Rocuronium plasma concentrations during three phases of liver transplantation: relationship with early postoperative graft liver function

Background. Previous studies have suggested that neuromuscularblocking agents might be used to assess liver function duringliver transplantation. This study examines changes in rocuroniumplasma concentration during liver transplantation, to assessgraft function. Methods. A constant-rate infusion of rocuronium was administeredto 17 adult patients undergoing liver transplantation. Bloodsamples were taken at 30-min intervals throughout the procedure,which was divided into three phases: paleo-, an-, and neohepatic.Assay of plasma concentrations of rocuronium was by a gas chromatographic–massspectrometry technique. Postoperative liver function was followedfor up to five days by measuring plasma aminotransferases. Results. In 14 of the 15 patients who survived the transplantationprocedure, there was a 7–50% decrease in rocuronium concentrationduring the neohepatic phase compared with the anhepatic phase.In contrast, rocuronium concentrations increased in the twopatients who died after surgery, one as a result of primarynon-function and one from massive bleeding. In one patient whosurvived there was no change in rocuronium concentration. Theincrease in plasma rocuronium concentration during the neohepaticphase in the two patients who died was consistent with highlevels of plasma aminotransferases. Conclusions. Comparison of changes in plasma rocuronium concentrationduring the neohepatic phase with early postoperative liver functiontests suggests the potential use of rocuronium as a pharmacokineticprobe for predicting liver function during liver transplantation.Further study of rocuronium’s potential as an intraoperativepharmacodynamic probe of liver function by measuring neuromuscularparalysis is suggested. Br J Anaesth 2002; 88: 764–70     

Comparison of four strategies to reduce the pain associated with intravenous administration of rocuronium

Background. I.V. rocuronium produces intense discomfort at thesite of injection in conscious patients. Four strategies toreduce or prevent this discomfort were studied. Methods. Two hundred and fifty adult patients, ASA I–III,were randomized into five groups of 50 patients in a blinded,prospective study. The control group received rocuronium 10 mgalone. For the remaining four groups, rocuronium 10 mgwas mixed with sodium bicarbonate 8.4% 2 ml, fentanyl 100 µg,lidocaine 2% or normal saline. The pH and osmolality of allmixtures were measured. Patient data were analysed using ordinallogistic regression. Osmolality and pH data were analysed usingthe Kruskal–Wallis test with Dunn’s multiple comparisontest. Results. When compared with rocuronium alone, only the additionof saline failed to significantly reduce the pain reported bypatients. The addition of fentanyl reduced the complaint ofpain by 1.9 times (P<0.049) and the addition of lidocaine2% reduced it by 3.6 times (P<0.0001). Sodium bicarbonate8.4% reduced the reporting of pain by 18.4 times (P<0.0001). Conclusions. Sodium bicarbonate 8.4%, when added to rocuronium,markedly reduces the experience of pain during the i.v. administrationof a small dose of rocuronium. Br J Anaesth 2003; 90: 377–9     

Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery

Background. Ketorolac is approved for the relief of postoperativepain but concerns have been raised over a possible risk of seriousadverse effects and death. Two regulatory reviews in Europeon the safety of ketorolac found the data were inconclusiveand lacked comparison with other non-steroidal anti-inflammatorydrugs. The aim of this study was to compare the risk of seriousadverse effects with ketorolac vs diclofenac or ketoprofen inadult patients after elective major surgery. Methods. This prospective, randomized multicentre trial evaluatedthe risks of death, increased surgical site bleeding, gastrointestinalbleeding, acute renal failure, and allergic reactions, withketorolac vs diclofenac or ketoprofen administered accordingto their approved parenteral and oral dose and duration of treatment.Patients were followed for 30 days after surgery. Results. A total of 11 245 patients completed the trial at 49European hospitals. Of these, 5634 patients received ketorolacand 5611 patients received one of the comparators. 155 patients(1.38%) had a serious adverse outcome, with 19 deaths (0.17%),117 patients with surgical site bleeding (1.04%), 12 patientswith allergic reactions (0.12%), 10 patients with acute renalfailure (0.09%), and four patients with gastrointestinal bleeding(0.04%). There were no differences between ketorolac and ketoprofenor diclofenac. Postoperative anticoagulants increased the riskof surgical site bleeding equally with ketorolac (odds ratio=2.65,95% CI=1.51–4.67) and the comparators (odds ratio=3.58,95% CI=1.93–6.70). Other risk factors for serious adverseoutcomes were age, ASA score, and some types of surgery (plastic/ear,nose and throat, gynaecology, and urology). Conclusion. We conclude that ketorolac is as safe as ketoprofenand diclofenac for the treatment of pain after major surgery. Br J Anaesth 2002; 88: 227–33     

