不同剂量比例的纳络酮与吗啡合用于手术后硬膜外镇痛的临床观察

目的探讨将吗啡与小剂量纳络酮按不同比例混合作患者硬膜外术后镇痛（CEA＋PCEA模式）效果。方法选择90例ASAⅠ～Ⅲ级行择期下腹部手术、术后硬膜外镇痛的患者,随机分为A、B、C三组,每组各30例（n=30）。三组的镇痛配方中布比卡因与吗啡用量相同,A、B两组中纳络酮／吗啡的比例分别为1／50与1／100．C组不加纳络酮;观察术后48h内各组患者的副作用、镇痛以及呼吸抑制等情况。结果（1）恶心呕吐：在术后3—36小时内,A组明显轻于C组（P〈0．05）。（2）瘙痒：在术后大部分时间内（6～36h）C组均重于A、B两组（P〈0．05）。（3）三组患者术后的疼痛程度大致相当（P〉0．05）,三组患者术后神志、下肢活动及呼吸情况均未见异常。结论剂量比例为1／50的纳洛酮与吗啡合用于患者硬膜外镇痛,有明显减少恶心呕吐、瘙痒等吗啡的副作用．同时不影响患者的镇痛效果以及神志、下肢活动与呼吸情况。     

Depression of sighing in the first three postoperative days with epidural morphine analgesia

We have studied the effect of spontaneous sighs on maintaining arterial oxygenation in patients receiving epidural morphine for analgesia after upper abdominal surgery. Sixteen patients scheduled for elective gastrectomy were monitored continuously with pulse oximetry and respiratory inductive plethysmography (RIP) during one night preoperatively and for 60 h postoperatively with repeate arterial blood gas analysis. An average of 3.1±1.2 (±SD) sighs were observed per hour preoperatively during sleep while postoperative sighs were significantly depressed to an average less than one per hour throughout the 60 h of the monitoring period (P<0.05). Although postoperative Pao₂ values were significantly lower than preoperative values, there was no correlation between the decreases in Pao₂ values and number of sighs. Thus, it is unlikely that the long-term absence of spontaneous sighs observed may serve as a contributing factor for the long-lasting hypoxemia in the postoperative period.     

低背景剂量联合大剂量PCA在产妇硬膜外分娩镇痛中的应用

目的观察在持续输注联合硬膜外自控给药模式下低背景剂量持续输注联合大剂量PCA的参数设置对分娩镇痛临床效果的影响。方法选择自愿接受分娩镇痛足月、单胎和头位初产妇120例,年龄25~35岁,体重58~86kg,ASAⅠ或Ⅱ级,随机分为两组:常规组(A组)和低背景剂量组(B组)。在宫口扩张2~3cm时采用硬膜外分娩镇痛。每组均事先配置硬膜外注射混合液0.1%罗哌卡因+2μg/ml芬太尼100ml。A组为常规组,背景剂量6ml/h,PCA 5ml,间隔40min;B组为低剂量组,背景剂量2ml/h,PCA 10ml,间隔为40min。记录产妇镇痛前、镇痛后10min、30min、1h、2h、宫口开全时和分娩时VAS评分及改良Bromage评分;记录PCA追加次数;记录爆发痛例数;记录硬膜外混合液的用量;记录镇痛时间、产程时间、分娩方式;记录不良反应的发生情况和新生儿Apgar评分。结果镇痛期间两组产妇VAS评分差异无统计学意义;接受镇痛期间B组混合液用量(40.5±7.5)ml;明显少于A组(60.3±12.0)ml(P0.05);B组PCA实际追加次数(1.6±0.9)次明显少于A组(3.0±1.8)次(P0.05)。两组产妇的产程、镇痛时间、爆发痛例数、不良反应发生率、产妇分娩方式和新生儿Apgar评分差异无统计学意义。结论采用低背景剂量(2ml/h)联合大剂量PCA(10ml,间隔40min)的硬膜外自控镇痛参数设置不仅没有降低镇痛效果,还可减少硬膜外腔用药总量。     

