Early analgesic effects of parecoxib versus ketorolac following laparoscopic sterilization: a randomized controlled trial

Background. The aim of this prospective double blind randomizedcontrolled trial was to compare the effects of ketorolac andparecoxib on early postoperative pain. Method. We studied 36 ASA I/II patients who received a standardizedgeneral anaesthetic for laparoscopic sterilization. Patientswere allocated randomly to receive either parecoxib 40 mg i.v.or ketorolac 30 mg i.v., at induction. After surgery, patientswere assessed on awakening and then at 1, 2, and 3 h. Abdominalpain at rest and on inspiration, in addition to nausea and sedationwere assessed on a 100 mm visual analogue scale. Results. Of 36 patients, one was excluded from analysis. Inthe remaining patients, pain scores at rest and on inspirationwere significantly lower in patients given ketorolac comparedwith those given parecoxib. This difference was attributableto the higher pain scores on awakening and at 1 h postoperativelyin the parecoxib group compared with the ketorolac group. Despitethis initial difference, there was no significant differencebetween the two groups in the number of patients receiving rescueanalgesia. The median (interquartile range) time to consumptionof rescue cocodamol of 60 (46–74) min in the parecoxibgroup was not significantly shorter than that of 100 (70–130)min in the ketorolac group. The amount of cyclizine given, nauseaand sedation did not differ significantly between the groups. Conclusion. We found that parecoxib 40 mg i.v. given at inductionof anaesthesia was less effective than or ketorolac 30 mg i.v.,in the first hour after laparoscopic sterilization. Br J Anaesth 2004; 92: 846–9     

Preventive effects of perioperative parecoxib on post-discectomy pain

BACKGROUND: Cyclooxygenase inhibitor treatment is viewed increasingly critical because of safety considerations, and there are several open questions on their optimal use. METHODS: In a randomized placebo-controlled study in 320 patients undergoing discectomy, we administered parecoxib 40 mg either perioperatively (before operation and after operation), after operation (first dose given in the evening after surgery), or before operation (single parecoxib dose given 45 min before surgery). We measured the main outcome variables: average pain score, morphine consumption, and opioid-related symptom distress at 25, 49, and 73 h after surgery. RESULTS: Perioperative parecoxib significantly (i) improved the pain score compared with both placebo and postoperative parecoxib, (ii) decreased morphine consumption, and (iii) reduced the opioid-related symptom distress score. Neither a single preoperative dose nor postoperative parecoxib (first dose given in the evening after surgery) significantly improved morphine's analgesic effectiveness. CONCLUSIONS: Perioperative parecoxib compared with postoperative parecoxib improves post-discectomy pain and results in a reduction in adverse effects associated with opioid therapy. Postoperative parecoxib, or a single pre-incisional parecoxib dose, does not significantly improve post-discectomy pain or opioid side-effects up to 3 days after surgery.     

Adjunctive analgesia with intravenous propacetamol does not reduce morphine-related adverse effects

Background. Propacetamol is widely used in the management ofpostoperative pain. It decreases morphine requirements but itseffect on the incidence of morphine-related adverse effectsremains unknown. Methods. Patients (550) were randomly assigned to receive propacetamolor a placebo over the first 24 h after operation in a blindedstudy. Intravenous morphine titration was performed, after whichmorphine was administered s.c. every 4 h according to theirpain score. Pain was assessed using a visual analogue scale(VAS). The primary end-point was the incidence of morphine-relatedadverse effects. The main secondary end-points were morphinerequirements and VAS score. Results. After morphine titration, the VAS score and the numberof patients with pain relief did not differ between groups.Morphine requirements were decreased in the propacetamol group(21 vs 14.5 mg, P<0.001) but the incidence of morphine-relatedadverse effects did not differ between groups (42 vs 46%, notsignificant). In patients with moderate pain (n=395), morphinerequirements decreased by 37% (P<0.001) and the percentageof patients requiring no morphine was greater (21 vs 8%, P=0.002)in the propacetamol group. In patients with severe pain (n=155),morphine requirements decreased by 18% (P=0.04) in the propacetamolgroup and the number of patients who did not require morphine(3 vs 8%) did not differ significantly. Conclusions. Although propacetamol induced a small morphine-sparingeffect, it did not change the incidence of morphine-relatedadverse effects in the postoperative period. Moreover, no benefitcould be demonstrated in patients with severe postoperativepain. Br J Anaesth 2003; 90: 314–19     