Outcome of ASA III patients undergoing day case surgery

Background. Day case surgery is becoming more acceptable, evenfor patients with complex medical conditions. Current recommendationssuggest that patients who are graded as American Society ofAnaesthesiologists physical status (ASA) III may be suitablefor this approach. There is only a small amount of publisheddata available to support this. We present a retrospective reviewof ASA III patients who had undergone day surgical proceduresin our unit. Methods. We carried out a retrospective case controlled reviewof 896 ASA III patients who had undergone day case proceduresbetween January 1998 and June 2002 using the existing computerizedpatient information system. The system records admission rates,unplanned contact with healthcare services and post-operativecomplications in the first 24 h after discharge. Results. We demonstrated no significant differences in unplannedadmission rates, unplanned contact with health care services,or post-operative complications in the first 24 h after dischargebetween ASA III and ASA I or II patients. Conclusion. With good pre-assessment and adequate preparationASA III patients can be treated safely in the day surgery setting. Br J Anaesth 2004; 92: 71–4     

Double lumen tube location predicts tube malposition and hypoxaemia during one lung ventilation

Background. Poor positioning of an endobronchial double lumentube (DLT) could affect oxygenation during one lung ventilation(OLV). We set out to relate DLT position to hypoxaemia and DLTmisplacement during OLV. Methods. We recruited 152 ASA physical status I–II patientsabout to have elective thoracic surgery. The trachea was intubatedwith a left-sided DLT. Tube position was assessed by fibre-opticscope and correction was made after patient positioning andduring OLV. If Pa_O2 was less than 10.7 kPa, the DLT positionwas checked and then PEEP, continuous positive airway pressure(CPAP), oxygen insufflation, or two lung ventilation (TLV) weretried. Results. The DLT was found to be misplaced in 49 patients (32%)after patient positioning, and in 38 patients (25%) during OLV.PEEP to the dependent lung, CPAP or apneic oxygen insufflationto the non-dependent lung, or brief periods of TLV, were appliedin 46 patients (30%). Patients who had DLT malposition afterplacing the patient in the lateral position had a greater incidenceof DLT malposition during OLV (59 vs 9%) and also required eachintervention more frequently (57 vs 10%). Patients with DLTmalposition during OLV also required interventions more often(84 vs 12%). Conclusions. Patients who have DLT malposition after placingthe patient in the lateral position had more DLT malpositionduring OLV and hypoxaemia during OLV. Br J Anaesth 2004; 92: 195–201     

Perioperative lower limb venous haemodynamics in patients under general anaesthesia

