Nefopam and ketamine comparably enhance postoperative analgesia

Opioids alone sometimes provide insufficient postoperative analgesia. Coadministration of drugs may reduce opioid use and improve opioid efficacy. We therefore tested the hypothesis that the administration of ketamine or nefopam to postoperative patients with pain only partly alleviated by morphine reduces the amount of subsequent opioid necessary to produce adequate analgesia. Patients (n=77) recovering from major surgery were given up to 9 mg of IV morphine. Those who still had pain were randomly assigned to blinded administration of 1) isotonic saline (control group; n=21), 2) ketamine 10 mg (ketamine group; n=22), or 3) nefopam 20 mg (nefopam group; n=22). Three-milligram morphine boluses were subsequently given at 5-min intervals until adequate analgesia was obtained, until 60 min elapsed after the beginning of study drug administration, or until ventilation became insufficient (respiratory rate <10 breaths/min or saturation by pulse oximetry <95%). Supplemental morphine (i.e., after test drug administration) requirements were significantly more in the control group (mean +/- sd; 17 +/- 10 mg) than in the nefopam (10 +/- 5 mg; P <0.005) or ketamine (9 +/- 5 mg; P <0.001) groups. Morphine titration was successful in all ketamine and nefopam patients but failed in four control patients (two because of respiratory toxicity and two because of persistent pain). Tachycardia and profuse sweating were more frequent in patients given nefopam, and sedation was more intense with ketamine; however, the incidence of other potential complications did not differ among groups.     

Preincisional treatment to prevent pain after ambulatory hernia surgery

We designed this study as a randomized comparison of postoperative pain after inguinal hernia repair in patients treated with triple preincisional analgesic therapy versus standard care. Triple therapy consisted of a nonsteroidal antiinflammatory, a local anesthetic field block, and an N-methyl-D-aspartate inhibitor before incision. The treatment group (n = 17) received rofecoxib, 50 mg PO, a field block with 0.25% bupivacaine/0.5% lidocaine, and ketamine 0.2 mg/kg IV before incision; controls (n = 17) received a placebo PO before surgery. The anesthetic protocol was standardized. Postoperative pain was treated by fentanyl IV and oxycodone 5 mg/acetaminophen 325 mg PO as required for pain. Pain scores (0-10) and analgesic were recorded for the first 7 days after surgery. Pain scores were 47% lower in the treatment group before discharge (3.1 +/- 0.6 versus 5.9 +/- 0.6, P = 0.0026) (mean +/- SE) and 18% less in the first 24 h after discharge (5.6 +/- 0.4 versus 6.8 +/- 0.5, P = 0.05); oral analgesic use was 34% less in the treatment group (4.6 +/- 0.8 doses versus 7.1 +/- 0.7 doses, P = 0.02) in the first 24 h after surgery. We conclude that triple preincisional therapy diminishes pain and analgesic use after outpatient hernia repair, and encourage further evaluation of this technique. IMPLICATIONS: Outpatients undergoing inguinal hernia repair under general anesthesia report moderate-to-severe pain after surgery. Triple preincisional therapy that included rofecoxib, 50 mg PO, ketamine, 0.2 mg/kg IV, and local anesthetic field block reduced pain scores and analgesic use in the first 24 h after discharge.     

Postoperative Morphine Use and Hyperalgesia Are Reduced by Preoperative but Not Intraoperative Epidural Analgesia: Implications for Preemptive Analgesia and the Prevention of Central Sensitization

Background: The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control.

Methods: Patients undergoing major gynecologic surgery by laparotomy were randomly assigned to three groups and studied in a double-blinded manner. Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision. Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision. Group 3 received a sham epidural control (with saline injected into a catheter taped to the back) before and 40 min after incision. All patients underwent surgery with general anesthesia.

