FUNCTIONAL AND METABOLIC EFFECTS OF BUPIVACAINE AND LIGNOCAINE IN THE RAT HEART-LUNG PREPARATION

We have examined the effects of bupivacaine and lignocaine onmyocardial metabolism in the rat isolated heart-lung preparation.Bupivacaine 1, 5 or 25 µg ml^–1 or lignocaine 4,20 or 100 µg ml^–1 was administered 5 min after thestart of perfusion. Both bupivacaine 25 µg ml^–1and lignocaine 100 µg ml^–1 reduced heart rate significantly.Bupivacaine 25 µg ml^–1 was associated with a higherincidence of arrhythmias than the other groups. Three heartsin the bupivacaine 25 µg ml^–1 group (n = 8) andtwo hearts in the lignocaine 100 µg ml^–1 group (n= 8) failed (zero cardiac output) at the end of the experiment.Although there were no significant differences in myocardiallactate and glycogen concentrations between groups, ATP contentin the bupivacaine 25 µg ml^–1 and lignocaine 100µg ml^–1 groups was significantly less than thatin the control group. The results suggest that myocardial depressionand subsequent metabolic deterioration occurred with both thehigh doses of local anaesthetics; these findings do not accountfor the apparent increased cardiotoxicity of bupivacaine.     

THIOPENTONE AND ETOMIDATE CONCENTRATIONS IN MATERNAL AND UMBILICAL PLASMA, AND IN COLOSTRUM

We have measured concentrations of etomidate and thiopentonein maternal plasma, umbilical venous plasma and colostrum afterinduction of anaesthesia in 40 patients undergoing Caesareansection. Mean plasma etomidate concentration declined rapidly(1242.0 ng ml^–1 at 5 min, 434.0 ng mt1 at 15 min, 64.2ng ml^–1 at 30 min, 7.0 ng ml^–1 at 60 min and undetectable2 h after the injection). Mean plasma concentrations of thiopentonedeclined more slowly (6.09 µg ml^–1 at 5 min, 2.64µg ml^–1 at 2 h, 1.35 ng ml^–1 at 4 h, 0.86ng ml^–1 at 9 h and 0.59 ng ml^–1 at 12.h). Mean umbilicalvenous thiopentone concentration was 4.72 µg ml^–1.whereas the thiopentone concentration in the maternal sampleat 5 min was 6.09 g ml^–1, giving an umbilical.maternalvein ratio of 1:1.3. Mean umbilical etomidate concentrationwas 51.7 ng ml^–1 and the corresponding maternal vein sample(5 min) was 1242.0 ng ml^–1 (P < 0.001), giving an umbilical:maternal vein ratio of 1:24. Mean concetrations of thioptonein colostrum were 1.98 µg mt^–1 at 30 min, 0.91 gmt1 at 4 h and 0.59 µg ml^–1 at 9 h, colostrum .plasmaratios at 4 h and 9 h being 0.67 and 0.68, respectively. Meanconcentrations of etomidate in colostrum were 79.2 ng ml^–1at 30 min and 16.3 ng ml^–1 at 2 h. being undetectableat 4 h. The colostrum:plasma etomidate concentration ratio was1.2 at 30 min. We conclude that, although plasma and colostrumconcentrations of thiopentone and etomidate declined rapidly,the decrease was faster with etomidate.     

EFFECTS OF THIOPENTONE ON IMMUNOGLOBULIN PRODUCTION IN VITRO

Thiopentone is known to depress several granulocyte and lymphocytefunctions. This study assessed the effects of thiopentone onlgG, lgM and lgA production by pokeweed mitogen-activated lymphocytesas a measure of B-lymphocyte function. Thiopentone decreasedlgG production at > 25 µg ml^–1 (91 µmollitre^–1) concentrations and that of lgM and lgA at >50 µg ml^–1 (182 µmol litre^–1) concentrationsover 7 days of culture. Preincubation of lymphocytes for 1 hwith thiopentone 0–500 µg ml^–1 (0–1820µmol litre^–1) had no effect on immunoglobulin production,whereas incubation for 2 and 3 h decreased lgG and lgM productionwith toxic thiopentone concentrations of 500 µg ml^–1.Hydrocortisone-sensitive suppressor cells and concanavalin A-induciblesuppressor cells were more sensitive to high concentrationsof thiopentone than the other cell populations. These findingsmay be important in patients receiving barbiturate treatmentfor cerebral protection.     

