Single-dose oral naproxen for acute postoperative pain: a quantitative systematic review

BACKGROUND: Naproxen and naproxen sodium are non-steroidal anti-inflammatory drugs used in a variety of painful conditions, including the treatment of postoperative pain. This review aims to assess the efficacy, safety and duration of action of a single oral dose of naproxen/naproxen sodium for moderate to severe acute postoperative pain in adults, compared with placebo. METHODS: The Cochrane Library (issue 4 2002), EMBASE, PubMed, MEDLINE and an in-house database were searched for randomised, double blind, placebo controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with acute postoperative pain. Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over 4 to 6 hours. Relative benefit and number-needed-to-treat were then calculated. The percentage of patients with any adverse event, number-needed-to-harm, and time to remedication were also calculated. RESULTS: Ten trials with 996 patients in met the inclusion criteria. Six trials compared naproxen sodium 550 mg (252 patients) with placebo (248 patients); the NNT for at least 50% pain relief over six hours was 2.6 (95% confidence interval 2.2 to 3.2). There was no significant difference between the number of patients experiencing any adverse event on treatment compared with placebo. Weighted mean time to remedication was 7.6 hours for naproxen sodium 550 mg (206 patients) and 2.6 hours for placebo (205 patients). Four other trials used lower doses. CONCLUSION: A single oral dose of naproxen sodium 550 mg is an effective analgesic in the treatment of acute postoperative pain. A low incidence of adverse events was found, although these were not reported consistently.     

Individual patient meta-analysis of single-dose rofecoxib in postoperative pain

BACKGROUND: Individual patient meta-analysis to determine the analgesic efficacy and adverse effects of single-dose rofecoxib in acute postoperative pain. METHODS: Individual patient information was available from 14 trials; 13 in dental and one in postsurgical pain. For each patient the percentage of maximum possible pain relief (%maxTOTPAR) was determined at different time points. The proportion of patients with at least 50% maxTOTPAR, and number-needed-to-treat (NNT) for at least 50% maxTOTPAR, were then calculated, with time when 50% of patients had remedicated (TTR50) and number-needed-to-harm (NNH) for adverse effects. RESULTS: In dental pain, for rofecoxib 50 mg (1330 patients) compared with placebo (570 patients) the NNT was 1.9 (95% confidence interval 1.8 to 2.1) for six hours, 2.0 (1.8 to 2.1) at eight, 2.4 (2.2 to 2.6) at 12, and 2.8 (2.5 to 3.1) at 24 hours. The TTR50 was 15.5 hours. Adverse effects were uncommon, though post-extraction alveolitis (dry socket) occurred more often with rofecoxib 50 mg than with placebo, NNH 24 (14 to 80). For postsurgical pain in one trial (163 patients), the NNT for rofecoxib 50 mg for six hours was 3.9 (2.6 to 7.8), the TTR50 was 5.8 hours, and multiple-dose adverse effects over five days occurred at similar rates with rofecoxib 50 mg and placebo. CONCLUSIONS: Single-dose rofecoxib 50 mg is an effective treatment with long-lasting analgesia and few adverse effects in dental pain. More information is required to confirm efficacy in postsurgical pain.     

Systematic review of dexketoprofen in acute and chronic pain

Background

Dexketoprofen, an NSAID used in the management of acute and chronic pains, is licensed in several countries but has not previously been the subjected of a systematic review. We used published and unpublished information from randomised clinical trials (RCTs) of dexketoprofen in painful conditions to assess evidence on efficacy and harm.

Methods

PubMed and Cochrane Central were searched for RCTs of dexketoprofen for pain of any aetiology. Reference lists of retrieved articles and reviews were also searched. Menarini Group produced copies of published and unpublished studies (clinical trial reports). Data were abstracted into a standard form. For studies reporting results of single dose administration, the number of patients with at least 50% pain relief was derived and used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief compared with placebo.

