An isobolographic analysis of diamorphine and levobupivacaine for epidural analgesia in early labour

Background: Few data describe the pharmacological interactions between localanaesthetics and opioids. The aim of this study was to measurethe median effective concentration (MEC) of diamorphine andlevobupivacaine when given separately and as mixtures for epiduralanalgesia, and determine whether the combination is additiveor synergistic. Methods: One hundred and twenty patients were enrolled in this prospectiverandomized, two-phase, double-blind study. In the first phase,60 women were randomized to receive a fixed 20 ml volumeof either levobupivacaine or diamorphine epidurally . Dosingwas determined using up-down sequential allocation with testingintervals, respectively, of 0.01%w/v and 12.5 µg ml^–1.After estimations of the MEC of levobupivacaine and diamorphine,a further 60 patients were randomized in the second phase toone of the three mixtures: (a) diamorphine 70 µg ml^–1(fixed) and levobupivacaine (testing interval 0.004%w/v, startingat 0.044%w/v); (b) levobupivacaine 0.044%w/v (fixed) and diamorphine(testing interval 7 µg ml^–1, startingat 70 µg ml^–1); and (c) bivariate diamorphineand levobupivacaine (testing intervals of 7 µg ml^–1and 0.004%w/v starting at 70 µg ml^–1 and0.044% w/v respectively). Results: The MEC estimates from the first phase were 143.8 µg ml^–1(95% CI 122.2–165.3) for diamorphine and 0.083%w/v (95%CI 0.071–0.095) for levobupivacaine. In the second phase,the MEC and interaction index () of the three combinations were:diamorphine 65.5 µg ml^–1 (56.8–74.2), = 0.99; levobupivacaine 0.041%w/v (0.037–0.049), = 0.98;and for the fixed combination diamorphine 69.5 µg ml^–1(60.5–78.5) and levobupivacaine 0.044%w/v (0.039–0.049), = 1.02. Conclusion: The combination of diamorphine and levobupivacaine is additiveand not synergistic when used for epidural analgesia in thefirst stage of labour.     

Effect of intrathecal diamorphine on block height during spinal anaesthesia for Caesarean section with bupivacaine

Background. Opioid analgesics are commonly added to intrathecalbupivacaine to improve patient comfort during Caesarean sectionunder spinal anaesthesia, and provide post-operative pain relief.We sought to discover if the addition of diamorphine influencedblock height when given with 0.5% w/v hyperbaric bupivacaine. Method. Eighty ASA I and II women of at least 37 weeks gestationand planned for elective Caesarean section under combined spinal–epiduralanaesthesia were recruited. They were randomized into two groupsto receive intrathecal hyperbaric bupivacaine 0.5% at an initialdose of 13 mg, with the next dose determined by the responseof the previous patient (dose interval 1 mg). One group alsoreceived diamorphine 400 µg intrathecally. If a blockheight of T5 to blunt light touch had been achieved after 20min, the block was deemed effective. A difference in the ED₅₀for hyperbaric bupivacaine between the groups would indicatethat diamorphine influenced block height. Intraoperative patientdiscomfort and need for analgesic supplementation was noted. Results. The median effective dose (ED₅₀) to achieve a T5 blockto light touch for Caesarean section using hyperbaric bupivacaine0.5% was 9.95 mg [95% confidence interval (CI) 9.0–10.90]and with the addition of diamorphine it was 9.3 mg (95% CI 8.15–10.40),while the ED₉₅ was 13.55 mg (95% CI 10.10–17.0) and 13.6mg (95% CI 9.15–18.05), respectively. Five women who hadreceived intrathecal diamorphine and 13 who had not receiveddiamorphine needed intraoperative supplementation (not significant). Conclusion. The addition of intrathecal diamorphine does notappear to influence block height.     