Continuous epidural infusion of bupivacaine and morphine for postoperative analgesia after hysterectomy

The analgesic efficacy and side-effects of combined epidural infusion of bupivacaine and morphine, in comparison with these drugs alone, for postoperative analgesia after hysterectomy (60 patients) were evaluated. Before general anaesthesia, all patients had an epidural catheter placed (Th11-12) and 20 ml of 0.5%, bupivacaine was injected. In random order, epidural infusion was continued for 24 h with either 0.25% bupivacaine 4 ml.h-1 (BUPI-group), a bolus of 2 mg of morphine followed by morphine 0.2 mg.h-1 (MO-group), or a combination of the two drugs (COMB-group). A urinary bladder catheter was kept for 24 h. Supplementary postoperative pain medications were i.m. morphine 0.1 mg.kg-1 or rectal indomethacin 50 mg, on request. Immediately after awakening from general anaesthesia and transfer to the recovery room, 18/20 of the BUPI-group patients, 17/20 of the MO-group patients and 19/20 of the COMB-group patients were pain-free. In the postoperative evening and the first postoperative morning, the corresponding figures were 7/20 and 10/20 in the BUPI-group, 15/20 and 15/20 in the MO-group, and 18/20 and 15/20 in the COMB-group (postop, evening; P less than 0.01 BUPI vs. others). The number of patients requiring supplementary analgesics (morphine and indomethacin during the first 24 h was greatest in the BUPI-group P less than 0.01). The number of patients who vomited during the 24-h period was 3 in the BUPI-group, 9 in the MO-group and 5 in the COMB-group.(ABSTRACT TRUNCATED AT 250 WORDS)     

腰椎后路手术三种术后镇痛方式的比较分析

目的本研究对三种后路腰椎手术后疼痛控制的方法的镇痛效果和恶心呕吐(PONV)的情况进行观察比较。方法选取2013-2015间的65例患者,均行单节段腰椎后路减压融合内固定术。术后疼痛控制,20例接受小剂量吗啡硬膜外缓释法,22例患者接受了静脉自控镇痛泵,23例患者接受哌替啶注入。患者的评级疼痛强度(视觉模拟量表得分从0(没有痛苦)到10(最多剧烈的疼痛),恶心(从0(没有恶心)到10(严重恶心)),和呕吐(从0(没有呕吐)到10(严重呕吐)),记录术后4 h,1 d,2 d,3 d的数据。结果硬膜外小剂量吗啡缓释组和静脉自控镇痛泵组相比哌替啶组的镇痛增强效果在术后1 d和2 d无明显差异(P0.05)。在术后1 d、2 d和3 d,恶心、呕吐(PONV)并发症静脉自控镇痛泵组比其他两组更严重(P0.05)。结论硬膜外小剂量吗啡缓释法能够有效的控制腰椎后路手术术后的疼痛并最小化恶心呕吐(PONV)的程度。     

硬脂酸纳米吗啡用于硬膜外镇痛的实验研究

目的 观察硬脂酸纳米吗啡(SLN-M)单次注入大鼠硬膜外腔后的镇痛效应.方法 选择硬膜外置管后无神经损伤症状的SD雄性大鼠50只,随机均分为五组.A组(假给药组):经硬膜外腔给予硬脂酸纳米(SLN);B1组与B2组:分别给予0.2及1 mg普通吗啡;C1组与C2组:分别给予含0.2及1 mg吗啡的SLN-M.用药后测定热痛阈值评价镇痛效果,以最大镇痛效应(MPE)表示,以SpO2、角膜反射的变化、僵直症的发生率对药物不良反应进行评估.结果 B1与C1组及B2与C2组的MPE最高值差异无统计学意义.但随时间延长,B1与B2组MPE逐渐下降,12 h后开始显著低于C1与C2组(P＜0.05).B1与B2组达到MPE最高值的时间显著快于C1与C2组(P＜0.05),但持续时间显著缩短(P＜0.05).B1与B2组SpO2显著低于C1与C2组(P＜0.05),角膜反射的变化和僵直症的发生率要高于C1与C2组(P＜0.05),且与吗啡剂量呈正相关.结论 硬膜外腔单次给予SLN-M后可达到与普通吗啡一样的镇痛效果,有效镇痛时间明显延长,不良反应显著降低.     