Results

Thirty-five trials were found in acute pain and chronic pain; 6,380 patients were included, 3,381 receiving dexketoprofen. Information from 16 trials (almost half the total patients) was obtained from clinical trial reports from previously unpublished trials or abstracts. Almost all of the trials were of short duration in acute conditions or recent onset pain. All 12 randomised trials that compared dexketoprofen (any dose) with placebo found dexketoprofen to be statistically superior. Five trials in postoperative pain yielded NNTs for 12.5 mg dexketoprofen of 3.5 (2.7 to 4.9), 25 mg dexketoprofen of 3.0 (2.4 to 3.9), and 50 mg dexketoprofen of 2.1 (1.5 to 3.5). In 29/30 active comparator trials, dexketoprofen at the dose used was at least equivalent in efficacy to comparator drugs. Adverse event withdrawal rates were low in postoperative pain and somewhat higher in trials of longer duration; no serious adverse events were reported.

Conclusion

Dexketoprofen was at least as effective as other NSAIDs and paracetamol/opioid combinations. While adverse event withdrawal was not different between dexketoprofen and comparator analgesics, the different conditions and comparators studies precluded any formal analysis. Exposure was limited, and no conclusions could be drawn about safety in terms of serious adverse events like gastrointestinal bleeding or cardiovascular events.     

Anesthesiologists' practice patterns for treatment of postoperative nausea and vomiting in the ambulatory Post Anesthesia Care Unit

Background

Induction of the COX-2 isoenzyme appears to play a major role in the genesis of central sensitization after nociceptive stimulation. This study aimed to investigate the efficacy of a single, oral dose of the specific COX-2 inhibitor-valdecoxib in attenuating the central sensitization – induced secondary hyperalgesia in a heat/capsaicin pain model in healthy volunteers.

Methods

The study was a randomized, double blind, placebo controlled, crossover, single dose efficacy trial using 20 healthy volunteers. Two hours following placebo or 40 mg, PO valdecoxib, participants underwent skin sensitization with heat/capsaicin, as well as supra-threshold pain and re-kindling measurements according to an established, validated pain model. Subjects rated pain intensity and unpleasantness on a visual analog scale and the area of secondary hyperalgesia was serially mapped.

Results

The area of secondary hyperalgesia produced after 40 mg of valdecoxib was no different than that after placebo. Furthermore, there were no significantly relevant differences when volunteers were treated with valdecoxib or placebo in relation to either cold- or hot pain threshold or the intensity of pain after supra-threshold, thermal pain stimulation.

Conclusion

We demonstrated that a single, oral dose of valdecoxib when does not attenuate secondary hyperalgesia induced by heat/capsaicin in a cutaneous sensitization pain model in healthy volunteers.     

Duloxetine for painful diabetic neuropathy and fibromyalgia pain: systematic review of randomised trials

Background

Duloxetine hydrochloride is a reuptake inhibitor of 5-hydroxytryptamine and norepinephrine used to treat depression, generalized anxiety disorder, neuropathic pain, and stress incontinence in women. We investigated the efficacy of duloxetine in painful diabetic neuropathy and fibromyalgia to allow comparison with other antidepressants.

Methods

We searched PubMed, EMBASE (via Ovid), and Cochrane CENTRAL up to June 2008 for randomised controlled trials using duloxetine to treat neuropathic pain.

Results

We identified six trials with 1,696 patients: 1,510 were treated with duloxetine and 706 with placebo. All patients had established baseline pain of at least moderate severity. Trial duration was 12 to 13 weeks. Three trials enrolled patients with painful diabetic neuropathy (PDN) and three enrolled patients with fibromyalgia. The number needed to treat (NNT) for at least 50% pain relief at 12 to 13 weeks with duloxetine 60 mg versus placebo (1,211 patients in the total comparison) was 5.8 (95% CI 4.5 to 8.4), and for duloxetine 120 mg (1,410 patients) was 5.7 (4.5 to 5.7). There was no difference in NNTs between PDN and fibromyalgia. With all doses of duloxetine combined (20/60/120 mg) there were fewer withdrawals for lack of efficacy than with placebo (number needed to treat to prevent one withdrawal 20 (13 to 42)), but more withdrawals due to adverse events (number needed to harm (NNH) 15 (11 to 25)). Nausea, somnolence, constipation, and reduced appetite were all more common with duloxetine than placebo (NNH values 6.3, 11, 11, and 18 respectively). The results for duloxetine are compared with published data for other antidepressants in neuropathic pain.