Background. This study prospectively determined the haemodynamicchanges in the lower limb venous circulation during and shortlyafter elective abdominal surgery, performed under general anaesthesia. Methods. Ten females, aged 36–65 yr, ASA I or II, undergoingtotal abdominal hysterectomy had their peak, mean and minimumvelocities, diameter, volume flow and venous pulsatility (peak–minimum/meanvelocity) measured in the left popliteal vein on recumbencywith duplex at: (i) baseline, (ii) 15 min after induction, (iii)during surgery, and (iv) in recovery 30 min after extubation.Anaesthesia was induced with fentanyl and propofol, paralysiswith vecuronium, maintenance with isoflurane in nitrous oxide66%, and analgesia with morphine. Results are presented as percentagedifference from baseline mean value. The Friedman and Wilcoxon_{[corrected^*]}tests were applied. Results. Mean velocity decreased by 23.6% during surgery andby 34.6% in recovery (P<0.05^*). Minimum velocity was decreasedby 56% during surgery and by 78% in recovery (P<0.05). Thevolume flow decreased by 26% during surgery, and by 54.4% inrecovery (P<0.001). Diameter and peak velocity changed littleat surgery and recovery (P>0.2). In contrast, the pulsatilityincreased by 30% on induction, 83% on surgery and 109% in recovery(P<0.05). Compared with baseline, haemodynamic changes oninduction were small (P>0.1^*). Conclusions. A significant decrease in the volume flow, meanand minimum velocities was noted during and immediately afterelective total abdominal hysterectomy under general anaesthesiain ASA I and II patients. Flow changes in early recovery mirroredor enhanced those noted intraoperatively. Despite venous flowattenuation, haemodynamic readjustments produced a significantand progressive enhancement of venous flow pulsatility duringthe course of the procedure.      

Urinary, biliary and faecal excretion of rocuronium in humans

The excretion of rocuronium and its potential metabolites wasstudied in 38 anaesthetized patients, ASA I–III and 21–69yr old. Rocuronium bromide was administered as an i.v. bolusdose of 0.3 or 0.9 mg kg^–1. In Part A of the study, theexcretion into urine and bile, and the liver content were studied.Plasma kinetics (n=19) were similar to those reported previously.Urinary recovery within 48 h after administration was 26 (8)%(mean (SD)) (n=8) of the dose. In bile obtained from T-drains,the recovery within 48 h was 7 (6)% (n=11). The rocuronium concentrationin bile declined bi-exponentially, with half-lives of 2.3 (0.7)and 16 (11) h respectively (n=6). In three patients from whomstoma fluid was collected, the amount of rocuronium recoveredranged from 0.04 to 12.0% of the dose. In liver tissue obtainedfrom four patients undergoing hemihepatectomy, the estimatedamount of rocuronium at 2–5 h after administration rangedbetween 6.3 and 13.2% (n=4). In the second part of the study(Part B), urine and faeces were collected over 4–8 daysand the recovery was 27 (13)% and 31 (23)% of the dose respectively(n=10). In most samples, irrespective of the type of biologicalmaterial, only small amounts of the metabolite 17-desacetyl-rocuroniumwas found. The results demonstrate that rocuronium is takenup by the liver and excreted into bile in high concentrations.The faecal and urinary excretion of unchanged rocuronium arethe major routes of rocuronium elimination. Br J Anaesth 2000; 85: 717–23 ^* Corresponding author     

Activated thrombelastogram in neonates and infants with complex congenital heart disease in comparison with healthy children

Background. The goal of the study was to determine activatedthrombelastographic (TEG®) parameters with the rotationalTEG® (ROTEG or ROTEM) device (Pentapharm GmbH, Munich, Germany)in neonates and infants <1 yr with complex congenital heartdisease (CCHD) and to compare them with those of healthy children. Methods. A total of 59 children were included: Group I (Gr I)24 children, ASA I, scheduled for minor surgery; and Group II(Gr II) 35 children with CCHD, ASA III–IV, scheduled forcardiac surgery. Each group was subdivided into four age groups.Blood samples were obtained before the surgical procedure. Results. Statistically significant differences (two-way ANOVAanalysis) between Gr I and Gr II [mean (SD); P-value] were foundin INTEG-CT [Gr I 175(19), Gr II 271(162); P=0.049], EXTEG-MCF[Gr I 63(8), Gr II 56(8); P=0.013], EXTEG-MCE [Gr I 186(65),Gr II 137(41); P=0.003], FIBTEG-MCF [Gr I 24(7), Gr II 19(5);P=0.012], FIBTEG-MCE [Gr I 32(13), Gr II 24(8); P=0.012] andEXTEG-MCE–FIBTEG-MCE [Gr I 155(55), Gr II 113(37); P=0.003].Clotting time via contact activation was prolonged in Gr IIand varied widely, mainly in the age group 0–1 month andto a lesser extent in 1–3 months, and maximum clot firmnesswas reduced in the same age groups. In comparison with Gr II,the healthy children showed relatively homogenous TEG valueswith a tendency to hypercoagulability; the maximum was foundin age group 1–3 months, decreasing towards adult valuesin the course of the first year of life. Conclusions. These preliminary TEG results indicate that thecoagulation-fibrinolytic system in CCHD patients <1 yr isfunctionally intact and balanced but at a lower level than inhealthy children. This could be interpreted as a reduction inthe haemostatic potential with less reserve.     

