Epidural versus intrathecal morphine for postoperative analgesia after Caesarean section

Background. Perispinal anaesthesia for Caesarean section allowsinjection of epidural (ED) or intrathecal (i.t.) morphine toprovide long-lasting postoperative analgesia. To compare thesetwo routes, a prospective, randomized, double-blinded studyof 53 patients undergoing elective Caesarean section was performed. Methods. Combined spinal-epidural anaesthesia with 6 mg of i.t.hyperbaric bupivacaine plus sufentanil 5 µg, and additionalED lidocaine was used. Additionally, each patient received either2 mg (2 ml) of ED morphine plus 1 ml of i.t. normal saline (EDgroup, n=28), or 0.075 mg (1 ml) of i.t. morphine plus 2 mlof ED normal saline (i.t. group, n=25). Additional postoperativeanalgesia was given in the form of propacetamol and ketoprofen,plus self-administered i.v. morphine. Results. No major respiratory depression occurred. Time to firstdemand of morphine was similar in the ED (307.5 min) and i.t.(310 min) groups, as was the incidence of side-effects suchas sedation, pruritis, nausea, and vomiting. During the first24 postoperative hours, VAS pain scores were greater in thei.t. group (P=0.032), as was additional morphine consumption(4 vs 1.5 mg) (P=0.03). Conclusions. The ED protocol was more effective than the i.t.protocol, whilst side-effects were similar. Br J Anaesth 2003; 91: 690–4     

Effect of intrathecal tramadol administration on postoperative pain after transurethral resection of prostate

Background. Tramadol administered epidurally has been demonstratedto decrease postoperative analgesic requirements. However, itseffect on postoperative analgesia after intrathecal administrationhas not yet been studied. In this double-blind, placebo-controlledstudy, the effect of intrathecal tramadol administration onpain control after transurethral resection of the prostate (TURP)was studied. Methods. Sixty-four patients undergoing TURP were randomizedto receive bupivacaine 0.5% 3 ml intrathecally premixed witheither tramadol 25 mg or saline 0.5 ml. After operation, morphine5 mg i.m. every 3 h was administered as needed for analgesia.Postoperative morphine requirements, visual analogue scale forpain at rest (VAS) and sedation scores, times to first analgesicand hospital lengths of stay were recorded by a blinded observer. Results. There were no differences between the groups with regardto postoperative morphine requirements (mean (SD): 10.6 (7.9)vs 9.1 (5.5) mg, P=0.38), VAS (1.6 (1.2) vs 1.2 (0.8), P=0.18)and sedation scores (1.2 (0.3) vs 1.2 (0.2), P=0.89). Timesto first analgesic (6.3 (6.3) vs 7.6 (6.2) h, P=0.42) and lengthof hospital stay (4.7 (2.8) vs 4.4 (2.2) days, P=0.66) weresimilar in the two groups. Conclusion. Intrathecal tramadol was not different from salinein its effect on postoperative morphine requirements after TURP. Br J Anaesth 2003; 91: 536–40     

Emetic effects of morphine and piritramide

Background. Successful management of postoperative pain requiresthat adequate analgesia is achieved without excessive adverseeffects. Opioid-induced nausea and vomiting is known to impairpatients’ satisfaction, but there are no studies providingsufficient power to test the hypothesis that the incidence ofopioid-induced nausea and vomiting differs between µ-opioidreceptor agonists. Thus, we tested the hypothesis that the incidenceof vomiting and nausea differs between morphine and piritramide. Methods. In a prospective, randomized, double-blind fashion,we administered either morphine (n=250) or piritramide (n=250)by patient-controlled analgesia (PCA) for postoperative painrelief. We used a bolus dose of 1.5 mg with a lockout time of10 min. Incidence and intensity (numerical rating scale) ofpostoperative nausea, vomiting, pain, patient satisfaction (score0–10), side-effects (score 0–3) and drug consumptionwere measured. Results. Mean drug consumption did not differ between the piritramideand morphine groups (30.8 (SD 22.4) mg day^–1 vs 28.4 (21.8)mg day^–1) during the first postoperative day and therewere no significant differences in the overall incidence ofnausea (30% vs 27%) and vomiting (19% vs 15%). Intensity ofnausea correlated inversely (P=0.01) with morphine consumptionbut not with piritramide consumption. Pain scores both at rest(2.2 (1.9) vs 2.6 (2)) and during movement (4.4 (2.2) vs 4.9(2.3)) were slightly but significantly less with morphine. Conclusions. Opioid-induced emesis was observed in about one-thirdof the patients using morphine and piritramide for PCA and theincidence of vomiting was one-half of that. Potential differencesin the incidence of vomiting during PCA therapy between theseµ-opioid receptor agonists can be excluded. Br J Anaesth 2003; 91: 218–23     

