Efficacy of three doses of tramadol with bupivacaine for caudal analgesia in paediatric inguinal herniotomy

Background. This study was designed to evaluate the analgesicefficacy of three doses of tramadol, administered caudally withbupivacaine, in providing postoperative pain relief in children. Methods. Eighty children, aged between 2 and 8 yr, undergoinginguinal herniotomy were randomly allocated to receive bupivacaine0.25% 0.75 ml kg^–1 (Group B; n=20), bupivacaine 0.25%0.75 ml kg^–1 with tramadol 1 mg kg^–1 (Group BT1;n=20), bupivacaine 0.25% 0.75 ml kg^–1 with tramadol 1.5mg kg^–1 (Group BT1.5; n=20), or bupivacaine 0.25% 0.75ml kg^–1 with tramadol 2 mg kg^–1 (Group BT2; n=20)by the caudal route immediately after induction of general anaesthesia.Heart rate, arterial pressure and oxygen saturation were monitored.Postoperative pain was assessed at regular intervals for 24h using All India Institute of Medical Sciences pain score.Analgesia was supplemented whenever pain score was 4. Durationof analgesia and requirement for additional analgesics was noted. Results. Duration of analgesia was longer in Group BT2 [(mean(SD) 12 (0.9) h] compared with Group B [4 (1) h], Group BT1[8 (0.9) h], or Group BT1.5 [11 (1) h]; all P<0.001. Totalconsumption of rescue analgesic was significantly lower in groupBT2 compared with other groups (P<0.001). There were no significantchanges in heart rate, arterial pressure and oxygen saturationbetween groups. Adverse effects were not observed. Conclusions. Caudal tramadol 2 mg kg^–1, combined withbupivacaine 0.25% 0.75 ml kg^–1, provided longer durationof postoperative analgesia and reduced requirement for rescueanalgesic compared with tramadol 1 mg kg^–1 or 1.5 mg kg^–1in children undergoing inguinal herniotomy.     

Double-blind randomized controlled trial of caudal versus intravenous S(+)-ketamine for supplementation of caudal analgesia in children

Background. The postoperative analgesic efficacy of S(+)-ketamineafter caudal or i.v. administration following sub-umbilicalsurgery in children was studied to investigate its principalsite of analgesic action. Methods. Sixty children undergoing caudal block during generalanaesthesia for hernia repair or orchidopexy were prospectivelyrandomized to one of three groups: the bupivicaine group receivedplain bupivacaine 0.25% 1 ml kg^–1; the caudal ketaminegroup received caudal plain bupivacaine 0.25% 1 ml kg^–1with S(+)-ketamine 0.5 mg kg^–1; the i.v. ketamine groupreceived caudal plain bupivacaine 0.25% 1 ml kg^–1 plusS(+)-ketamine 0.5 mg kg^–1 i.v.. Postoperative measurementsincluded analgesic requirements and modified objective painscore for the first 24 h. Results. The median time to first analgesia was significantlylonger in the caudal ketamine group (10 h) than in the i.v.ketamine (4.63 h) or bupivacaine (4.75 h) groups (P=0.01). Significantlyfewer doses of analgesia were required over the first postoperative24 h by subjects in the caudal ketamine group (median 1) comparedwith the i.v. ketamine (median 2) or bupivacaine (median 2.5)groups (P<0.05). There was no difference between the groupsin the incidence of postoperative nausea and vomiting or psychomotorreactions. Conclusions. We have demonstrated that the addition of caudalS(+)-ketamine to bupivacaine prolongs the duration of postoperativeanalgesia. However, the same dose of i.v. S(+)-ketamine combinedwith a plain bupivacaine caudal provides no better analgesiathan caudal bupivacaine alone, indicating that the principalanalgesic effect of caudal S(+)-ketamine results from a localneuroaxial rather than a systemic effect. Br J Anaesth 2004; 92: 344–7     

Effect of intraoperative intravenous crystalloid infusion on postoperative nausea and vomiting after gynaecological laparoscopy: comparison of 30 and 10 ml kg(-1)

