Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia

Background. We have reviewed the analgesic efficacies of rectaland parenteral paracetamol and tested the evidence for a possibleadditive analgesic effect of the combination of paracetamolwith a non-steroidal anti-inflammatory drug (NSAID) in postoperativepain. Methods. Randomized controlled trials were evaluated. Outcomemeasures were pain scores and demand for supplementary analgesia. Results. Eight studies compared rectal paracetamol with placebo.One study of single-dose administration of rectal paracetamol40–60 mg kg^–1 and three studies of repeatdosing with 14–20 mg kg^–1 showed significantanalgesic efficacy, while studies of a single dose of 10–20 mg kg^–1were negative. Ten studies compared parenteral paracetamol withplacebo and eight studies showed improved pain relief with paracetamol.Of the nine studies comparing paracetamol with a combinationof paracetamol and an NSAID, six studies showed improved painrelief for the combination while only two of the six studiescomparing an NSAID with a combination of an NSAID and paracetamolshowed improved pain relief for the combination. Conclusions. Considering the few studies available, evidencewas found of a clinically relevant analgesic effect of rectaland parenteral paracetamol. Concurrent use of paracetamol andan NSAID was superior to paracetamol alone but no evidence wasfound of superior analgesic effect of the combination comparedwith the NSAID alone. Br J Anaesth 2002; 88: 215–26     

Double-blind, placebo-controlled analgesic study of ibuprofen or rofecoxib in combination with paracetamol for tonsillectomy in children

Background. The analgesics used for paediatric tonsillectomymay be associated with side-effects such as sedation, respiratorydepression and vomiting (opioids) or increased bleeding [non-steroidalanti-inflammatory drugs (NSAIDs)]. In our institution, we employa combination of paracetamol, NSAID and opioid, although thereis no published evidence of analgesic benefit from adding NSAIDsto paracetamol in children. Methods. This randomized, double-blinded clinical study examinedthe analgesic effectiveness of combining paracetamol (20 mg kg^–1)with rofecoxib (0.625 mg kg^–1), ibuprofen (5 mg kg^–1)or placebo as premedication for (adeno)tonsillectomy (n=98)in children aged 3–15 yr. Intravenous fentanyl 1–2 µg kg^–1was given intraoperatively. Regular oral paracetamol (15 mg kg^–1,4 hourly) was given after operation and could be supplementedon request from the child with oral ibuprofen 5 mg kg^–1or oral codeine 1 mg kg^–1. The primary outcomevariable was need for early supplementary analgesia (within2 h after surgery). Results. The addition of ibuprofen to paracetamol reduced theneed for early analgesia from 72% to 38% of children (difference34%; 95% confidence interval 4–64%). The addition of rofecoxibto paracetamol did not significantly alter the need for earlyanalgesia (68 vs 72%). Pain scores were higher in those childrenwho required early analgesia. There were no differences betweenthe groups in operative blood loss or complications, total 24-hanalgesic consumption, pain scores at 4 and 8 h, vomiting orantiemetic use. Conclusion. This study provides evidence to support the combinationof ibuprofen (but not rofecoxib) with paracetamol for perioperativeanalgesia in children. Br J Anaesth 2002; 88: 72–7     

The preoperative administration of ketoprofen improves analgesia after laparoscopic cholecystectomy in comparison with propacetamol or postoperative ketoprofen