Dolasetron prophylaxis reduces nausea and postanaesthesia recovery time after remifentanil infusion during monitored anaesthesia care for extracorporeal shock wave lithotripsy

Background. Remifentanil is used as an analgesic for differentprocedures performed during monitored anaesthesia care. Opioid-inducednausea and vomiting can be troublesome. Methods. This prospective, randomized, double-blind study wasperformed to evaluate the efficacy of prophylaxis with dolasetronin reducing the frequency of postoperative nausea and durationof discharge time. Forty urological patients, undergoing electiveambulatory extracorporeal shock wave lithotripsy (ESWL) receivedrandomly either dolasetron 12.5 mg i.v. (Group 1) or placebo(Group 2) 10 min before a patient-adapted continuous infusionof remifentanil 0.15–0.4 µg kg^–1 min^–1was administered. Frequency and intensity (VAS 0–100 mm)of nausea, retching, and vomiting were assessed by patientsand blinded investigators during and after the procedure. Results. Patient characteristics, baseline values, durationof ESWL, and total dose of remifentanil did not differ betweengroups. The frequency (Group 1/Group 2; 20/55%; P<0.05) andmean (SD) maximal intensity [15 (9)/45 (14) mm; P<0.05] ofnausea during 24 h was significantly reduced after dolasetronand discharge times in Group 1 were less than Group 2[22 (14)/45 (28) min; P<0.05]. Br J Anaesth 2003; 90: 194–8     

Analgesic efficacy of rectal acetaminophen and ibuprofen alone or in combination for paediatric day-case adenoidectomy

Background. Acetaminophen and non-steroidal anti-inflammatorydrugs have different mechanisms of action. We investigated ifcombining rectal acetaminophen with ibuprofen would providebetter postoperative analgesia compared with either drug aloneafter adenoidectomy in children. Methods. 160 children, aged 1–6 yr, undergoing day-caseadenoidectomy, were randomized to receive either acetaminophen40 mg kg^–1, ibuprofen 15 mg kg^–1, their combination,or placebo rectally immediately after anaesthetic induction.A standard anaesthetic method was used and all children receivedalfentanil 10 µg kg^–1 i.v. during induction. Meperidine5–10 mg i.v. was used for rescue analgesia for a painscore (Objective Pain Scale) over 3. Recovery times, sedationscores and the need for rescue analgesia and adverse eventsduring the first 24 h after anaesthesia were recorded. Rescueanalgesic at home was ibuprofen 10 mg kg^–1. Results. Total meperidine requirements were significantly lessin the groups receiving acetaminophen, ibuprofen, or their combinationcompared with the group receiving placebo indicating an opioid-sparingeffect of 19–28% (P<0.05). Children given acetaminophenwere more sedated than those given ibuprofen (P<0.05). Dischargecriteria were fulfilled earlier in the ibuprofen group thanin all the other groups (P<0.05). At home, less children(49%) needed rescue analgesia in the combination group comparedwith the other groups (74–77%) (P<0.02). Conclusions. We conclude that prophylactically administeredrectal acetaminophen combined with ibuprofen does not improveanalgesia after adenoidectomy in the immediate postoperativeperiod compared with either drug alone but does decrease theneed for analgesia at home. Ibuprofen results in lesser sedationand faster discharge than when acetaminophen is used. Br J Anaesth 2003; 91: 363–7     

Codeine phosphate in paediatric medicine

Br J Anaesth 2001; 86: 413–21     

Spread of subarachnoid block, intraoperative local anaesthetic requirements and postoperative analgesic requirements in Caesarean section and total abdominal hysterectomy