Ocular microtremor: a tool for measuring depth of anaesthesia?

Ocular microtremor (OMT) is a fine high frequency tremor ofthe eyes caused by extra-ocular muscle activity stimulated byimpulses emanating in the brain stem. Several studies have shownthat the frequency of this tremor is reduced in patients whoseconsciousness is reduced by anaesthesia or head injury. Therefore,OMT may possibly be used to determine depth of anaesthesia.Twenty-two unpre-medicated subjects undergoing surgery withgeneral anaesthesia were studied. OMT activity was measuredat admission using the open eye piezoelectric strain gauge technique.Anaesthesia was induced with propofol using a target controlledinfusion delivery system (Diprifusor^TM). OMT activity was thenrecorded at predicted plasma propofol concentrations of 1, 2,3 and 5 µg ml^–1. The patient’s level of consciousness(response to command or stimulation) was assessed after eachOMT measurement. OMT activity was reduced progressively at predictedplasma concentrations of propofol of 1 and 2 µg ml^–1and then plateaued between 3 and 5 µg ml^–1. Therewas a significant difference between the last awake OMT recordingand the first recording at loss of consciousness (P<0.001).OMT recording holds promise as a practical indicator of thedepth of anaesthesia. Br J Anaesth 2001; 86: 519–22     

PLASMA CONCENTRATIONS OF BUPIVACAINE AND TWO OF ITS METABOLITES DURING CONTINUOUS INTERSCALENE BRACHIAL PLEXUS BLOCK

An interscalene brachial plexus block was performed via a catheterwith 20–28 ml of 0.75% bupivacaine plus adrenaline forsurgery of the shoulder region in 12 patients. Constant infusionof 0.25% bupivacaine 0.25 mg kg^–1 h^–1 was continuedfor 24 h. During surgery light general anaesthesia, withoutanalgesics, was maintained. Plasma concentrations of total andunbound (free fraction) bupivacaine, desbutylbupivacaine (DBB),4-hydroxybupivacaine (4-OHB) and alpha₁-acid glycoprotein (AAG)were measured at predetermined intervals during the continuousblock. The greatest mean plasma concentrations of bupivacainewere measured at 30 min (1.63 (SD 0.55) µg ml^–1)and 60 min (1.38 (0.48) µg ml^–1). There was a smallbut statistically significant increase in the plasma concentrationof bupivacaine between 12 and 24 h of infusion. The mean unboundconcentration of bupivacaine in plasma decreased from 0.044(0.015) µg ml^–1 (3.6 (1.1)% of total bupivacaineconcentration) at 3 h to 0.023 (0.011) µg ml^–1 (2.1(1.0)%) at 24 h. The AAG concentration in plasma increased by38% in 24 h. The metabolites DBB and 4-OHB were detectable inplasma from 30 min, with a gradual increase during infusion.At 24 h the mean concentrations of DBB and 4-OHB were 0.33 (0.22)µg ml^–1 and 0. 13 (0.04) µg ml^–1, respectively.There were no toxic reactions during the blocks.     

Propofol sparing effect of remifentanil using closed-loop anaesthesia

Background. General anaesthesia is a balance between hypnosisand analgesia. We investigated whether an increase in remifentanilblood concentration would reduce the amount of propofol requiredto maintain a comparable level of anaesthesia in 60 patientsundergoing ambulatory surgery. Methods. Patients were allocated randomly to receive remifentanilto a target blood concentration of 2 ng ml^–1 (low), 4ng ml^–1 (medium), or 8 ng ml^–1 (high), administeredby target-controlled infusion (TCI). After equilibration, propofolTCI was commenced in closed-loop control, with auditory evokedpotentials (AEPex) as the input signal, aiming for an AEPexof 35. This was to ensure a comparable and unbiased level ofanaesthesia in all patients. Results. We found a dose-dependent decrease in propofol requirementswith increasing remifentanil concentrations. The mean (95% CI)propofol target blood concentration during adequate anaesthesiawas 4.96 (3.85–6.01) µg ml^–1 in the low, 3.46(2.96–3.96) µg ml^–1 in the medium, and 3.01(2.20–3.38) µg ml^–1 in the high group. Therewas no significant difference when recovery end points wereachieved between the groups. Cardiovascular changes were moderate,but most pronounced in the high concentration group, with adecrease in heart rate of 21% compared with baseline. The meancalculated effect site propofol concentration at loss of consciousnesswas 2.08 (1.85–2.32) µg ml^–1, and at recoveryof consciousness was 1.85 (1.68–2.00) µg ml^–1. Conclusions. This study confirms a synergistic interaction betweenremifentanil and propofol during surgery, whereas the contributionof remifentanil in the absence of stimulation seems limited.In addition, our results suggest that the propofol effect siteconcentration provides a guide to the value at which the patientrecovers consciousness. Br J Anaesth 2003; 90: 623–9     