Concentration of rocuronium in cerebrospinal fluid of patients undergoing cerebral aneurysm clipping

Background. This study assessed the concentration of rocuroniumin the cerebrospinal fluid (CSF) of patients undergoing cerebralaneurysm clipping, and investigated whether the mode of administration(single bolus vs continuous infusion) influenced the CSF concentration. Methods. Twenty patients with subarachnoid haemorrhage wererandomly allocated to receive a bolus dose (bolus group), ora bolus followed by a continuous infusion of rocuronium (infusiongroup) (n=10 for each group). Arterial blood and ventricularCSF were sampled 2 h after the rocuronium bolus. Samples wereanalysed by liquid chromatography electrospray ionization-tandemmass spectrometry. Results. Rocuronium could be detected in all the CSF samples.The mean (range) CSF concentration was 2.2 (0.9–4.6) ngml^–1 in the bolus group and 12.4 (2.4–34.6) ng ml^–1in the infusion group; P<0.01. Conclusions. This study demonstrated that rocuronium, normallynot considered to cross the blood–brain barrier, is regularlyfound in the CSF of patients undergoing cerebral clipping; continuousinfusion of the drug led to higher plasma and CSF concentrationsthan after a single bolus dose. Br J Anaesth 2004; 92: 419–21     

Optimal rocuronium dose for intubation during inhalation induction with sevoflurane in children

Background. We studied 120 children aged 2–7 yr in a prospective,randomized, assessor-blinded fashion to define the optimal rocuroniumdose which provides a 95% probability of acceptable intubationconditions (ED_95TI) during inhalation induction with sevoflurane. Methods. After inhalation induction with 8% sevoflurane in 60%nitrous oxide and 40% oxygen, and loss of the eyelash reflex,we administered rocuronium (0.1, 0.15, 0.22, 0.3, or 0.6 mgkg^–1) or placebo. We quantified neuromuscular functionby stimulation of the ulnar nerve at 0.1 Hz to produce contractionof the adductor pollicis muscle using accelerometry. Intubationconditions were assessed 2 min after test drug injection. Theoptimal rocuronium dose was defined as the lowest dose, whichallowed acceptable intubation conditions in 95% of children(ED_95TI). Results. Two minutes after injection of placebo or rocuronium,intubation conditions were acceptable in 35, 45, 80, 90, 95,and 100% of children, respectively. Rocuronium 0.07 [CI 0.02–0.11],0.24 [0.19–0.31], and 0.29 [0.23–0.38] mg kg^–1provided 50, 90, and 95% probability of acceptable intubatingconditions. When thumb acceleration was depressed by 50% ormore, intubating conditions were considered acceptable in 97%of children. Recovery of the train-of-four ratio to 0.8 averaged12 (7), 16 (7), 24 (7), 24 (8), and 50 (22) min after the respectivedose of rocuronium. Conclusions. During inhalation induction with 8% sevofluranein 60% nitrous oxide, rocuronium 0.29 mg kg^–1 (ED₉₅) optimizesintubation conditions for surgery of short duration. Br J Anaesth 2002; 89: 277–81     

Randomized, double-blind, phase III, controlled trial comparing levobupivacaine 0.25%, ropivacaine 0.25% and bupivacaine 0.25% by the caudal route in children