Conclusion

Duloxetine is equally effective for the treatment of PDN and fibromyalgia, judged by the outcome of at least 50% pain relief over 12 weeks, and is well tolerated. The NNT of 6 for 50% pain relief suggests that this is likely to be a useful drug in these difficult-to-treat conditions, where typically only a minority of patients respond. Comparing duloxetine with antidepressants for pain relief in DPN shows inadequacies in the evidence for efficacy of antidepressants, which are currently recommended in PDN care pathways.

     

全膝关节置换术后多模式镇痛中非选择与选择性COX-2抑制剂的对比应用研究

目的：评价全膝关节置换术后病人早期功能锻炼过程中应用选择性环氧化酶-2（COX-2）抑制剂帕瑞昔布钠与非选择性环氧化酶（COX）抑制剂氟比洛芬酯之间的镇痛效果是否存在差异,以及对早期功能锻炼结果的影响。方法：前瞻性、随机、双盲、平行对照研究,根据纳入/排除标准,连续选取2009年6月至2010年3月在我科行单侧人工全膝关节置换术的病人60名。手术均采用腰麻联合硬膜外阻滞麻醉,由同一组手术医师完成,术中假体安装前关节周围软组织注射＂鸡尾酒＂镇痛液（罗哌卡因注射液150mg＋肾上腺素（1：1000）0.5ml,由生理盐水稀释为100ml）。手术结束后进行病人自控静脉镇痛（PCIA）。术后当天患者在护士的指导下进行股四头肌收缩功能锻炼及直腿抬高功能锻炼。术后第一天起行膝关节被动伸屈功能锻炼（CPM）及主动伸屈功能锻炼。术后第3至5天患者停PCIA镇痛后,进行试验干预。帕瑞昔布钠组给予注射用帕瑞昔布钠40mg,静注1/12小时。氟比洛芬酯组给予氟比洛芬酯注射液100mg,静注1/12小时。观察病人术后第3至5天静息状态下和活动锻炼时膝关节最大主动屈曲时的疼痛强度（VAS评分）,手术侧膝关节的主动伸屈活动度及术后1月复查时的手术侧膝关节的主动伸屈活动度,KSS评分,术后第2天与第6天的血红蛋白值。结果：两组病人给药后在静息状态及膝关节最大主动屈曲时,在不同时间点的VAS评分、膝关节主动活动度及术后1月患者膝关节的主动活动度和KSS评分的差异均无统计学意义（P〉0.05）。应用抗凝治疗后,帕瑞昔布钠组患者血红蛋白下降值与氟比洛芬酯组存在差异（P=0.042）。结论：尚不能认为人工全膝关节置换术后多模式镇痛中同时抑制COX-1和COX-2与选择性抑制COX-2之间存在差异。但应用选择性COX-2抑制剂（帕瑞昔布钠）镇痛更安全,因其有利于减少全膝关节置换术后患者抗凝治疗过程中的隐性失血。     

Efficacy and Safety of Parecoxib/Phloroglucinol Combination Therapy Versus Parecoxib Monotherapy for Acute Renal Colic: A Randomized,Double-Blind Clinical Trial