Results: One hundred forty-one patients completed the study (group 1, n = 45; group 2, n = 49; group 3, n = 47). Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower (P = 0.04) in group 1 (89.8 +/- 43.3 mg) than group 3 (112.5 +/- 71.5 mg) but not group 2 (95.4 +/- 60.2 mg), although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower (P < 0.0009) in group 1 (1.25 +/- 0.02 mg/h) than group 2 (1.41 +/- 0.02 mg/h). Twenty-four hours after surgery, the visual analog scale pain score on movement was significantly less intense (P = 0.005) in group 1 (4.9 +/- 2.2 cm) than group 3 (6.0 +/- 2.6 cm) but not group 2 (5.3 +/- 2.5 cm), and the von Frey pain threshold near the wound was significantly higher (P = 0.03) in group 1 (6.4 +/- 0.6 log mg) than in group 3 (6.1 +/- 0.8 log mg) but not group 2 (6.2 +/- 0.7 log mg).     

The associations between severity of early postoperative pain, chronic postsurgical pain and plasma concentration of stable nitric oxide products after breast surgery

In this study, we compared the effects of two analgesic regimens on perioperative nitric oxide index (NOx) and the likelihood of subsequent development of chronic postsurgical pain (CPSP) after breast surgery and sought to determine the association among early postoperative pain, NOx, and the likelihood of subsequent development of CPSP. Twenty-nine consecutive ASA I or II patients undergoing breast surgery with axillary clearance were randomly allocated to one of two groups. Patients in group S (n = 15) received a standard intraoperative and postoperative analgesic regimen (morphine sulfate, diclofenac, dextropropoxyphene hydrochloride + acetaminophen prn). Patients in group N (n = 14) received a continuous paravertebral block (for 48 h) and acetaminophen and parecoxib (followed by celecoxib up to 5 days). Visual analog scale pain scores at rest and on arm movement were recorded regularly until the fifth postoperative day. A telephone interview was conducted 10 wk postoperatively. The McGill Pain Questionnaire was used to characterize pain. NOx was estimated preoperatively, at the end of surgery, 30 min and 2, 4, 12, 24, 48 h postoperatively. Twelve (80%) patients in group S and no patient in group N developed CPSP (P = 0.009). Compared with patients with a pain rating index > or =1 (n = 18) 10 wk postoperatively, patients with a pain rating index = 0 (n = 11) had lesser visual analog scale pain scores on movement at each postoperative time point from 30 min until 96 h postoperatively (P < 0.005) and at rest 30 min (0.6 +/- 1.5 versus 30.2 +/- 26.8; P = 0.004), 4 h (2.3 +/- 7.5 versus 19.0 +/- 25.8; P = 0.013), 8 h (4.4 +/- 10.2 versus 21.4 +/- 27.0; P = 0.03) and 12 h (0.7 +/- 1.2 versus 15.4 +/- 27.0; P = 0.035) postoperatively. NOx values were greater in group N compared with group S 48 h postoperatively (40.6 +/- 20.1 versus 26.4 +/- 13.5; P = 0.04).     

Postoperative morphine use and hyperalgesia are reduced by preoperative but not intraoperative epidural analgesia: implications for preemptive analgesia and the prevention of central sensitization

BACKGROUND: The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control. METHODS: Patients undergoing major gynecologic surgery by laparotomy were randomly assigned to three groups and studied in a double-blinded manner. Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision. Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision. Group 3 received a sham epidural control (with saline injected into a catheter taped to the back) before and 40 min after incision. All patients underwent surgery with general anesthesia. RESULTS: One hundred forty-one patients completed the study (group 1, n = 45; group 2, n = 49; group 3, n = 47). Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower (P = 0.04) in group 1 (89.8 +/- 43.3 mg) than group 3 (112.5 +/- 71.5 mg) but not group 2 (95.4 +/- 60.2 mg), although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower (P < 0.0009) in group 1 (1.25 +/- 0.02 mg/h) than group 2 (1.41 +/- 0.02 mg/h). Twenty-four hours after surgery, the visual analog scale pain score on movement was significantly less intense (P = 0.005) in group 1 (4.9 +/- 2.2 cm) than group 3 (6.0 +/- 2.6 cm) but not group 2 (5.3 +/- 2.5 cm), and the von Frey pain threshold near the wound was significantly higher (P = 0.03) in group 1 (6.4 +/- 0.6 log mg) than in group 3 (6.1 +/- 0.8 log mg) but not group 2 (6.2 +/- 0.7 log mg). CONCLUSIONS: Preincisional administration of epidural lidocaine and fentanyl was associated with a significantly lower rate of morphine use, lower cumulative morphine consumption, and reduced hyperalgesia compared with a sham epidural condition. These results highlight the importance of including a standard treatment control group to avoid the problems of interpretation that arise when two-group studies of preemptive analgesia (preincisional vs. postsurgery) fail to find the anticipated effects.     