Background. I.V. fluid administration has been shown to reducepostoperative nausea and vomiting (PONV). The optimum dose isunknown. We tested the hypothesis that administration of i.v.crystalloid of 30 ml kg^–1 would reduce the incidence ofPONV compared with 10 ml kg^–1 of the same fluid. Methods. A total of 141 ASA I female patients undergoing electivegynaecological laparoscopy were randomized, in double-blindfashion, to receive either 10 ml kg^–1 (n=71; CSL-10 group)or 30 ml kg^–1 (n=70; CSL-30 group) of i.v. compound sodiumlactate (CSL). Results. In the first 48 h after anaesthesia, the incidenceof vomiting was lower in the CSL-30 group than in the CSL-10group (8.6% vs 25.7%, P=0.01). Anti-emetic use was less in theCSL-30 group at 0.5 h (2.9% vs 14.3%, P=0.04). The incidenceof severe nausea was significantly reduced in the treatmentgroup at awakening (2.9% vs 15.7%, P=0.02), 2 h (0.0% vs 8.6%,P=0.04) and cumulatively (5.7% vs 27.1%, P=0.001). The numbersneeded to treat to prevent vomiting, severe nausea and antiemeticuse in the first 48 h were 6, 5 and 6, respectively. Conclusion. I.V. administration of CSL 30 ml kg^–1 to healthywomen undergoing day-case gynaecological laparoscopy reducedthe incidence of vomiting, nausea and anti-emetic use when comparedwith CSL 10 ml kg^–1.     

Pharmacokinetics of 0.75% ropivacaine and 0.5% bupivacaine after ilioinguinal-iliohypogastric nerve block in children

Background. Blockade of the ilioinguinal and iliohypogastricnerves is a useful procedure in paediatric patients undergoinginguinal surgery. Bupivacaine 2 mg kg^–1 has been recommendedfor this block. We compared the plasma concentrations of ropivacaineand bupivacaine following an ilioinguinal–iliohypogastricblock. Methods. Forty children scheduled for elective inguinal surgerywere randomized to receive 2 mg kg^–1 of either 0.75% ropivacaineor 0.5% bupivacaine. Surgical anaesthesia was maintained withmask inhalation of oxygen, nitrous oxide and sevoflurane. Venousblood samples were drawn at regular intervals for up to 2 hand plasma was separated. Total venous plasma concentrationswere determined by gas chromatography. Results. The groups were similar with respect to age, weightand dose of local anaesthetic. The peak plasma concentrationachieved was significantly higher in the bupivacaine group comparedwith the ropivacaine group (2.2 vs 1.2 µg ml^–1,P=0.025). The time to peak plasma concentration was significantlyshorter in the bupivacaine group (24 vs 35 min, P=0.024). Theinitial distribution half time of bupivacaine was significantlyshorter (3.6 vs 6.5 min, P=0.020) compared with that of ropivacaine. Conclusions. Bupivacaine is more rapidly absorbed from the injectionsite and leads to higher plasma concentrations than ropivacaine. Br J Anaesth 2002; 89: 438–41     

Influence of acute normovolaemic haemodilution on the dose-response relationship, time-course of action and pharmacokinetics of rocuronium bromide