To investigate whether the addition of phloroglucinol to parecoxib could improve the efficacy in patients with acute renal colic. Patients of acute renal colic were randomly allocated to receive intravenous Parecoxib 40 mg plus placebo or Parecoxib 40 mg plus phloroglucinol 80 mg, respectively. Pain intensity was recorded using a visual analog scale (VAS) before drug administration and 5, 15, 30, 60, and 120 min after treatment start. The primary outcome was the mean pain intensity difference (PID) at each checkpoint and the effectiveness of drugs (≥50 % decrease in VAS score at the end checkpoint). The need for rescue analgesics and the incidence of adverse effects were considered as secondary outcome of the study. Among 236 patients enrolled in the study, 119 patients received intravenous parecoxib plus placebo and 114 patients received intravenous parecoxib plus phloroglucinol, the remaining 3 patients given up treatment. Baseline demographics were similar between two groups. There are significant differences in the PID at 15 and 30 min between two groups (P _15 min = 0.011, P _30 min = 0.013). Rescue analgesics were required by 17 patients (14.3 %) receiving parecoxib, 7 patients (6.1 %) receiving parecoxib plus phloroglucinol (P = 0.041). There were no differences in PID at other checkpoints between two groups, as well as in the incidence of adverse events and the drug effectiveness. Parecoxib in combination with phloroglucinol for acute renal colic has a faster action, also reduces the demand of rescue analgesics.     

Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial

Objective To evaluate the effect of the oral synthetic δ-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis.Design Randomised double blind placebo controlled crossover trial.Setting Outpatient clinic, University Hospital of Aarhus, Denmark.Participants 24 patients aged between 23 and 55 years with multiple sclerosis and central pain.Intervention Orally administered dronabinol at a maximum dose of 10 mg daily or corresponding placebo for three weeks (15-21 days), separated by a three week washout period.Main outcome measure Median spontaneous pain intensity (numerical rating scale) in the last week of treatment.Results Median spontaneous pain intensity was significantly lower during dronabinol treatment than during placebo treatment (4.0 (25th to 75th centiles 2.3 to 6.0) v 5.0 (4.0 to 6.4), P = 0.02), and median pain relief score (numerical rating scale) was higher (3.0 (0 to 6.7) v> 0 (0 to 2.3), P = 0.035). The number needed to treat for 50% pain relief was 3.5 (95% confidence interval 1.9 to 24.8). On the SF-36 quality of life scale, the two items bodily pain and mental health indicated benefits from active treatment compared with placebo. The number of patients with adverse events was higher during active treatment, especially in the first week of treatment. The functional ability of the multiple sclerosis patients did not change.Conclusions Dronabinol has a modest but clinically relevant analgesic effect on central pain in patients with multiple sclerosis. Adverse events, including dizziness, were more frequent with dronabinol than with placebo during the first week of treatment.     

First-dose analgesic effect of the cyclo-oxygenase-2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled comparison with celecoxib [NCT00267215]

Cyclo-oxygenase-2 selective inhibitors are frequently used to manage osteoarthritis. We compared the analgesic efficacy of the novel cyclo-oxygenase-2 selective inhibitor lumiracoxib (Prexige) versus placebo and celecoxib in patients with knee osteoarthritis. This seven day, double-blind, placebo and active comparator controlled, parallel group study included 364 patients aged > or = 50 years with moderate-to-severe symptomatic knee osteoarthritis. Patients received lumiracoxib 400 mg/day (four times the recommended chronic dose in osteoarthritis; n = 144), placebo (n = 75), or celecoxib 200 mg twice daily (n = 145). The primary variable was actual pain intensity difference (100 mm visual-analogue scale) between baseline and the mean of three hour and five hour assessments after the first dose. Actual pain intensity difference, average and worst pain, pain relief and functional status (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]) were measured over seven days. Patients also completed a global evaluation of treatment effect at study end or premature discontinuation. For the primary variable, the superiority of lumiracoxib versus placebo, the noninferiority of lumiracoxib versus celecoxib, and the superiority of lumiracoxib versus celecoxib were assessed by closed test procedure adjusting for multiplicity, thereby maintaining the overall 5% significance level. In addition, celecoxib was assessed versus placebo in a predefined exploratory manner to assess trial sensitivity. Lumiracoxib provided better analgesia than placebo 3-5 hours after the first dose (P = 0.004) through to study end. The estimated difference between lumiracoxib and celecoxib 3-5 hours after the first dose was not significant (P = 0.185). Celecoxib was not significantly different from placebo in this analysis (P = 0.069). At study end 13.9% of lumiracoxib-treated patients reported complete pain relief versus 5.5% and 5.3% of celecoxib and placebo recipients, respectively. WOMAC total and subscales improved for both active treatments versus placebo except for difficulty in performing daily activities, for which celecoxib just failed to achieve significance (P = 0.056). In the patient's global evaluation of treatment effect, 58.1% of patients receiving lumiracoxib rated treatment as 'excellent' or 'good', versus 48.6% of celecoxib and 25.3% of placebo patients. Lumiracoxib was well tolerated. The overall incidence of adverse events was similar across treatment groups.     

