CARDIOVASCULAR EFFECTS OF DOXACURIUM, PANCURONIUM AND VECURONIUM IN ANAESTHETIZED PATIENTS PRESENTING FOR CORONARY ARTERY BYPASS SURGERY

The cardiovascular effects of bolus doses of doxacurium 0.037mg kg^–1 were compared with those following equipotentdoses of pancuronium (0.09 mg kg^–1) and vecuronium (0.075mg kg^–1) and with those following high-dose doxacurium(0.075 mg kg^–1), in patients with coronary artery disease.Anaesthetic technique comprised premedication with lorazepam,papaveretum and hyoscine, induction with diazepam, fentanyl,thiopentone, atropine and suxamethonium, and the trachea wasintubated. At least 20 min later, during stable nitrous oxidein oxygen anaesthesia, a single bolus of neuromuscular blockingdrug was administered and the effects measured at 1, 5 and 10min. There was a small decrease in heart rate following doxacurium0.075 mg kg^–1, but no other significant or dose-relatedchanges in mean heart rate, arterial pressure or cardiac indexwith doxacurium. Similar results were found following vecuronium,but the reduction in heart rate was more pronounced. In contrast,significant increases in mean arterial pressure, heart rateand cardiac index occurred after pancuronium. Presented in part at The Anaesthetic Research Society, WarwickMeeting, April 7–8, 1989.     

Pharmacodynamics of mivacurium in infants

A computerized infusion system was used to determine mivacuriuminfusion requirements to maintain 95% and 50% neuromuscularblock in 15 infants less than 1 yr of age. Neuromuscular blockwas measured by adductor pollicis EMG and anaesthesia maintainedwith 66% nitrous oxide in oxygen and alfentanil 50–100µg kg^–1 h^–1. Neuromuscular block was producedby repeated bolus doses of mivacurium 0.1 mg kg^–1; subsequentlythe target neuromuscular block was maintained by a closed loopinfusion. Dose potency of mivacurium was similar to that previouslypublished in children with a similar anaesthetic technique.Mean mivacurium requirement for 95% neuromuscular block was820 (SD 300) µg kg^–1 h^–1, which representedan hourly requirement of 6.6 (1.5) individual ED₉₅ doses. Infusionrequirement for 50% neuromuscular block was 320 (150) µgkg^–1 h^–1. These infusion rates were similar to thosein children. No side effects of mivacurium were noticed.     

PHARMACODYNAMICS OF MIVACURIUM IN CHILDREN, USING A COMPUTER-CONTROLLED INFUSION

A computerized infusion system was used to determine requirementfor a mivacurium infusion to maintain a 95% and a 50% neuromuscularblock in 21 children aged 1–15 yr. Neuromuscular blockwas measured by adductor pollicis EMG and anaesthesia maintainedwith 66% nitrous oxide in oxygen and alfentanil 50–100µg kg^–1 h^–1. The targeted neuromuscular blockwas reached within mean 5 (SD 3) min from initiation of an infusion.Mivacurium requirement for 95% neuromuscular block was 950 (350)µg kg^–1 h^–1, which represented an hourly requirementof 6.8 (1.6) individual ED₉₅ doses. Infusion requirement for50% neuromuscular block averaged 350 (150) µg kg^–1h^–1. There was a significant negative correlation betweeninfusion rate and age of a patient. Great individual variationof the infusion rate makes a computerized infusion an easy methodto achieve and maintain a desired level of neuromuscular block.No side effects of mivacurium were noticed.     