鞘内注射吗啡用于胸腔镜肺叶切除术患者术后镇痛的半数有效剂量

目的 探讨鞘内注射吗啡（ITM）用于胸腔镜肺叶切除术患者术后镇痛的半数有效剂量（ED50）。
方法 选择拟行全麻下胸腔镜肺叶切除术患者22例,年龄35～64岁,BMI 18～30 kg/m²,ASA Ⅰ或Ⅱ级。所有患者于术前在L_2-3间隙行蛛网膜下腔穿刺。患者鞘内吗啡的初始给药剂量为5 μg/kg,相邻药物剂量比值为1∶1.1,剂量梯度依次为5.00、4.55、4.14、3.76、3.42、3.11 μg/kg。根据上一例患者术后镇痛效果,下一例患者上升或下降一个剂量梯度。术后镇痛有效标准：若术后6、12、24、48 h活动时VAS疼痛评分均≤3分,则认为术后镇痛有效;若任一时刻活动时VAS疼痛评分＞3分,则认为镇痛无效。采用Probit法计算ED50、ED95及其95%可信区间（CI）。记录呼吸抑制、恶心呕吐、皮肤瘙痒、尿潴留等不良反应的发生情况。
结果 ITM用于胸腔镜肺叶切除术的ED50为3.468 μg/kg（95%CI 2.926～3.782 μg/kg）,ED95为4.037 μg/kg（95%CI 3.746～7.127 μg/kg）。有2例（9%）出现皮肤轻微瘙痒,3例（14%）出现恶心呕吐,未观察到其他不良反应发生。
结论 鞘内注射吗啡用于胸腔镜肺叶切除术的ED50为3.468 μg/kg（95%CI 2.926～3.782 μg/kg）。     

Low doses of epidural ketamine or neostigmine, but not midazolam, improve morphine analgesia in epidural terminal cancer pain therapy

Study Objective: To examine analgesia and adverse effects of combination epidural pain therapy consisting of administration of morphine with either low dose of ketamine, neostigmine, or midazolam in terminal cancer pain patients.

Design: Randomized double-blind study.

Setting: Teaching hospital.

Patients: 48 terminal cancer patients suffering from chronic pain.

Interventions: Patients were randomized to one of four groups (n = 12). The concept of visual analog scale (VAS), which consisted of a 10-cm line with 0 equaling “no pain at all” and 10 equaling “the worst possible pain” was introduced. All patients were taking oral amitriptyline 50 mg at bedtime. Pain was initially treated with epidural morphine 2 mg twice daily (12-hr intervals) to maintain the VAS below 4/10. Afterwards, VAS scores ≥4/10 at any time were treated by adding the epidural study drug (2 ml), which was administered each morning, just after the 2-mg epidural morphine administration. The control group (CG) received 2 mg of epidural morphine (2 ml). The ketamine group (KG) received 0.2 mg/kg epidural ketamine (2 ml). The neostigmine group (NG) received 100 μg epidural neostigmine (2 ml). The midazolam group (MG) received 500 μg epidural midazolam (2 ml). Patients received the study drugs on a daily basis.

Measurements and Main Results: Duration of effective analgesia was measured as time from the study drug administration to the first patient’s VAS score ≥4/10 recorded in days. The groups were demographically the same. The VAS pain scores prior to the treatment were also similar among groups. Only the patients in the KG demonstrated lower VAS scores compared to the MG (p = 0.018). Time since the epidural study drug administration until patient complaint of pain VAS ≥4/10 was higher for both the KG and NG compared to the CG (KG > CG, p = 0.049; NG > CG; p = 0.0163). Only the KG used less epidural morphine compared to the CG during the period of study (25 days) (p = 0.003).

Conclusion: The association of either low-dose epidural ketamine or neostigmine (but not midazolam) to epidural morphine increased the duration of analgesia in the population studied (gt;20 days) compared to the CG and MG (8 to 10 days) when administered in the early stages of terminal cancer pain therapy, without increasing the incidence of adverse effects.     

