阿芬太尼干预烧伤患者换药操作性疼痛的临床研究

A prospective randomized controlled study of alfentanil for procedural pain analgesia in burn patients

目的探索清醒烧伤患者经静脉用阿芬太尼的最大耐受剂量(MTD),评价阿芬太尼对烧伤患者换药操作性疼痛的镇痛效果及临床安全性。方法采用传统“3+3”设计法确定阿芬太尼MTD(该试验于2022年3—7月进行)。验证阿芬太尼镇痛效果试验纳入2022年8月—2023年7月就诊于上海交通大学医学院附属瑞金医院的烧伤患者128例,其中男86例、女42例,年龄18~65岁,BMI<40 kg/m^(2),ASA分级Ⅰ至Ⅲ级,烧伤面积1%~50%,烧伤部位不限。采用随机数字表法将患者分入阿芬太尼组和0.9%氯化钠溶液组(对照组),每组64例。在换药开始前5~10 min,开始静脉恒速泵注阿芬太尼500μg/mL或0.9%氯化钠溶液直至换药结束。记录患者的一般资料[性别构成、年龄、身高、体重、BMI、烧伤表皮总面积(TBSA)、ASA分级、烧伤分度、焦虑程度、既往史],换药前5~10 min(T_(1))、清除敷料时(T_(2))、清创时(T_(3))、更换敷料时(T_(4))、换药后即刻(T_(5))、换药后1 h(T_(6))、换药后2 h(T_(7))的生命体征[平均血压(MBP)、心率、指脉搏氧饱和度(SpO_(2))、呼吸频率(RR)]、疼痛VAS评分。测定患者T_(1)、T_(7)时间点的炎症因子(IL-4、IL-5、IL-6、TNF-α)水平。记录T_(7)时间点患者的换药满意度、换药时长、用药(阿芬太尼或0.9%氯化钠溶液)总剂量,以及阿芬太尼组用药后不良反应发生情况。结果采用传统“3+3”试验确定60μg/(kg•h)为阿芬太尼MTD。阿芬太尼组TBSA显著大于对照组(P=0.002)。两组间换药全程MBP、心率、SpO_(2)、RR的差异均无统计学意义(P值均>0.05);与对照组同时间点比较,阿芬太尼组T_(5)时间点的MBP显著增高(P<0.05),T_(3)至T_(5)时间点的RR均显著降低(P值均<0.05)。换药全程阿芬太尼组的疼痛VAS评分显著低于对照组(P<0.05),阿芬太尼组T_(1)至T_(7)时间点的疼痛VAS评分均显著低于对照组同时间点(P值均<0.05);换药操作期间(T_(2)至T_(4)时间点),阿芬太尼组最大疼痛VAS评分和最小疼痛VAS评分分别显著小于对照组(Z=4.355、6.624,P值均为0.000)。与同组T_(1)时间点比较,两组T_(7)时间点IL-4、IL-5、TNF-α水平的差异均无统计学意义(P值均>0.05),两组T_(7)时间点的IL-6水平均显著升高(P值均<0.05)。与对照组同时间点比较,阿芬太尼组T_(1)、T_(7)时间点IL-4、IL-5、TNF-α水平的差异均无统计学意义(P值均>0.05),T_(7)时间点IL-6水平显著降低(P<0.05);阿芬太尼组T_(1)时间点IL-6水平较对照组同时间点有下降趋势,但差异无统计学意义(P>0.05)。阿芬太尼组患者换药满意度显著高于对照组(P<0.05)。阿芬太尼组换药时长显著长于对照组(P=0.002),用药总量显著多于对照组(P=0.001)。阿芬太尼组有6例患者用药后出现轻微头晕、嗜睡的症状,停药后明显好转。结论60μg/(kg•h)阿芬太尼可安全、有效地缓解烧伤患者的换药操作性疼痛,且无明显不良反应发生,可改善患者的治疗体验和提高换药满意度。