TOTAL I.V. ANAESTHESIA WITH PROPOFOL AND ALFENTANIL: DOSE REQUIREMENTS FOR PROPOFOL AND THE EFFECT OF PREMEDICATION WITH CLONIDINE

We determined in 51 healthy patients undergoing body surfacesurgery the dose requirements for propofol, as part of a totali.v. anaesthesia technique with an alfentanil infusion. Afterpremedication with temazepam, patients received alfentanil 50µg kg^–1 followed by an infusion of 50 µg kg^–1h^–1. Patients were anaesthetized with a loading dose ofpropofol followed by a three-stage infusion designed to reachone of five preselected blood concentrations of propofol. Themotor response to the initial surgical incision was noted andprobit analysis was used to derive the ED₅₀ (2.94 mg kg^–1h^–1; 95% confidence limits: 2.35–3.37 mg kg^–1h^–1). and ED₉₅ (4.98 mg kg^–1 h^–1; 95% limits:4.13–8.8 mg kg^–1 h^–1) for the final propololinfusion rate under these conditions. Whole blood concentrationof propofol at the time of the incision was related linearlyto the infusion rate and the EC₅₀ and EC₉₅ (probit analysis)were derived as 1.44 (95% confidence limits 0.62–1.87)and 4.05 (95% confidence limits 2.78–30.5) µg ml^–1,respectively. Postoperative recovery was rapid, uncomplicatedand uneventful. In a subgroup of eight patients, the additionof clonidine 0.6mg to the premedication significantly decreasedthe requirement for propofol (P <0.05) during surgery, butresulted in prolonged recovery times. Pilot study presented to the Anaesthetic Research Society, June24, 1988 [1].     

OESOPHAGEAL CONTRACTILITY DURING TOTAL I.V. ANAESTHESIA WITH AND WITHOUT GLYCOPYRRONIUM

Somatic movement and spontaneous and provoked oesophageal contractionswere noted at time of incision in 51 patients receiving totali.v. anaesthesia with alfentanil and propofol. Probit analysisof the dose of propofol required to prevent spontaneous movementrevealed an ED₅₀ (95% confidence limits) of 2.5 (1.8-2.9) mgkg^–1 h^–1 and ED₉₅ of 4.7 (4.0-7.5) mg kg^–1h^–1. Corresponding venous blood concentrations gave anEC₅₀ of 1.2 (0.4-1.6) µg ml^–1 and an EC₉₅ of 4.0(2.8-18.5) µg ml^minus;1. ED₅₀ of propofol for preventingspontaneous oesophageal contraction was 3.0 (1.9-3.6) mg kg^–1h^–1. ED₉₅ was 6.9 (5.0-27.3) mg kg^–1 h^–1;EC₅₀ for oesophageal contractions was 1.7 (0.7-2.3) µgml^–1 and EC₉₅ was 5.9 (3.7-70.6) µg ml^–1.Another group of 10 patients were given glycopyrronium 5 µgkg^–1 at induction; oesophageal contractility was significantlyreduced in this group. Preliminary results of this research were presented to the AnaestheticResearch Society, Nottingham, July 1990. ^*Department of Anaesthesia, Derriford Hospital, Plymouth, DevonPL6 8DH. Department of Anaesthesia, Darlington Memorial Hospital, Darlington,Durham DL3 6HX.     

Relative potency of vecuronium in male and female patients in Britain and Australia

We compared the potency of vecuronium when given to similarpatients in Brisbane, Australia, and Cardiff, United Kingdom.Forty patients in each centre were anaesthetized using the sametechnique with propofol, fentanyl, nitrous oxide and vecuroniumeither 20 or 30 µg kg^–1 by random allocation. Neuromuscularblock was measured with similar Datex Relaxographs. There wasno significant difference in potency between British and Australianpatients. The ED₅₀, and ED₉₅ for a British male of average weightwere 29.5 µg kg^–1 (95% confidence limits 27.3–32.3µg kg^–1) and 51.3 µg kg^–1 (44.3–63.9µg kg^–1), respectively. ED₅₀ and ED₉₅ for Australianswere 5.5% greater, with confidence limits from 4% less to 17%greater. Females were significantly more sensitive to vecuroniumthan males, requiring 22% less drug to achieve the same degreeof neuromuscular block (confidence limits 12–32%). Theresults are consistent with the ED₅₀ being independent of bodyweight when the dose is expressed as µg kg^–2/3,but not as µg or µg kg^–     