Background. Pregnancy is associated with a higher spread ofsubarachnoid anaesthesia and increased pain threshold. The studywas designed to assess the spread of subarachnoid block andthe intra- and postoperative analgesic requirements in pregnantvs non-pregnant women. Methods. We assessed the level of subarachnoid anaesthesia after1.8 ml of hyperbaric lidocaine 5% and the postoperative analgesicrequirements in women undergoing Caesarean section and undergoingabdominal hysterectomy (30 each group). Intraoperatively epiduralropivacaine was given as required. All patients received 10ml of ropivacaine 0.2% epidurally 2, 10, and 24 h after operationand the VAS pain score was assessed. They also had access topatient controlled analgesia i.v. morphine. Results. Duration of surgery was 64 (13.7) vs 127 (33.8) min(P<0.0001) in the pregnant and non-pregnant groups. Ten minutesafter subarachnoid injection, sensory block was higher by threedermatomes in the pregnant group (P<0.0001). Time to firstropivacaine dose was 37 (19.7) vs 19 (12.2) min (P<0.001)and the ropivacaine normalized for the duration of anaesthesiawas 0.8 (0.6) vs 1.3 (0.5) mg^–1 (P=0.001) in the pregnantand non-pregnant groups, respectively. The time between thefirst and second ropivacaine dose was similar in the two groups(P=0.070). Fewer pregnant women (81 vs 100%) required ropivacaineintraoperatively (P=0.017). The VAS scores were similar butparturients consumed more i.v. morphine (33 (14) vs 24 (12)mg, P=0.016) during the first 24 h after operation. Conclusions. Pregnant patients exhibited a higher level of subarachnoidsensory block and required more i.v. morphine after operation.     

Lack of analgesic effect of parecoxib following laparoscopic cholecystectomy

BACKGROUND: The cyclo-oxygenase-2 inhibitor, parecoxib, can be administered parenterally. The recommended dose for post-operative use is 40 mg twice daily, which may not be the appropriate dose for the treatment of visceral pain. We studied the effect of a single dose of parecoxib of either 40 or 80 mg in laparoscopic cholecystectomy, and its effect on opioid-induced side-effects. METHODS: Seventy-three patients scheduled for elective laparoscopic cholecystectomy were enrolled in this prospective, randomized, double-blind study. Patients were randomized into three groups: a placebo-treated control group, a 40-mg parecoxib-treated group (P40) and an 80-mg parecoxib-treated group (P80). We recorded the cumulative fentanyl consumption during the first 20 h post-operatively by patient-controlled analgesia equipment, the pain scores during rest, coughing and mobilization (visual analogue scale, 0-10), the worst pain during the first 2 h post-operatively and in the following 18 h, and the side-effects by questionnaire. RESULTS: No significant differences in fentanyl consumption between the three groups could be detected. The worst pain experienced between 2 and 20 h post-operatively on the ward was significantly lower in the P80 group than in the control group. CONCLUSION: The recommended dose of parecoxib, 40 mg, is not effective for the treatment of pain during the early post-operative period after laparoscopic cholecystectomy. Doubling the dose to 80 mg seems to improve the results.     

Rectal acetaminophen does not reduce morphine consumption after major surgery in young infants

BACKGROUND: The safety and value of acetaminophen (paracetamol) in additionto continuous morphine infusion has never been studied in newbornsand young infants. We investigated the addition of acetaminophento evaluate whether it decreased morphine consumption in thisage group after major thoracic (non-cardiac) or abdominal surgery. METHODS: A randomized controlled trial was performed in 71 patients giveneither acetaminophen 90–100 mg kg^–1 day^–1orplacebo rectally, in addition to a morphine loading dose of100 µg kg^–1 and 5–10 µg kg^–1h^–1 continuous infusion. Analgesic efficacy was assessedusing Visual Analogue Scale (VAS) and COMFORT scores. Extramorphine was administered if VAS was 4. RESULTS: We analysed data of 54 patients, of whom 29 received acetaminophenand 25 received placebo. Median (25–75th percentile) agewas 0 (0–2) months. Additional morphine bolus requirementsand increases in continuous morphine infusion were similar inboth groups (P = 0.366 and P = 0.06, respectively). There wasno significant difference in total morphine consumption, respectively,7.91 (6.59–14.02) and 7.19 (5.45–12.06) µg kg^–1 h^–1for the acetaminophen and placebo group (P = 0.60). COMFORT[median (25–75th percentile) acetaminophen 10 (9–12)and placebo 11 (9–13)] and VAS [median (25–75thpercentile) acetaminophen 0.0 (0.0–0.2) and placebo 0.0(0.0–0.3)] scores did not differ between acetaminophenand placebo group (P = 0.06 and P = 0.73, respectively). CONCLUSIONS: Acetaminophen, as an adjuvant to continuous morphine infusion,does not have an additional analgesic effect and should notbe considered as standard of care in young infants, 0–2months of age, after major thoracic (non-cardiac) or abdominalsurgery.     