2-chloroprocaine antagonism of epidural morphine analgesia

Background: 2-chloroprocaine (2-CP) used for lumbar epidural anesthesia (LEA) reportedly decreases the efficacy of epidural morphine (EM) administered for post-cesarean section (CS) analgesia. The amount of supplemental i.v. morphine self-administered by the patient via the patient-controlled analgesia device (PCA) is used to study the interaction between EM and 2-CP.
Methods: Forty-two patients scheduled for elective CS were randomly divided into 3 equal groups, and received 2-CP, 2-CP+epinephrine (Epi, 5 μg ml^-1) or 2% lidocaine (Lido) with Epi for LEA. All patients received 5 mg EM and i.v. PCA morphine for postoperative pain. Cumulative amount of i.v. morphine used in the first 24 hours as well as the amount of the drug used during each 2-h period were noted. Nonparametric analysis of variance and Chi-squared analysis were used for statistical comparisons.
Results: The mean cumulative 24-h i.v. PCA morphine requirement in the 2-CP, 2-CP+Epi and Lido+Epi groups respectively was 20.5±24, 33.1.5±27 and 4.07±6.3 (mean±SD). The Lido+Epi group used significantly less morphine ( P = 0.01) compared to either of the 2-CP groups with no significant difference between the 2-CP groups. The maximum i.v. PCA morphine use occurred in the first 4 hours following surgery in all three groups.
Conclusion: Analgesic efficacy of EM is decreased when 2-CP is used for LEA compared to when Lido+Epi is used.     

单次剂量吗啡复合罗比卡因用于剖宫产术后PCEA的效果评价

目的 用单次剂量吗啡复合持续剂量不同浓度罗比卡因应用于剖宫产术后硬膜外自控镇痛（patient controlled epidural analgesia,PCEA)，与持续剂量吗啡和罗比卡因相比较，寻求一种减少吗啡用量，更适合下腹部手术的硬膜外自控镇痛方法。方法 80例ASAⅠ-Ⅱ级行子宫下段剖宫产的产妇，随机分为四组，单次剂量吗啡分三组；SMR0.1组，0.1%罗比卡因；SMR0.2组，0.2%罗比卡因，SMR0.05组，0.05%罗比卡因，三组均先单次静注吗啡1mg 氟哌利多持续硬膜外给药，观察产妇24小时内VAS，镇静评分，Prine Henry评分，改良Bromage分级的变化，PONV等不良反应的发生率，记录产妇24小时内用药量。结果 VAS评分；CM组，SMR0.2组大于SMR0.1组，SM0.05组和CM组。SMR0.1组，SMR0.05组尿潴留，排气时间延长发生率明显低于SMR0.2组，CM组，结论 1mg吗啡单次给药复合维持剂量0.1%罗比卡因用于剖宫产术后PCEA能够取得良好的镇痛效果。感觉-运动阻滞分离效果好，不良反应少。     

维拉帕米在硬膜外术后镇痛中对吗啡的增效作用

目的　比较硬膜外单独注射吗啡与吗啡加维拉帕米在术后镇痛方面的疗效。方法　2 70例在硬膜外麻醉下行腹部手术的患者 ,随机分为三组 ,吗啡加维拉帕米组 (MV组 )、吗啡 1mg组(M 1组 )、吗啡 2mg组 (M2组 ) ,每组 90例。MV组 :吗啡 1mg +维拉帕米 0 2 5mg +0 9%NaCl稀释到 10ml;M 1组 :吗啡 1mg +0 9%NaCl稀释到 10ml;M2组 :吗啡 2mg +0 9%NaCl稀释到10ml。均于手术结束时由硬膜外导管缓慢注入硬膜外腔。观察 15min后拔除硬膜外导管送回病房。手术后 12、2 4、4 8h记录疼痛评分 (VAS)、平均动脉压和呼吸频率、脉搏血氧饱和度 ,以及尿潴留、恶心、呕吐等不良反应情况。结果　术后 4 8h内MV组镇痛效果明显优于M 1组 (P <0 0 5 ) ,与M2组相近 (P >0 0 5 ) ,但不良反应发生率MV组明显低于M2组 (P <0 0 1)。三组的呼吸循环及脉搏血氧饱和度无显著差异。结论　维拉帕米在硬膜外术后镇痛中对吗啡有增效作用 ,可减少吗啡的用量 ,从而减少吗啡的不良反应 ,并取得良好的术后镇痛效果     