CLINICAL PHARMACOLOGY OF VECURONIUM IN CHILDREN: Studies During Nitrous Oxide and Halothane in Oxygen Anaesthesia

Forty-seven children (ASA I or II) were studied during nitrousoxide-oxygen, halothane anaesthesia. The dose-response curvefor vecuronium was determined after the injection of a singlebolus (40, 55 or 70 µg kg-¹) to 33 patients. The ED₅₀and ED₉₅ were 31 and 64 µg kg^–1 respectively. Fourteenchildren received a larger dose (100 µg kg^–1); goodintubating conditions were obtained in all of these within 2min. After a single bolus (100 µg kg^–1) the durationof action was 36.5 min and the recovery index was 9.3 min. Inpatients who received small maintenance doses (25 µg kg^–1)after a single bolus (100 µg kg^–1) the recoveryindex after the last maintenance dose was not increased. Therewere no significant changes in heart rate or arterial pressure.In children, has a vecuronium has a short duration of actionand lacks cumulative or cardiovascular side affects.     

DOSE-RESPONSE RELATIONSHIPS AND NEUROMUSCULAR BLOCKING EFFECTS OF VECURONIUM AND PANCURONIUM DURING KETAMINE ANAESTHESIA

The dose-response curves of vecuronium and pancuronium werecompared during ketamine anaesthesia in 60 patients (ASA I).The relationship between the probit transformed depression oftwitch height and the logarithm of the dose was analysed by1ink regression. Vecuronium was found to be 1.2 times more potentthan pancuronium. ED₅₀ of vecuronium and pancuronium were 30.5µg kg^–1 and 37.0 µg kg^–1, and the ED₉₅45.6 µg kg^–1 and 59.5 µg kg^–1, respectively.Using equipment doses of vecuronium and pancuronium (1.6ED₉₅)indices of neuromuscular blockade were compared in a further20 patients (ASAI). No statistically signifimnt difference wasfound in onset time. The duration of action following vecuroniumwas significantly shorter than after pancuronium. The time to25% recovery of twitch height following vecuronium 73 µgkg^–1 was 22.2 min compared with 66.6 min following pancuronium99 µg kg^–1. Following supplementary doses of vecuronium,a statistically significant increase in duration of action wasseen following the fourth and fifth doses. Reversal timr ofvecuronium to a train-of-four ratio of 0.7 was significantlyshorter than that of pancuronium (8.3 min and 13.6 min, respectively)     

NEUROMUSCULAR BLOCK WITH DOXACURIUM (BW A938U) IN PATIENTS WITH NORMAL OR ABSENT RENAL FUNCTION

The characteristics of neuromuscular block inducedby doxacuriumwere compared in patientswith and without renal function. Seventeenpatientswith end stage chronic renal failure and18 patients with normalrenal function were anaesthetized with 0.5% halothane and nitrousoxidein oxygen and received doxacurium in aninitial dose of 25 µgkg^–1 (estimated from availabledata as an ED95 dose), withincremental doses of 5 µg kg^–1. At the end of surgery,residualneuromuscular block was antagonized witheither edrophonium1.0 mg kg^–1 or neostigmine 0.08 mg kg^–1. There wasno significant difference between the mean maximum blocks achievedwith doxacurium: 17.4% (renal failure group)and 11.6% (controlgroup) of control twitch heights, or between the mean timesto achieve maximum block (10.9 min and 10.8 min, respectively).Themean duration of action of doxacurium, indicated by the timefor twitch height to recover to 25% of control, was longerinthe renal failure group (120.8 min vs 66.7 minin the controlgroup) (ns). Similarly, the meanduration of action of incrementswas longer inthe renal failure group (27.4 min vs 20.5 min inthecontrol group). The rate of spontaneous recovery from doxacuriumas indicated by the time for twitch height to recover from 0to 5%, 5 to 10% and 10 to 25%, was not significantly differentin the two groups. Antagonism of doxacurium was achieved morereliably with neostigmine than with edrophonium in bothgroups.The administration of doxacurium was associated with minimalcardiovascular effects. ^*Department of Anaesthetics, St George's Hospital, BlackshawRoad, London SW17 OQT     