Comparison of hyperbaric and plain ropivacaine 15 mg in spinal anaesthesia for lower limb surgery

Background. Previously, plain ropivacaine 15 mg given intrathecallyhas been shown to be feasible for ambulatory surgery of lower-extremities.Hypothetically, hyperbaric solution could improve and shortenthe block. Methods. This prospective, randomized, double-blind study included56 patients undergoing surgery of lower extremities. They receivedintrathecally either 1.5 ml of ropivacaine 10 mg ml^–1and 0.5 ml of glucose 300 mg ml^–1 (HYP) or 2 ml of ropivacaine7.5 mg ml^–1 (PL). Results. All patients in Group HYP achieved T₁₀ dermatome analgesiabut only 64% (18/28) of Group PL. T₁₀ analgesia was reachedin 5 min (median, range 5–20 min) in the HYP group vs10 min (5–45 min) in the PL group (P=0.022), and fullmotor block in 10 min (5–45 min) vs 20 min (5–60min) (P=0.003), respectively. Group HYP had a longer durationof analgesia at T₁₀; 83 min (5–145 min) vs 33 min (0–140min) (P=0.004). Duration of sensory block from injection ofthe anesthetic to complete recovery was shorter in Group HYPthan in Group PL, 210 min (120–270 min) vs 270 min (210–360min) (P<0.001), as was duration of motor block, 120 min (5–150min) vs 210 min (120–330 min) (P<0.001). Patients ofGroup HYP attained discharge criteria earlier than those ofGroup PL (P=0.009). Conclusion. In comparison with the plain solution, 15 mg ofintrathecal hyperbaric ropivacaine produced a faster onset,greater success rate of analgesia at the level of T₁₀ dermatome,and faster recovery of the block.     

Block of the sacral segments in lumbar epidural anaesthesia

Background. Block of the first sacral segment is often delayedin lumbar epidural anaesthesia. The addition of either epinephrineor sodium bicarbonate to the local anaesthetic enhances theefficacy of epidural block. We assessed the block of lumbo-sacralsegments in lumbar epidural anaesthesia adding epinephrine and/orbicarbonate to lidocaine. Methods. Twenty-seven patients undergoing lumbar epidural anaesthesiawith lidocaine 2%, 17 ml at L4-5 or L5-S1 were randomly dividedinto three groups. Plain lidocaine, lidocaine with 1:200 000epinephrine or lidocaine–epinephrine–bicarbonatewas administrated via an epidural catheter. The pain thresholdafter repeated electrical stimulation was used to assess thesensory block at the L2, S1, and S3 segments. Motor block wasevaluated using the Bromage scale. Results. Patient characteristics were comparable between thegroups. The pH of lidocaine in the lidocaine–epinephrine–bicarbonategroup was significantly higher than that in other groups. Painthresholds at the S1 and S3 segments in the lidocaine–epinephrine–bicarbonategroup were significantly higher than those in the lidocaine–epinephrinegroup. However, differences in the pain threshold at the L2segment between groups were insignificant. The time to onsetof sensory block at the S1 and S3 in the lidocaine–epinephrine–bicarbonategroup was significantly shorter than that in the lidocaine group.Pain threshold by pinprick test was approximately within the30–50 mA range. Conclusion. A combination of lidocaine, bicarbonate, and epinephrineincreases the pain threshold over the sacral segments. Br J Anaesth 2003; 90: 173–8     

Small dose of clonidine mixed with low-dose ropivacaine and fentanyl for epidural analgesia after total knee arthroplasty

Background. We studied whether a small dose of clonidine addedto a ropivacaine–fentanyl mixture improves epidural analgesiawithout provoking side effects typically related to larger amountsof epidural clonidine. Methods. In this randomized, double-blinded study, patients(     

Comparison of ropivacaine 0.5% (in glucose 5%) with bupivacaine 0.5% (in glucose 8%) for spinal anaesthesia for elective surgery

Background. Hyperbaric solutions of ropivacaine have been usedsuccessfully to provide spinal anaesthesia. This study was designedto compare the clinical efficacy of hyperbaric ropivacaine withthat of the commercially available hyperbaric preparation ofbupivacaine. Methods. Forty ASA grade I–II patients undergoing lower-abdominal,perineal or lower-limb surgery under spinal anaesthesia wererecruited and randomized to receive ropivacaine 5 mg ml^–1(with glucose 50 mg ml^–1), 3 ml or bupivacaine 5 mg ml^–1(with glucose 80 mg ml^–1), 3 ml. The level and durationof sensory block, intensity and duration of motor block, andtime to mobilize and micturate were recorded. Patients wereinterviewed at 24 h and at 1 week to identify any residual problems. Results. All blocks were adequate for the proposed surgery,but there were significant differences between the two groupsin mean time to onset of sensory block at T10 (ropivacaine 5min; bupivacaine 2 min; P<0.005), median maximum extent (ropivacaineT7; bupivacaine T5; P<0.005) and mean duration of sensoryblock at T10 (ropivacaine 56.5 min; bupivacaine 118 min; P=0.001).Patients receiving ropivacaine mobilized sooner (ropivacainemean 253.5 min; bupivacaine 331 min; P=0.002) and passed urinesooner (ropivacaine mean 276 min; bupivacaine 340.5 min; P=0.01)than those receiving bupivacaine. More patients in the bupivacainegroup required treatment for hypotension (>30% decrease insystolic pressure; P=0.001). Conclusions. Ropivacaine 15 mg in glucose 50 mg ml^–1 providesreliable spinal anaesthesia of shorter duration and with lesshypotension than bupivacaine. The recovery profile for ropivacainemay be of interest given that more surgery is being performedin the day-case setting. Br J Anaesth 2003; 90: 304–8     