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.     

Postoperative analgesia by epidural methylprednisolone after posterolateral thoracotomy

The aim of this study was to evaluate the potential analgesiceffect of epidural methylprednisolone (MP) after posterolateralthoracotomy (PLT). Adult male patients undergoing PLT for lungsurgery were included in a prospective, randomized, double blindstudy. Peroperative analgesia (bupivacaine plus sufentanil)was given by a thoracic epidural catheter associated with generalanaesthesia. After surgery, patients received either MP 1 mgkg^–1 followed by a continuous epidural infusion of MP1.5 mg kg^–1 during 48 h (MP group) or 0.9% saline as abolus injection and continuous epidural infusion (P group).Additional morphine analgesia was administered by i.v. patient-controlledanalgesia. Pain was assessed at rest and with mobilization every4 h after operation during 48 h with a visual analogue scale(VAS). The primary end-point was the total morphine requirementsduring the 48 first postoperative hour. Twenty-four patientswere allocated to MP (n=12) and P (n=12) groups. Characteristicsof the two groups were similar. There were no differences betweengroups for morphine requirements (median and interquartile range)during the 48 h: 59 mg (40–78) in MP group vs 65 mg (59–93)in P group. There were no differences between groups for morphinerequirements every 4 h during the 48 h and VAS for pain at restand evoked pain. No side effects were reported. It was concludedin this small study that these results did not support the useof epidural steroids for postoperative analgesia after PLT. Br J Anaesth 2001; 87: 635–8     

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     

Dextromethorphan and intrathecal morphine for analgesia after Caesarean section under spinal anaesthesia

Background. Dextromethorphan is an N-methyl-D-aspartic acidantagonist which can attenuate acute pain with few side-effects.In this prospective, randomized, double-blind study of dextromethorphanand intrathecal morphine, we investigated postoperative pain,pruritus, nausea and vomiting in women undergoing Caesareansection under spinal anaesthesia. Methods. Women were allocated randomly to one of six groups,to receive intrathecal morphine 0.05, 0.1 or 0.2 mg plusoral dextromethorphan 60 mg or placebo. Results. The addition of dextromethorphan did not reduce postoperativepain scores (P=0.83). Compared with women receiving intrathecalmorphine 0.05 mg, women receiving higher doses had a significantlyhigher incidence of nausea and vomiting [odds ratio for intrathecalmorphine 0.1 mg, 4.0 (95% confidence interval 1.2–14.1);for intrathecal morphine 0.2 mg, 7.9 (2.3–27.1)].Compared with women receiving intrathecal morphine 0.05 mg,women receiving higher doses also had a significantly higherincidence of pruritus [odds ratio for intrathecal morphine 0.1 mg,3.2 (95% confidence interval 1.3–8.2); for intrathecalmorphine 0.2 mg, 3.7 (1.4–9.5)]. Women receivingdextromethorphan had a lower incidence of nausea and vomiting[odds ratio 2.6 (1.1–6.3)]. Conclusions. Postoperative pain after Caesarean section underspinal anaesthesia was not reduced by the addition of oral dextromethorphanto a multimodal approach including intrathecal morphine. Br J Anaesth 2003; 90: 653–8     

Epinephrine and clonidine do not improve intrathecal sufentanil analgesia after total hip replacement