CARDIOVASCULAR AND NEUROLOGICAL EFFECTS OF LAUDANOSINE: Studies in Mice and Rats, and in Conscious and Anaesthetized Dogs

The effects of laudanosine, a metabolite of atracurium, on thebehaviour of conscious mice, rats and dogs, and on cardiovascularfunction in conscious and anaesthetized dogs have been evaluated:EEG studies were performed in anaesthetized dogs. In mice andrats, i. v. bolus doses of laudanosine 10–20 mg kg^–1,caused convulsions and hind limb extensions; these effects wereprevented by pretreatment with diazepam. After the continuousinfusion of laudanosine to conscious dogs, plasma concentrationsin the order of 1.2 µg ml^–1 did not cause behaviouraldisturbances. In anaesthetized dogs, laudanosine plasma concentrationsof more than 6 µ ml^– caused hypotension and bradycardia,laudanosine concentrations greater than 10 µg ml^–1induced epileptic EEG spiking and plasma concentrations greaterthan 17 µg ml^–1 produced prolonged seizures. Thereis a wide difference between laudanosine plasma concentrationsin patients given atracurium by bolus injection or by short-terminfusion for surgical use and those required to induce epilepticactivity in dogs. However, during the prolonged infusion ofatracurium to patients this difference will be decreased. Itis unlikely that the use of atracurium, in patients, would resultin plasma concentrations of laudanosine capable of producingneurological or cardiovascular disturbances.     

CONCENTRATIONS OF ATRACURIUM AND LAUDANOSINE IN CEREBROSPINAL FLUID AND PLASMA IN THREE INTENSIVE CARE PATIENTS

We have measured concentrations of atracurium and laudanosinein cerebrospinal fluid (CSF) and plasma in three intensive carepatients receiving atracurium infusions of 22.5–106 hduration to maintain neuromuscular block. Two patients had sufferedsevere closed head injuries and the third patient had developedrespiratory failure following the clipping of two intracranialaneurysms. The total dose of atracurium given was 14.3–136.6mg kg^–1; rate of infusion was 0.6–1.38 mg kg^–1h^–1. Plasma concentrations of atracurium and laudanosinewere 0.73–3.11 µg ml^–1 and 0.48–8.65µg ml^–1, respectively; CSF concentration of laudanosinewas 70–440 ng ml^–1. No adverse effects attributableto these concentrations of laudanosine were observed.     

Blood propofol concentration and psychomotor effects on driving skills

We studied psychomotor performance in 10 healthy volunteersduring recovery after a target-controlled infusion of propofol.Choice reaction time, dual task tracking with secondary reactiontime and a within-list recognition task were assessed at targetblood propofol concentrations of 0.8, 0.4 and 0.2 µg ml^–1.Performance was impaired most at the highest blood propofolconcentration (choice reaction time increased by a mean of 247ms and secondary reaction time by a mean of 178 ms). Choicereaction time and dual task tracking with secondary reactiontime were the most sensitive and reliable methods of assessment(significant difference from baseline (P<0.05) at a propofolconcentration of 0.2 µg ml^–1 with choice and secondaryreaction time testing). Within-list recognition assessment ofmemory was not sufficiently sensitive at very low propofol concentrations.The impairment in choice and secondary reaction time with ablood propofol concentration of 0.2 µg ml^–1 wasless than that observed with a blood alcohol concentration of50 mg 100 ml^–1 and no greater than that observed witha blood alcohol concentration of 20 mg 100 ml^–1 in a previousstudy involving healthy volunteers. Br J Anaesth 2000; 85: 396–400 ^* Corresponding author     