Influence of carbamazepine on the dose-response relationship of vecuronium

We have determined the cumulative dose-response relationshipfor vecuronium from the evoked compound electromyogram of thehypothenar muscles in eight patients who were receiving carbamazepine.The ED₅₀, ED₉₀ and ED₉₅ were 29, 52 and 64 µg kg^–1,respectively, and were significantly different (P < 0.05)from those of a control group (ED₅₀, ED₉₀ and ED₉₅ 21, 36 and44 µg kg^–1, respectively). (Br. J. Anaesth. 1994;72: 125–126) Presented at the 10th World Congress of Anaesthesiologists,The Hague, The Netherlands, June 1992.     

DOSE-RESPONSE RELATIONSHIPS FOR EDROPHONIUM AND NEOSTIGMINE ANTAGONISM OF MIVACURIUM-INDUCED NEUROMUSCULAR BLOCK

We have studied the dose-response relationships for neostigmineand edrophonium during antagonism of neuromuscular block inducedby mivacurium chloride. Sixty-four ASA group I or II adultswere given mivacurium 0.15 mg kg^–1 during fentanyl-thiopentone-nitrousoxide-iso flurane anaesthesia. Train-of-four stimulation (TOF)was applied to the ulnar nerve every 10 s, and the force ofcontraction of the adductor pollicis muscle was recorded. Whenspontaneous recovery of first twitch height reached 10% of itsinitial control value, edrophonium 0.1, 0.2, 0.4, or 1 mg kg^–1or neostigmine 0.005, 0.01, 0.02, or 0.05 mg kg^–1 wasadministered by random allocation. Neuromuscular function inanother 16 subjects was allowed to recover spontaneously. Spontaneousrecovery from 90% mivacurium block to 95% twitch height andTOF ratio 0.75 occurred within 15 min. This study demonstratedthat the dose-response curves for these two drugs for antagonismof neuromuscular block (first twitch and train-of-four ratio)were parallel. The doses of neostigmine required to achieve50% (ED₅₀) and 70% (ED₇₀) recovery of the first twitch after10 min were 2 (1.5– 2.5) µg kg^–1 and 4.7 (4.1–5.4)µg kg^–1 (mean (95% confidence intervals)), respectively.Corresponding ED₅₀ and ED₇₀ values for edrophonium were 2.8(0.75–10.2) pg kg^–1 and 9.2 (3.6–23.6) µgkg^–1, respectively. These values corresponded to neostigmine:edrophonium potency ratios of 1.4 (0.4–2.4) and 1.95(0.9–2.9) for first twitch ED₅₀ and ED₇₀ height, respectively.The calculated doses producing 50% (ED₅₀ recovery of the TOFratio at 10 min were neostigmine 2.57 (1.8–3.6) µgkg^–1 and edrophonium 26.9 (14.6–49.6) pg kg^–1.These values corresponded to a potency ratio of 10.4 (0.7–20).(Br. J. Anaesth. 1993; 71: 709–714)     

Neuromuscular interactions between suxamethonium and magnesium sulphate in the cat