静脉注射吗啡病人自控镇痛与经硬膜外吗啡镇痛的观察

目的:比较术后静脉注射吗啡病人自控镇痛与硬膜外吗啡镇痛的临床效果和安全性。方法:60例在硬膜外麻醉下行妇科手术的患者随机分为硬膜外吗啡镇痛(EPI)组和静脉注射吗啡病人自控镇痛(PCIA)组。EPI组在手术结束时经硬膜外导管一次性注入吗啡2mg,PCIA组在术后患者感觉到疼痛时。自行给药镇痛,给药剂量每次1mg,锁定时间为5分钟。术后4、8、12、24小时进行随访并记录吗啡用药量、疼痛评分(VAPS)、平均动脉压和呼吸频率、镇静程度及恶心、呕吐等副作用情况。结果:术后24小时用药总量PCIA组(19.1±5.1mg)明显高于EPI组(2mg)。术后0～12小时EPI组镇痛效果优于PCIA组,镇静程度PCIA组高于EPI组。PCIA组恶心、呕吐发生率均高于EPI组,皮肤瘙痒EPI组2例,PCIA组1例。两组患者对术后镇痛总体满意度评估良好至优秀者百分率无显著性差异。两组患者术后呼吸频率及平均动脉压均在正常范围。结论:对于硬膜外麻醉术后需短期镇痛患者,单次剂量硬膜外吗啡镇痛效果优于PCIA组,副作用较少。     

不含局麻药单用吗啡行术后硬膜外持续镇痛的可行性

吗啡配伍局麻药行术后硬膜外持续镇痛已广泛应用于临床,目前一般认为,配伍局麻药可以减少吗啡的用量,从而降低吗啡的不良反应（如呼吸抑制、恶心呕吐、皮肤瘙痒、尿潴留等）,3年来我们在术后硬膜外镇痛病人中,观察和探讨较低剂量的吗啡不含局麻醉药是否也可达到良好的镇痛效果,同时针对性地应用一些药物如恩丹西酮、苯海拉明、胃复安、地塞米松等,试图降低吗啡不良反应的发生率。     

罗比卡因背景输注下有或无吗啡负荷剂量对硬膜外PCA效应影响的比较

目的　研究妇科手术后病人在罗比卡因 (Rop)不同背景剂量输注下 ,有或无吗啡 (Mor)负荷剂量对硬膜外PCA效应的影响。方法　选择经腹子宫全切术病人 12 0例 (ASAⅠ～Ⅱ级 )随机分成六组 ,通过三通管硬膜外给予背景剂量 0、2、4、6、4和 6ml/h 0 2 %Rop输注 ;另一泵镇痛液为0 0 1%Mor ,前四组 (C0 、C2 、C4 、C6组 )以LP模式 (负荷剂量 +PCA)加强镇痛 ,后两组 (C4N和C6N组 )以P模式 (仅用PCA)辅助 ,观察镇痛评分、运动阻滞及不良反应等情况。结果　六组镇痛效果均达到满意程度 ,其质量分数C0 组 0 0 5 ) ;各组低血压和心动过缓发生率无统计学差异 ,均无呼吸抑制。结论　妇科经腹手术后以 0 2 %Rop 4～ 6ml/h背景剂量输注 ,可采用有或无负荷剂量模式 ,     

A comparative study of patient-controlled epidural fentanyl and single dose epidural morphine for post-caesarean analgesia

