Intercostal catheter analgesia is more efficient vs. intercostal nerve blockade for post-thoracotomy pain relief

A pain after thoracotomy may result in a postoperative hypoventilation and lead to atelectases and pneumonia. This study was aimed to compare two analgesic regimens after posterolateral thoracotomy. 80 patients (40-70 years) undergoing thoracotomy were randomized to intercostal catheter analgesia (group A, n = 40) and intercostal nerve block (group B, n = 40). Patients in group A were given 20 mL of 0.5% bupivacaine injections twice a day by intercostal catheter. Intercostal nerve blockade was performed using 5 mL of 0.5% bupivacaine. Intercostal nerve in thoracotomy wound, nerves below and above thoracotomy wound was also injected. PaO2, PaCO2, FVC, FEV1 and visual analog pain scale (VAS) were obtained preoperatively, 24, 48 and 72 hours after operation. Postoperative complications were recorded at the patient discharge. Differences between groups were calculated using Mann-Whitney, KW test and chi square test. The arterial blood gas analyses did not show statistically significant change in any group and time according to the baseline values. FVC and FEV1 decreased significantly in both groups at first postoperative day according to baseline measurements. Patients in B group had significantly higher FEV1 values in the third postoperative day (73.05 +/- 11.25 in A vs. 83.50 +/- 9.17 in B group, p < 0.05). Intercostal catheter analgesia resulted in significantly lower postoperative VAS scores and reduced opioid requirement as compared to intercostal nerve blockade. No differences in the postoperative complications were observed between groups.     

Cardiopulmonary effects of nalbuphine hydrochloride and butorphanol tartrate in sheep

The cardiopulmonary, sedative and analgesic effects of butorphanol tartrate and nalbuphine hydrochloride were evaluated in six adult crossbred Dorset sheep (Ovis aries). The animals were divided randomly into two groups of three. The first group received butorphanol tartrate (0.5mg/Kg s.c.) followed in 3 days by nalbuphine hydrochloride (1 mg/Kg, s.c.). The second group received nalbuphine followed in 3 days by butorphanol. Cardiopulmonary parameters were evaluated at baseline (once the animal had accommodated to restraint); immediately following analgesic administration; and at 15, 30, 60, 90 and 120 minutes after analgesic administration. No significant changes (alpha greater than .05) from baseline were seen in any of the measured cardiopulmonary parameters from either the butorphanol or nalbuphine groups. Butorphanol produced the most dramatic analgesic and sedative effects with onset of both within 15 minutes of administration and peak effects occurring 30 minutes post injection. The degree of analgesia was diminished at 120 minutes while the sedative effect returned to near baseline by 90 minutes. The nalbuphine group also showed an onset of analgesia 15 minutes post injection reaching a peak effect after 30 minutes. However, onset of sedation occurred 30 minutes post injection achieving a peak effect at 60 minutes which was markedly less than that of butorphanol. As in the butorphanol group, analgesia was diminished at 120 minutes.     

A comparison of pre- and post-surgical administration of bupivacaine or buprenorphine following laparotomy in the rat

The effects of bupivacaine, a long-acting local anaesthetic, and buprenorphine, an opioid analgesic, administered either pre- or post-operatively, were investigated in a rat laparotomy model. Surgical anaesthesia was induced and maintained with halothane. The type of analgesic treatment was a significant factor in the reduction in body weight and food and water intake which occurred following surgery. The largest reductions were seen in the bupivacaine-treated groups and those animals which received no analgesics. The timing of administration of analgesics had no influence on the effect of bupivacaine administration. The group receiving buprenorphine before surgery showed less depression in food intake than the group receiving buprenorphine at the end of surgery. Animals which received buprenorphine showed less depression of activity than those receiving saline or bupivacaine.     