Background. Acute normovolaemic haemodilution (ANH) is an effectivestrategy for avoiding or reducing allogeneic blood transfusion.We aimed to study its effect on the pharmacological profileof rocuronium. Methods. In two study centres, 28 patients undergoing majorsurgery with ANH were matched with 28 control patients. In thedose–response groups, using the mechanomyograph, neuromuscularblock of six consecutive incremental doses of rocuronium 50µg kg^–1, followed by 300 µg kg^–1, wasevaluated. In the pharmacokinetics groups, serial arterial bloodsamples were withdrawn for rocuronium assay after a single doseof rocuronium 600 µg kg^–1. Results. ANH resulted in a shift to the left of rocuronium dose–responsecurve. Rocuronium effective dose₉₅ (ED₉₅) was 26% lower (P<0.05)in the ANH group [283.4 (92.0) µg kg^–1] comparedwith the control group [383.5 (127.3) µg kg^–1].Times from administration of last incremental dose until 25%of first response of train-of-four (TOF) recovery (Dur₂₅) and0.8 TOF ratio recovery (Dur_0.8) were 28% longer in the ANH group[39.9 (8.4), 66.7 (14.2) min] compared with the control group[31.1 (6.6), 52.1 (15.8) min] (P<0.01, P<0.05), respectively.Volume of distribution was higher (P<0.01), central clearancewas lower (P<0.05) and terminal elimination half-life waslonger (P<0.0001) in the ANH group [234.97 (47.11) ml kg^–1,4.70 (0.94) ml kg^–1 min^–1, 77.29 (12.25) min] comparedwith the control group [181.22 (35.73) ml kg^–1, 5.71 (1.29)ml kg^–1 min^–1, 56.86 (10.05) min, respectively]. Conclusion. ANH resulted in prolongation of rocuronium time-courseof action, thus careful monitoring of neuromuscular block isrecommended in patients who undergo ANH.     

Validation of volume kinetic analysis of glucose 2.5% solution given by intravenous infusion

Background. The distribution and elimination of glucose solutionscan be analysed by means of a volume kinetic model, but theability of the model to predict plasma dilution (‘modellinearity’) has not been evaluated. Methods. Six male volunteers received four separate infusionsof glucose 2.5%: 10 ml kg^–1 and 15 ml kg^–1 over30 min, and 15 ml kg^–1 and 25 ml kg^–1 over 60 min.The kinetic model was fitted to measurements of plasma glucoseconcentration and haemodilution. Results. The mean volume of distribution for the glucose was9.2 (SEM 0.4) litres while the infused fluid expanded a centralbody fluid space (V₁) of 3.1 (0.3) litres. Increasing the amountof infused fluid, but not the infusion rate, resulted in a proportionalincrease in the area under the curve for plasma glucose andplasma dilution, the only confounder being glycosuria. The biasof computer simulation was slightly increased by rebound hypoglycaemia,which could occur with the highest infusion rates, but the accuracywas almost identical regardless of whether the kinetic parametersfrom all 24 experiments or from any of the subgroups were used. Conclusion. The volume kinetic model for glucose 2.5% is linearand can therefore be used for computer simulation as long asmarked glycosuria does not occur. Br J Anaesth 2003; 90: 600–7     

Early recovery after remifentanil-pronounced compared with propofol-pronounced total intravenous anaesthesia for short painful procedures

Background. We compared recovery from high-dose propofol/low-doseremifentanil (‘propofol-pronounced’) compared withhigh-dose remifentanil/low-dose propofol (‘remifentanil-pronounced’)anaesthesia. Methods. Adult patients having panendoscopy, microlaryngoscopy,or tonsillectomy were randomly assigned to receive either propofol-pronounced(propofol 100 µg kg^–1 min^–1; remifentanil0.15 µg kg^–1 min^–1) or remifentanil-pronounced(propofol 50 µg kg^–1 min^–1; remifentanil 0.45µg kg^–1 min^–1) anaesthesia. In both groups,the procedure was started with remifentanil 0.4 µg kg^–1,propofol 2 mg kg^–1, and mivacurium 0.2 mg kg^–1.Cardiovascular measurements and EEG bispectral index (BIS) wererecorded. To maintain comparable anaesthetic depth, additionalpropofol (0.5 mg kg^–1) was given if BIS values were greaterthan 55 and remifentanil (0.4 µg kg^–1) if heartrate or arterial pressure was greater than 110% of pre-anaestheticvalues. Results. Patient and surgical characteristics, cardiovascularmeasurements, and BIS values were similar in both groups. Therewere no differences in recovery times between the groups (timeto extubation: 12.7 (4.5) vs 12.0 (3.6) min, readiness for transferto the recovery ward: 14.4 (4.4) vs. 13.7 (3.6) min, mean (SD)). Conclusions. In patients having short painful surgery, lesspropofol does not give faster recovery as long as the same anaestheticlevel (as indicated by BIS and clinical signs) is maintainedby more remifentanil. However, recovery times were less variablefollowing remifentanil-pronounced anaesthesia suggesting a morepredictable recovery. Br J Anaesth 2003; 91: 580–2     