Background. Non-opioid analgesics, paracetamol and non-steroidanti-inflammatory drugs (NSAIDs) are proposed for pain reliefafter laparoscopy. We compared perioperative propacetamol (P)and ketoprofen (K) to provide analgesia after laparoscopic cholecystectomy. Methods. After ethical committee approval, we included 104 ASAI–II patients, without preoperative analgesic drugs, whowere scheduled to undergo laparoscopic cholecystectomy. Anaesthesiawas standardized using propofol, fentanyl, atracurium, isofluraneand N₂O 50%. Ketoprofen 100 mg or propacetamol 2 g or a salinedrip (a 100-ml unit of saline in 10 min) was infused blindlyand randomly. Patients received either ketoprofen (group K1)or propacetamol (group P1) before induction of anaesthesia andsaline after surgery, or saline before surgery and ketoprofen(group K2) or propacetamol (group P2) after surgery. Postoperativevisual analogue pain scores (VAS 0–100 mm) were recordedduring 24 h. If VAS was >30, a second dose (placebo, ketoprofenor propacetamol) was infused. Nalbuphine 0.2 mg kg^–1 i.v.was given as rescue analgesic if VAS was 50. Results. Ninety-eight patients were studied The number of patientsnot requiring the second analgesic was greater in K1 (33.5%)than the others (K2 0%, P1 0%, P2 7.5%). VAS scores were significantlylower in K1 (P=0.001), with less nalbuphine consumption comparedwith P1. VAS and opioid request were similar in K2 and P2. Conclusion. Preoperative administration of ketoprofen improvespostoperative analgesia after laparoscopic cholecystectomy comparedwith its postoperative administration and pre- and postoperativepropacetamol.     

合用对乙酰氨基酚（扑热息痛）和非甾体抗炎药物对急性术后疼痛镇痛效能的定性系统回顾

背景目前合用非甾体抗炎药（nonsteroidalantiinflammatorydrug，NSAID）和对乙酰氨基酚（扑热息痛）治疗疼痛已经成为趋势。然而，合用两种药物比单一药物治疗的优势仍存在争议。我们比较了各种急性疼痛模型中合用对乙酰氨基酚和NSAID与单用一种药物的疗效。方法系统检索MEDLINE、Embase、CumulativeIndextoNursingandAlliedHealthLiterature和PubMed数据库，时间从1988年1月至2009年6月，选定临床随机对照试验，特别是比较对乙酰氨基酚合用各种NSAIDs与其中一种药物的镇痛。选定的研究资料分为2组：对乙酰氨基酚／NSAID组合与对乙酰氨基酚或NSAIDs。我们将镇痛强度评分和补充镇痛药需求作为主要的评价标准。此外，应用经过验证的量表对每项研究进行质量评分。结果21项临床研究包括1909例患者。使用的NSAIDs包括布洛芬（n：6）、双氯芬酸（n=8）、酮洛芬（n=3）、痛力克（n：1）、阿司匹林（n=1）、替诺昔康（n：1）和罗非昔布（n=1）。分别有85％的研究表明合用两药比单用对乙酰氨基酚有效，64％表明合用两药比单用NSAID有效。在疼痛强度和镇痛药补充方面，阳性结果中联合用药比单用对乙酰氨基酚组分别降低35．0％±10．9％和38．8％±13．1％，联合用药比单用NSAID组分别降低37．7％±26．6％和31．3％±13．4％。实验组之间质量评分中位数无明显差异。结论目前的证据表明，合用对乙酰氨基酚和NSAID比单用任一种药物可能提供更好的镇痛效果。     

Effect of peri- and postoperative epidural anaesthesia on pain and gastrointestinal function after abdominal hysterectomy

In a double blind study we have investigated the effects ofepidural local anaesthesia (LA), when added to general anaesthesia(GA) and postoperative paracetamol and NSAID, on postoperativepain and gastrointestinal function in patients undergoing openhysterectomy. Sixty patients were randomized into three studygroups: GA, and postoperative paracetamol and NSAID (GA, n=20);GA, paracetamol, NSAID, intraoperative epidural lidocaine and24-h postoperative epidural saline (Saline, n=20); or GA, paracetamol,NSAID, intraoperative epidural lidocaine and 24-h postoperativeepidural bupivacaine (Bupi, n=20). Patients were observed for72 h postoperatively. Pain at rest, during cough, and mobilization,request for supplementary morphine, and time to first postoperativeflatus, was reduced in patients receiving 24-h postoperativeepidural anaesthesia, compared with the two other groups. However,these effects of epidural LA, were not sustained beyond theperiod of infusion, and no differences in PONV, time to firstpostoperative defecation, mobilization or time to dischargefrom hospital were observed between groups. A 24 h postoperativeepidural infusion with bupivacaine, when added to postoperativeparacetamol and NSAID, reduces pain and opioid requirements,but has only limited effects on gastrointestinal function andpatient recovery. Br J Anaesth 2001; 87: 577–83     