PANCURONIUM IN CAESAREAN SECTION AND ITS PLACENTAL TRANSFER

Pancuronium bromide was used in 49 patients undergoing repeatelective Caesarean section. In 26 patients who received onlypancuronium 0.1 mg kg^–1, pancuronium was detected in allumbilical venous or arterial samples (0.12 µg ml^–1).In 23 other patients who received suxamethonium 1.0 mg kg^–1followed by pancuronium 0.05 mg kg^–1, pancuronium wasdetected in fetal blood 2 min after injection; the concentrationof pancuronium in umbilical venous or arterial samples in 14subjects was 0.08 µg ml^–1, and less than 0.05 µgml^–1 in nine subjects. There was no evidence that suchconcentrations of pancuronium were detrimental to the fetus.The use of suxamethonium before pancuronium resulted in reductionof pancuronium dosage, induction-delivery time, and fetal concentrationsof pancuronium, and was associated with better condition ofthe neonate.     

Effects of levobupivacaine and ropivacaine on rat sciatic nerve blood flow

Background. Ischaemia is one of the causative mechanisms ofperipheral nerve injury, a documented complication of regionalanaesthesia. Local anaesthetics per se and/or vasopressor adjuvantsmay account for changes in peripheral nerve blood flow. Theaim of this study was to test the effects of levobupivacaineand ropivacaine in a rat sciatic nerve model with respect tolocal blood flow and histopathological changes. Methods. Forty-eight female Sprague–Dawley rats were anaesthetizedfor left sciatic nerve exposure. After baseline nerve bloodflow measurement with a laser Doppler flowmeter, 0.2 ml of oneof the following solutions was applied topically to the nervein a random fashion: saline 0.9%; lidocaine 10 mg ml^–1;levobupivacaine 2.5 mg ml^–1; levobupivacaine 5 mg ml^–1;levobupivacaine 7.5 mg ml^–1; ropivacaine 2 mg ml^–1;ropivacaine 7.5 mg ml^–1; and ropivacaine 7.5 mg ml^–1plus epinephrine 5 µg ml^–1; all in saline 0.9%.Nerve blood flow was evaluated at 5-min intervals up to 30 minafter local application of anaesthetic solution. Three animalsper group were killed for histological evaluation 48 h later.Multiple one-way analyses of variance followed by Scheffé'spost hoc test was used for statistical analysis. P<0.05 wasconsidered significant. Results. Local anaesthetics at all concentrations tested causedsignificant reduction in nerve blood flow. The combination ofropivacaine 7.5 mg ml^–1 plus epinephrine did not reducenerve blood flow to a greater extent than ropivacaine 7.5 mgml^–1 alone. Low concentrations of levobupivacaine (2.5and 5 mg ml^–1) reduced nerve blood flow to the same extentas lidocaine 10 mg ml^–1. No significant histological changeswere observed at 48 h. Conclusion. Despite acute reductions in peripheral nerve bloodflow, significant histopathological changes were not observedin this rat sciatic nerve model after topical application oflevobupivacaine and ropivacaine at concentrations relevant toclinical practice.     

DOSE REQUIREMENTS OF PROPOFOL BY INFUSION DURING NITROUS OXIDE ANAESTHESIA IN MAN: II: Patients Premedicated with Lorazepam

The infusion rate of propofol required to supplement 67% nitrousoxide in oxygen to maintain surgical anaesthesia was determinedin 72 patients premedicated with lorazepam. Following an inductiondose of propofol 2 mg kg^–1, groups of eight patients receivedan infusion of propofol varying from 60 to 200 µg kg^–1.Probit analysis was used to determine the ED₅₀ (130 µgkg^minus;1 min^–1; 95% confidence limits: 106–167µg kg^–1 min^–1) and ED₉₅ (348 µg kg^–1min^–1; 95% confidence limits: 233–1296 µgkg^–1 min^–1;) for propofol infusion. Whole bloodpropofol concentrations at the time of surgical incision correlatedstrongly with the infusion rate, giving an EC₅₀ value of 2.5µg ml ^–1, and an EC₉₅ value of 5.92 µg ml^–1.There was no significant correlation between the rate of infusionof propofol, or the total propofol dose, and the times to responseto command, or to recall of birthdate.     