Background. We compared analgesia after intrathecal sufentanilalone, sufentanil with epinephrine 200 µg and sufentanilwith clonidine 30 µg in patients after total hip replacement,the endpoints being onset and duration of action. Methods. We performed a randomized double-blind study of 45patients for elective total hip arthroplasty using continuousspinal anaesthesia. As soon as a pain score higher than 3 ona 10 cm visual analogue scale was reported, sufentanil 7.5 µgalone, sufentanil 7.5 µg + epinephrine 200 µg orsufentanil 7.5 µg + clonidine 30 µg in 2 ml normalsaline was given intrathecally. Pain scores, rescue analgesia(diclofenac and morphine) and adverse effects (respiratory depression,postoperative nausea and vomiting, itching) were observed for24 h after surgery. Results. Time to a pain score of <3 [6 (SD 1) vs 6 (1) vs5 (1) min], time to the lowest pain score [7 (2) vs 8 (2) vs8 (2) min] and time to the first dose of systemic analgesicfor a pain score >3 [281 (36) vs 288 (23) vs 305 (30) min]were similar in all three groups. Adverse effects and analgesicrequirements during the first 24 h were also similar. Conclusion. After total hip replacement, all three analgesicregimens gave good analgesia with comparable onset and durationof action, and minor adverse effects. Br J Anaesth 2002; 89: 562–6     

Intrathecal morphine and clonidine for coronary artery bypass grafting

Background. After cardiac surgery adequate postoperative analgesiais necessary. We assessed analgesia using intrathecal morphineand clonidine. Methods. In a double-blind randomized study, 45 patients havingcoronary artery bypass graft surgery were allocated randomlyto receive i.v. patient-controlled analgesia (PCA) morphine(bolus, 1 mg; lock-out interval, 7 min) (control group), eitheralone or combined with intrathecal morphine 4 µg kg^–1or with both intrathecal morphine 4 µg kg^–1and clonidine 1 µg kg^–1. Intrathecal injectionswere performed before the induction of general anaesthesia.Pain was measured after surgery using a visual analogue scale(VAS). We recorded i.v. PCA morphine consumption during the24 h after operation. Results. Morphine dosage [median (25th–75th percentiles)]was less in the first 24 h in the patients who were given intrathecalmorphine + clonidine [7 (0–37) mg] than in other patients[40.5 (15–61.5) mg in the intrathecal morphine group and37 (30.5–51) mg in the i.v. morphine group]. VAS scoreswere lower after intrathecal morphine + clonidine compared withthe control group. Time to extubation was less after intrathecalmorphine + clonidine compared with the i.v. morphine group [225(195–330) vs 330 (300–360) min, P<0.05]. Conclusion. Intrathecal morphine and clonidine provide effectiveanalgesia after coronary artery bypass graft surgery and allowearlier extubation. Br J Anaesth 2003; 90: 300–3     

Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability

Background. Codeine analgesia is wholly or mostly due to itsmetabolism to morphine by the cytochrome P450 enzyme CYP2D6,which shows significant genetic variation in activity. The aimsof this study were to investigate genotype, phenotype and morphineproduction from codeine in children undergoing adenotonsillectomy,and to compare analgesia from codeine or morphine combined withdiclofenac. Methods. Ninety-six children received either codeine 1.5 mg kg^–1or morphine 0.15 mg kg^–1 in a randomized, double-blinddesign. Genetic analysis was performed and plasma morphine concentrationsat 1 h were determined. Postoperative analgesia and side-effectswere recorded. Results. Forty-seven per cent of children had genotypes associatedwith reduced enzyme activity. Mean (SD) morphine concentrationswere significantly lower (P<0.001) after codeine [4.5 (0.3)ng ml^–1] than after morphine [24.7 (1.5) ng ml^–1],and morphine and its metabolites were not detected in 36% ofchildren given codeine. There was a significant relationshipbetween phenotype and plasma morphine (P=0.02). More childrenrequired rescue analgesia after codeine at both 2 (P<0.05)and 4 h after administration (P<0.01). Fifty-six per centof children vomited after morphine and 29% after codeine (P<0.01).Neither phenotype nor morphine concentration was correlatedwith either pain score or the need for rescue analgesia (r=–0.21,95% confidence interval –0.4, –0.01). Conclusions. Reduced ability for codeine metabolism may be morecommon than previously reported. Plasma morphine concentration1 h after codeine is very low, and related to phenotype.Codeine analgesia is less reliable than morphine, but was notwell correlated with either phenotype or plasma morphine inthis study. Br J Anaesth 2002; 89: 839–45     