Addition of clonidine enhances postoperative analgesia from epidural morphine: a double-blind study

This study was undertaken to evaluate the analgesic effect of the combination of epidural morphine and clonidine versus epidural morphine alone in patients with postoperative pain. A randomized double-blind design was used, and 91 patients scheduled for post-operative pain relief by epidural morphine were studied. Patients received either a continuous epidural infusion of morphine and clonidine (group 1; n = 45) or morphine alone (group 2; n = 46) over the 72 h after major abdominal surgery. In the first 24 h, the dose of morphine was 6 mg per 24 h; during the second 24 h, it was decreased to 4 mg per 24 h; and in the final 24 h, it was decreased to 2 mg per 24 h in both groups. Group 1 patients received clonidine (450 micrograms) during each 24-h period. Additional epidural bolus injections of 2 mg morphine and intravenous meperidine were given on demand. The pain score, blood pressure, heart rate, respiratory rate, and relative forced vital capacity were measured at fixed times during the first 72 h after operation. Total consumption of analgesics and side effects were recorded. Although the total consumption of analgesics was significantly higher in group 2 (P less than 0.05), pain scores were lower in group 1 than group 2 during the entire observation period (P less than 0.05). Epidural clonidine produced a significant decrease (P less than 0.05) in heart rate and blood pressure, whereas the respiratory rate was not affected. Due to the better pain relief in group 1, the forced vital capacity was increased (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Dose-dependency of intra-articular morphine analgesia

We have examined if the analgesic effects of intra-articular morphine are dose-dependent in patients undergoing elective arthroscopic knee surgery. At the end of surgery, patients were allocated randomly to one of four groups to receive intra-articular saline (n = 22), or morphine 1 mg (n = 24), 2 mg (n = 21) or 4 mg (n = 19). After operation, patients remained in hospital overnight and pain intensity was assessed using a visual analogue scale at 1, 2, 3, 6, 9, 12, 18 and 24 h after intra-articular injection. Patients requesting additional analgesia received a loading dose of piritramide 0.1 mg kg-1 i.v. and were connected to a PCA device using the same drug. Increasing doses of intra-articular morphine were associated with greater analgesic effects and less supplementary analgesic requirements.      

Analgesic effect of continuous intravenous nefopam after urological surgery

OBJECTIVES:To evaluate the efficacy of continuous infusion of nefopam. Indeed this analgesic is commonly used by continuous infusion by many anaesthetists to reduce its adverse effects. However whether the analgesic effect of an intermittent administration of nefopam has been proven, the efficacy of continuous infusion has not been established. STUDY DESIGN: Double-blind placebo controlled prospective randomised study. PATIENTS AND METHODS: Sixty patients ASA 1 to 3 undergoing planned urological surgery with laparotomy were included. At the end of surgery, bolus doses of placebo (Group 3) or nefopam 20 mg (Group 1 and 2) were administered to all the patients. Placebo (Group 3), nefopam 80 mg (Group 1) or 120 mg (Group 2) was thereafter continuously infused over 24 hours. All patients received additional analgesia with PCA morphine. We measured pain at rest and on cough with VAS.Adverse side effects such as nausea and vomiting, sedation and respiratory depression were evaluated. Mental performance was measured with mini mental status tests. RESULTS: Patients were older in the placebo group by approximately six years but anesthetic and surgical variables were not different between groups. Pain at rest and on cough was not statistically different between groups. In the placebo group, the median (interquartile range) morphine consumption reached 29 mg (13-53) whereas in patients receiving 80 and 120 mg nefopam, it levelled to 44 mg (11-54) and 35 mg (9-82) respectively (p > 0.05). Patients needed morphine during the same time period whether they received nefopam or not. Patients suffering from adverse effects were similar between groups. CONCLUSION: In this study, continuous administration of nefopam did not reduce morphine consumption nor ameliorate analgesia and thus may not be recommended in urological surgery. Nefopam pharmacokinetics when used with continuous infusion as well as surgery types and differences in age between groups may explain these results.     