The effects of surgical procedures, halothane anaesthesia and nalbuphine on locomotor activity and food and water consumption in rats

A study was undertaken to investigate the effects of surgical procedures on food and water intake and spontaneous locomotor activity in laboratory rats. The influence of anaesthesia with halothane and administration of the opioid analgesic nalbuphine was investigated in normal rats and in animals which underwent either unilateral nephrectomy or jugular vein cannulation. Both nephrectomy and jugular cannulation were associated with a significant reduction in food and water consumption and a depression in locomotor activity levels. The reduction in activity following nephrectomy was reversed by administration of 6 doses of nalbuphine at 4 hourly intervals. Administration of nalbuphine at the same dose rate following halothane anaesthesia in normal rats resulted in a stimulation of activity. The prevention of the depressant effects of surgery by this opioid appears to be due to its stimulatory effect rather than a specific analgesic action. The degree of depression of food and water consumption after nephrectomy was significantly reduced following 6 doses of nalbuphine. This beneficial effect of repeated administration of an opioid may be related to the compound's analgesic action.     

肋间神经阻滞复合全麻联合静脉自控镇痛对胸腔镜肺大疱切除术患者术后镇痛效果及恢复情况的影响

摘要 目的：探讨在胸腔镜肺大疱切除术中应用肋间神经阻滞复合全麻联合静脉自控镇痛的术后镇痛效果及患者恢复情况。方法：研究对象选取进行胸腔镜肺大疱切除术的80例患者,依据简单数字表法分为对照组和观察组,每组各40例。对照组接受全麻联合静脉自控镇痛,观察组在此基础上复合肋间神经阻滞,比较两组术后镇痛效果及恢复情况。结果：与术前比,术后12 h、24 h两组患者的CD4⁺、CD4⁺/CD8⁺均先降低后升高,且观察组各时间点均高于对照组;两组患者的CD8⁺均先升高后降低,且观察组各时间点均低于对照组（P<0.05）。术后24 h、48 h,观察组比对照组在镇痛泵按压次数和输注镇痛药物总量有减少（P<0.05）。与对照组比,观察组患者的术毕到拔管时间、下床活动时间、住院时间均更短（P<0.05）。与对照组（22.50%、20.00%）比,观察组患者的并发症、不良反应总发生率（2.50%、5.00%）更低（P<0.05）。结论：在胸腔镜肺大疱切除术中应用肋间神经阻滞复合全麻联合静脉自控镇痛,取得了显著的镇痛成效,不仅能够减轻患者的术后疼痛,还能减轻机体免疫抑制,同时不增加并发症和不良反应发生风险,临床应用安全性较高。     

胸神经阻滞和肋间神经阻滞对乳腺癌根治术患者血流动力学、术后镇痛及呼吸功能的对比研究

目的:比较胸神经阻滞和肋间神经阻滞对乳腺癌根治术患者血流动力学、术后镇痛以及呼吸功能的影响,为乳腺癌根治术患者的临床麻醉选择提供参考。方法:选择2017年3月至2018年3月医院收治的120例行乳腺癌根治术的患者作为研究对象,按照麻醉方式不同分为观察组和对照组各60例,其中观察组患者给予胸神经阻滞复合全身麻醉,对照组患者给予肋间神经阻滞复合全身麻醉。比较两组患者术后2h、6h、12h、24h、48h的静态和动态的视觉模拟评分(VAS)评分,并比较两组患者切皮前5 min(T_0)、切皮即刻(T_1)、切皮后15 min(T_2)、30 min(T_3)、钉皮即刻(T_4)及拔管后15 min(T_5)的血流动力学以及呼吸功能指标,并分析两组患者术中用药、术后镇痛泵使用情况以及术后不良反应。结果:两组患者术后静息状态下不同时点的VAS评分差异无统计学意义(P0.05);动态状态下,观察组患者的VAS评分明显低于对照组(P0.05)。T_1-T_5期间,观察组患者的平均动脉压(MAP)、心率(HR)均明显低于对照组,每分钟通气量(MV)明显高于对照组(P0.05)。观察组患者的术中瑞芬太尼消耗量、丙泊酚用量、镇痛泵有效按压次数以及补救镇痛例数均明显低于对照组;恶心呕吐(PONV)、尿潴留、嗜睡等不良反应明显低于对照组(P0.05)。结论:与肋间神经阻滞相比,胸神经阻滞治疗乳腺癌根治术患者可以有效增强术后镇痛效果,术中血流动力学平稳,减少阿片类药物用量,降低术后不良反应发生率,改善术后呼吸功能,效果显著,值得临床推广使用。     

Sufentanil and Bupivacaine Combination versus Bupivacaine Alone for Spinal Anesthesia during Cesarean Delivery: A Meta-Analysis of Randomized Trials

Objective

The addition of lipophilic opioids to local anesthetics for spinal anesthesia has become a widely used strategy for cesarean anesthesia. A meta-analysis to quantify the benefits and risks of combining sufentanil with bupivacaine for patients undergoing cesarean delivery was conducted.