Minimum dose of intrathecal diamorphine required to prevent intraoperative supplementation of spinal anaesthesia for Caesarean section

Background. Intraoperative discomfort during spinal anaesthesiafor Caesarean section is the commonest cited anaesthetic causeof litigation in obstetric practice. Intrathecal opioids areused to improve intraoperative comfort and postoperative analgesiafor these operations. The minimum intrathecal diamorphine dosethat prevents intraoperative supplementation requires determination. Method. After ethics committee approval, 200 ASA I, II womenwith     

Epidural test dose with levobupivacaine and ropivacaine: determination of ED(50) motor block after spinal administration

Background. When a test is required to detect a possible intrathecalcatheter, many would seek to use the same local anaestheticas that used for epidural analgesia. The rapid onset of inappropriatemotor block after a local anaesthetic administered epidurallyimplies intrathecal spread. Because of claims of greater sensory–motorseparation, or because of reduced potency compared with bupivacaine,the efficacy of the new local anaesthetics in intrathecal testinghas been questioned. The aim of this study was to establishthe feasibility of a test dose for an inadvertent intrathecalcatheter using ropivacaine and levobupivacaine, and to establishthe dose required. Methods. Sixty women undergoing elective Caesarean section witha combined spinal– epidural technique were enrolled intothis prospective, double-blind sequential allocation study.The women were randomized to receive plain levobupivacaine 0.5%or ropivacaine 0.5% intrathecally. The dose was determined accordingto up–down sequential allocation. The end-point was anyevidence of lower limb motor block within 5 min of injection. Results. The ED₅₀ motor block at 5 min was 4.8 mg (95% CI, 4.49,5.28) for levobupivacaine and 5.9 mg (95% CI, 4.82, 6.98) forropivacaine (95% CI difference, 0.052, 1.98) (P=0.04). The estimatedED₉₅ motor block was 5.9 mg (95% CI 5.19, 6.71) for levobupivacaineand 8.3 mg (95% CI, 6.30, 10.44) for ropivacaine. The potencyratio between the two drugs was 0.83 (95% CI, 0.69, 0.99). Conclusions. Both local anaesthetics produce evidence of motorblock within 5 min of intrathecal injection and could serveas tests of intrathecal administration. Derived ED₉₅ valuessuggest 10 mg doses should be effective, but this study didnot measure predictive value. Ropivacaine is less potent formotor block than levobupivacaine by a factor of 0.83 (P<0.04). Br J Anaesth 2004; 92: 850–3     

Randomized controlled trial of patient-controlled epidural analgesia after orthopaedic surgery with sufentanil and ropivacaine 0.165% or levobupivacaine 0.125%

BACKGROUND: Ropivacaine, and to a lesser extent also levobupivacaine, is commonly used for postoperative epidural analgesia. Despite ED50 data suggesting a potency difference between these drugs, clinically they can be difficult to distinguish. As a consequence, it is unclear which concentration of each drug to use when comparing them for long-term analgesia. METHODS: One hundred patients undergoing total hip or knee replacement were selected to participate in a double-blind randomized study comparing ropivacaine 0.165% with levobupivacaine 0.125% to which was added sufentanil 1 microg ml(-1) for postoperative analgesia by the epidural route. Patient-controlled epidural analgesia (PCEA) was offered for 48 h. After the first 24 h, the basal infusion was omitted. RESULTS: Pain scores both at rest and on mobilization were similar between both groups. The volume of local anaesthetic solution consumed during the first 48 h after surgery was 25% higher in those patients receiving ropivacaine (P=0.02). Patients receiving ropivacaine made a mean (SD) of 38.5 (16) PCEA demands in the first 48 h after surgery compared with 28 (13) in the levobupivacaine group (P=0.04). CONCLUSIONS: Both local anaesthetics provided effective postoperative analgesia but, even in a 25% weaker concentration, a small volume of levobupivacaine and opiate substance was consumed. These differences may be explained by a potency difference or by the duration of action of levobupivacaine.     