Perioperative nimodipine and postoperative analgesia

There is experimental evidence that nimodipine, an L-type dihydropiridine calcium channel blocker with relatively high blood-brain barrier penetration, enhances the antinociceptive properties of morphine. We tested the hypothesis that oral nimodipine taken preoperatively and 6 hourly for 48 h postoperatively would reduce visual analog scale pain scores and morphine consumption in morphine-naive patients with acute postoperative pain. Forty patients undergoing total knee replacement surgery (age 70 +/- 7 yr, 28 male) were randomized by computer-generated numbers to receive capsules containing either nimodipine 30 mg or placebo in a double-blind study design. All patients received 3 capsules (nimodipine 90 mg or placebo) 1-2 h before induction of anesthesia followed by oral nimodipine 30 mg or placebo 6 hourly for 48 hours postoperatively. Spinal anesthesia was induced with hyperbaric bupivacaine 0.5% (2.4-3.0 mL) and fluids and ephedrine were given at the discretion of the anesthesiologist. Morphine patient-controlled analgesia (PCA, bolus 1 mg, lockout 5 min) was given for postoperative analgesia. Primary outcome measures were visual analog pain scores at rest and on moving (sitting forward) and PCA morphine consumption. Morphine consumption was significantly larger in nimodipine patients at 12 h (39 +/- 18 versus 29 +/- 15; P = 0.04), 24 h (62 +/- 23 versus 45 +/- 24; P = 0.02), and 48 h (88 +/- 34 versus 61 +/- 27; P = 0.01). There were no significant differences in pain scores at rest or moving or in time to first use of morphine analgesia. This study has demonstrated increased morphine consumption after 12 h in postoperative patients receiving nimodipine, suggesting that, in patients undergoing knee replacement surgery, it has no adjunctive analgesic effect and may actually inhibit the analgesic effect of morphine.     