Methods

A comprehensive literature search without language or date limitation was performed to identify clinical trials that compared the addition of sufentanil to bupivacaine with bupivacaine alone for spinal anesthesia in healthy parturients choosing cesarean delivery. The Q and I² tests were used to assess heterogeneity of the data. Data from each trial were combined using relative ratios (RRs) for dichotomous data or weighted mean differences (WMDs) for continuous data and corresponding 95% confidence intervals (95% CIs) for each trial. Sensitivity analysis was conducted by removing one study a time to assess the quality and consistency of the results. Begg’s funnel plots and Egger’s linear regression test were used to detect any publication bias.

Results

This study included 9 trials containing 578 patients in the final meta-analysis. Sufentanil addition provided a better analgesia quality with less breakthrough pain during surgery than bupivacaine alone (RR = 0.10, 95% CI 0.06 to 0.18, P < 0.001). Sensory block onset time was shorter and first analgesic request time was longer in sufentanil added group compared with the bupivacaine-alone group (WMD = −1.0 min, 95% CI −1.5 to −0.58, P < 0.001 and WMD = 133 min, 95% CI 75 to 213, P < 192, respectively). There was no significant difference in the risk of hypotension and vomiting between these two groups. But pruritus was more frequentely reported in the group with sufentanil added (RR = 7.63, 95% CI 3.85 to 15.12, P < 0.001).

Conclusion

Bupivacaine and sufentanil combination is superior to that of bupivacaine alone for spinal anesthesia for cesarean delivery in analgesia quality. Women receiving the combined two drugs had less breakthrough pain, shorter sensory block onset time, and longer first analgesic request time. However, the addition of sufentanil to bupivacaine increased the incidence of pruritus.     

Epidural Analgesia in Dogs with Special Reference to the Intraarterial Blood Pressure

In order to investigate whether epidural analgesia in dogs employing mepivacaine chloride gives rise to complications, mainly changes in blood pressure, such analgesia was carried out in 35 dogs brought to the clinic for orthopedic, abdominal or perineal operations. Intra-arterial blood pressure measurements were made in 16 dogs. Three different solutions of mepivacaine chloride were used: 1 % solution with adrenaline 1:200,000; 2% solution with adrenaline 1:100,000 and 2% solution with adrenaline 1:200,000. The various solutions showed no significant difference in analgesic effect. Nor was any blood pressure change found during the epidural blockade. As a solution with a higher concentration causes a higher blood level of the analgesic and also greater toxic effects it is recommended that first preference be given to use of a 1 % solution with adrenaline 1:200,000; second choice is a 2 % solution with adrenaline 1:200,000 and third choice the 2 % solution with adrenaline 1:100,000.     

纳布啡在围手术期镇痛的研究进展

纳布啡是一种新型的菲族镇痛药,属于混合型阿片类受体激动/拮抗剂,可在脊髓水平激动κ受体发挥强效的镇痛效果,其镇痛作用起效迅速、药效持久、疗效确切;同时由于纳布啡独特的部分μ受体拮抗特性,使其与吗啡相比,在发挥镇痛作用的同时呼吸抑制轻、血流动力学平稳以及恶心呕吐、皮肤瘙痒、成瘾性等不良反应发生率更低,因此,纳布啡在围手术期镇痛和临床麻醉等多个领域有着广阔的应用前景。现结合纳布啡独特的药代动力学、药理学特点及作用机制,对纳布啡在围手术期镇痛的研究进展作一综述,以期为临床上合理、有效镇痛提供理论参考和实践依据。     

A Comparison of the Analgesia Efficacy and Side Effects of Paravertebral Compared with Epidural Blockade for Thoracotomy: An Updated Meta-Analysis

Objective

The most recent systematic review and meta-analysis comparing the analgesic efficacy and side effects of paravertebral and epidural blockade for thoracotomy was published in 2006. Nine well-designed randomized trials with controversial results have been published since then. The present report constitutes an updated meta-analysis of this issue.