Background. The rationale for replacing racemic bupivacainewith the s-enantiomers levobupivacaine and ropivacaine is toprovide a wider margin of safety with the same analgesic efficacyand less postoperative motor block. In a randomized, double-blind,phase III, controlled trial we compared the caudal administrationof levobupivacaine 0.25% and ropivacaine 0.25% with bupivacaine0.25% in children. Methods. Ninety-nine ASA I–II children less than 10 yrold scheduled for elective sub-umbilical surgery were randomizedto receive caudal block with bupivacaine 0.25%, ropivacaine0.25% or levobupivacaine 0.25%. The primary outcome of the studywas the clinical efficacy of the caudal block during the operation.Secondary outcome measures were analgesic onset time, pain reliefafter the operation and residual motor blockade. Results. The proportion of children with effective analgesiaduring the operation was similar among groups. There were nosignificant differences in the analgesic onset time of the caudalblock. Bupivacaine produced a significant incidence of residualmotor block compared with levobupivacaine or ropivacaine atwake-up (P<0.01). There were no significant differences inthe number of patients receiving rescue analgesia after surgery.However, analgesic block lasted significantly longer in patientsreceiving bupivacaine (P=0.03). Conclusion. During sub-umbilical surgery, caudal levobupivacaine,ropivacaine and bupivacaine provided comparable analgesic efficacy.Bupivacaine produced a higher incidence of residual motor blockadeand a longer analgesic block than ropivacaine and levobupivacaine.      

Effects of remifentanil and alfentanil on the cardiovascular responses to induction of anaesthesia and tracheal intubation in the elderly

Background. We compared the effects of remifentanil and alfentanilon arterial pressure and heart rate at induction of anaesthesiaand tracheal intubation in 40 ASA I–III patients agedgreater than 65 yr, in a randomized double-blind study. Methods. Patients received either remifentanil 0.5 µgkg^–1 over 30 s, followed by an infusion of 0.1 µgkg min^–1 (group R) or alfentanil 10 µg kg^–1over 30 s, followed by an infusion of saline (group A). Anaesthesiawas then induced with propofol, rocuronium, and 1% isofluranewith 66% nitrous oxide in oxygen. Results. Systolic arterial pressure (SAP) and mean arterialpressure (MAP) decreased after the induction of anaesthesia(P<0.05) and increased for 3 min after intubation in bothgroups (P<0.05), but remained below baseline values throughout.Heart rate remained stable after induction of anaesthesia butincreased significantly from baseline after intubation for 1and 4 min in groups R and A, respectively (P<0.05). Therewere no significant between-group differences in SAP, MAP, andheart rate. Diastolic pressure was significantly higher in groupA than group R at 4 and 5 min after intubation (P<0.05).Hypotension (SAP <100 mm Hg) occurred in four patients ingroup R and three patients in group A. Conclusions. Remifentanil and alfentanil similarly attenuatethe pressor response to laryngoscopy and intubation, but theincidence of hypotension confirms that both drugs should beused with caution in elderly patients. Br J Anaesth 2002; 88: 430–3     

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.     

Comparison of efficacy of oxybutynin and tolterodine for prevention of catheter related bladder discomfort: a prospective, randomized, placebo-controlled, double-blind study

Background. Bladder discomfort related to intraoperative catheterizationof urinary bladder is a distressing symptom and more so in patientsawakening from anaesthesia. These symptoms are similar to symptomsof overactive bladder. Muscarinic receptor antagonists havebeen reported to be effective in the treatment of overactivebladder. This study was therefore undertaken to evaluate theefficacy of oxybutynin and tolterodine in preventing catheterrelated bladder discomfort. Methods. Two hundred and thirty-four consecutive adult patients,ASA I and II, of either sex, undergoing elective percutaneousnephrolithotomy surgery requiring urinary bladder catheterizationwere randomized into three equal groups of 78 each. Group C(control) received placebo, Group O (oxybutynin) received oxybutynin5 mg and Group T (tolterodine) received tolterodine 2 mg orally1 h before surgery. After induction of anaesthesia patientswere catheterized with a 16 Fr Foley's catheter and the balloonwas inflated with 10 ml distilled water. The bladder discomfortwas assessed at 0, 1, 2 and 6 h after patient's arrival in thepost-anaesthesia care unit. Severity of bladder discomfort wasgraded as mild, moderate and severe. Results. Incidence of bladder discomfort observed in the controlgroup was higher, i.e. 58% (45/78), compared with oxybutyninand tolterodine groups where it was 35% (28/78) and 33% (26/78),respectively (P<0.05). Significant reduction in the severityof bladder discomfort was also observed after oxybutynin andtolterodine therapy compared with control (P<0.05). Conclusion. Pretreatment with either oxybutynin or tolterodinereduces the incidence and severity of catheter related bladderdiscomfort.     

