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医药导报, 2017, 36(4): 417-419
doi: 10.3870/j.issn.1004-0781.2017.04.015
氢吗啡酮超前镇痛对妇科腔镜手术应激反应的影响
Pre-emptive Analgesia Effects of Hydromorphone on Stress Reaction in Patients Undergoing Gynecological Laparoscopic Surgery
张杨1,, 丁楠楠2,, 徐阳1, 吴金晶1

摘要:

目的 观察氢吗啡酮超前镇痛对妇科腔镜手术应激反应的影响。方法 择期全麻下行全子宫切除术患者40例,年龄45~58岁,ASA分级Ⅰ或Ⅱ级,体重指数18~24 kg·(m2)-1,采用随机数字表法分为治疗组和对照组(n=20)。治疗组患者麻醉前静脉注射氢吗啡酮1 mg ,两组患者常规诱导、插管,术中持续泵注瑞芬太尼0.2 μg·min-1·kg-1,异丙酚0.1 mg·min-1·kg-1,间断推注顺式阿曲库铵,缝皮时停止泵注瑞芬太尼和丙泊酚。记录入手术室(t1)、气腹前(t2)、气腹后1 h(t3)、患者清醒拔管时(t4)血浆肾上腺素(E)和去甲肾上腺素(NE)的浓度,手术结束至拔管时间、拔管时患者心率、血压。结果 两组患者手术后拔管时间无差异,治疗组苏醒期心率、收缩压低于对照组(P<0.05)。t2、t3、t4时两组患者E值和NE值均高于t1浓度(P<0.05),但3个时间段治疗组E值和NE值低于对照组(P<0.05)。结论 氢吗啡酮超前镇痛能够减少妇科腔镜手术患者E和NE释放,不影响全麻苏醒时间,能够减小拔管时心率、血压上升幅度。

关键词: 氢吗啡酮 ; 超前镇痛 ; 应激反应 ; 腹腔镜手术

Abstract:

Objective To investigate the pre-emptive analgesia effects of hydromorphone on stress reaction in patients undergoing gynecological laparoscopic surgery. Methods Forty ASA Ⅰ or Ⅱ patients [age: 45-58 years, body mass index: 18-24 kg·(m2)-1] undergoing gynecological laparoscopic surgery were randomly divided into 2 groups (n=20 for each group): treatment group and control group. Hydromorphone (1 mg) was intravenously injected before anesthesia in treatment group. In the two groups, after routine induction and incubation, remifentanil (0.2 μg·min-1·kg-1) and propofol (0.1 mg·min-1·kg-1) were injected with micro perfusion pump, cisatracurium was injected intermittently. Injection of remifentanil and propofol was stopped when skin suture started. The concentrations of epinephrine(E) and norepinephrine(NE) were obtained before induction (t1), pneumoperitoneum (t2), 1 h after pneumoperitoneum (t3) and extubation (t4), respectively. The heart rate, blood pressure and the time of operation to extubation of the patients were recorded. Results There were no significant changes in extubation time after operation among the groups. Heart rate and systolic blood pressure were significantly lower in the treatment group than in the control group (P<0.05). Plasma E and NE levels at t1 were significantly lower than those at t2 ,t3 and t4. Plasma E and NE were significantly lower in treatment group than that of control group at t2, t3 and t4 (P<0.05). Conclusion Pre-emptive analgesia of hydromorphone can significantly decrease the release of epinephrine and norepinephrine during and after laparoscopic surgery, restrain the increase of heart rate and systolic blood pressure during extubation, without influence of revival time.

Key words: Hydromorphone ; Pre-emptive analgesia ; Stress reaction ; Laparoscopic surgery

超前镇痛是在患者受到手术刺激之前,通过防止外周神经和中枢神经系统敏感化,来阻止伤害性刺激传导,减轻手术所造成的应激反应。笔者通过妇科腔镜手术患者注射氢吗啡酮进行超前镇痛,探讨其对手术应激反应的影响,评价其在临床中应用的价值。