Summary of Background

Thoracotomy is a major surgical procedure and is associated with severe postoperative pain. Epidural analgesia is the gold standard for post-thoracotomy pain management, but has its limitations and contraindications, and paravertebral blockade is increasingly popular. However, it has not been decided whether the analgesic effect of the two methods is comparable, or whether paravertebral blockade leads to a lower incidence of adverse side effects after thoracotomy.

Methods

Two reviewers independently searched the databases PubMed, EMBASE, and the Cochrane Library (last performed on 1 February, 2013) for reports of studies comparing post-thoracotomy epidural analgesia and paravertebral blockade. The same individuals independently extracted data from the appropriate studies.

Result

Eighteen trials involving 777 patients were included in the current analysis. There was no significant difference in pain scores between paravertebral blockade and epidural analgesia at 4–8, 24, 48 hours, and the rates of pulmonary complications and morphine usage during the first 24 hours were also similar. However, paravertebral blockade was better than epidural analgesia in reducing the incidence of urinary retention (p<0.0001), nausea and vomiting (p = 0.01), hypotension (p<0.00001), and rates of failed block were lower in the paravertebral blockade group (p = 0.01).

Conclusions

This meta-analysis showed that PVB can provide comparable pain relief to traditional EPI, and may have a better side-effect profile for pain relief after thoracic surgery. Further high-powered randomized trials are to need to determine whether PVB truly offers any advantages over EPI.     

Postoperative analgesia: a comparison of intravenous on-demand fentanyl with epidural bupivacaine.

In a randomised trial postoperative pain relief was provided by either epidural injections of bupivacaine or an infusion of fentanyl adjusted by the patient to achieve adequate pain relief. Both techniques produced satisfactory analgesia without respiratory depression after peripheral arterial surgery. The technique of infusing intravenously a potent analgesic in a dose adjusted by the patient appears to offer several advantages in postoperative care.     

A Single-Dose Intra-Articular Morphine plus Bupivacaine versus Morphine Alone following Knee Arthroscopy: A Systematic Review and Meta-Analysis

Objectives

The purpose of this study was to compare the efficacy and safety of a single-dose intra-articular morphine plus bupivacaine versus morphine alone in patients undergoing arthroscopic knee surgery.

Methods

Randomized controlled trials comparing a combination of morphine and bupivacaine with morphine alone injected intra-articularly in the management of pain after knee arthrocopic surgery were retrieved (up to August 10, 2014) from MEDLINE, the Cochrane Library and Embase databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95% confidence intervals (CIs) were calculated using RevMan statistical software.

Results

Thirteen randomized controlled trials were included. Statistically significant differences were observed with regard to the VAS values during the immediate period (0-2h) (WMD -1.16; 95% CI -2.01 to -0.31; p = 0.007) and the time to first request for rescue analgesia (WMD = 2.05; 95% CI 0.19 to 3.92; p = 0.03). However, there was no significant difference in the VAS pain score during the early period (2-6h) (WMD -0.36; 95% CI -1.13 to 0.41; p = 0.35), the late period (6-48h) (WMD 0.11; 95% CI -0.40 to 0.63; p = 0.67), and the number of patients requiring supplementary analgesia (RR = 0.78; 95% CI 0.57 to 1.05; p = 0.10). In addition, systematic review showed that intra-articular morphine plus bupivacaine would not increase the incidence of adverse effects compared with morphine alone.

Conclusion

The present study suggested that the administration of single-dose intra-articular morphine plus bupivacaine provided better pain relief during the immediate period (0-2h), and lengthened the time interval before the first request for analgesic rescue without increasing the short-term side effects when compared with morphine alone.