Electrophysiological effects of morphine in an in vitro model of the 'border zone' between normal and ischaemic-reperfused guinea-pig myocardium

Background. Morphine is commonly used in clinical practice inpain management. Although morphine has been shown to preconditionthe myocardium, its effects on action potential parameters andischaemia–reperfusion-induced arrhythmias and conductionblocks remain unknown. Methods. In a double-chamber bath, guinea-pig right ventricularmuscle strips were subjected partly to normal conditions andpartly to 30 min of simulated ischaemia (hypoxia, hyperkalaemia,acidosis, and lack of nutritional substrate) followed by 30 minof reperfusion. Action potential parameters were recorded continuouslyin the normal zone and in the ischaemic– reperfused zone.Spontaneous arrhythmias and conduction blocks were noted. Theelectro physiological effects of morphine were studied at 0.01and 0.1 µM. Results. In control conditions, morphine did not modify actionpotential parameters of resting membrane potential, maximalupstroke velocity (V_max), action potential amplitude (APA) andaction potential duration at 50 and 90% of repolarization. Morphinereduced ischaemia-induced depolarization and lessened the ischaemia-induceddecrease in APA and V_max. Morphine significantly decreased theoccurrence of conduction block during simulated ischaemia (20%at 0.01 and 0.1 µM vs 67% in the control group, P<0.05)and reperfusion-induced arrhythmias (40% at 0.01 µMand 30% at 0.1 µM vs 92% in the control group, P<0.05). Conclusions. In ischaemic–reperfused guinea-pig myocardium,morphine at clinically relevant concentrations decreased ischaemia-inducedconduction blocks and reperfusion-induced ventricular arrhythmias. Br J Anaesth 2002; 89: 888–95     

Intrathecal sufentanil and morphine for post-thoracotomy pain relief

In this double-blind randomized study we compared a group of15 patients undergoing thoracotomy who received a spinal injectionof sufentanil 20 µg combined with morphine (200 µg)after induction of general anaesthesia with a control groupof the same size. Post-operative pain was rated on a visualanalogue scale (VAS) and a verbal rating scale at rest and witha VAS on coughing. In the recovery room, patients received titratedi.v. morphine until the VAS score was <30, and were followedby patient-controlled analgesia (PCA) for 72 h. The intrathecalsufentanil and morphine group had a lower intra-operative requirementfor i.v. sufentanil and needed less i.v. morphine for titrationin the recovery room. I.v. PCA morphine consumption and painscores were lower in the active group than in the control groupduring the first 24 h. There were no differences afterthis time. Spirometric data (peak expiratory flow, forced vitalcapacity and forced expiratory volume in 1 s) were similarin the two groups. We conclude that the combination of intrathecalsufentanil and morphine produces analgesia of rapid onset andwith a duration of 24 h. Br J Anaesth 2001; 86: 236–40.     

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     

Randomized prospective study of the analgesic effect of nefopam after orthopaedic surgery

