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不同麻醉技术在改变儿童心脏手术期间应激反应中的作用:一项前瞻性、双盲、随机研究。

The role of different anesthetic techniques in altering the stress response during cardiac surgery in children: a prospective, double-blinded, and randomized study.

机构信息

Department of Anesthesiology and Pediatrics, The Ohio State University, Columbus, OH, USA.

出版信息

Pediatr Crit Care Med. 2013 Jun;14(5):481-90. doi: 10.1097/PCC.0b013e31828a742c.

Abstract

OBJECTIVES

Our goal was to evaluate the role of three anesthetic techniques in altering the stress response in children undergoing surgery for repair of congenital heart diseases utilizing cardiopulmonary bypass in the setting of fast tracking or early tracheal extubation. Furthermore, we wanted to evaluate the correlation between blunting the stress response and the perioperative clinical outcomes.

DESIGN

Prospective, randomized, double-blinded study.

SETTING

Single center from December 2008 to May of 2011.

PATIENTS

Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied between ages 30 days to 3 years old who were scheduled to undergo repair for a ventricular septal defect, atrioventricular septal defect, or Tetralogy of Fallot.

METHODS

Children undergoing surgical repair of congenital heart disease were randomized to receive low-dose fentanyl (10 mcg/kg; low-dose fentanyl), high-dose fentanyl (25mcg/kg; high-dose fentanyl), or low-dose fentanyl plus dexmedetomidine (as a 1 mcg/kg loading dose followed by infusion at 0.5mcg/kg/hr until separation from cardiopulmonary bypass. In addition, patients received a volatile anesthetic agent as needed to maintain hemodynamic stability. Blood samples were tested for metabolic, hormonal and cytokine markers at baseline, after sternotomy, after the start of cardiopulmonary bypass, at the end of the procedure and at 24 hours postoperatively.

MEASUREMENTS AND MAIN RESULTS

Forty-eight subjects (low-dose fentanyl plus placebo, n = 16; high-dose fentanyl plus placebo, n = 17; low-dose fentanyl plus dexmedetomidine, n = 15) were studied. Subjects in the low-dose fentanyl plus placebo group had significantly higher levels of adrenocorticotropic hormone, cortisol, glucose, lactate, and epinephrine during the study period. The lowest levels of stress markers were seen in the high-dose fentanyl plus placebo group both over time (adrenocorticotropic hormone, p= 0.01; glucose, p = 0.007) and at individual time points (cortisol and lactate at the end of surgery, epinephrine poststernotomy; p < 0.05). Subjects in the low-dose fentanyl plus dexmedetomidine group had lower lactate levels at the end of surgery compared with the low-dose fentanyl plus placebo group (p < 0.05). Although there were no statistically significant differences in plasma cytokine levels between the three groups, the low-dose fentanyl plus placebo group had significantly higher interleukin-6:interleukin-10 ratio at 24 hours postoperatively (p < 0.0001). In addition, when compared with the low-dose fentanyl plus placebo group, the low-dose fentanyl plus dexmedetomidine group showed a lower norepinephrine level from baseline at poststernotomy, after the start of cardiopulmonary bypass, and at the end of surgery (p ≤ 0.05). Subjects in the low-dose fentanyl plus placebo group had more postoperative narcotic requirement (p = 0.004), higher prothrombin time (p ≤ 0.03), and more postoperative chest tube output (p < 0.05). Success of fast tracking was not significantly different between groups (low-dose fentanyl plus placebo 75%, high-dose fentanyl plus placebo 82%, low-dose fentanyl plus dexmedetomidine 93%; p = 0.39).

CONCLUSIONS

The use of low-dose fentanyl was associated with the greatest stress response, most coagulopathy, and highest transfusion requirement among our cohorts. Higher dose fentanyl demonstrated more favorable blunting of the stress response. When compared with low-dose fentanyl alone, the addition of dexmedetomidine improved the blunting of the stress response, while achieving better postoperative pain control.

摘要

目的

我们的目标是评估三种麻醉技术在加速康复或早期气管拔管条件下,对接受体外循环先天性心脏病修复手术的儿童应激反应的影响。此外,我们还想评估应激反应减弱与围手术期临床结果之间的相关性。

设计

前瞻性、随机、双盲研究。

地点

2008 年 12 月至 2011 年 5 月的单中心。

患者

48 名患者(小剂量芬太尼加安慰剂组,n = 16;高剂量芬太尼加安慰剂组,n = 17;小剂量芬太尼加右美托咪定组,n = 15),年龄在 30 天至 3 岁之间,计划接受室间隔缺损、房室隔缺损或法洛四联症修复手术。

方法

接受先天性心脏病手术修复的儿童被随机分为小剂量芬太尼(10 mcg/kg;小剂量芬太尼)、高剂量芬太尼(25 mcg/kg;高剂量芬太尼)或小剂量芬太尼加右美托咪定(负荷剂量为 1 mcg/kg,然后以 0.5 mcg/kg/hr 的速度输注,直至与体外循环分离。此外,患者需要接受挥发性麻醉剂以维持血流动力学稳定。在基线、胸骨切开后、体外循环开始后、手术结束时和术后 24 小时测试血液样本的代谢、激素和细胞因子标志物。

测量和主要结果

48 名患者(小剂量芬太尼加安慰剂组,n = 16;高剂量芬太尼加安慰剂组,n = 17;小剂量芬太尼加右美托咪定组,n = 15)参与了研究。小剂量芬太尼加安慰剂组在研究期间的应激激素如促肾上腺皮质激素、皮质醇、葡萄糖、乳酸和肾上腺素水平明显更高。高剂量芬太尼加安慰剂组的应激标志物水平最低,无论是在时间上(促肾上腺皮质激素,p = 0.01;葡萄糖,p = 0.007)还是在各个时间点(皮质醇和乳酸在手术结束时,肾上腺素在胸骨切开后;p < 0.05)。小剂量芬太尼加右美托咪定组在手术结束时的乳酸水平低于小剂量芬太尼加安慰剂组(p < 0.05)。尽管三组之间的血浆细胞因子水平没有统计学上的显著差异,但小剂量芬太尼加安慰剂组在术后 24 小时的白细胞介素-6:白细胞介素-10 比值明显更高(p < 0.0001)。此外,与小剂量芬太尼加安慰剂组相比,小剂量芬太尼加右美托咪定组在胸骨切开后、体外循环开始后和手术结束时的去甲肾上腺素水平更低(p ≤ 0.05)。小剂量芬太尼加安慰剂组的术后阿片类药物需求更多(p = 0.004),凝血酶原时间更长(p ≤ 0.03),术后胸腔引流更多(p < 0.05)。各组的快速康复成功率无显著差异(小剂量芬太尼加安慰剂组 75%,高剂量芬太尼加安慰剂组 82%,小剂量芬太尼加右美托咪定组 93%;p = 0.39)。

结论

与我们的队列中的其他组相比,小剂量芬太尼与最大的应激反应、最严重的凝血障碍和最高的输血需求相关。高剂量芬太尼表现出更有利的应激反应减弱。与单独使用小剂量芬太尼相比,添加右美托咪定可改善应激反应减弱,同时实现更好的术后疼痛控制。

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