Level of Evidence

Level I, meta-analysis of Level I studies.     

Stereoselectivity in the placental transfer and kinetic disposition of racemic bupivacaine administered to parturients with or without a vasoconstrictor

The aim of the present study was to investigate the stereoselectivity in the kinetic disposition and the transplacental distribution of bupivacaine in term parturients during labor. Maternal age ranged from 18-37 years and fetal gestational age from 37.6-41.5 weeks. Healthy parturients (n = 23) received epidural 0.5% racemic bupivacaine alone (group A) or combined with epinephrine (group B). Maternal venous blood was sampled at regular intervals until 8 h after drug administration and umbilical venous blood was obtained at delivery. Bupivacaine enantiomers were determined in plasma samples by HPLC using a Chiralcel(R) OD-R column and a UV detector. One- or two-compartment models were fitted to data and differences between the (+)-(R) and (-)-(S) enantiomers were compared with the paired Wilcoxon test (P< 0.05). The influence of epinephrine was evaluated using the unpaired Mann-Whitney test (P< 0.05). The disposition of bupivacaine in maternal plasma was stereoselective, with higher V(d/f) (140.60 vs. 132.81 L for group A and 197.86 vs. 169.46 L for group B) and C(l/f) (29.00 vs. 25.43 L/h for group A and 33.15 vs. 26.39 L/h for group B) and lower t(1/2)beta (3.24 vs. 3.30 h for group A and 4.36 vs. 4.45 h for group B) being observed for (+)-(R)-bupivacaine. The combined administration of epinephrine resulted in higher V(d/f) (197.86 vs. 140.60 L for (+)-(R) and 169.46 vs. 132.81 L for (-)-(S)) and t(1/2)beta values (4.36 vs. 3.24 h for (+)-(R) and 4.45 vs. 3.30 h for (-)-(S)). The transplacental distribution of bupivacaine was stereoselective only when bupivacaine was administered without epinephrine (group B), with a higher cord blood/maternal blood ratio being observed for (-)-(S)-bupivacaine (0.40 vs. 0.35). Chirality 16:65-71, 2004.     

经腹子宫全切术后舒芬太尼和芬太尼自控静脉镇痛的比较

目的观察舒芬太尼用于经腹子宫全切术后静脉镇痛效果、临床副作用,并与等效价的芬太尼比较有无优越性。方法选择择期硬膜外阻滞麻醉下经腹行子宫全切术患者80例,随机分为A组（芬太尼组）40例,B组（舒芬太尼组）40例。A组给予负荷量芬太尼40μg;B组给予负荷量舒芬太尼4μg。两组均采用珠海福尼亚电子微量泵（CPE-101—200型）行自控静脉镇痛。观察术后4、8、16、24h的疼痛、镇静、恶心呕吐的评分,记录血氧饱和度、镇痛液消耗量。疼痛情况用水平视觉模拟评分法（VAS）评估,镇静程度按Ramsay评分法评估。结果与A组比较,B组各时点VAS评分普遍低于A组,但仅术后24h差异有显著统计学意义（P〈0．05）。两组患者镇静评分均无达到3分者,B组各时点Ramsay评分普遍高于A组,其中术后16、24h差异有显著统计学意义（P〈0．05）。B组患者术后各时点镇痛液消耗量普遍低于A组,其中术后16、24h差异有显著统计学意义（P〈0．05）。两组术后恶心呕吐发生率均低,其中术后4h差异有统计学意义（P〈0．05）。结论经腹子宫全切术后舒芬太尼组的静脉镇痛效果略优于芬太尼组,镇静作用亦明显高于芬太尼组,而且减少恶心呕吐等副作用的发生率。     

Reversal of fentanyl/fluanisone neuroleptanalgesia in the rabbit using mixed agonist/antagonist opioids