Intravenous ketoprofen in thyroid and parathyroid surgery

We compared the ketoprofen-propacetamol combination relative to propacetamol alone in thyroid and parathyroid surgery in terms of postoperative analgesic efficacy, bleeding, and incidence of nausea and vomiting to determine whether ketoprofen results in any benefit in this type of surgery. Patients were distributed in two parallel groups to be managed by anesthesiologists habitually prescribing (Ketoprofen group) or not prescribing (Control group) ketoprofen in this situation. The same anesthetic technique was used for all patients. Postoperative analgesia consisted of 2 g of propacetamol every 6 h and morphine boluses if the pain score measured by the numerical rating scale pain exceeded 40 (3 mg IV every 10 min in the recovery room, then 5 mg SC every 4 h in the ward). The Ketoprofen group received 100 mg of ketoprofen IV during surgery (starting on resection of specimen) and 8 h later. In the recovery room, patients received oxygen if the SpO(2) while they were breathing room air was < 95% on admission and at 1 and 2 h. Pain scores, opioid consumption, the volume of the cervical draining fluid, and the concentration and mass of hemoglobin in this fluid collected over 24 h were recorded. The 214 patients were distributed into two groups (n = 107 in each group) that were comparable in terms of age, weight, sex, duration of surgery, type of endocrinopathy, surgeon involvement, and the intraoperative dose of sufentanil (P > 0.2). The Ketoprofen group had lower numerical rating scale (P < 0.05), received less morphine during the first 24 h after surgery (7.4 +/- 5 vs 11.7 +/- 6 mg, P < 0.05), had fewer nausea and vomiting episodes (21 vs 38, P < 0.05), and were less likely to require oxygen breathing after 1 h in the recovery room (33 vs 59 patients, P < 0.05). The two groups had the same 24-h volume of cervical draining fluid (72.5 +/- 43 vs 70 +/- 42 mL, P > 0.2) and the same concentration (5.9 +/- 3.4 vs 6.4 +/- 2.8 g per 100 mL, P > 0.1) and mass of hemoglobin (3.9 +/- 2.8 vs 4.2 +/- 2.5 g, P > 0.2) in this collected fluid. Two cervical hematomas necessitating reintervention occurred in the Control group, compared with none in the Ketoprofen group. Ketoprofen reduces the pain score after thyroid and parathyroid surgery, as well as morphine requirements and related adverse effects, without increasing the risk of cervical bleeding. IMPLICATIONS: In a prospective open study, ketoprofen reduced the pain score after thyroid and parathyroid surgery, as well as morphine requirements and related adverse effects, without increasing the risk of cervical bleeding.     

术前口服罗非昔布对双膝关节置换术后疼痛和全身炎性反应的影响

目的探讨术前环氧化酶2抑制剂罗非昔布是否能增强双膝关节置换术后吗啡的镇痛作用,及其对术后全身炎性反应的影响.方法 30例因关节炎需行双膝关节置换手术患者,通过抓阄方法随机分为罗非昔布加硬膜外镇痛组(RE组)和硬膜外镇痛组(E组),每组15例.RE组在术晨口服罗非昔布25 mg,其余同E组.所有患者均以异氟醚、硬膜外0.75%布比卡因复合维持麻醉.术毕连接患者自控镇痛泵 (1.2 mg/ml布比卡因加0.1 mg/ml吗啡加0.02 mg/ml氟哌利多)镇痛72 h.分别在术前、术毕、及术后2、6、12、24、48 h时抽取股静脉血,检测白细胞总数及分类,以及炎性细胞因子白介素6、8、10和肿瘤坏死因子-α.术后24、48、72 h各进行疼痛评分,记录比较每日吗啡用量、镇痛满意度、镇痛期间副作用以及术中出血量和术后关节引流量.结果复合罗非昔布可明显降低术后24 h静息、48 h静息和活动时疼痛评分.RE组提高术后24 h镇痛满意度为100%,高于E组60%(χ2＝6.71,P<0.01).RE组术后24 h平均吗啡消耗量为6.8 mg明显低于E组8.1 mg,(t=-2.71,P<0.05).RE组血白细胞和嗜中性粒细胞数在12 h和24 h明显低于E组.RE组血浆白介素6含量在术后48 h,白介素8含量在术后24 h明显低于E组.RE组术毕、术后6 h、12 h肿瘤坏死因子-α明显低于E组(t值分别为-2.4、-2.25、-2.41,P值均<0.05).结论术前口服罗非昔布可明显改善双膝置换术后疼痛,增加镇痛满意度,减轻全身炎性反应,减少吗啡用量.     

Low-dose intravenous ketamine potentiates epidural analgesia after thoracotomy

BACKGROUND: Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain. METHODS: Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg . kg(-1) . h(-1) [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery. RESULTS: The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03). CONCLUSIONS: Very-low-dose ketamine (0.05 mg . kg(-1) . h(-1)) potentiated morphine-ropivacaine analgesia and reduced postthoracotomy pain.     

Low-dose Intravenous Ketamine Potentiates Epidural Analgesia after Thoracotomy

Background: Ketamine potentiates intravenous or epidural morphine analgesia. The authors hypothesized that very-low-dose ketamine infusion reduces acute and long-term postthoracotomy pain.