1 资料与方法
1.1 临床资料

择期拟在全身麻醉下行腹腔镜下子宫肌瘤剥除术患者40例,年龄45~58岁,术前美国麻醉医师协会(American Society of Anesthesiologist,ASA)分级Ⅰ或Ⅱ级,体重指数(body mass index,BMI)18~24 kg·(m2)-1。入选患者均无中枢神经系统疾病;无高血压、心脏病史;无酒精滥用史、无阿片类药物依赖史。本研究经湖北医学院附属襄阳医院伦理委员会批准,入选患者签署知情同意书。采用随机数字表法,将患者随机分为治疗组和对照组各20例。两组患者年龄、体质量、手术时间、心率、收缩压等差异无统计学意义(P>0.05)。见表1。

表1 两组患者一般资料比较
Tab.1 Comparison of baseline data between two groups of patientsヌ±s,n=20
组别 年龄/岁 体质量/kg 手术时间/min 心率/(次·min-1) 收缩压/mmHg
对照组 54.21±3.45 54.45±5.63 75.45±13.34 80.45±5.33 109.45±14.45
治疗组 53.14±3.36 55.45±6.74 87.28±11.85 76.45±4.76 114.28±17.67

表1 两组患者一般资料比较

Tab.1 Comparison of baseline data between two groups of patientsヌ±s,n=20

1.2 治疗方法

麻醉前禁食禁水8 h,均未使用术前药。入室监测心电图、血压(blood pressure,BP)、心率(heart rate,HR)、血氧饱和度(blood oxygen saturation,SpO2)、动脉穿刺置管测压。入室后麻醉前治疗组患者静脉注射盐酸氢吗啡酮注射液(宜昌人福药业有限责任公司,批准文号:国药准字H20120100,规格:2 mg)1 mg ,两组患者常规麻醉诱导,静脉注射咪达唑仑0.1 mg·kg-1、罗库溴铵0.5~0.7 mg· kg-1、丙泊酚1~2 mg· kg-1、舒芬太尼0.4~0.5 μg·kg-1诱导插管后行机械通气,设定潮气量(VT)8~10 mL·kg-1,频率12次·min-1,气腹时VT6~8 mL· kg-1,频率14次·min-1,气道压维持于0.22~0.24 kPa。两组患者术中持续泵注瑞芬太尼0.2 μg· min-1· kg-1,丙泊酚0.1 mg· min-1· kg-1,间断推注顺式阿曲库铵0.05~0.1 mg·kg-1,缝皮时停止泵注瑞芬太尼和丙泊酚。分别记录手术结束至拔管时间、拔管时患者心率、血压。在入手术室(t1)、气腹前(t2)、气腹后1 h(t3)、患者清醒拔管时(t4)分别抽取外周动脉血2 mL,装入肝素抗凝试管,送检验科用高效液相色谱仪检测血浆肾上腺素(epinephrine,E)和去甲肾上腺素(norepinephrine,NE)的浓度。

1.3 统计学方法

采用SPSS13.0版统计学软件进行分析,计量资料以均数±标准差( x ̅ ±s)表示,组间比较采用t检验,以P<0.05为差异有统计学意义。

2 结果
2.1 两组患者全麻苏醒期一般情况

对照组与治疗组手术后拔管时间比较,差异无统计学意义(t=1.735,P>0.05),治疗组苏醒期心率、收缩压低于对照组,差异有统计学意义(t=4.856,2.303,P<0.05)。见表2。

表2 两组患者全麻苏醒期一般情况比较
Tab.2 Comparison of anesthesia recovery between two groups of patients ヌ±s,n=20
组别 术后拔管
时间/min
拔管时
心率/(次·min-1)
拔管时收缩
压/mmHg
对照组 13.52±5.31 122.58±22.56 132.45±18.54
治疗组 12.21±3.52 98.33±15.72*1 124.83±16.63*1

Compared with control group,*1P<0.05

与对照组比较, *1P<0.05

表2 两组患者全麻苏醒期一般情况比较

Tab.2 Comparison of anesthesia recovery between two groups of patients ヌ±s,n=20

2.2 两组患者E和NE浓度

入室时两组E值和NE值差异无统计学意义(t=1.698,1.958,P>0.05),t2、t3、t4时两组患者E值和NE值均高于t1时浓度,差异有统计学意义(t=4.562,5.847,5.962,3.984,4.326,5.623,2.374,3.194,3.215,5.186,4.316,3.724,P<0.05),组间比较,治疗组t2、t3、t4 E值和NE值低于对照组,差异有统计学意义(t=2.574,3.128,4.695,2.894,2.626,3.143,P<0.05)。见表3。