A prospective evaluation of pharmacokinetic model controlled infusion of propofol in paediatric patients

We have tested a published algorithm for pharmaco-kinetic modelcontrolled infusion of propofol to supplement 67% nitrous oxidefor general anaesthesia in Chinese children aged 4–10yr. Initially we studied 10 children undergoing minor procedureswith spontaneous ventilation; mean duration of surgery was 38min and mean propofol infusion rate 497 µg kg^–1min^–1. The precision of the model was 24.8% and bias –18.5%.The model was revised using an iterative linear least squaresregression procedure and the revised model tested prospectivelyin another 20 children. The precision of the revised model was21.5% (range in individuals 8.4–43.1%) and bias –0.1%(range –30 to 42%). Mean propofol infusion rate requiredto maintain anaesthesia was 474 µg kg^–1 min^–1(range 125–737 µg kg^–1 min^–1). The meanblood concentration required for satisfactory anaesthesia was6.6 µg ml^–1 (range 3–11 µg ml^–1)and the mean blood concentration at the time of waking, whichoccurred 40 min after switching off the infusion, 0.86 µgml^–1 (range 0.40–1.45 µg ml^–1). Ourpatient population required different pharmacokinetic variablesfrom those in the previous study. Recovery was slow becauseof the high infusion rates required to maintain satisfactoryanaesthesia and large difference between the blood concentrationrequired for anaesthesia and that at which waking occurred.(Br. J. Anaesth. 1994; 72: 302–306)     

PROLONGED PARALYSIS AFTER LONG-TERM, HIGH-DOSE INFUSION OF PANCURONIUM IN ANAESTHETIZED CATS

We have studied the neuromuscular effects of a 48-h infusionof high-dose pancuronium (400µg kg^–1 h^–1)in four cats anaesthetized with pentobarbitone, using contractionof tibialls anterior muscles after direct and indirect stimulation.After cessation of the pancuronium in fusion, prolonged paralysisexisted. The first twitch in the train-of-four stimuli (TOF)reappeared 8–12 h after termination of the pancuroniuminfusion. Twenty-four hours after termination of the infusion,TOF ratios were less than 0.08 and twitch contraction averaged39 (SE 8) % of initial values. Twitch contraction after directstimulation did not differ from initial values. Antagonism ofparalysis was accomplished with neostigmine 60 µg kg^–1in two animals and neostigmine 90 µg kg^–1 and 4-aminopyridine500 µg kg^–1 in the others. Steady-state plasma concentrationof pancuronium (2000 ng ml^–1) decreased rapidly aftertermination of the infusion, but then stabilized at about 130ng ml^–1. These results indicate that prolonged paralysisafter long-term administration of high-dose pancuronium is causedprimarily by failure of neuromuscular transmission, most likelycaused by the persistent plasma concentrations of the drug inthe pharmacologically active range. (Br. J. Anaesth. 1993; 71:393–397)     

Relationship between bispectral index, electroencephalographic state entropy and effect-site EC50 for propofol at different clinical endpoints

Background. State entropy (SE) is a newly available monitorfor depth of anaesthesia. We investigated whether the relationshipbetween predicted effect-site propofol concentration and bothbispectral index (BIS) and SE values is useful for predictingloss of verbal contact and loss of consciousness during steady-stateconditions. Methods. Twenty unpremedicated patients undergoing electivemajor abdominal surgery were recruited. A target-controlledinfusion of propofol was administered using Schneider's pharmacokineticmodel. The propofol infusion was set at an initial site-effectconcentration of 1.0 µg ml^–1, and increased by 1.0µg ml^–1 steps every 4 min, up to 6.0 µg ml^–1.A 4-min interval was chosen to ensure that steady-state site-effectconcentrations were obtained. Propofol site-effect concentrationsand BIS and SE values were recorded at loss of verbal contact(LVC) and loss of consciousness (LOC). Population values forpredicted effect-site concentrations at the clinical endpointswere estimated and correlated with BIS and SE values. Results. For LVC, the effect-site concentration for 90% of patientswas 1.1 (1.1–3.2) µg ml^–1 and for LOC 2.8(2.8–5.65) µg ml^–1. LVC occurred in 90% ofpatients at a BIS value of 70.2 (70.2–90.2) and an SEvalue of 60.3 (60.3–75.5) and LOC occurred at a BIS valueof 38.2 (38.2–70.4) and an SE value of 42.2 (42.2–60.4). Conclusions. LVC and LOC occurred within a defined range ofpredicted effect-site concentrations. SE had a smaller rangethan BIS and higher correlation with effect-site concentrationand may be more useful than BIS in predicting both LVC and LOC.     