Rilonacept in the treatment of acute gouty arthritis: a randomized,controlled clinical trial using indomethacin as the active comparator

Introduction

In phase-3 clinical trials, the interleukin (IL-1) blocker, rilonacept (IL-1 Trap), demonstrated efficacy for gout flare prevention during initiation of urate-lowering therapy. This trial evaluated rilonacept added to a standard-of-care, indomethacin, for treatment of acute gout flares.

Methods

Adults, aged 18-70 years, with gout presenting within 48 hours of flare onset and having at least moderate pain as well as swelling and tenderness in the index joint were randomized to subcutaneous (SC) rilonacept 320 mg at baseline plus oral indomethacin 50 mg TID for 3 days followed by 25 mg TID for up to 9 days (n = 74); SC placebo at baseline plus oral indomethacin as above (n = 76); or SC rilonacept 320 mg at baseline plus oral placebo (n = 75). The primary efficacy endpoint was change in pain in the index joint (patient-reported using a Likert scale (0 = none; 4 = extreme)) from baseline to the average of values at 24, 48 and 72 hours (composite time point) for rilonacept plus indomethacin versus indomethacin alone. Comparison of rilonacept monotherapy with indomethacin monotherapy was dependent on demonstration of significance for the primary endpoint. Safety evaluation included clinical laboratory and adverse event (AE) assessments.

Results

Patient characteristics were comparable among the groups; the population was predominantly male (94.1%), white (75.7%), with mean ± SD age of 50.3 ± 10.6 years. All treatment groups reported within-group pain reductions from baseline (P < 0.0001). Although primary endpoint pain reduction was greater with rilonacept plus indomethacin (-1.55 ± 0.92) relative to indomethacin alone (-1.40 ± 0.96), the difference was not statistically significant (P = 0.33), so formal comparison between monotherapy groups was not performed. Pain reduction over the 72-hour period with rilonacept alone (-0.69 ± 0.97) was less than that in the other groups, but pain reduction was similar among groups at 72 hours. Treatment with rilonacept was well-tolerated with no reported serious AEs related to rilonacept. Across all groups, the most frequent AEs were headache and dizziness.

Conclusions

Although generally well-tolerated, rilonacept in combination with indomethacin and rilonacept alone did not provide additional pain relief over 72 hours relative to indomethacin alone in patients with acute gout flare.

Trial registration

ClinicalTrials.gov registration number {"type":"clinical-trial","attrs":{"text":"NCT00855920","term_id":"NCT00855920"}}NCT00855920.     

Oral acyclovir in acute herpes zoster.

Oral acyclovir at a dose of 800 mg five times daily for seven days was compared with placebo in a randomised double blind trial conducted at three centres in the United Kingdom. The study group comprised 205 elderly immune competent patients suffering from herpes zoster who were entered within 72 hours of the onset of rash. Acyclovir significantly reduced the times to arrest of new lesion formation (p = 0.005), loss of vesicles (p less than 0.001), and full crusting (p = 0.02) in those patients entered within 48 hours of the onset of rash. In addition, there was a significant reduction in pain during treatment with acyclovir as compared with placebo (p = 0.008). Of the patients with severe pain on entry, 40% (10/25) of those treated with acyclovir had no or only mild pain at the end of treatment, whereas in the placebo group all had residual moderate or severe pain (p less than 0.001). No clinically important adverse effects of acyclovir were reported. Oral acyclovir may modify acute herpes zoster and reduce pain.     