Background. Balanced postoperative analgesia combines non-narcoticdrugs and opioids. We organized a large study to evaluate nefopamanalgesia and tolerance in combination with morphine for patient-controlledanalgesia (PCA) after orthopaedic surgery. Methods. Two hundred and one patients scheduled to undergo hiparthroplasty were included in this multicentre (n=24), double-blind,randomized study comparing nefopam (20 mg every 4 h for 24 h)with placebo, the first dose being infused peroperatively. Theprimary outcome measure was the cumulative morphine dose receivedpostoperatively by PCA over 24 h. Secondary outcome measureswere the amount of morphine received as a loading dose in thepostanaesthesia care unit (PACU) and during the 24-h observationperiod, and pain assessments using a visual analogue scale (VAS)and a verbal pain scale (VPS), patient’s satisfactionwith analgesia and treatment tolerance. Results. The two groups were comparable with respect to theircharacteristics and preoperative pain assessment. PCA-administeredmorphine over 24 h was significantly less for the nefopam groupthan the control group (21.2 (15.3) and 27.3 (19.2) mg respectively;P=0.02). This morphine-sparing effect was greater (35.1%) forpatients with severe preoperative pain (VAS>30/100). Forthe entire study period (loading dose and PCA), morphine usewas less for the nefopam group (34.5 (19.6) vs 42.7 (23.6) mg;P=0.01). Pain VAS at PACU arrival and during the whole PACUperiod was significantly lower for the nefopam than for theplacebo group (P=0.002 and 0.04 respectively). Patient satisfactionwas similar for the nefopam and placebo groups. Conclusion. In combination with PCA morphine, nefopam givessignificant morphine-sparing with lower immediate postoperativepain scores without major side-effects. This analgesic effectseems to be particularly notable for patients with intense preoperativepain. Br J Anaesth 2003; 91: 836–41     

Predictive factors of early morphine requirements in the post-anaesthesia care unit (PACU)

Use of morphine by titration in the post-anaesthesia care unit(PACU) is often the first step in postoperative pain management.This approach provides rapid analgesia but shows a wide inter-individualvariability in morphine requirements and may prolong patientstay in the PACU. The aim of this study was to identify thepatient characteristics, surgical, anaesthetic, and postoperativefactors predictive of early morphine requirements. The studyincluded 149 patients undergoing various non-cardiac surgicalprocedures under general anaesthesia. In the multiple regressionanalysis of nine variables, only ethnicity (Caucasian), emergencysurgery, major surgery, surgery exceeding 100 min, and painscore on arrival in PACU were predictive factors of morphinerequirements. This observational study identifies for the firsttime independent predictive factors of morphine requirementsin the early postoperative period. Future studies are warrantedto evaluate the impact of intervention on these factors andany resulting improvement in postoperative pain treatment. Br J Anaesth 2001; 87: 385–9     

Effects of a loading dose of morphine before i.v. morphine titration for postoperative pain relief: a randomized, double-blind, placebo-control study

Background. I.V. morphine titration (MT) allows adjustment ofthe dose needed for pain relief in the post-anaesthesia careunit (PACU). However, MT has limitations such as a delay toachieve pain relief. We thus assessed the effect of a fixedintraoperative loading dose of morphine administered beforetitration. Methods. One hundred patients who were undergoing major orthopaedicsurgery were included in a double-blind, randomized study comparinga loading dose of morphine (0.15 mg kg^–1) with placeboadministered intraoperatively. MT was then administered in thePACU followed by patient-controlled analgesia (PCA) over 24h. Data are expressed as mean (SD). Results. The initial VAS [41 (36) vs 52 (35), NS] was not decreasedin the morphine group. The VAS was lower in the morphine groupin the PACU and PCA periods. The time to achieve effective painrelief was not decreased in the morphine group. The total doseof morphine administered in the PACU (including the loadingdose) was significantly increased in the morphine group (+31%in mg kg^–1, P<0.05). Morphine requirements during thePCA period were not different between groups. The incidenceof sedation was increased and a severe episode of ventilatorydepression occurred in the morphine group. Conclusions. A loading dose of morphine administered at theend of surgery slightly decreased the VAS but did not reducethe time to pain relief or morphine consumption within the first24 h. This slight improvement in analgesia was obtained at theexpense of morphine-related adverse events.     