Objective To investigate the maximum tolerated dose(MTD)of intravenous alfentanil for analgesia in conscious burn patients,and to evaluate the safety and analgesic effect of alfentanil during dressing changes.Methods To find out the MTD of alfentanil,we used the traditional“3+3”design method and conducted the trial in Ruijin hospital from March to July 2022.To verify the analgestic effect of alfentanil.A total of 128 burn patients treated at Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine from August 2022 to July 2023 were enrolled in a validation trial for analgesic effect.There were 86 males and 42 females,aged 18 to 65 years,with a body mass index(BMI)less than 40 kg/m^(2),American Society of Anesthesiologists(ASA)classification ofⅠtoⅢ,and burn area ranging from 1%to 50%,with no limitation on the burn site.The patients were randomly assigned to alfentanil group and control group,with 64 cases in each group.Five to ten minutes before dressing change,a continuous intravenous infusion of alfentanil(500μg/mL)or 0.9%saline solution was given until the end of the dressing change.The basic information of the patients was recorded,including gender composition,age,height,weight,BMI,total burn surface area(TBSA),ASA classification,degree of burns,anxiety level,and medical history.Vital signs(mean blood pressure[MBP],heart rate[HR],oxygen saturation[SpO_(2)],respiratory rate[RR])and pain visual analogue scale(VAS)scores were documented at 5-10 minutes before dressing change(T_(1)),during the removal of dressings(T_(2)),during debridement(T_(3)),during the application of new dressings(T_(4)),immediately after dressing change(T_(5)),1 hour after dressing change(T_(6)),and 2 hours after dressing change(T_(7)).Inflammatory factor levels(interleukin[IL]-4,IL-5,IL-6,and tumor necrosis factor[TNF]-α)were measured at T_(1) and T_(7).Patient satisfaction with the dressing change at T_(7),the duration of dressing change,total dose of medication(alfentanil or 0.9%saline solution),and adverse reactions were recorded.Results The MTD of alfentanil was 60μg/(kg•h).The TBSA in the alfentanil group was significantly larger than that in the control group(P=0.002).There were no statistically significant differences in the MBP,HR,SpO_(2),or RR between the two groups throughout the dressing change(all P>0.05).However,compared with the control group at the same time points,MBP in the alfentanil group was significantly increased and T_(5)(P<0.05),while RR were significantly decreased from T_(3) to T_(5)(all P<0.05).The pain VAS score throughout the dressing change in the alfentanil group was significantly lower than that in the control group(P<0.05),and there were significant differences in pain VAS scores at each time point between the two groups(all P<0.05).The maximum and minimum pain VAS scores in the alfentanil group were significantly lower than those in the control group from T_(2) to T_(4)(Z=4.355,6.624,both P=0.000).Compared with those at T_(1),no significant difference was found in the levels of IL-4,IL-5,or TNF-αat T_(7) in both groups(all P>0.05),but the IL-6 levels were significantly increased at T_(7) in both groups(all P<0.05).There were no statistically significant differences in the IL-4,IL-5,or TNF-αat T_(1) and T_(7) between the two groups(all P>0.05).The IL-6 level in the alfentanil group was significantly lower than that in the control group at T_(7)(P<0.05).The degree of satisfaction with the dressing change in the alfentanil group was significantly higher than that in the control group(P<0.05).The duration of dressing change in the alfentanil group was significantly longer than that in the control group(P=0.002).The total amount of medication in the alfentanil group was significantly more than that in the control group(P=0.001).In the alfentanil group,6 patients experienced mild dizziness and drowsiness after medication,which significantly improved after discontinuation of the drug.Conclusion 60μg/(kg•h)of alfentanil can safely and effectively alleviate procedural pain during dressing changes for burn patients,with no significant adverse reactions,thereby improving the patients’treatment experience and increasing satisfaction with the dressing change process.