Pretreatment with remifentanil to prevent withdrawal after rocuronium in children

Background. Pain from rocuronium injection is a common side-effectreported to occur in 50–80% of the patients. This randomized,double-blind, placebo-controlled study was designed to evaluatethe efficacy of pretreatment with i.v. remifentanil on preventionof withdrawal response during rocuronium injection in paediatricpatients. Methods. After obtaining parental consents, 70 paediatric patientswere randomly allocated into two groups to receive either i.v.remifentanil 1 µg kg^–1 (remifentanil group, n=35)or i.v. saline 5 ml (saline group, n=35). Anaesthesia was inducedwith thiopental sodium 2.5% (5 mg kg^–1) and the test drugwas injected over 30 s. One minute after the test drug injection,rocuronium 1% (0.6 mg kg^–1) was injected over 5 s andthe response was recorded. Mean arterial pressure (MAP) andheart rate were recorded on arrival in the operating theatre,before and 1 min after the tracheal intubation. Results. The overall incidence of withdrawal movements was significantlyhigher in the saline group (33 patients; 94%) than that in theremifentanil group (8 patients; 23%) (P<0.001). No patientin the remifentanil group showed generalized movement, whereas51% of patients in the saline group did. Remifentanil preventedsignificant increase in MAP after intubation. Conclusion. This study demonstrated that pretreatment with remifentanil1 µg kg^–1 provided a safe and simple method forreducing the incidence of rocuronium-associated withdrawal movementwith haemodynamic stability in children.     

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     

Pharmacokinetics of remifentanil and its major metabolite, remifentanil acid, in ICU patients with renal impairment

Background. The pharmacokinetics of remifentanil, an opioidanalgesic metabolized by non-specific esterases, and its principalmetabolite, remifentanil acid (RA), which is excreted via thekidneys, were assessed as part of an open-label safety studyin intensive care unit (ICU) patients with varying degrees ofrenal impairment. Methods. Forty adult ICU patients with normal/mildly impairedrenal function (creatinine clearance [CL_cr] 62.9 (SD) 14.5 mlmin^–1; n=10) or moderate/severe renal impairment (CL_cr14.7 (15.7) ml min^–1; n=30) were included. Remifentanilwas infused for up to 72 h, at a starting rate of 6–9µg kg^–1 h^–1 titrated to achieve a target sedationlevel, with additional propofol (0.5 mg kg^–1 h^–1)if required. Intensive arterial sampling was performed for upto 72 h after infusion. Pharmacokinetic parameters obtainedby simultaneous modelling of remifentanil and RA data were statisticallycompared between the two groups. Results. Remifentanil pharmacokinetics were not significantlyaffected by renal status. RA clearance in the moderate/severegroup was reduced to about 25% that of the normal/mild group(41 (29) vs 176 (49) ml kg^–1 h^–1, P<0.0001).Metabolic ratio, a predictor of the ratio of RA to remifentanilconcentrations at steady state, was approximately eight-foldhigher in the moderate/severe group relative to the normal/mildgroup (116 (110) vs 15 (4), P<0.0001). Maximum RA levelsapproached 700 ng ml^–1 in the moderate/severe group. Conclusions. Although RA accumulates in patients with moderate/severerenal impairment, pharmacokinetic modelling predicts that RAconcentrations during a 9 µg kg^–1 h^–1 remifentanilinfusion for up to 15 days would not exceed those reported inthe present study, for which no associated prolongation of µ-opioideffects was observed. Br J Anaesth 2004; 92: 493–503