表3 两组患者不同时间点E和NE浓度
Tab.3 Comparison of the concentration of E and NE between two groups of patients at diffenent time point ng·mL-1,ヌ±s,n=20
组别与时间 E NE
对照组
t1 88.5±40.5 369±121
t2 153.0±39.6*1 557±93*1
t3 193.0±75.6*1 839±157*1
t4 168.8±55.1*1 591±87*1
治疗组
t1 97.9±52.8 340±113
t2 125.0±49.7*1*2 469±75*1*2
t3 167.0±68.2*1*2 773±175*1*2
t4 136.2±48.2*1*2 510±62*1*2

Compared with the same group at t1,*1P<0.05;compared with control group at the same time point, *2P<0.05

与本组t1比较, *1P<0.05;与对照组同时间点比较,*2P<0.05

表3 两组患者不同时间点E和NE浓度

Tab.3 Comparison of the concentration of E and NE between two groups of patients at diffenent time point ng·mL-1,ヌ±s,n=20

3 讨论

超前镇痛主要是抑制周围组织细胞活性,充分镇痛后可以减少炎性递质释放,提高痛阈[1]。ERIKSSON等[2]观察到术前注射吗啡与术中注射吗啡相比,尽管术后镇痛药物无差异,但术前注射吗啡组术后早期血浆氢化可的松水平较低,表明术前给吗啡,能够减弱创伤性应激导致的内分泌反应。许多研究提示超前镇痛对手术镇痛效果明显,镇痛药物并发症也大大减少[3-5]

手术中通过心率、血压的变化来评价镇痛是否完全,但是存在诸如牵拉反应、肌肉收缩、心率变异性等因素的影响,因此不能完全反映体内镇痛效果。交感-肾上腺髓质兴奋所致儿茶酚胺( 肾上腺素和去甲肾上腺素等) 分泌增多,是应激反应早期敏感的主要指标之一。当体内儿茶酚胺分泌增加后,心率增加、血压增高、凝血功能紊乱,血糖升高,因此,抑制手术中的应激反应也是手术中需要关注的重要方面。

疼痛传入神经脊髓后角和胶状质含有高浓度的阿片受体。在大鼠脊髓阿片受体中大约 70%为 μ 受体, 24%为 δ 受体, 6%为κ 受体。分子生物学研究表明,人类和实验动物阿片受体分布相似。阿片类药物作为外周镇痛可能是由于μ受体激动剂可预防炎性递质所致的伤害性感受器增敏,κ受体及δ受体位于交感神经,可阻滞神经末梢缓激肽释放所致的伤害性感受器增敏。镇痛最佳方案是针对疼痛的传导途径,多种方案联合镇痛,但是临床工作中,需要全身麻醉的患者,对增加硬膜外阻滞仍有顾虑,因此笔者在本研究采用外周静脉超前镇痛对全麻手术。

氢吗啡酮作为肿瘤患者的长期疼痛治疗的替代物,虽然有阿片类药物不良反应[6],但由于其代谢物无毒,镇痛强度高于吗啡,既可以单次推注又能持续输注,可以安全应用于急性镇痛[7-8]

本研究结果表明,手术提前应用氢吗啡酮,手术后拔管时间没有延迟,而手术中治疗组苏醒期心率、收缩压低于对照组,3个时间点治疗组血浆E和NE浓度低于对照组。综上,使用氢吗啡酮超前镇痛,对抑制患者术中的应激反应有着非常好的效果,血流动力学更加稳定。但是手术中E和NE浓度依旧高于手术前,是否有更好的抑制手术中应激反应的方案,需进一步研究。

The authors have declared that no competing interests exist.

参考文献

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关键词(key words)
氢吗啡酮
超前镇痛
应激反应
腹腔镜手术

Hydromorphone
Pre-emptive analgesia
Stress reaction
Laparoscopic surgery

作者
张杨
丁楠楠
徐阳
吴金晶

ZHANG Yang
DING Nannan
XU Yang
WU Jinjing