The reversal of the neuroleptanalgesic combination of fentanyl/fluanisone using mixed agonist/antagonist opioids has been investigated in the rabbit. All of the compounds studied (naloxone, nalbuphine, meptazinol, butorphanol, buprenorphine, pentazocine, doxapram) reversed the respiratory depression and sedation produced by fentanyl/fluanisone. Fentanyl/fluanisone produced profound analgesia for 180 min, which was rapidly and completely antagonized by naloxone. The mixed agonist/antagonist opioids produced a reduction in the degree of analgesia but, in contrast to naloxone, analgesic activity persisted from 120 min (meptazinol) to 420 min (buprenorphine). Administration of buprenorphine to rabbits anaesthetized with fentanyl/fluanisone and midazolam confirmed that the reversal of respiratory depression was accompanied by the return of arterial pH, PCO2 and PCO2 to preanaesthetic values. The use of neuroleptanalgesic anaesthetic regimens, which have been shown to provide effective surgical anaesthesia, combined with reversal using a mixed agonist/antagonist opioid to provide postoperative analgesia, appears to be a valuable refinement of current laboratory animal anaesthetic practice.     

Long term backache after childbirth: prospective search for causative factors.

OBJECTIVES--To assess in a prospective randomised study the association between motor block resulting from high and low dose epidural infusions of bupivacaine in labour and the incidence of long term backache after childbirth, and to compare the incidence of backache in women not receiving epidural analgesia. DESIGN--Women requesting epidural analgesia in labour between October 1991 and March 1994 were randomised to receive infusions of either bupivacaine alone or low dose bupivacaine with opioid. Data were collected during labour and the immediate postpartum period from these women and from women recruited at random over the same time from those who had laboured without epidural analgesia. A postal questionnaire about symptoms was sent three months after childbirth to all women. Further data were collected one year after childbirth from those who had reported new backache at three months. SETTING--St Thomas''s Hospital, London. SUBJECTS--599 women were recruited, of whom 450 (75%) replied to a follow up questionnaire. RESULTS--152 women (33.8% of responders) reported backache lasting three months after delivery and, of these, 33 (7.3%) had not previously suffered with backache. There were no significant differences between the treatment groups in the incidence of postnatal backache overall or of new backache or any symptoms after childbirth. Among all demographic, obstetric, and epidural variables examined the only factors significantly associated with backache after childbirth were backache before and during pregnancy. CONCLUSIONS--The incidence of new long term backache was not significantly increased in women who received epidural analgesia in labour. Motor block resulting from epidural local anaesthetic administration was not a significant factor in the development of backache.     

Comparative trial of rectal indomethacin and cryoanalgesia for control of early postthoracotomy pain.

A randomised double blind trial was carried out over the first two days after thoracotomy to compare the analgesic effects of rectal indomethacin 100 mg administered eight hourly, cryoanalgesia, and a combination of both of these with the effects of conventional intramuscular opiate analgesia. Pain scores were significantly reduced with both rectal indomethacin alone and cryoanalgesia alone; these treatments had an additive effect when used in combination. Pain on movement was significantly increased, and indomethacin was more effective in reducing this than cryoanalgesia. Groups receiving either indomethacin alone or the combination treatment required significantly less opiate on the first day and exhibited improved peak flow values over the first two days. It is concluded that rectal indomethacin, in this dosage, can provide good, safe analgesia after thoracotomy with minimum administrative difficulty. When used as an adjunct to cryoanalgesia it has an additive effect. There are many potential uses for this drug in other branches of surgery.     

地佐辛联合舒芬太尼对开胸患者术后镇痛镇静效果、血流动力学及免疫功能的影响

目的:探讨地佐辛联合舒芬太尼对开胸患者术后镇痛镇静效果、血流动力学及免疫功能的影响。方法:选取2017年1月~2018年12月期间新疆医科大学附属第一医院收治的拟行开胸手术患者70例,根据术后镇痛药物的不同将患者分为对照组(n=35)和研究组(n=35),对照组术后给予舒芬太尼镇痛,研究组术后给予地佐辛联合舒芬太尼镇痛。比较两组患者镇痛镇静效果、血流动力学、免疫功能及不良反应发生情况。结果:研究组术后6 h、12 h、24 h视觉疼痛模拟评分法(VAS)评分呈逐渐递减趋势,且低于对照组(P<0.05)。研究组术后3 h、6 h、12 h、24 h Ramsay镇静评分均低于对照组(P<0.05)。研究组术后5 min、3 h、12 h心率(HR)、舒张压(DBP)、收缩压(SBP)均低于对照组(P<0.05)。两组患者术后1 d、7 d CD3^+、CD4^+/CD8^+、自然杀伤(NK)细胞水平均呈先降低后升高趋势,术后7 d可恢复至术前水平(P<0.05),研究组术后1 d CD3^+、CD4^+/CD8^+、NK细胞水平高于对照组(P<0.05)。研究组不良反应发生率低于对照组(P<0.05)。结论:开胸患者术后应用地佐辛联合舒芬太尼,镇静镇痛效果较好,可有效维持患者血流动力学稳定,减轻机体免疫功能抑制,安全可靠。     