In order to study the neuromuscular interactions between suxamethoniumand magnesium sulphate (MgSO₄), we have determined the dose-responserelationship of suxamethonium and the neuromuscular actionsof 1.25xED₅₀ dose of suxamethonium, both before and after pretreatmentwith MgSO₄. We have also compared the effect of 1.25xED₅₀ doseof suxamethonium in the absence and in the presence of 50%neuromuscularblock, established previously by infusion of MgSO₄. Twenty-onecats were anaesthetized with urethane. Train-of-four stimulationwas applied every 12s to the sciatic nerve and the force ofcontraction of the tibialis anterior muscle was measured. Thepotency of suxamethonium decreased in each instance with pretreatmentwith MgSO₄. The ED₅₀ of suxamethonium increased significantlyfrom mean 21.0 (SEM 1.9) µg kg^–1 before MgSO₄ to25.6 (2.3) µg kg^–1 after MgSO₄ 60 mg kg^–1and to 26.6 (2.2) µg kg^–1 after MgSO₄ 90 mg kg^–1(P<0.05). Twitch depression produced by 1.25xED₅₀ dose ofsuxamethonium decreased significantly with MgSO₄ pretreatment,from 76.7 (2.6)% before MgSO₄ to 61.7 (6.4)% after MgSO₄ 60mg kg^–1 and 48.7 (7.5)% after MgSO₄ 90 mg kg^–1 (P<0.05).With stable 50% neuromuscular block, established previouslyby infusion of MgSO₄ the 1.25xED₅₀ dose of suxamethonium producedmore twitch augmentation (133 (6.3)%vs 108.3 (1.3)%; P<0.05)and less twitch depression (31.6 (9.6)% vs 74.1 (0.6)%, P<0.05)than in the absence of MgSO₄. The results of all three methodsdemonstrated that the pharmacological interaction between suxamethoniumand magnesium was antagonistic.     

Interaction of magnesium sulphate with vecuronium-induced neuromuscular blockt

We have investigated the interaction between magnesium sulphate40 mg kg^–1 i.v. and vecuronium. First, we determined theeffect of pretreatment with magnesium on the potency of vecuroniumusing a single bolus dose-response technique. In addition, wecompared the time course of vecuronium-induced neuromuscularblock (vecuronium 100 µg kg^–1) with and withoutmagnesium pretreatment. For both parts, neuromuscular blockwas assessed by electromyography. In addition, the effect ofmagnesium pretreatment on vecuronium-induced neuromuscular blockwas investigated in the context of rapid sequence inductionof anaesthesia. We found that the neuromuscular potency of vecuroniumwas increased by pretreatment with magnesium sul phate. TheED₅₀ and ED₉₀ of vecuronium with MgSO₄ were 25% lower than withoutMgSO₄ (ED₅₀ 21.3 vs 26.9 µg kg^–1 ED₉₀ 34.2 vs 45.7µg kg^–1 P < 0.05 for both). Mean onset time was147.3 (SD 22.2) s in the MgSO₄ group vs 297.3 (122) s for controls(P < 0.05). Clinical duration was prolonged (MgSO₄-vecuronium43.3 (9) min vs 25.2 (5.1) min for controls; P < 0.05). Thiswas also true for the recovery index (20.1 (6.6) mm vs 10.6(3.4) min; P < 0.05) and duration to 75% recovery (63.4 (9.9)min vs 35.8 (6.9) min; < 0.05). In the context of rapid sequenceinduction, pretreatment with MgSO₄ improved the intubating scoreof vecuronium compared with vecuronium without MgSO₄ reach ingthe same quality as that with suxamethonium 1 mg kg^–1.We conclude that magnesium pretreat ment increased the neuromuscularpotency of vecuronium, in addition to modifying the time courseof its neuromuscular block.      