Postoperative morphine requirements, nausea and vomiting following anaesthesia for tonsillectomy. Comparison of intravenous morphine and non-opioid analgesic techniques

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be as effective as opioid analgesia following tonsillectomy in children. Opioids are still frequently used but tonsillectomy is associated with a high incidence of vomiting. This study has attempted to assess postoperative analgesic consumption and nausea and vomiting after general anaesthesia for tonsillectomy using either paracetamol premedication, paracetamol plus a NSAID or intravenous morphine to provide postoperative analgesia. Some children required a rescue dose of morphine in the recovery room, including some who had received intravenous morphine at induction. Least supplementary morphine was required by those who had received paracetamol plus ketorolac. Postoperative nausea and vomiting was significantly less in the two groups which were not given intraoperative morphine. The number of vomiting incidents was also much less. We conclude that the preoperative administration of paracetamol alone provides satisfactory analgesia in many children but that supplementary analgesia is still required for some.     

Effects of acetaminophen on morphine side-effects and consumption after major surgery: meta-analysis of randomized controlled trials

Background. Acetaminophen is commonly used for the managementof perioperative pain. However, there is a marked discrepancybetween the extent to which acetaminophen is used and the availableevidence for an analgesic effect after major surgery. The aimof this systematic review is to determine the morphine-sparingeffect of acetaminophen combined with patient-controlled analgesia(PCA) with morphine and to evaluate its effects on opioid-relatedadverse effects. Methods. MEDLINE and the Cochrane Library were searched to selectrandomized controlled trials which compared PCA morphine alonewith PCA morphine plus acetaminophen administered orally orintravenously. Studies were evaluated for their quality basedon the Oxford Quality Scale. Outcome measures were morphineconsumption over the first 24 h after surgery, patient satisfactionand the incidence of morphine side-effects, including nauseaand vomiting, sedation, urinary retention, pruritus and/or respiratorydepression. Results. Seven prospective randomized controlled trials, including265 patients in the group with PCA morphine plus acetaminophenand 226 patients in the group with PCA morphine alone, wereselected. Acetaminophen administration was not associated witha decrease in the incidence of morphine-related adverse effectsor an increase in patient satisfaction. Adding acetaminophento PCA was associated with a morphine-sparing effect of 20%(mean, –9 mg; CI –15 to –3 mg; P=0.003) overthe first postoperative 24 h. Conclusion. Acetaminophen combined with PCA morphine induceda significant morphine-sparing effect but did not change theincidence of morphine-related adverse effects in the postoperativeperiod.      

Is morphine-induced sedation synonymous with analgesia during intravenous morphine titration?

Background. Postoperative morphine titration frequently inducessedation. The assumption is made that patients sleep when theirpain is relieved. Some patients complain of persistent painwhen they awake. We studied the time-course of sedation andanalgesia to understand the determinants of patients’sleep during morphine titration. Methods. Seventy-three patients requiring morphine titrationin a post-anaesthetic care unit after major surgery, were studied.Fifty-two patients slept (Sleep group) and 21 did not (Awakegroup). When a patient slept during titration, morphine wasdiscontinued. Visual analogue pain scale (VAS), Ramsay score(RS), and the bispectral index (BIS) were recorded at the beginningof titration (STonset), at sleep onset (STsleep), then 5, 10,20, and 30 min afterwards (ST4). Results. In the Sleep group, mean (SD) RS increased from 1.7(0.4) to 2.4 (0.6) (P<0.05 vs STonset) and BIS decreasedfrom 95 (5.0) to 89.8 (10.2) between STonset and STsleep (P<0.05),RS remained stable thereafter. Conversely, RS and BIS remainedunaltered in the Awake group. The reduction in VAS was comparablebetween groups (from 78 (17) to 39 (21), and from 64 (16) to30.4 (11), respectively). Even though mean (SD) VAS was 39 (21)at ST4 in the Sleep group, 13 patients (25%) maintained a VASabove 50 mm. Conclusion. We observed dissociated effects of morphine on thetime-course of sedation and analgesia with sedation occurringfirst, followed by analgesia. Therefore, morphine-induced sedationshould not be considered as an indicator of an appropriate correctlevel of analgesia during i.v. morphine titration. Br J Anaesth 2002; 89: 697–701     

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     

A systematic review of COX-2 inhibitors compared with traditional NSAIDs, or different COX-2 inhibitors for post-operative pain