Methods: Forty-nine patients scheduled to undergo open thoracotomy were randomly assigned to receive one of two anesthesia regimens: continuous epidural infusion of ropivacaine and morphine, along with intravenous infusion of ketamine (0.05 mg [middle dot] kg-1 [middle dot] h-1 [approximately 3 mg/h], ketamine group, n = 24) or placebo (saline, control group, n = 25). Epidural analgesia was continued for 2 days after surgery, and infusion of ketamine or placebo was continued for 3 days. Pain was assessed at 6, 12, 24, and 48 h after surgery. Patients were asked about their pain, abnormal sensation on the wound, and inconvenience in daily life at 7 days and 1, 3, and 6 months after surgery.

Results: The visual analog scale scores for pain at rest and on coughing 24 and 48 h after thoracotomy were lower in the ketamine group than in the control group (pain at rest, 9 +/- 11 vs. 25 +/- 20 and 9 +/- 11 vs. 18 +/- 13; pain on coughing, 26 +/- 16 vs. 50 +/- 17 and 30 +/- 18 vs. 43 +/- 18, mean +/- SD; P = 0.002 and P = 0.01, P < 0.0001 and P = 0.02, respectively). The numerical rating scale scores for baseline pain 1 and 3 months after thoracotomy were significantly lower in the ketamine group (0.5 [0-4] vs. 2 [0-5] and 0 [0-5] vs. 1.5 [0-6], median [range], respectively; P = 0.02). Three months after surgery, a higher number of control patients were taking pain medication (2 vs. 9; P = 0.03).     

The median effective dose of nefopam and morphine administered intravenously for postoperative pain after minor surgery: a prospective randomized double-blinded isobolographic study of their analgesic action

The aim of this study was to characterize the nature of analgesic interaction between nefopam and morphine administered i.v. for postoperative pain after minor surgery. To do so, we defined the median effective analgesic dose (ED(50)) for each drug and also the median ED(50) of their combination and compared them using the isobolographic method. Determination of median effective doses was performed by the up-and-down sequential drug administration in a two-stage study. First, in a prospective, randomized, double-blinded study, we enrolled 60 patients with mild to moderate pain after minor surgery; this was followed by an open study enrolling 30 patients. The end-point was a pain score less than 3 on a Numerical Pain Scale (0-10). Initial doses were 16 mg in group N, 5 mg in group M, and 7.5 mg of N combined with 2.5 mg of M in group N+M. The testing interval was 2 mg in group N, 1 mg in group M, and 1.5 mg of N combined with 0.5 mg of M in group N+M. ED(50) (95% confidence interval) was 5 mg (4-6 mg) for morphine, 18 mg (16-18 mg) for nefopam, and 4 mg (3.5-4.5 mg) with 12 mg (10.5-13.5 mg) for the combination of morphine and nefopam administered at a 3:1 dose ratio. Isobolographic analysis demonstrated a significant infra-additive interaction. The incidence of side effects did not differ significantly among morphine, nefopam, and their combination. These findings suggest that the combination of nefopam and morphine does not offer any advantage compared to each drug administered i.v. or alone after minor surgery. This study is the first to define the ED(50) of nefopam and morphine in postoperative patients. In conclusion, the addition of nefopam has a morphine-sparing effect, but the combination is infra-additive. IMPLICATIONS: Pharmacologic interaction between nefopam and morphine shows infra-additivity but their combination may be clinically useful as morphine consumption is decreased in postoperative patients.     