Model-based control of mechanical ventilation: design and clinical validation

Background. We developed a model-based control system usingend-tidal carbon dioxide fraction (FE'_CO2) to adjust a ventilatorduring clinical anaesthesia. Methods. We studied 16 ASA I–II patients (mean age 38(range 20–59) yr; weight 67 (54–87) kg) during i.v.anaesthesia for elective surgery. After periods of normal ventilationthe patients were either hyper- or hypoventilated to assessprecision and dynamic behaviour of the control system. Thesedata were compared with a previous group where a fuzzy-logiccontroller had been used. Responses to different clinical events(invalid carbon dioxide measurement, limb tourniquet release,tube cuff leak, exhaustion of carbon dioxide absorbent, simulationof pulmonary embolism) were also noted. Results. The model-based controller correctly maintained thesetpoint. No significant difference was found for the staticperformance between the two controllers. The dynamic responseof the model-based controller was more rapid (P<0.05). Themean rise time after a setpoint increase of 1 vol% was 313 (SD90) s and 142 (17) s for fuzzy-logic and model-based control,respectively, and after a 1 vol% decrease was 355 (127) s and177 (36) s, respectively. The new model-based controller hada consistent response to clinical artefacts. Conclusion. A model-based FE'_CO2 controller can be used in aclinical setting. It reacts appropriately to artefacts, andhas a better dynamic response to setpoint changes than a previouslydescribed fuzzy-logic controller. Br J Anaesth 2004; 92: 800–7     

Rocuronium for muscle relaxation in two children with Friedreich's ataxia

Friedreich’s ataxia is a rare hereditary neurodegenerativedisease caused by a defect in the gene that encodes a mitochondrialprotein called frataxin. We report the use of rocuronium 0.6mg kg^–1 in two adolescent girls with Friedreich’sataxia undergoing propofol–sufentanil–oxygen–airanaesthesia for spinal surgery. Neuromuscular transmission wasmonitored using acceleromyography, and onset and recovery timeswere recorded. The clinical duration of rocuronium was comparableto that of children without neuromuscular disease (25% recoveryT₁=44 and 24 min for patients 1 and 2 respectively). Br J Anaesth 2004; 92: 592–6     

Comparison of local anaesthetic effects of tramadol with prilocaine for minor surgical procedures

Background. Recent studies have shown that a local anaestheticaction of tramadol 5% was able to induce a sensory block topinprick, touch, and cold similar to that of lidocaine 1%. Theaim of this study was to compare the local anaesthetic effectsof tramadol hydrochloride with prilocaine. Methods. Sixty ASA I or II patients, undergoing excision ofthe cutaneous lesions under local anaesthesia, were includedin the study. Patients were randomly assigned to receive either1 ml of tramadol 5% (Group T, n=30) or 1 ml of prilocaine 2%(Group P, n=30) intradermally, in a double-blinded fashion.The degree of the burning sensation and pain at the injectionsite was documented. Sensory block was assessed 1 min afterinjection. The patient was asked to report the degree of sensationand to grade touch and pinprick sensation. Two minutes afterdrug administration, incision was performed and intensity ofpain, felt by the patient was evaluated on a four-point scale(0–3). Any local adverse effects were recorded. Results. There was no difference in the quality of block betweenthe two groups. Side effects were noted in both groups witha significant increase in the incidence of local reaction (rash)in Group T (seven patients) when compared with Group P (onepatient) (P<0.05). Seven patients in Group T vs four patientsin Group P complained of burning at the injection site (P>0.05). Conclusions. Intradermal tramadol 5% can provide a local anaesthesiasimilar to the prilocaine but the incidence of local adverseeffects is higher. Br J Anaesth 2003; 90: 320–2     

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.     