BACKGROUND: We have reviewed the analgesic efficacy of cyclooxygenase-2 (COX-2) inhibitors compared with traditional non-steroidal anti-inflammatory drugs (NSAIDs), different COX-2 inhibitors, and placebo in post-operative pain. METHODS: Randomized controlled trials were evaluated. Outcome measures were pain scores and demand for supplementary analgesia 0-24 h after surgery. RESULTS: Thirty-three studies were included in which four COX-2 inhibitors, rofecoxib 50 mg, celecoxib 200 and 400 mg, parecoxib 20, 40 and 80 mg, and valdecoxib 10, 20, 40, 80 mg were evaluated. Ten of these studies included 18 comparisons of rofecoxib, celecoxib, or parecoxib with NSAIDs. Rofecoxib 50 mg and parecoxib 40 mg provided analgesic efficacy comparable to that of the NSAIDs in the comparisons, and with a longer duration of action after dental surgery but possibly not after major procedures. Celecoxib 200 mg and parecoxib 20 mg provided less effective pain relief. Four studies included five comparisons of rofecoxib 50 mg with celecoxib 200 and 400 mg. Rofecoxib 50 mg provided superior analgesic effect compared with celecoxib 200 mg. Data on celecoxib 400 mg were too sparse for firm conclusions. Thirty-three studies included 62 comparisons of the four COX-2 inhibitors with placebo and the COX-2 inhibitors significantly decreased post-operative pain. CONCLUSION: Rofecoxib 50 mg and parecoxib 40 mg have an equipotent analgesic efficacy relative to traditional NSAIDs in post-operative pain after minor and major surgical procedures, and after dental surgery these COX-2 inhibitors have a longer duration of action. Besides, rofecoxib 50 mg provides superior analgesic effect compared with celecoxib 200 mg.     

Prevention of postoperative nausea and vomiting after spinal morphine for Caesarean section: comparison of cyclizine,dexamethasone and placebo

Background. Low-dose intrathecal (spinal) morphine (0.1–0.2mg) for Caesarean section delivers excellent postoperative analgesiabut is associated with significant nausea and vomiting. We comparedthe antiemetic efficacy of cyclizine, dexamethasone, and placeboin this clinical setting. Methods. Ninety-nine women undergoing elective Caesarean sectionunder spinal anaesthesia were allocated randomly, in a double-blindstudy design, to receive either cyclizine 50 mg, dexamethasone8 mg, or placebo as a single-dose infusion in saline 0.9%, 100ml on completion of surgery. Spinal anaesthesia consisted of:hyperbaric bupivacaine 0.5%, 2.0 ml; fentanyl 10 µg; andspinal morphine 0.2 mg. The primary outcome measure was theincidence of nausea. Results. The incidence of nausea was significantly less in patientsreceiving cyclizine compared with dexamethasone and placebo(33 vs 60 and 67%, respectively, P<0.05). Severity of nauseaand number of vomiting episodes were also less at 3–6h in cyclizine patients. Overall satisfaction with postoperativecare at 24 h, expressed on a 100 mm visual analogue scale, wasgreater in cyclizine [78 (28)] than either dexamethasone [58(31), P=0.03] or placebo [51 (28), P=0.008]. Conclusion. We conclude that following spinal morphine 0.2 mgand fentanyl 10 µg analgesia for Caesarean section, cyclizine50 mg i.v. reduces the incidence of nausea compared with dexamethasone8 mg i.v. or placebo. It also lessens the severity of nauseaand vomiting, and increases maternal satisfaction in the earlypostoperative period. Br J Anaesth 2003; 90: 665–70     

Gabapentin: a multimodal perioperative drug?

Gabapentin is a second generation anticonvulsant that is effective in the treatment of chronic neuropathic pain. It was not, until recently, thought to be useful in acute perioperative conditions. However, a growing body of evidence suggests that perioperative administration is efficacious for postoperative analgesia, preoperative anxiolysis, attenuation of the haemodynamic response to laryngoscopy and intubation, and preventing chronic post-surgical pain, postoperative nausea and vomiting, and delirium. This article reviews the clinical trial data describing the efficacy and safety of gabapentin in the setting of perioperative anaesthetic management.     