A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain

We compared the analgesic effect of lumbar intrathecal (IT) 0.5 mg morphine (Group M, n = 10), 50 microg sufentanil (Group S, n = 10), and their combination (Group S-M, n = 10) given before general anesthesia and patient-controlled analgesia with IV morphine (Group C, n = 19) in a randomized, double-blinded study performed in patients undergoing thoracotomy. Pain visual analog scale (VAS) and morphine consumption were assessed for 24 h. In Group S-M the number of patients initially titrated with IV morphine was less than in group C (30 vs 84%, P < 0.05). Morphine requirement was higher in Group C (71 +/- 30 mg) than in Groups S (46 +/- 34 mg, P < 0.05), M (38 +/- 31 mg, P < 0.05) and S-M (23 +/- 16 mg, P < 0.01). VAS scores were significantly decreased during the first 0-11 postoperative h at rest and during the first 0-8 postoperative h on coughing in Groups M and S-M rather than in Group C. The incidence of side effects was infrequent except for urinary retention. Preoperative IT morphine or combined sufentanil and morphine could be given as a booster to achieve rapidly effective analgesia in the immediate postoperative period. Implications: As compared with IV patient-controlled analgesia, intrathecal morphine or combined sufentanil and morphine provided superior postoperative pain relief both at rest (11 h) and on coughing (8 h) than did IV patient-controlled analgesia morphine alone. IV morphine requirement was decreased during the first postoperative day after posterolateral thoracotomy.     

Perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine consumption after major abdominal surgery

Sodium channel blockers are approved for IV administration in the treatment of neuropathic pain states. Preclinical studies have suggested antihyperalgesic effects on the peripheral and central nervous system. Our objective in this study was to determine the time course of the analgesic and antihyperalgesic mechanisms of perioperative lidocaine administration. Forty patients undergoing major abdominal surgery participated in this randomized and double-blinded study. Twenty patients received lidocaine 2% (bolus injection of 1.5 mg/kg in 10 min followed by an IV infusion of 1.5 mg. kg(-1). h(-1)), and 20 patients received saline placebo. The infusion started 30 min before skin incision and was stopped 1 h after the end of surgery. Lidocaine blood concentrations were measured. Postoperative pain ratings (numeric rating scale of 0-10) and morphine consumption (patient-controlled analgesia) were assessed up to 72 h after surgery. Mean lidocaine levels during surgery were 1.9 +/- 0.7 microg/mL. Patient-controlled analgesia with morphine produced good postoperative analgesia (numeric rating scale at rest, 相似文献   

Development of acute opioid tolerance during infusion of remifentanil for pediatric scoliosis surgery

We tested the hypothesis that continuous intraoperative infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery. Thirty adolescents were randomly assigned to receive an intraoperative analgesic regimen consisting of continuous remifentanil infusion or intermittent morphine alone. Postoperative analgesic consumption was assessed with a patient-controlled analgesia device that was used to self-administer morphine. Cumulative postoperative morphine consumption, pain scores, and sedation scores were recorded by a blinded investigator every hour for the first 4 h postoperatively and then every 4 h for a total of 24 h. Cumulative morphine consumption in the remifentanil group was significantly more than that in the morphine group at each time point in the initial 24 h after surgery (P < 0.0001). At 24 h after surgery, cumulative morphine consumption was 30% greater in the remifentanil group (1.65 +/- 0.41 mg/kg) than in the morphine group (1.27 +/- 0.32 mg/kg) (95% confidence interval for the difference, 0.11 to 0.65 mg/kg). Differences in pain and sedation scores were not statistically significant. These data suggest that intraoperative infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery.     

Evaluation of buprenorphine hydrochloride suppositories for postoperative pain relief]

An analgesic is often administered upon the occurrence of pain following surgery. Buprenorphine hydrochloride suppository (0.2 mg) was given immediately postoperatively to patients who had undergone surgery under general anesthesia. Post-operative pain has been observed after 782 +/- 41 minutes (n = 148, mean +/- SE) in the patients with suppository and 127 +/- 18 minutes (n = 57) in the control group (P less than 0.01). Analgesics were given to 68% of the control group within 2 hours, while it was given to 14% of the study group. Further 57% of the latter did not complain of any pain after 20 hours. The pharmacokinetics of buprenorphine was studied in 7 patients. Intrarectal administration of 0.2 mg buprenorphine suppository just after surgery had a sufficient analgesic action and did not induce any adverse reactions of any clinical importance.     