Relationship between Bispectral Index, electroencephalographic state entropy and effect-site EC50 for propofol at different clinical endpoints

Background. State entropy (SE) is a newly available monitorfor depth of anaesthesia. We investigated whether the relationshipbetween predicted effect-site propofol concentration and BispectralIndex (BIS) and SE values is useful for predicting loss of verbalcontact and loss of consciousness during steady-state conditions. Methods. Twenty unpremedicated patients undergoing electivemajor abdominal surgery were recruited. A target-controlledinfusion of propofol was administered using Schneider's pharmacokineticmodel. The propofol infusion was set at an initial site effectconcentration of 1.0 µg ml^–1 and increased by 1.0µg ml^–1 steps every 4 min up to 6.0 µg ml^–1.A 4-min interval was chosen to ensure that steady-state effect-siteconcentrations were obtained. Propofol site effect concentrationsand BIS and SE values were recorded at loss of verbal contact(LVC) and loss of consciousness (LOC). Population values forpredicted effect-site concentrations at the clinical endpointswere estimated and correlated with BIS and SE values. Results. For LVC, the effect-site concentration for 90% of patientswas 1.1 (1.1–3.2) µg ml^–1 and for LOC it was2.8 (2.8–5.65) µg ml^–1. LVC occurred in 90%of patients at a BIS value of 70.2 (70.2–90.2) and anSE value of 60.3 (60.3–75.5), and LOC occurred at a BISvalue of 38.2 (38.2–70.4) and an SE value of 42.2 (42.2–60.4). Conclusions. LVC and LOC occurred within a defined range ofpredicted effect-site concentrations. SE had a smaller rangethan BIS and greater correlation with effect-site concentrationand may be more useful than BIS in predicting both LVC and LOC.     

DOSE REQUIREMENTS OF PROPOFOL BY INFUSION DURING NITROUS OXIDE ANAESTHESIA IN MAN: I: Patients Premedicated with Morphine Sulphate

The study was performed to determine the ED₅₀ and ED₉₅ of acontinuous infusion of the emulsion formulation of propofolduring 67% nitrous oxide anaestheisa in 57 patients premed-icatedwith morphine sulphate 0.15 mg kg^–1. Anaesthesia was inducedwith propofol 2 mg kg^–1, and maintained before incisionwith a fixed-rate infusion of propofol to supplement nitrousoxide. The response to the first surgical incision, made atleast 30 min after induction of anaesthesia, was observed. TheED₅₀; was 53.5 µg kg^–1 min^–1 and the ED₉₅was 112.2 µg kg^–1 min^–1. At the time of thefirst surgical incision, the venous whole blood concentrationsof propofol at the ED₅₀ and ED₉₅ infusion rates (EC₅₀and EC₉₅were 1.66 µg ml^–1 and 3.39 fig ml^–1 respectively.The satisfactory maintenance of anaesthesia provided by nitrousoxide supplemented with propofol was associated with stabilityand rapid, uncomplicated recovery.     

Effect of propofol anaesthesia on the event-related potential mismatch negativity and the auditory-evoked potential N1