手术前后注射帕瑞昔布钠对脑膜瘤切除术后的镇痛效果评价

目的:比较手术前后注射帕瑞昔布钠对脑膜瘤切除术后的镇痛效果。方法:收集我院收治的120例行脑膜瘤切除术患者,随机分为术前组、术后组以及对照组,每组40例。术前组在麻醉前15 min静注帕瑞昔布钠40 mg所有患者行麻醉诱导(咪达唑仑+异丙酚+罗库溴铵+舒芬太尼)静脉注射,维持麻醉采用异丙酚+瑞芬太尼静脉泵注,行脑膜瘤切除术术毕根据患者具体情况停用异丙酚、瑞芬太尼术后组患者在手术结束前15 min静注帕瑞昔布钠40 mg,对照组患者在手术结束前15 min静注生理盐水2mL。观察并比较三组患者各时间点的疼痛视觉模拟评分(VAS)、简易智能状态量表(MMSE)评分、血清皮质醇(cortisol)水平以及患者不良反应发生率。结果:与对照组相比术前组、术后组患者术后1 h的VAS评分水平较低差异具有统计学意义(P0.05);与术后组相比术前组患者的术后1 h的VAS评分水平较低差异具有统计学意义(P0.05);术后三组患者的MMSE评分与术前相比均下降(P0.05),与对照组相比术前组患者的术后1 h、术后24h MMSE评分较高差异具有统计学意义(P0.05);与对照组相比术前组、术后组患者术后1 h以及术后24 h的皮质醇水平较低差异具有统计学意义(P0.05);与术后组相比术前组患者的皮质醇水平较低差异具有统计学意义(P0.05);三组患者的副作用发生率相比无明显差异(P0.05)。结论:术前注射帕瑞昔布钠的镇痛效果较术后注射更好术后认知功能恢复较快。     

Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.

OBJECTIVE: To review the effectiveness and safety of topical non-steroidal anti-inflammatory drugs in acute and chronic pain conditions. DESIGN: Quantitative systematic review of randomised controlled trials. DATA SOURCES: 86 trials involving 10,160 patients. MAIN OUTCOME MEASURES: Measures of treatment success approximating at least 50% reduction in pain, local and systemic adverse effects. Analysis at 1 week for acute and 2 weeks for chronic conditions with relative benefit and number needed to treat. RESULTS: In acute pain conditions (soft tissue trauma, strains, and sprains) placebo controlled trials had a relative benefit of 1.7 (1.5 to 1.9), the number needed to treat was 3.9 (3.4 to 4.4). With analysis by drug (at least three trials), ketoprofen (number needed to treat 2.6), felbinac (3.0), ibuprofen (3.5), and piroxicam (4.2) had significant efficacy. Benzydamine and indomethacin were no different from placebo. In chronic pain conditions (osteoarthritis, tendinitis) placebo controlled trials had a relative benefit of 2.0 (1.5 to 2.7); the number needed to treat was 3.1 (2.7 to 3.8). Small trials (< 40 treated patients) exaggerated effectiveness of topical non-steroidals by 33% in acute conditions but not in chronic conditions. There was no relation between trial quality and treatment effect. In both acute and chronic pain local and systemic adverse events and withdrawal from the study related to the drug had a low incidence and were no different from placebo. CONCLUSION: Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions.     

A randomized,placebo controlled,trial of preoperative sustained release Betamethasone plus non-controlled intraoperative Ketorolac or Fentanyl on pain after diagnostic laparoscopy or laparoscopic tubal ligation [ISRCTN52633712