Preoperative ketamine improves postoperative analgesia after gynecologic laparoscopic surgery

In this study, we evaluated the preemptive effect of a small dose of ketamine on postoperative wound pain. In a randomized, double-blinded, controlled trial, we compared the analgesic requirement in patients receiving preincision ketamine with ketamine after skin closure or placebo after gynecologic laparoscopic surgery. One-hundred-thirty-five patients were randomly assigned to receive preincision or postoperative ketamine 0.15 mg/kg or saline IV. Anesthetic technique was standardized. Patients were interviewed regularly up to 4 wk after surgery. Pain score, morphine consumption, side effects, and quality of recovery score were recorded. Patients receiving preincision ketamine had a lower pain score in the first 6 h after operation compared with the postoperative (P = 0.001) or placebo groups (P < 0.001). The mean (95% confidence intervals) time to first request for analgesia in the preincision group, 1.8 h (1.4-2.1), was longer than the postoperative group, 1.2 h (0.9-1.5; P < 0.001), or the placebo group, 0.7 h (0.4-0.9; P < 0.001). The mean +/- SD morphine consumption in the preincision group, 1.5 +/- 2.0 mg, was less than that in the postoperative group, 2.9 +/- 3.1 mg (P = 0.04) and the placebo group, 3.4 +/- 2.7 mg (P = 0.003). There was no significant difference among groups with respect to hemodynamic variables or side effects. No patient complained of hallucinations or nightmares. We conclude that a small dose of ketamine is not only safe, but it also provides preemptive analgesia in patients undergoing gynecologic laparoscopic surgery. IMPLICATIONS: In women undergoing laparoscopic gynecologic surgery, a small preoperative dose of ketamine (0.15 mg/kg) produced preemptive analgesia. There were no significant hemodynamic and psychological side effects with this dose.     

Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery

BACKGROUND: Intravenous acetaminophen injection (paracetamol) is marketed in Europe for the management of acute pain. A repeated-dose, randomized, double-blind, placebo-controlled, three-parallel group study was performed to evaluate the analgesic efficacy and safety of intravenous acetaminophen as compared with its prodrug (propacetamol) and placebo. Propacetamol has been available in many European countries for more than 20 yr. METHODS: After orthopedic surgery, patients reporting moderate to severe pain received either 1 g intravenous acetaminophen, 2 g propacetamol, or placebo at 6-h intervals over 24 h. Patients were allowed "rescue" intravenous patient-controlled analgesia morphine. Pain intensity, pain relief, and morphine use were measured at selected intervals. Safety was monitored through adverse event reporting, clinical examination, and laboratory testing. RESULTS: One hundred fifty-one patients (intravenous acetaminophen: 49; propacetamol: 50; placebo: 52) received at least one dose of study medication. The intravenous acetaminophen and propacetamol groups differed significantly from the placebo group regarding pain relief from 15 min to 6 h (P < 0.05) and median time to morphine rescue (intravenous acetaminophen: 3 h; propacetamol: 2.6 h; placebo: 0.8 h). Intravenous acetaminophen and propacetamol significantly reduced morphine consumption over the 24-h period: The total morphine doses received over 24 h were 38.3 +/- 35.1 mg for intravenous acetaminophen, 40.8 +/- 30.2 mg for propacetamol, and 57. 4 +/- 52.3 mg for placebo, corresponding to decreases of -33% (19 mg) and -29% (17 mg) for intravenous acetaminophen and propacetamol, respectively. Drug-related adverse events were reported in 8.2%, 50% (most of them local), and 17.3% of patients treated with intravenous acetaminophen, propacetamol, and placebo, respectively. CONCLUSION: Intravenous acetaminophen, 1 g, administered over a 24-h period in patients with moderate to severe pain after orthopedic surgery provided rapid and effective analgesia and was well tolerated.