Background. Studies on the effects of anaesthesia on event-relatedpotentials and long latency auditory-evoked potentials (AEP)are sparse. Both provide information on cortical processingand may have potential as monitors of awareness. We studiedthe effect of propofol on the event-related potential mismatchnegativity (MMN) and the long-latency AEP N1. Methods. Twenty-one patients received 1 µg ml^–1stepped increases in the target concentration of propofol usingDiprifusor^TM until a maximum of 6 µg ml^–1 was achievedor the patient had lost consciousness. Neurophysiological responses(MMN and N1) and the patients’ level of consciousnesswere recorded before the administration of propofol and at atarget effector site concentration of propofol of 1, 2, 3, 4,and 6 µg ml^–1. Grand average evoked potentials werecomputed at baseline, before the administration of propofol(A); at the highest propofol concentration at which each patientwas responsive (B); and at the concentration of propofol atwhich the patient became unconscious (C). Results. Patients lost consciousness at different target concentrationsof propofol, all being unresponsive by 4 µg ml^–1.The response to the deviant stimuli used to elicit duration-shiftMMN was significantly more negative than to the standard stimuliat A (mean difference 2.58 µV, P=0.0011) but this differencewas virtually abolished at point B, before the patients lostconsciousness (mean difference 0.63 µV, P=ns). The amplitudeof N1 evoked by standard stimuli was negative compared withelectrical baseline at both point A (mean amplitude –3.81µV, P<0.001) and at point B (mean amplitude –2.2µV, P=0.002), but was no longer significantly differentto baseline at point C (mean amplitude 0.51 µV, P=ns).The change in the mean amplitude of N1 from last awake (pointB) to first unconscious (point C) was also significant (meandifference in amplitude 1.69 µV, P=0.02). Conclusions. MMN is unlikely to be a clinically useful toolto detect awareness in surgical patients. In contrast, the lossof N1 may identify the transition from consciousness to unconsciousnessand deserves further study. Br J Anaesth 2002; 89: 382–8     

Optimal concentration of epidural fentanyl in bupivacaine 0.1% after thoracotomy

Background. The aim of this prospective, double-blind, randomizedcontrolled trial was to investigate the analgesic and adverseeffects of three commonly used concentrations of thoracic epiduralfentanyl with bupivacaine in patients undergoing thoracotomyfor lung resection. Methods. We studied 99 patients who were randomized to receivefentanyl 2 µg ml^–1 (group 2), fentanyl 5 µgml^–1 (group 5) and fentanyl 10 µg ml^–1 (group10) in bupivacaine 0.1% via a thoracic epidural. Postoperatively,pain on coughing was assessed using a visual analogue scale(VAS) and an observer verbal rating score (OVRS) at 2, 8, 16and 24 h. At the same times, sedation, pruritus and nausea wereassessed. Results. Of 29, 28 and 32 patients who completed the study ingroups 2, 5 and 10 respectively, there was no significant differencein baseline characteristics between the three groups. The numberof patients with episodes of unsatisfactory pain, i.e. VAS scores>30 mm and OVRS >1, at each of the four assessments postoperativelywas significantly (P<0.01) higher in group 2 than in groups5 and 10. In group 10, 16 patients had sedation scores >1compared with 10 each in groups 2 and 5. In addition, 19 patientsin group 10 experienced pruritus compared with 12 each, in groups2 and 5. These differences were not significant. Nausea wasnot significantly different between the three groups. Conclusion. We conclude that thoracic epidural fentanyl 5 µgml^–1 with bupivacaine 0.1% provides the optimum balancebetween pain relief and side effects following thoracotomy. Br J Anaesth 2004: 92: 670–4     

COMBINED I.V. BOLUS AND INFUSION OF PANCURONIUM BROMIDE

An i.v. bolus and concomitant infusion of pancuronium is proposedfor use in prolonged anaesthesia. Plasma concentrations of pancuroniumwere measured in 16 patients receiving this regime. The desiredsteady-state concentration of 0.2 µg ml^–1 was achievedin most instances at approximately 45 min. Following the bolus,the neuromuscular twitch response decreased to low values orwas abolished completely. Thereafter the response remained relativelyconstant or increased in intensity consistent with the meansteady-state plasma concentrations of 0.214 µg ml^–1(SEM 0.012) maintained by the infusion. When the infusion wasstopped, the mean twitch height was 23% of control and increasedthereafter at approximately 1 % per min, while plasma concentrationsdecreased by half in 69 min. One patient with renal artery stenosesexhibited complete neuromuscular blockade at a steady-stateplasma concentration of 0.29 µg ml^–1; followingcessation of infusion the twitch response was detected after30 min (plasma concentration 0.20 µg ml^–1) and recoverywas uneventful. Plasma clearance and apparent volume of distributionof pancuronium used to calculate the dosage regime were foundnot to differ significantly from those reported for a singledose. Following cessation of infusion, plasma concentrationsdeclined in either a mono- or bi-exponential form dependingon the ratio of the hybrid disposition rate constants (ß/).In all instances a two-compartment open model was used to describethe time course of the plasma concentrations.