In a prospective, randomized, double-blinded study, 23 patients who had undergone Caesarean delivery under epidural anaesthesia were assessed to evaluate the effectiveness of patientcontrolled epidural analgesia (PCEA) with fentanyl compared with a single dose of epidural morphine for postoperative analgesia. Group A (n = 11) received epidural fentanyl 100 μg intraoperatively, then self-administered a maximum of two epidural fentanyl boluses 50 μg (10 μg · ml^?1) with a lockout period of five minutes for a maximum of two doses per hour. Group B (n = 11) received a single bolus of epidural morphine 3 mg (0.5 mg · ml^?1) intraoperatively and received the same instructions as Group A but had their PCA devices filled with 0.9% NaCl. Patients were assessed up to 24 hr for pain, satisfaction with pain relief, nausea and pruritus using visual analogue scales (VAS). The treatments for inadequate analgesia, nausea and pruritus as well as time to first independent ambulation were recorded. The ventilatory response to carbon dioxide challenge was measured at four and eight hours. Pain relief, satisfaction with pain relief, and the use of supplemental analgesics were similar in both groups. The mean 24 hr dose of epidural fentanyl used by group A patients was 680 μg. Pruritus was less common in Group A patients at the 8 and 24 hr observation periods (P < 0.0125). Both groups experienced the same degree of nausea and clinically unimportant respiratory depression. We conclude that PCEA with fentanyl provides analgesia equal to a single dose of epidural morphine and may be suitable for patients who have experienced considerable pruritus after epidural morphine adminstration.     

Comparison of bupivacaine and fentanyl as an adjuvant of epidural morphine for postoperative analgesia

We conducted a retrospective study to determine whether bupivacaine or fentanyl is a better adjuvant to epidural morphine for postoperative analgesia using 108 patients. Following epidural lidocaine anesthesia with or without light general anesthesia for major gynecological surgeries, 59 patients received epidural morphine (EPM) 2 mg (group M), 21 patients received morphine 2 mg plus 0.25% plain bupivacaine 6–10 ml epidurally (group B), and 28 patients received morphine 2 mg plus fentanyl 100 μg epidurally (group F). The analgesic interval, defined as the duration from EPM injection to the first request of analgesics for incisional pain, was significantly longer in group F than in group M (29±11vs 19±17 h,P<0.05), but similar to group B (22±14 h). Group F patients required the least amount of analgesics for incisional pain of the three groups during the first 24 h postoperatively (P<0.01). The incidence of adverse effects was similar among all three groups. In conclusion, fentanyl appears to be a better adjuvant to epidural morphine than bupivacaine.     

Pharmacokinetics of intravenous, intrathecal and epidural morphine and fentanyl in the goat

Intrathecal and epidural catheters and an intravenous cannula were inserted in 10 goats. After administration of either morphine 4 mg, intravenously, 1 mg intrathecally or 4 and 8 mg epidurally, or fentanyl 0.1 mg intravenously, 0.05 mg intrathecally or 0.1 and 0.2 mg epidurally, venous blood and CSF were sampled at 2, 5, 10, 15, 30 min and 1, 2, 4, 6, 8 and 24 h. The concentrations of the drugs were measured by radioimmunoassay. After administration of intravenous morphine the plasma concentration-time curve fitted a 3-compartment model (body clearance = 84 +/- 23 ml/min/kg, mean +/- s.d., N = 5), while after fentanyl the plasma concentration-time curve was best described by a 2-compartment model (body clearance = 3.9-5.8 ml/min/kg, N = 3]. After intrathecal injection the elimination rates of the opioids from CSF were 0.3 to 2.0 and 0.6 to 2.4 ml/h/kg for morphine and fentanyl, respectively (N = 3). The time to reach maximum CSF concentration after epidural administration was 0.22 +/- 0.14 h for morphine (N = 6) and 0.22 +/- 0.13 h for fentanyl (N = 8). In the same goat the CSF availability was 2.3 and 11.3% for morphine and 0.8 and 3.3% for fentanyl following epidural administration of the low and high doses, respectively. After epidural administration, morphine and fentanyl are absorbed into CSF at the same rate but the relative amount of drug absorbed may be higher for morphine than fentanyl. Bulk flow is supposed to be the principal mechanism of opioid elimination from CSF.