Intramuscular ephedrine reduces emesis during the first three hours after abdominal hysterectomy

BACKGROUND: We tested the hypothesis that intramuscularly administered ephedrine prevents postoperative nausea and vomiting. Ephedrine is cheap, and for this indication poorly documented. METHODS: One hundred and nine patients undergoing elective abdominal hysterectomy under general anaesthesia were studied in a randomized, double-blind placebo-controlled study. Ten minutes before the end of the procedure patients received either ephedrine 0.5 mg/kg i.m. or placebo. The patients were closely observed for 24 h for postoperative nausea or vomiting (PONV) and received a standardized two-step antiemetic treatment of i.v. metoclopramide 10 mg, supplemented with ondansetron 4 mg i.v. if needed. RESULTS: The ephedrine treated patients had significantly less nausea, retching and vomiting, and need of antiemetic rescue during the first 3 h postoperatively compared with the placebo patients. No difference between the groups was evident in the 3-24 h postoperative observation period. All the patients with PONV during 0-3 h experienced PONV in the 3-24 h period. Treatment or prophylaxis with one drug was less efficient than two or more drugs combined. No significant differences in hypotension, tachycardia or other side-effects between the groups were noted. CONCLUSION: Ephedrine 0.5 mg/kg i.m. administered at the end of abdominal hysterectomy has a significant antiemetic effect during the first 3 h after administration with no evident side-effects.     

Parecoxib sodium has opioid-sparing effects in patients undergoing total knee arthroplasty under spinal anaesthesia

Background. This multicentre, double-blind, placebo-controlledstudy compared the opioid-sparing effectiveness and clinicalsafety of parecoxib sodium over 48 h, in 195 postoperativepatients after routine total knee replacement surgery. Methods. Elective total primary knee arthroplasty was performedunder spinal anaesthesia, with a single dose of spinal bupivacaine10–20 mg, and intraoperative sedation with midazolam0.5–1.0 mg i.v., or propofol <6 mg kg^–1h^–1. Patients were randomized to receive either parecoxibsodium 20 mg twice daily (bd) i.v. (n=65), parecoxib sodium40 mg bd i.v. (n=67), or placebo (n=63) at the completionof surgery, and after 12, 24, and 36 h. Morphine (1–2 mg)was taken by patient-controlled analgesia or by bolus dosesafter 30 min. Results. Patients receiving parecoxib sodium 20 mg bd and40 mg bd consumed 15.6% and 27.8% less morphine at 24 hthan patients taking placebo (both P<0.05). Both doses ofparecoxib sodium administered with morphine provided significantlygreater pain relief than morphine alone from 6 h (P<0.05).A global evaluation of study medication demonstrated a greaterlevel of satisfaction among patients taking parecoxib sodiumthan those taking placebo. Parecoxib sodium administered incombination with morphine was well tolerated. However, a reductionin opioid-type side-effects was not demonstrated in the parecoxibsodium groups. Conclusion. Parecoxib sodium provides opioid-sparing analgesiceffects in postoperative patients. Br J Anaesth 2003; 90: 166–72     

Influence on platelet aggregation of i.v. parecoxib and acetaminophen in healthy volunteers

Background. Acetaminophen (paracetamol) alone or in combinationwith other analgesics is widely used for postoperative analgesia.While acetaminophen and non-steroidal anti-inflammatory drugsinhibit platelet function, the cyclooxygenase-2 (COX-2) selectivelyinhibiting coxibs show no interference with platelet function.The authors studied the effect of a combination of i.v. parecoxiband acetaminophen on platelet function in healthy volunteers. Methods. Eighteen healthy, male volunteers (22–33 yr)received i.v. acetaminophen 1 g, parecoxib 40 mg+acetaminophen1 g or placebo in a double-blind, crossover study. Plateletfunction was assessed by photometric aggregometry and by measuringthe release of thromboxane B₂. Plasma acetaminophen concentrationswere measured by high-performance liquid chromatography. Results. Platelet aggregation (median area under the curve)triggered with arachidonic acid 500 µM was 24.6, 3.9 and4.2x10³ area units (P=0.02, all groups) after placebo, acetaminophenand parecoxib+acetaminophen, respectively. Inhibition of plateletaggregation showed no difference between acetaminophen aloneand the combination (P=0.82). Aggregation triggered with arachidonicacid 750 or 1000 µM, adenosine diphosphate (ADP) 1.5 or3 µM, or epinephrine 5 µM showed no differencesbetween the groups. Release of thromboxane B₂ in response toADP was inhibited similarly by both acetaminophen and the combination.Plasma acetaminophen concentrations were similar after acetaminophenand the combination. Conclusions. Acetaminophen and parecoxib showed no interactionin inhibiting platelet function. In combination they cause amild degree of COX-1 inhibition corresponding to that of acetaminophenalone.