Efficacy of prophylactic ketamine in preventing postoperative shivering

Background. Treatment with ketamine and pethidine is effectivein postoperative shivering. The aim of this study was to comparethe efficacy of low-dose prophylactic ketamine with that ofpethidine or placebo in preventing postoperative shivering. Methods. A prospective randomized double-blind study involved90 ASA I and II patients undergoing general anaesthesia. Patientswere randomly allocated to receive normal saline (Group S, n=30),pethidine 20 mg (Group P, n=30) or ketamine 0.5 mg kg^–1(Group K, n=30) intravenously 20 min before completion of surgery.The anaesthesia was induced with propofol 2 mg kg^–1, fentanyl1 µg kg^–1 and vecuronium 0.1 mg kg^–1. It wasmaintained with sevoflurane 2–4% and nitrous oxide 60%in oxygen. Tympanic temperature was measured immediately afterinduction of anaesthesia, 30 min after induction and beforeadministration of the study drug. An investigator, blinded tothe treatment group, graded postoperative shivering using afour-point scale and postoperative pain using a visual analoguescale (VAS) ranging between 0 and 10. Results. The three groups did not differ significantly regardingpatient characteristics. The number of patients shivering onarrival in the recovery room, and at 10 and 20 min after operationwere significantly less in Groups P and K than in Group S. Thetime to first analgesic requirement in Group S was shorter thanin either Group K or Group P (P<0.005). There was no differencebetween the three groups regarding VAS pain scores. Conclusion. Prophylactic low-dose ketamine was found to be effectivein preventing postoperative shivering.     

Bispectral index changes following etomidate induction of general anaesthesia and orotracheal intubation

Background. Etomidate-associated hypnosis has only been studiedusing standard clinical criteria and raw EEG variables. We conducteda BIS-based investigation of etomidate induction of generalanaesthesia. Methods. Thirty hydroxyzine-premedicated ASA I patients wererandomly allocated to receive etomidate 0.2, 0.3, or 0.4 mgkg^–1 intravenously over 30 s. The BIS was continuouslyrecorded. A tourniquet was placed on a lower limb to recordpurposeful movements and myoclonia. Tracheal intubation wasfacilitated using rocuronium 0.6 mg kg^–1 when the BISvalue was 50. The times to disappearance of the eyelash reflex,to a decrease in the BIS to 50, and to tracheal intubation werecompared. The BIS values 30 s following tracheal intubation,and mean arterial pressure (MAP) and heart rate (HR) at alltime points were also recorded. Results. The BIS value decreased to 50 for tracheal intubationwith no purposeful movement in all but one patient in the 0.2mg kg^–1 group. There was no difference between the etomidategroups (0.2, 0.3, and 0.4 mg kg^–1) in regards to timeto loss of the eyelash reflex (103 (67), 65 (34), 116 (86) s,P=0.2), or to a decrease in BIS to 50 (135 (81), 82 (36), 150(84) s, P=0.1). Also, the BIS value 30 s after intubation (41(10), 37 (4), 37 (4), P=0.4), and plasma etomidate concentrations(161 [29–998], 308 [111–730], 310 [90–869]ng ml^–1, P=0.2) did not differ between groups. The timeto loss of the eyelash reflex was 12–140 s shorter thanthe time to a decrease in BIS to 50 in three patients in eachgroup who received etomidate 0.2 and 0.4 mg kg^–1, andin four patients who received 0.3 mg kg^–1. No awarenesswas recorded. MAP and HR increases following tracheal intubationwere comparable between groups. Conclusions. Etomidate induction doses do not predict the timefor BIS to decrease to 50 as this variable varies markedly followingthree etomidate dose regimen. Br J Anaesth 2003; 91: 341–6