联合用药对重症脑损伤患者的镇静效果观察

Sedative effect of combination dexmedetomidine and propofol for patients with severe brain injury

目的 观察右美托咪定联合丙泊酚对重症脑损伤患者镇静疗效及预后的影响.方法 采用前瞻性随机对照研究方法,选择2016年10月至2017年3月贵州医科大学附属医院重症医学科(ICU)收治的53例重症脑损伤患者,按随机数字表法分为丙泊酚组(28例)和右美托咪定联合丙泊酚组(联合组,25例).两组患者入住ICU后均持续静脉泵入芬太尼0.3~1.0 μg·kg-1·h-1镇痛,维持镇痛评分在0~3分;调整镇静药物剂量并持续监测脑电双频指数(BIS),维持Richmond躁动-镇静评分(RASS)-2~0分及BIS值65~85.丙泊酚组持续静脉泵入丙泊酚0.5~4.8 mg·kg-1·h-1;联合组泵入右美托咪定0.2~0.4 μg·kg-1·h-1+丙泊酚0.3~1.0 mg·kg-1·h-1.记录两组患者呼吸、循环、动脉血气分析指标和药物起效时间、机械通气时间、ICU住院时间、不良反应发生情况、28 d病死率,以及60 d和90 d格拉斯哥预后评分(GOS).结果 丙泊酚组和联合组分别有2例和1例患者因ICU住院时间不足48 h而被排除,各有1例中途放弃治疗、1例失访;最终丙泊酚组24例、联合组22例患者的数据纳入统计分析.与丙泊酚组比较,联合组的药物起效时间更短(min:4.1±0.6比5.1±0.9),芬太尼用量更少(μg·kg-1·h-1:0.4±0.1比0.5±0.1),差异均有统计学意义(均P<0.01).两组患者心率(HR)随用药时间延长呈下降趋势,且联合组用药30 min起HR下降较丙泊酚组更加显著,并持续至12 h (次/min:30 min为82.3±11.0比90.0±12.8,12 h为78.1±8.2比90.8±9.3,均P<0.05);两组用药前后各时间点循环、动脉血气等指标和BIS值比较差异均无统计学意义(均P>0.05).丙泊酚组与联合组不良反应发生率比较差异无统计学意义〔低血压:12.5%(3/24)比13.6%(3/22),心动过缓:4.1%(1/24)比18.2%(4/22),谵妄:8.3%(2/24)比4.5%(1/22),均P>0.05〕.两组机械通气时间、ICU住院时间、28 d病死率比较差异均无统计学意义;但联合组60 d(分:3.8±1.5比3.0±1.2)和90 d(分:4.0±1.6比3.2±1.4)GOS评分明显高于丙泊酚组(均P<0.05).结论 右美托咪定联合丙泊酚用于重症脑损伤患者可取得满意的镇静效果,与单用丙泊酚相比,可减少镇痛药物用量,改善远期预后,但易引起HR下降.

Objective To investigate the sedative effect and prognosis of combination of dexmedetomidine and propofol for the patients with severe brain injury. Methods A prospective randomized controlled trial was conducted. Fifty-three patients with severe brain injury admitted to intensive care unit (ICU) of Guizhou Medical University Affiliated Hospital from October 2016 to March 2017 were enrolled, and they were randomly divided into propofol group (n = 28) and dexmedetomidine combined with propofol group (combination group, n = 25). The patients in the two groups were treated with intravenous infusion of fentanyl 0.3 - 1.0 μg·kg-1·h-1after ICU admission for analgesia, and maintained the analgesic score at 0 - 3. The dosage of sedative drugs was adjusted, the bispectral index monitor (BIS) was continuously monitored, and maintained the Richmond agitation-sedation scale (RASS) score at -2 to 0, and BIS at 65 - 85. Additionally, the patients in propofol group were continuously received propofol by continuous intravenous pump at a speed of 0.5 - 4.8 mg·kg-1·h-1, and those in combination group continuously received dexmedetomidine 0.2 - 0.4 μg·kg-1·h-1and propofol 0.3 - 1.0 mg·kg-1·h-1. The parameters of respiratory, circulatory and arterial blood gas analysis, drug onset time, duration of mechanical ventilation, the length of ICU stay, adverse reactions, 28-day mortality, and 60-day and 90-day Glasgow outcome scale (GOS) score in both groups were recorded. Results There were 2 patients and 1 patient who were excluded because of the length of ICU stay less than 48 hours, 1 case gave up treatment and 1 case lost follow-up in propofol group and combination group, respectively. Finally, 24 patients in propofol group and 22 in combination group were enrolled in the analysis. Compared with propofol group, the drug onset time of combination group was shortened (minutes: 4.1±0.6 vs. 5.1±0.9). the dosage of fentanyl was lowered (μg·kg-1·h-1: 0.4±0.1 vs. 0.5±0.1), with significant differences (both P < 0.01). The heart rate (HR) of two groups decreased with the prolongation of treatment time, and the decrease in HR of combination group was more significant than that of propofol group from 30 minutes to 12 hours after treatment (bmp: 82.3±11.0 vs. 90.0±12.8 at 30 minutes, 78.1±8.2 vs. 90.8±9.3 at 12 hours, both P < 0.05). There was no significant difference in the parameters of circulatory and arterial blood gas analysis or BIS between the two groups. There was also no significant difference in the incidence of adverse reactions between propofol group and combination group (hypotension: 12.5% (3/24) vs. 13.6% (3/22), bradycardia:4.1% (1/24) vs. 18.2% (4/22), delirium: 8.3% (2/24) vs. 4.5% (1/22), all P > 0.05)The difference in duration of mechanical ventilation, the length of ICU stay or 28-day mortality showed no statistical significance between the two groups, but 60-day (3.8±1.5 vs. 3.0±1.2) and 90-day (4.0±1.6 vs. 3.2±1.4) GOS scores in combination group were significantly higher than those of propofol group (both P < 0.05). Conclusion The combined use of dexmedetomidine and propofol can obtain satisfactory sedative effects for severe brain injury patients, which can reduce the dosage of analgesic drugs, improve the long-term prognosis as compared with propofol alone, but easy to cause HR to decrease.