Choice of opioid for initiation of combined spinal epidural analgesia in labour--fentanyl or diamorphine

Sixty-two women requesting regional analgesia in labour wereallocated to receive a 1.5 ml intrathecal injection aspart of a combined spinal–epidural (CSE) analgesic technique.This contained either bupivacaine 2.5 mg plus fentanyl25 µg (group F) or bupivacaine 2.5 mg plus diamorphine250 µg (group D). Times of analgesic onset and offsetwere recorded, motor and proprioceptive assessments made andside-effects noted. Analgesic onset was not significantly differentbetween the groups (group F, 8.0 min; group D, 9.5 min; P=0.3)but time to first top-up request was significantly longer inthe diamorphine group (group F, 73 min; group D, 101 min; P=0.003).Motor loss, assessed by the modified Bromage score, was statisticallybut not clinically greater in the fentanyl group (P=0.01). Maternalhypotension, pruritis, proprioceptive loss, nausea and fetalbradycardia were rare and not severe, and their incidences didnot differ between groups. No respiratory depression was observedafter CSE. This use of diamorphine was not associated with increasedside-effects compared with fentanyl/bupivacaine, and it hasa longer duration of action. Br J Anaesth 2001; 86: 567–9     

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     

Density of spinal anaesthetic solutions of bupivacaine, levobupivacaine, and ropivacaine with and without dextrose

Background. Spread of intrathecal local anaesthetics is determinedprincipally by baricity and position of the patient. Hypobaricsolutions of bupivacaine are characterized by an unpredictablespread of sensory block whereas addition of dextrose 80 mg ml^–1provides a predictable spread but to high thoracic levels. Incontrast, dextrose concentrations between 8 and 30 mg ml^–1have shown reliable and consistent spread for surgery. Hence,the aim of this study was to determine the density of bupivacaine,levobupivacaine, and ropivacaine with and without dextrose atboth 23 and 37°C before embarking on clinical studies. Methods. Density (mg ml^–1) was measured using the methodof mechanical oscillation resonance, accurate to five decimalplaces on 1250 samples. 500 density measurements were performedin a randomized, blind fashion at 23 and 37°C on 10 plainsolutions of bupivacaine (2.5, 5, and 7.5 mg ml^–1) levobupivacaine(2.5, 5, and 7.5 mg ml^–1) and ropivacaine (2, 5, 7.5,and 10 mg ml^–1). Following this, 750 density measurementswere taken at 23 and 37°C on the 5 mg ml^–1 solutionsof bupivacaine, levobupivacaine, and ropivacaine with addeddextrose (10, 20, 30, 50, and 80 mg ml^–1). Results. There was a linear relationship between density anddextrose concentration for all three local anaesthetics (R²=0.99)at 23 and 37°C. The mean density of levobupivacaine 5 mgml^–1 was significantly greater than the densities of bupivacaine5 mg ml^–1 and ropivacaine 5 mg ml^–1 after adjustingfor dextrose concentration using analysis of covariance. Thisdifference existed both at 23 and 37°C. The mean (SD) densityof levobupivacaine 7.5 mg ml^–1 was 1.00056 (0.00003) mgml^–1, the lower 0.5% percentile (1.00047 mg ml^–1)lying above the upper limit of hypobaricity for all patientgroups. Conclusions. The density of local anaesthetics decreases withincreasing temperature and increases in a linear fashion withthe addition of dextrose. Levobupivacaine 5 mg ml^–1 hasa significantly higher density compared with bupivacaine 5 mgml^–1 and ropivacaine 5 mg ml^–1 at 23 and 37°Cboth with and without dextrose. Levobupivacaine 7.5 mg ml^–1is an isobaric solution within all patient groups at 37°C. Br J Anaesth 2004; 92: 547–51     

Intrathecal ropivacaine for total hip arthroplasty: double-blind comparative study with isobaric 7.5 mg ml(-1) and 10 mg ml(-1) solutions