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     

Intrathecal morphine reduces breakthrough pain during labour epidural analgesia

BACKGROUND: When using the combined spinal-epidural (CSE) technique forlabour analgesia, parturients often experience breakthroughpain after the spinal medication has receded. We tested thehypothesis that a small dose of intrathecal morphine would reducebreakthrough pain. METHODS: This was a randomized, double-blind, placebo-controlled trial.Subjects were randomized to receive either 100 µgof morphine (MS) or placebo (PLCB) with the spinal injectionof bupivacaine and fentanyl. Assessments included need for supplementationduring labour analgesia, use of pain medications for 24 hafter delivery, and side-effects. The primary end-point wasthe rate of breakthrough pain. RESULTS: Sixty subjects were enrolled, 55 subjects completed the trial.The MS group had a significantly lower rate of breakthroughpain than the PLCB group [0.6 (0.6) vs 1.1 (0.8) episodes perpatient; P < 0.01], and longer time to first episode of breakthroughpain (300 vs 180 min; P = 0.03). The MS group used 75%less opioid medications during the subsequent 24 h, buthad a 17% incidence of nausea. CONCLUSIONS: The addition of small dose of morphine to the spinal componentof the CSE technique improved the effectiveness of epidurallabour analgesia and reduced the need for pain medications over24 h, but resulted in a small increase in nausea.     

Pre-emptive analgesic efficacy of tramadol compared with morphine after major abdominal surgery

Background. Studies of pre-emptive analgesia in humans haveshown conflicting results. This prospective, randomized, double-blind,controlled study was designed to test the hypothesis that areduction in postoperative morphine consumption can be achievedby tramadol administered after induction of anaesthesia. Methods. Ninety patients were allocated randomly to receivei.v. tramadol (1 mg kg^–1) (Group T), morphine(0.1 mg kg^–1) (Group M) or saline 2 ml(Group S) after induction of anaesthesia. At peritoneal closure,a standardized (0.1 mg kg^–1) morphine loadingdose was given to all patients for postoperative pain management.Patients were allowed to use a patient-controlled analgesia(PCA) device giving bolus doses of morphine 0.025 mg kg^–1.Discomfort, sedation, pain scores, cumulative morphine consumption,and side-effects were recorded at 1, 2, 6, 12 and 24 hafter the start of PCA. Results. There were no significant differences between groupsin mean pain, discomfort, and sedation scores at any study period.Cumulative morphine consumption was significantly lower in GroupM at 12 and 24 h after starting the PCA than in Group S.In Group T, it was lower only after 24 h (28% less in GroupM and 17% less in Group T; P<0.017). There were no significantdifferences in morphine consumption between Groups T and M. Conclusions. Tramadol (1 mg kg^–1), administeredafter induction of anaesthesia, offered equivalent postoperativepain relief, and similar recovery times and postoperative PCAmorphine consumption compared with giving morphine 0.1 mg kg^–1.These results also suggest that presurgical exposure to systemicopioid analgesia may not result in clinically significant benefits Br J Anaesth 2003; 91: 209–13     

Antiemetic and analgesic-sparing effects of diphenhydramine added to morphine intravenous patient-controlled analgesia

Background. This study was designed to examine the analgesicand dose-related antiemetic efficacy of diphenhydramine–morphinemixture for intravenous patient-controlled analgesia (PCA). Methods. Healthy women, undergoing abdominal total hysterectomywere recruited to this double-blinded randomized placebo-controlledstudy. Patients were randomly allocated to one of three groups(n=40 each). In group 1, patients received saline at inductionand morphine 1 mg ml^–1 alone for postoperative PCA. Patientsin groups 2 and 3 received diphenhydramine 30 mg i.v. at inductionand were given a 1.2:1 or a 4.8:1 ratio, respectively, of diphenhydramine–morphinemixture for postoperative PCA. Results. A total of 112 patients completed the study. The incidenceof postoperative nausea (31.6% vs 67.6%, P<0.01) and vomiting(15.8% vs 40.5%, <0.05) was significantly lower in group3 than in group 1. Furthermore, the incidence of severe nauseawas significantly lower in group 3 than in group1 (2.6% vs 24.3%,P<0.05). The rescue antiemetic requirements were also significantlyless in group 3 than in group 1 (5.3% vs 24.3%, P<0.05).However, there was no significant difference between group 2and group 1 in any of the comparisons. Pain intensity, 24-hmorphine consumption and diphenhydramine-related side-effects,such as sedation or dry mouth, did not differ among the threegroups. Conclusion. An initial bolus of diphenhydramine 30 mg at anaestheticinduction followed by postoperative PCA with a 4.8:1, but not1.2:1, diphenhydramine–morphine mixture provides an effectiveantiemetic efficacy without morphine-sparing effects.