Synthesis and evaluation of hydrolyzable hyaluronan-tethered bupivacaine delivery systems

Local anesthetics are useful for reducing acute pain, but their short duration precludes them from use in solely managing postoperative pain. To prolong the duration of local anesthesia, we conjugated bupivacaine to native hyaluronan (HA) and divinyl sulfone cross-linked Hylan A (Hylan B particles) using a hydrolyzable linker incorporating an imide. Bupivacaine was prepared for conjugation to HA by forming the acryl imide derivative. Separately, the carboxyl group of HA was reacted with nipsylethylamine (NEA) using carbodiimide-mediated coupling to provide HA-NEA that was subsequently reduced with tris(2-carboxyethylphosphine) hydrochloride to yield HA carrying a free sulfhydryl (HA-SH). The HA-bupivacaine conjugate was assembled by reacting HA-SH with acrylbupivacaine. Characterization of the conjugates showed 22% degree of modification by 1 mol of carboxyl. In vitro release studies comparing bupivacaine admixed in HA with bupivacaine conjugated to HA showed half-lives of 0.4 +/- 0.1 h, and 16.9 +/- 0.2 h, respectively, and the bupivacaine was released chemically unaltered as confirmed by LC-MS. In vivo studies to assess the duration of anesthetic activity were performed in a rat sciatic nerve blockade model. For these studies, bupivacaine was conjugated to Hylan B following a similar procedure, and the degree of modification obtained was 14%. Free bupivacaine (3 and 16 mg/kg) and free bupivacaine (3 mg/kg) admixed with Hylan B particles showed nerve block over 4, 9, and 6 h, respectively. Free bupivacaine (3 mg/kg) admixed with bupivacaine (13 mg/kg) conjugated to Hylan B particles showed a four to 5-fold longer impairment of motor function over the free bupivacaine formulations with a total block time of 19 h. Bupivacaine conjugated to Hylan B particles has the potential to prolong the duration of local anesthesia.     

多模式术后镇痛在腹腔镜结肠手术中的应用

目的:理论上联合使用不同机制镇痛药较镇痛药单独使用镇痛效果更完善,在妇科、骨科等手术中已有结论;笔者观察比较腹腔镜结肠手术术使用单一止痛药及联合使用不同机制镇痛药在术后镇痛的效果以及各自不良反应的发生率。方法:择期腹腔镜结肠手术患者90例,随机分为3组,每组30例。A组使用地佐辛+氟比洛酚酯行术后镇痛为多模式镇痛组;B组使用地佐辛行术后镇痛;C组使用氟比洛酚酯行术后镇痛。记录每组术后4、8、12、24 h视觉模糊评分(VAS)及术后不良反应包括嗜睡、躁动、恶心呕吐的发生率。结果:A组术后4 h、8 h的VAS评分低于B、C两组,差异有显著性,A组无嗜睡及躁动发生,发生呕吐1例,不良反应发生率A组低于B、C两组,差异有显著性。结论:地佐辛+氟比洛酚酯联合用药可安全有效应用于腹腔镜结肠手术术后镇痛,是一种有效的多模式术后镇痛方式,在减弱疼痛的放大效应及对中枢神经的作用两方面起效,因而较单独使用地佐辛及氟比洛酚酯有更好的镇痛效果,且不良反应低于单独使用地佐辛及氟比洛酚酯。