This study was designed to evaluate the efficacy and safetyof two concentrations of intrathecal ropivacaine, 7.5 and 10mg ml^–1, in patients undergoing total hip arthroplasty.One hundred and four patients, ASA I–III, were randomizedto receive an intrathecal injection of one of two concentrationsof isobaric ropivacaine. Group 1 (n=51) received 2.5 ml of 7.5mg ml^–1 ropivacaine (18.75 mg). Group 2 (n=53) received2.5 ml of 10 mg ml^–1 ropivacaine (25 mg). The onset andoffset of sensory block at dermatome level T10, maximum upperand lower spread of sensory block and the onset, intensity andduration of motor block were recorded, as were safety data.Onset of motor and sensory block was rapid with no significantdifferences between the two groups. The median time of onsetof sensory block at the T10 dermatome was 2 min (range 1–25min) in Group 1 and 2 min (range 1–21 min) in Group 2.The median duration of sensory block at the T10 dermatome was3.0 h (range 0.5–4.2 h) in Group 1 and 3.4 h (1.1–5.9h) in Group 2 (P=0.002). The median duration of complete motorblock was significantly prolonged (P<0.05) in Group 2 comparedwith Group 1 (1.9 vs 1.2 h, respectively). Anaesthetic conditionswere excellent in all but one patient. Intrathecal ropivacaine,in doses of 18.75 and 25 mg, was well tolerated and providedeffective anaesthesia for total hip arthroplasty. Br J Anaesth 2001; 87: 743–7     

Comparison of ropivacaine 2 mg ml(-1) and prilocaine 5 mg ml(-1) for i.v. regional anaesthesia in outpatient surgery

Background. Ropivacaine 2 mg ml^–1 (0.2%) provides longer-lastinganalgesia after deflation of the tourniquet cuff, with fewerside-effects, than lidocaine 5 mg ml^–1 (0.5%) after i.v.regional anaesthesia (IVRA). Whether ropivacaine 2 mg ml^–1also exerts this advantage over prilocaine 5 mg ml^–1,the local anaesthetic of choice in IVRA in most European countrieswas investigated in this study. Methods. Sixty outpatients scheduled for forearm or hand surgeryreceived IVRA with 40 ml of ropivacaine 2 mg ml^–1 (Ropi)or prilocaine 5 mg ml^–1 (Prilo) in a randomized, double-blindedfashion. The development and recovery of pin-prick analgesiaand motor power of the hand, as well as ropivacaine and prilocaineplasma concentrations (n=30), were assessed during and afteroperation. Results. Anaesthesia for surgery was adequate in both groups.Pin-prick analgesia was achieved at a similar rate, except inthe radial nerve distribution area where at 10 min 60% of Ropiand 90% of Prilo patients had analgesia (P=0.017). At 10 min100 and 97% had motor block of the hand in the Ropi and Prilogroups, respectively. Recovery of the sensory block in all innervationareas was already observed 2 min after the tourniquet cuff release.At 10 min after releasing the tourniquet cuff 31% of the Ropipatients and none of the Prilo patients still had analgesiain the median nerve distribution (P=0.004). At 12 min, 42% inthe Ropi group and none in the Prilo group had decreased gripstrength. After the release of the tourniquet, mean plasma concentrationsof ropivacaine were higher than those of prilocaine. The highestindividual concentration of ropivacaine was 1.65 µg ml^–1and that of prilocaine 0.6 µg ml^–1. None of theRopi patients experienced any symptoms of local anaesthetictoxicity. Conclusions. Compared with prilocaine 5 mg ml^–1, analgesiain IVRA with ropivacaine 2 mg ml^–1 developed slightlymore slowly, while motor block developed at a similar rate.After the release of the tourniquet, sensation recovered quicklyand at a similar rate in the two groups, except for a slightlyslower recovery after ropivacaine in the innervation area ofthe median nerve, but no surgically useful extended analgesiaafter the cuff deflation was observed. Despite a 60% lower milligram-dose,ropivacaine plasma concentrations were markedly higher thanthose of prilocaine.     