BACKGROUND: Gynecological laparoscopic surgery procedures are often complicated by postoperative pain resulting in an unpleasant experience for the patient, delayed discharge, and increased cost. Glucocorticosteroids have been suggested to reduce the severity and incidence of postoperative pain. METHODS: This study examines the efficacy of a sustained release betamethasone preparation to reduce postoperative pain and the requirement for pain relief drugs after either diagnostic laparoscopy or tubal ligation. Patients were recruited, as presenting, after obtaining informed consent. Prior to surgery, patients were randomly selected by a computer generated table to receive either pharmacy-coded betamethasone (12 mg IM Celestone trade mark ) or an optically identical placebo injection of Intralipid trade mark and isotonic saline mixture. The effect of non-controlled prophylactic intraoperative treatment with either fentanyl or ketorolac per surgeon's orders was also noted in this study. Blood samples taken at recovery and at discharge times were extracted and analyzed for circulating betamethasone. Visual analog scale data on pain was gathered at six post-recovery time points in a triple blind fashion and statistically compared. The postoperative requirement for pain relief drugs was also examined. RESULTS: Although the injection achieved a sustained therapeutic concentration, no beneficial effect of IM betamethasone on postoperative pain or reduction in pain relief drugs was observed during the postoperative period. Indeed, the mean combined pain scores during the 2 hour postoperative period, adjusted for postoperative opioids as the major confounding factor, were higher approaching statistical significance (P = 0.056) in the treatment group. Higher pain scores were also observed for the tubal ligation patients relative to diagnostic laparoscopy. Intraoperative fentanyl treatment did not significantly lower the average pain score during the 2 hour postoperative period. Intraoperative ketorolac treatment significantly lowered (P = 0.027) pain scores and reduced the postoperative requirement for additional pain relief drugs. CONCLUSIONS: There was a lack of efficacy of preoperative sustained release betamethasone in reducing postoperative pain despite maintaining a therapeutic concentration during the postoperative period. Intraoperative Ketorolac did afford some short-term pain relief in the postoperative period and reduced the need for additional pain relief drugs.     

地佐辛联合帕瑞昔布钠预防全身麻醉苏醒期躁动

目的：探讨术中应用地佐辛联合帕瑞昔布钠预防全麻苏醒期躁动的效果。方法：选择ASAI～II级全身麻醉下进行开腹胆囊切除术患者75例,随机分为3组,各25例。I组给予地佐辛5mg;II组给予地佐辛10mg;Ⅲ组给予地佐辛5mg联合帕瑞昔布钠40mg。在手术进行到关腹时静脉给药,观察比#苏醒期三组患者的躁动发生情况、疼痛评分及不良反应（恶心、呕吐等）。结果：II组和Ⅲ组患者躁动发生率和疼痛评分均低于I组（P〈O．05）,II组和Ⅲ组间差异无显著性（P〉0．05）。Ⅲ组不良反应发生率小于I组和II组（P〈0．05）。结论：术中应用地佐辛联合帕瑞昔布钠对预防全麻苏醒期躁动具有良好的效果,并能降低不良反应发生率。     

Assessment of dermal glyceryl trinitrate and isosorbide dinitrate for patients with angina pectoris.

Dermal nitrate preparations are claimed to be useful in the treatment of angina, as their slow absorption by-passing the liver leads to a sustained action. Ten patients with angina were exercised on a treadmill after dermal application of 16.64 mg glyceryl trinitrate or 100 mg isosorbide dinitrate or placebo. Exercise duration was significantly increased at one and three hours for both nitrate preparations but not at six hours after application. The calculated workload achieved was significantly increased (p less than 0.01) at one and three hours for both preparations and at six hours (p less than 0.05) for isosorbide dinitrate. Headaches were common with glyceryl trinitrate cream. The dermal nitrate preparations studied had a duration of antianginal action similar to that of oral nitrate tablets. Aside from their value when the oral route cannot be used or absorption may be delayed, dermal nitrate preparations have no advantage over oral preparations for angina pectoris.     