Propacetamol augments inhibition of platelet function by diclofenac in volunteers

Background. Acetaminophen (paracetamol) enhances the analgesiceffect of non-steroidal anti-inflammatory drugs (NSAIDs). Acetaminophenis a weak inhibitor of cyclooxygenase (COX), and its combinationwith an NSAID may augment COX inhibition-related side effects. Methods. Ten healthy male volunteers (21–30 yr) were givendiclofenac 1.1 mg kg^–1 alone, a combination of propacetamol30 mg kg^–1 (which is hydrolysed to 50% acetaminophen)and diclofenac 1.1 mg kg^–1 or placebo intravenously ina double blind, crossover study. Platelet function was assessedat 5 min, 90 min and 22–24 h by photometric aggregometry,platelet function analyser (PFA-100^TM) and by measuring therelease of thromboxane B₂ (TxB₂). Analgesia was assessed withthe cold pressor test. Results. Platelet aggregation induced with arachidonic acidwas fully inhibited by both diclofenac alone and the combinationat the end of the 30-min drug infusion. Propacetamol augmentedthe inhibition by diclofenac at 90 min (P=0.014). At 22–24h, platelet function had fully recovered. TxB₂ release was inhibitedby the combination of propacetamol and diclofenac at 90 minin comparison with diclofenac alone (P=0.027). PFA-100^TM detectedno difference in platelet function between these two groups.No analgesic effect was detected with the cold pressor test. Conclusions. The combination of propacetamol and diclofenacinhibits platelet function more than diclofenac alone. Thisshould be considered when assessing the risk of surgical bleeding. Br J Anaesth 2003; 91: 357–62     

Effect of oral gabapentin on postoperative epidural analgesia

Background. Gabapentin has been used successfully as a non-opioidanalgesic adjuvant for postoperative pain management. We hypothesizedthat gabapentin might be a useful adjuvant for postoperativeanalgesia provided with patient-controlled epidural analgesia(PCEA). Methods. Forty patients undergoing lower extremity surgery procedureswere randomly assigned to receive (i) placebo capsules (control)or (ii) gabapentin (1.2 g day^–1) before and for 2 daysafter surgery. Anaesthetic technique was standardized. Postoperativeassessments included verbal rating scale scoring for pain andsedation, PCEA usage, quality of recovery assessment, timesof GI function recovery, and patient satisfaction scoring forpain management. Results. Pain scores at 1, 4, 8, 12, and 16 h (P<0.001),PCEA bolus requirements (n) at 24 [21 (3), 14 (2)], 48 [15 (4),10 (3)] and 72 [8 (5), 2 (3)] (P<0.05) and paracetamol (mg)consumption [700 (523), 350 (400)]; P<0.05), were significantlylower in the gabapentin-treated patients than in the controlgroup. Patient satisfaction with postoperative pain managementat 24 h was better in gabapentin-treated patients [85.5 (7.5),66.5 (15)]; P<0.001). Gabapentin-treated patients had lessmotor block when compared with control group. Times of returnof bowel function, hospitalization, and resumption of dietaryintake were similar in the groups. However, the incidence ofdizziness was higher in the gabapentin group (35% vs 5%; P<0.05). Conclusions. Oral gabapentin (1.2 g day^–1) as an adjunctto epidural analgesia decreased pain and analgesic consumption.Despite an increased incidence of dizziness it also increasedpatient satisfaction.      

Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: a systematic review

Non-opioid analgesics, paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), or cyclo-oxygenase 2 (COX-2) inhibitors are often given along with morphine as part of multimodal analgesia after major surgery. We have undertaken a systematic review and a mixed treatment comparison (MTC) analysis in order to determine explicitly which class of non-opioid analgesic, paracetamol, NSAIDs, or COX-2 inhibitors is the most effective in reducing morphine consumption and morphine-related adverse effects. Sixty relevant studies were identified. The MTC found that when paracetamol, NSAIDs, or COX-2 inhibitors were added to patient-controlled analgesia (PCA) morphine, there was a statistically significant reduction in morphine consumption: paracetamol [mean difference (MD) -6.34 mg; 95% credibility interval (CrI) -9.02, -3.65], NSAIDs (MD -10.18; 95% CrI -11.65, -8.72), and COX-2 inhibitors (MD -10.92; 95% CrI -12.77, -9.08). There was a significant reduction in nausea and postoperative nausea and vomiting with NSAIDs compared with placebo (odds ratio 0.70; 95% CrI 0.53, 0.88) but not for paracetamol or COX-2 inhibitors, nor for NSAIDs compared with paracetamol or COX-2 inhibitors. There was no statistically significant difference in sedation between any intervention and comparator. On the basis of six trials (n=695), 2.4% of participants receiving an NSAID experienced surgical-related bleeding compared with 0.4% with placebo. The MTC found that there is a decrease in 24 h morphine consumption when paracetamol, NSAID, or COX-2 inhibitors are given in addition to PCA morphine after surgery, with no clear difference between them. Similarly, the benefits in terms of reduction in morphine-related adverse effects do not strongly favour one of the three non-opioid analgesics.     

Influence of peroperative opioid on postoperative pain after major abdominal surgery: sufentanil TCI versus remifentanil TCI. A randomized, controlled study

Background. Sufentanil and remifentanil are characterized bytwo different pharmacokinetic profiles. The aim of this studywas to compare the effects of sufentanil and remifentanil administeredusing target-controlled infusion (TCI) on recovery and postoperativeanalgesia after major abdominal surgery. Methods. Thirty adult patients scheduled for open colorectalsurgery were included in a prospective, randomized study. SufentanilTCI (sufentanil group) or remifentanil TCI (remifentanil group)was administered during surgery. In the remifentanil group,30 min before the anticipated end of surgery, morphine 0.15mg kg^–1 was administered i.v. In the sufentanil group,an effect-site concentration of 0.25 ng ml^–1 wastargeted at extubation. In both groups, postoperative pain wascontrolled by titration of i.v. morphine and then patient-controlledanalgesia with morphine. Results. The extubation time was similar in the two groups (mean(SD) 13 (6) and 14 (6) min in the sufentanil and remifentanilgroups respectively). Visual analogue scale scores were significantlygreater during the first 2 h after tracheal extubation in theremifentanil group than in the sufentanil group. The time tofirst analgesic request in the postanaesthesia care unit wassignificantly longer in the sufentanil group than in the remifentanilgroup (55 (64) (range 2–240) vs 11 (7) (1–29) min;P<0.001). The cumulative morphine dose for titration wassignificantly greater in the remifentanil group (P<0.01).The cumulative morphine dose used during titration and patient-controlledanalgesia was significantly greater in the remifentanil group4, 12 and 24 h after extubation (P<0.05). Conclusion. TCI sufentanil (0.25 ng ml^–1 effect-siteconcentration at extubation) is more effective than the intraoperativecombination of remifentanil TCI infusion with morphine bolus(0.15 mg kg^–1) for postoperative pain relief aftermajor abdominal surgery and does not compromise extubation andrecovery. Br J Anaesth 2003; 91: 842–9     

Intra-articular injection of warmed lidocaine improves intraoperative anaesthetic and postoperative analgesic conditions

Background. Although local anaesthesia for knee arthroscopyis a well-documented procedure, arthroscopy under local anaesthesiais often interrupted because of intolerable discomfort and pain.Warming local anaesthetic solutions may increase its anaestheticeffect. We tested whether intra-articular injection of warmedlidocaine solution could improve intraoperative anaestheticand postoperative analgesic conditions. Methods. Patients in the warmed group received 20 ml warmed(40°C) lidocaine 1% intra-articularly 20 min before surgery.The patients in the control group received 20 ml room-temperature(25°C) lidocaine 1% intra-articularly 20 min before surgery.During surgery, the patients reported pain on a visual analoguescale (VAS). Results. The median VAS pain score was 1.5 (range, 0.0–3.0)in the warmed lidocaine group and 5.0 (4.0–8.0) in thecontrol group (P<0.001). The median intra- and postoperativeanalgesic requirements in the control group were significantlygreater than that in the warmed group. Conclusion. Warmed lidocaine injected intra-articularly providesimproved intraoperative anaesthetic and postoperative analgesicconditions for patients undergoing knee arthroscopy.