Intrathecal ropivacaine or bupivacaine with fentanyl for labour

Combined spinal-epidural (CSE) is widely used to provide painrelief in labour while minimizing motor blockade. Aiming tofurther reduce associated motor weakness, we compared ropivacaine2.5 mg in the intrathecal injection with a standard bupivacaineCSE in a double-blind study. Forty women were randomized toreceive either bupivacaine 2.5 mg or ropivacaine 2.5 mg intrathecally,both with fentanyl 0.025 mg. There were no significant differencesbetween the groups regarding the onset, duration or qualityof analgesia or the level of sensory block attained. Forty percent of the women (8/20) receiving bupivacaine developed detectablemotor block compared with only 5% (1/20) in the ropivacainegroup (P<0.05). Vibration sense was impaired in one womanin each group. Adverse effects did not differ between groups.We conclude that intrathecal ropivacaine 2.5 mg in combinationwith fentanyl 0.025 mg as part of a CSE technique provides rapidand safe analgesia for labour as effective as that achievedwith bupivacaine 2.5 mg and with significantly less motor block. Br J Anaesth 2001; 87: 733–7     

Comparison of intrathecal isobaric bupivacaine-morphine and ropivacaine-morphine for Caesarean delivery

Background. This study was designed to evaluate the effectsof intrathecal isobaric bupivacaine 0.5% plus morphine and isobaricropivacaine 0.5% plus morphine combinations in women undergoingCaesarean deliveries. Method. Twenty-five parturients received ropivacaine 15 mg andmorphine 150 µg (RM group) and twenty-five parturientsreceived bupivacaine 15 mg and morphine 150 µg (BM group)for spinal anaesthesia. Sensory and motor block, haemodynamics,postoperative analgesia, fetal outcomes, and side-effects wereevaluated. Results. Intrathecal bupivacaine–morphine and ropivacaine–morphineprovided effective sensory anaesthesia and motor block. Timeto reach complete motor block was shorter and time to completerecovery from motor block was longer in the BM group than theRM group (P<0.05). The time to regression of two dermatomesand time for the block to recede to the S2 dermatome were similarin both groups (P>0.05). Time to first complaint of painand the mean total consumption of tenoxicam were similar inboth groups (P>0.05). APGAR scores at 1 and 5 min were similarin the two groups, as were mean umbilical blood pH values (P>0.05).Hypotension and pruritus were the most common side-effects inboth groups during the operation. Conclusion. Intrathecal isobaric ropivacaine 0.5% 15 mg plusmorphine 150 µg provides sufficient anaesthesia for Caesareandelivery. The ropivacaine–morphine combination resultedin shorter motor block, similar sensory and postoperative analgesia. Br J Anaesth 2003; 90: 659–64     

Comparison of 1% and 2% lidocaine epidural anaesthesia combined with sevoflurane general anaesthesia utilizing a constant bispectral index

Background. The authors compared the effects of epidural anaesthesiawith lidocaine 1% and lidocaine 2% on haemodynamic variables,sevoflurane requirements, and stress hormone responses duringsurgery under combined epidural/general anaesthesia with bispectralindex score (BIS) kept within the range 40–50. Methods. Thirty-three patients undergoing lower abdominal surgerywere randomly divided into two groups to receive lidocaine 1%or 2% by epidural with sevoflurane general anaesthesia. Sevofluranewas adjusted to achieve a target BIS of 40–50 during maintenanceof anaesthesia with nitrous oxide 60% in oxygen. Measurementsincluded the inspired (FI_SEVO) and the end-tidal sevofluraneconcentrations (E'_SEVO), blood pressure (BP), and heart rate(HR) before surgery and every 5 min during surgery for2 h. Plasma samples were taken immediately before and duringsurgery for measurements of catecholamines, cortisol, and lidocaine. Results. During surgery, both groups were similar for HR, BPand BIS, but FI_SEVO and E'_SEVO were significantly higher andmore variable with lidocaine 1% than with 2%. Intraoperativeplasma concentrations of epinephrine and cortisol were foundto be higher with lidocaine 1% as compared with 2%. Conclusions. To maintain BIS of 40–50 during combinedepidural/general anaesthesia for lower abdominal surgery, sevofluraneconcentrations were lower and less variable with lidocaine 2%than with 1%. In addition, the larger concentration of lidocainesuppressed the stress hormone responses better. Br J Anaesth 2003; 91: 825–9     

Pre-incisional epidural ropivacaine, sufentanil, clonidine, and (S)+-ketamine does not provide pre-emptive analgesia in patients undergoing major pancreatic surgery