帕瑞昔布在肺癌手术多模式镇痛效果及其对凝血功能的影响

目的:研究帕瑞昔布在胸部肺癌手术后多模式镇痛效果及其对凝血功能的影响。方法:自2012年1月到2013年12月期间,全麻复合硬膜外麻醉下实施肺癌手术病人120例,分为3组,对照组(C组)和不同帕瑞昔布钠处理组(P1组和P2组)。对照组采用硬膜外镇痛,P1此基础上术前静脉用帕瑞昔布,P2组在P1基础上术后加用帕瑞昔布。观察三组手术时间、术中出血量、术中瑞芬太尼及术后吗啡用量、不同时间段VAS和术前术后凝血功能。结果:C组、P1和P2组术中出血量三组间的差异有统计学意义,P2组出血量最少(p0.05)。C组、P1和P2组术中瑞芬太尼和术后吗啡使用剂量差异有统计学意义(P均0.05)。C组、P1组和P2组术后6个月时间内疼痛发生率和6个月时间内疼痛发生天数差异有统计学意义(P均0.05)。术中PT、APTT在三组间的差异有统计学意义(P0.05)。结论:帕瑞昔布可降低病人开胸术后慢性疼痛综合征的发生,增加凝血功能,减少吗啡用量,且不增加不良反应发生几率,临床应用安全性可靠。     

Comparative Analgesic Activity of Levomepromazine and Morphine in Patients with Chronic Pain

Apart from its ability to potentiate the action of narcotics, levomepromazine, a phenothiazine derivative, was shown to possess its own analgesic activity comparable to that of morphine at a 3:2 dose relationship.In a double-blind crossover study of 18 patients suffering from chronic pain (cancer and arthritis), levomepromazine (15 mg.) was compared with morphine (10 mg.) and placebo. Three hours after intramuscular administration, levomepromazine proved to be significantly superior to placebo (p < .05) and indistinguishable from morphine. Evaluations of pain relief by estimations of changes in pain intensity were found to correlate well with evaluations based on recognition of pain relief exceeding 50%.The potent analgesic effect of levomepromazine was obtained at the price of excessive sedation. This, however, was considered an acceptable side effect in a patient suffering from chronic pain. These results provide encouragement in the quest for a non-addicting substitute for morphine.     

Prolonged blood pressure reduction by orally active renin inhibitor RO 42-5892 in essential hypertension.

OBJECTIVE--To investigate the effects of a novel specific renin inhibitor, RO 42-5892, with high affinity for human renin (Ki = 0.5 x 10(-9) mol/l), on plasma renin activity and angiotensin II concentration and on 24 hour ambulatory blood pressure in essential hypertension. DESIGN--Exploratory study in which active treatment was preceded by placebo. SETTING--Inpatient unit of teaching hospital. PATIENTS--Nine men with uncomplicated essential hypertension who had a normal sodium intake. INTERVENTIONS--Two single intravenous doses of RO 42-5892 (100 and 1,000 micrograms/kg in 10 minutes) given to six patients and one single oral dose (600 mg) given to the three others as well as to three of the patients who also received the two intravenous doses. RESULTS--With both intravenous and oral doses renin activity fell in 10 minutes to undetectably low values, while angiotensin II concentration fell overall by 80-90% with intravenous dosing and by 30-40% after the oral dose. Angiotensin II concentration was back to baseline four hours after the low and six hours after the high intravenous dose and remained low for at least eight hours after the oral dose. Blood pressure fell rapidly both after low and high intravenous doses and after the oral dose and remained low for hours. With the high intravenous dose the daytime (0900-2230), night time (2300-0600), and next morning (0630-0830) systolic blood pressures were significantly (p less than 0.05) lowered by 12.5 (95% confidence interval 5.6 to 19.7), 12.2 (5.4 to 19.3), and 10.7 (3.2 to 18.5) mm Hg respectively, and daytime diastolic pressure was lowered by 9.3 (2.2 to 16.8) mmHg. With the oral dose daytime, night time, and next morning systolic blood pressures were lowered by 10.3 (5.5 to 15.4), 10.5 (4.2 to 17.2), and 9.7 (4.0 to 15.6) mm Hg, and daytime and night time diastolic pressures were lowered by 5.8 (0.9 to 11.0) and 6.0 (0.3-12) mm Hg respectively. CONCLUSIONS--The effect of the inhibitor on blood pressure was maintained over a longer period than its effect on angiotensin II. RO 42-5892 is orally active and has a prolonged antihypertensive effect in patients who did not have sodium depletion. This prolonged effect seems to be independent, at least in part, of the suppression of circulating angiotensin II.