药物辅助治疗撤机困难患者的临床研究

Investigation of adjuvant treatment for difficult weaning from mechanical ventilation

目的 探讨药物干预治疗对撤机困难患者的临床价值。方法 采用前瞻性随机对照单盲研究，选择2008年1月至2013年12月北京大学第三医院危重医学科120例撤机困难的患者，按照计算机生成的随机数字表将患者分为治疗组和对照组，每组60例。治疗组患者在撤机前3 d开始每日应用呋塞米控制液体负平衡直到撤机后48 h；撤机前1 d给予灌肠治疗降低腹压；撤机当日加用硝酸甘油，并给予倍他乐克或西地兰以预防和控制撤机过程中的血压升高和心率增快；拔管前2h静脉泵入微量山莨菪碱以减少气道分泌。对照组按常规撤机处理。比较两组患者研究开始时的心率、呼吸频率（RR）、平均动脉压（MAP）、脉搏血氧饱和度（SpO2）、血气指标、血红蛋白（HG）、白蛋白（ALB）、肌酐（Cr）；撤机困难的原因、镇静或镇痛药物的选择、撤机前腹胀情况和拔管前吸痰间隔时间；研究开始至撤机前、撤机后24 h和48 h的液体平衡情况，纳入研究后自主呼吸试验（SBT）失败次数、机械通气时间和重症监护病房（ICU）治疗时间以及住院期间总机械通气时间和ICU总治疗时间。结果 两组患者研究开始时心率、RR、MAP、SpO2、血气指标、HG、ALB、Cr比较差异均无统计学意义。两组患者撤机困难的主要原因均为气道和呼吸功能障碍、心功能不全、中枢神经系统功能障碍。治疗组患者使用丙泊酚联合右美托咪定治疗的比例明显高于对照组〔16.7%（10/60）比1.7%（1/60），χ^28.107，P＝0.004〕，而两组患者其余镇静、镇痛用药方案比较差异无统计学意义。治疗组撤机前的腹胀比例明显低于对照组〔10.0%（6/60）比25.0%（15/60），χ^24.675，P＝0.031〕，拔管前吸痰间隔时间较对照组明显延长〔h：1（1，2）比1（1，1），Z＝-2.209，P＝0.027〕，纳入研究后的SBT失败次数明显少于对照组〔次：0（0，1）比1（1，2）， Z＝-6.561，P＝0.000〕。治疗组研究开始至撤机前、撤机后24 h及48 h液体平衡量均少于对照组〔撤机前：-567.71（-755.95，-226.41）比1256.76（472.48，1796.63），Z＝-9.038，P＝0.000；撤机后24 h：-5.03（-530.28，245.09）比342.28（125.36，613.25），Z＝-4.711，P＝0.000；撤机后48 h：115.50（-450.26，485.00）比330.00（16.25，575.25），Z＝-1.932，P＝0.053〕。与对照组比较，治疗组纳入研究后的机械通气时间〔d：1.0（1.0，2.0）比2.0（2.0，3.0），Z＝-6.545，P＝0.000〕、ICU治疗时间〔d：3.0（3.0，4.0）比4.0（4.0，5.0），Z＝-6.545，P＝0.000〕以及住院期间总机械通气时间〔d：8.0（6.0，12.0）比11.0（8.0，15.0），Z＝-4.091，P＝0.000〕、ICU总治疗时间〔d：12.5（9.2，19.0）比17.0（12.0，29.5），Z＝-2.722，P＝0.006〕均明显缩短。结论 药物辅助治疗有助于撤机困难患者尽早撤机，并能缩短撤机过程，减少机械通气时间及ICU治疗时间；在镇静药物的选择上，丙泊酚联合右美托咪定更有助于撤机。

Objective To investigate the value of drug intervention for difficult weaning from mechanical ventilation. Methods A prospective single-blind randomized controlled trial was conducted. 120 patients with difficult weaning from mechanical ventilation encountered in Department of Critical Care Medicine of Peking University Third Hospital from January 2008 to December 2013 were included,and the patients were divided into treatment group and control group according to random number table,with 60 cases in each group. Patients received furosemide therapy in the treatment group 3 days before weaning up to 48 hours after weaning in order to control negative liquid balance. Enema was given the day before weaning to reduce abdominal pressure. On the weaning day,all of the patients received nitroglycerin and beta blocker or cedilanid to prevent or control elevation of blood pressure and heart rate in the process of weaning. All patients in treatment group received anisodamine in small dosage 2 hours before extubation.The patients in control group received conventional treatment without drug intervention. Baseline indexes of two groups were compared,including the heart rate,respiration rate（RR）,mean arterial pressure（MAP）,pulse blood oxygen saturation（SpO2）,blood gas,hemoglobin（HG）,albumin（ALB）and creatinine（Cr）. The main reasons of difficulty in weaning,sedative and analgesic drug selection,presence of abdominal discomfort before weaning,interval between sputum suction before extubation,liquid balance at the beginning of the investigation and at time of weaning,24 hours and 48 hours after weaning,failures of spontaneous breathing test（SBT）,length of mechanical ventilation,length of ICU stay,and total length of mechanical ventilation and total length of ICU stay during hospitalization. Results There was no statistically significant difference in the heart rate,RR,MAP,SpO2,blood gas,HG,ALB,Cr at the beginning of the investigation between the two groups. The main reasons for difficult weaning in both groups of patients were respiratory dysfunction,cardiac insufficiency,and central nervous system dysfunction. The use of propofol combined dexmedetomidine in the treatment group was more frequent than the control group〔16.7%（10/60）vs. 1.7%（1/60）,χ^28.107,P=0.004〕,and there was no statistically significant difference in the use of other combinations of sedative drugs between the two groups. Abdominal discomfort before weaning was milder in treatment group as compared with control group〔10.0%（6/60）vs. 25.0%（15/60）,χ^24.675,P=0.031〕. The interval between sputum suction before extubation in the treatment group was significantly longer than that of the control group〔hours：1（1,2）vs. 1（1,1）,Z=-2.209,P= 0.027〕. SBT failure was less frequent in treatment group compared with control group〔times：0（0,1）vs. 1（1,2）,Z=-6.561,P=0.000〕. Liquid balance was better in the treatment group than the control group at time of weaning,24 hours and 48 hours after weaning〔at time of weaning：-567.71 （-755.95,-226.41）vs. 1 256.76（472.48,1 796.63）,Z=-9.038,P=0.000;24 hours after weaning：-5.03 （-530.28,245.09）vs. 342.28（125.36,613.25）,Z=-4.711,P=0.000;48 hours after weaning：115.50（-450.26, 485.00）vs. 330.00（16.25,575.25）,Z=-1.932,P=0.053〕. Compared with control group,length of mechanical ventilation〔days：1.0（1.0,2.0）vs. 2.0（2.0,3.0）,Z=-6.545,P=0.000〕,ICU stay time〔days：3.0（3.0,4.0） vs. 4.0（4.0,5.0）,Z=-6.545,P=0.000〕,and total length of mechanical ventilation〔days：8.0（6.0,12.0）vs. 11.0（8.0,15.0）,Z=-4.091,P=0.000〕and total length of ICU stay during hospitalization〔days：12.5（9.2,19.0） vs. 17.0（12.0,29.5）,Z=-2.722,P=0.000〕were all significantly shorter in the treatment group. Conclusions Adjuvant drugs therapy is helpful in patients weaning from the mechanical ventilation,and can shorten length of mechanical ventilation and ICU stay time. Propofol,combined dexmedetomidine,is helpful for weaning.