BACKGROUND: The concept of pre-emptive analgesia remains controversial. This prospective, randomized, and double-blind study compared epidural administration of ropivacaine 2 mg ml(-1), sufentanil 0.5 microg ml(-1), clonidine 3 microg ml(-1), and S(+)-ketamine 0.25 mg ml(-1) (study solution) given before incision with the same combination started at the end of the operation. METHODS: After testing the stability of the solution using high performance liquid chromatography (HPLC) and examining 12 patients for possible side-effects in comparison with the epidural infusion of ropivacaine 2 mg ml(-1) and sufentanil 0.5 microg ml(-1), 30 patients undergoing major pancreatic surgery were recruited into the study. Before induction of anaesthesia, an epidural catheter was inserted (TH6-8). Patients in Group 1 received a bolus of 8 ml followed by a continuous infusion (8 ml h(-1)) of the study solution before induction of anaesthesia. In Group 2, patients received the same volume of saline before operation, the study solution was started at the end of surgery. After operation, the infusion was maintained for at least 96 h using a patient-controlled epidural analgesia (PCEA) pump in both groups. Patients were evaluated up to the seventh postoperative day for pain and side-effects. RESULTS: Visual analogue scale (VAS) values at rest were as follows: G1 vs G2: 24 h, 19 (sd 23) vs 6 (13); 48 h, 4 (10) vs 11 (21); and 72 h, 12 (22) vs 13 (21). VAS values during coughing and mobilization were also comparable. Total volume of epidural infusion was 904 (114) ml in G1 vs 892 (154) ml in G2. The incidence of side-effects (nausea, vomiting, and motor block) was low and not different between the groups. CONCLUSIONS: Pre-incisional epidural analgesic infusion did not provide pre-emptive analgesia compared with administration started at the end of surgery, but both groups had low pain scores.     

A double-blind comparison of epidural ketamine and diamorphine for postoperative analgesia

Twenty patients who had abdominal hysterectomy under general anaesthesia were randomly assigned to receive either epidural ketamine (30 mg), or epidural diamorphine (5 mg) peri-operatively and on first request for analgesia. Failure to obtain satisfactory analgesia with one of the agents was treated by epidural administration of the other. Pain was assessed by an independent observer, and by the patient using a visual analogue scale. The mean (SD) pain score on recovery from general anaesthesia, on a scale of 0-4, was 2.9 (1.2) for the ketamine group and 1.0 (1.0) for the diamorphine group (p less than 0.01). The mean (SD) time to first request for analgesia was 272 (206) and 72 (41) minutes in the diamorphine and ketamine groups respectively (p less than 0.01). All patients in the diamorphine group obtained adequate analgesia, but all patients in the ketamine group were changed to epidural diamorphine. Epidural ketamine does not appear to be a sufficiently effective alternative to epidural diamorphine for routine use in postoperative pain.     

Efficacy and uptake of ropivacaine and bupivacaine after single intra-articular injection in the knee joint

The efficacy of ropivacaine 100 mg (5 mg ml^–1),150 mg (7.5 mg ml^–1) and 200 mg (10 mg ml^–1)and bupivacaine 100 mg (5 mg ml^–1) givenby intra-articular injection into the knee after the end ofsurgery was studied in 72 ASA I–II patients scheduledfor elective knee arthroscopy under general anaesthesia in arandomized, double-blind study. Kapake (paracetamol 1 gand codeine 60 mg) was given as a supplementary analgesic.Pain scores were assessed 1–4 h after surgery and a verbalrating scale of overall pain severity was assessed on secondpostoperative day. Ropivacaine or bupivacaine concentrationswere determined in peripheral venous plasma up to 3 h afterinjection in eight patients in each group. Verbal rating painscores were lower with ropivacaine 150 mg compared withbupivacaine 100 mg (P<0.05). There was a tendency forlower analgesic consumption and pain scores with all doses ofropivacaine (not significant). The mean (SD) maximum total plasmaconcentrations of ropivacaine were 0.64 (0.25), 0.78 (0.43),and 1.29 (0.46) mg litre^–1 after 100, 150 and200 mg. The corresponding unbound concentrations were 0.018(0.009), 0.024 (0.020) and 0.047 (0.022) mg litre^–1.Both were proportional to the dose. The maximum total concentrationafter bupivacaine 100 mg was 0.57 (0.36) mg litre^–1.The time to reach maximum plasma concentration was similar forall doses and varied between 20 and 180 min. All concentrationswere well below the threshold for systemic toxicity. Br J Anaesth 2001; 87: 570–6