(2，2.75) 0(-0.75，1)a -2(-3，-1)ab -3(-3，-2)ab -2(-2，-1) -2(-2，-1) -1.5(-2，-1)
A组 HR 109.06±7.36 102.1±8.39 94.77±9.26 87.84±6.73 80.81±5.76 80.00±5.97 80.94±5.21
B组   107.73±9.03 97.88±12.68 86.97±12.65a 81.12±10.97a 78.73±8.30 78.55±4.93 78.91±4.86
C组   111.59±11.19 94.32±15.29a 78.00±14.80ab 75.06±9.95ab 79.97±7.31 79.97±6.27 80.74±4.83
A组 MAP 93.39±8.12 87.16±8.29 81.16±9.23 75.84±7.27 72.00±6.31 69.97±6.13 70.00±5.56
B组   90.48±7.20 83.67±10.47 77.00±10.09 73.36±8.66 70.30±7.13 70.58±4.36 70.82±4.43
C组   92.71±8.10 80.47±11.66a 71.21±9.76ab 68.47±7.01ab 71.85±4.61 72.29±5.95 71.62±4.72
A组 RR 27.16±5.03 24.32±6.45 21.77±7.05 17.68±3.33 15.87±2.80 15.35±2.92 16.00±2.67
B组   27.85±5.40 23.30±7.10 20.48±7.16 18.15±5.32 17.06±3.74 16.36±3.81 16.33±3.29
C组   26.56±7.17 21.06±4.96 17.15±4.14a 16.47±3.36 16.59±2.60 16.44±2.94 16.56±3.65
A组 OI 208.68±27.59 213.74±28.16 220.32±28.72 224.74±28.53 249.77±29.04 251.52±29.19 249.45±28.38
B组   216.79±26.87 224.39±28.49 230.76±28.90 230.94±27.85 254.85±25.16 257.21±27.89 256.45±27.70
C组   206.44±18.78 212.97±20.29 217.21±19.46 224.53±19.33 245.71±19.43 244.44±22.03 243.26±21.93
图1 不同镇静方案对重症患者呼吸及循环系统的影响注：RASS为镇静评分，HR为心率，MAP为平均动脉压，RR为呼吸频率，OI为氧合指数；同一时间点与A组相比：aP<0.05；同一时间点与B组相比：bP<0.05
表3 不同镇静方案三组重症患者T0~T6补救治疗及不良事件发生情况比较(例)
组别 补救镇静 低血压 心动过缓 呼吸抑制
A组 10 1 0 0
B组 4 2 3 2
C组 0 5 3 2
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