PULMONARY VASCULAR EFFECTS OF TRINITROGLYCERIN AND ISOSORBIDE DINITRATE AFTER CARDIOPULMONARY BYPASS

We have compared the systemic and right ventricular haemodynamiceffects of trinitroglycerin (TNG) and isosorbide dinitrate (ISDN)in patients recovering from coronary artery bypass grafting.Each of the 16 patients was given increasing i.v. doses of thetwo nitrates in a random order and double blind fashion untilthe target of a 25% decrease in mean pulmonary artery pressure(MPAP) was achieved. Total doses of TNG 9 (6–12) µgkg^–1 (mean, 95% confidence interval) and ISDN 148 (76–220)µg kg^–1 were given during infusions of 22 (18–25)min and 34 (28–41) min duration, respectively. The targetdecrease in MPAP was produced with infusion rates of TNG 0.5(0.4–0.7) µg kg^–1 min^–1 and ISDN 5.8(4.1–7.5) µg kg^–1 min^–1 These dosesproduced similar acute decreases in MPAP and similar effectson pulmonary and systemic vascular resistances and systemicand right ventricular haemodynamic variables. We conclude thatTNG is more than 10 times as potent as ISDN in its acute haemodynamic effects in cardiac surgical patients in the immediatepostoperative period. Both nitrates have relatively greatereffect on the pulmonary than the systemic vasculature. (Br.J. Anaesth. 1993; 71:720–724) Presented in part at the Annual Meeting of the Society of CardiovascularAnesthesiologists, San Antonio, Texas, May 1991.     

Reduction in standard MAC and MAC for intubation after clonidine premedication in children

We examined the relative effects of different doses of oralclonidine on the MAC for endotracheal intubation (MAC_EI) andthe MAC for skin incision (MAC) in children. We studied 90 children(15 in each group) (age range 2–8 yr, weight 10–27kg, height 89–124 cm) who received one of three preanaestheticmedications: placebo (control), oral clonidine 2 µg kg^–1,or oral clonidine 4 µg kg^–1 100 min before anaesthesia.Anaesthesia was induced and maintained with sevoflurane in oxygenand air without i.v. anesthetics and neuromuscular relaxants.The end-tidal sevoflurane concentration was kept constant for     

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.     

Pharmacodynamic effects of 51W89, an isomer of atracurium, in children during halothane anaesthesia

51W89 is one of the 10 stereoisomers of atracurium with lesspropensity to release histamine than atracurium. We evaluateddose-response data and neuromuscular effects of 2 x ED₉₅ doseand maintenance doses of 51W89 during halothane anaesthesiain 68 children, 2–12 yr old. Neuromuscular function wasmonitored by evoked adductor pollicis EMG. Log-probit, single-dose,dose-response data gave ED₅₀ and ED₉₅ values of 23 and 41 µgkg^–1, respectively, for 51W89. Twice the ED₉₅ dose (80µgkg^–1)had an onset time (time from administration to maximum effect)of 2.5 (SD 0.8) min, a clinical duration (time to 25% EMG recovery)of 31 (7) min and a recovery index (time from 25 to 75% EMGrecovery) of 11.1 (1.7) min. Seventy-nine incremental dosesof 51W89 of 0.5 x ED₉₅ dose were given in 16 children at 85–90%neuromuscular block. The mean duration of these doses was 13.4(3) min, with a calculated hourly maintenance requirement of51W89 of 94 (19) µg kg^–1. Duration of effect ofincremental doses remained constant within individuals reflectingnon-cumulative properties. There were insignificant changesin arterial pressure and heart rate after 51W89 and no sideeffects were observed. We regard 51W89 as a promising, non-cumulative,intermediate-acting neuromuscular.blocking agent the effectsof which can be antagonized easily by neostigmine.     

Oral clonidine vs midazolam in the prevention of sevoflurane-induced agitation in children. a prospective, randomized, controlled trial

Background: This randomized, double-blind study tested the hypothesis that,in comparison with midazolam, premedication with oral clonidinereduces the incidence of emergence agitation in preschool childrenanaesthetized with sevoflurane. Methods: Sixty-eight ASA I–II children undergoing circumcisionwere randomized into three groups to receive different oralpremedication given 30 min before anaesthesia: midazolam 0.5mg kg^–1, clonidine 2 µg kg^–1, and clonidine4 µg kg^–1. Sevoflurane anaesthesia was administeredvia a facemask (O₂/N₂O: 40/60). Analgesia was with penile block(bupivacaine 0.5% 0.3 ml kg^–1) and rectal paracetamol(30 mg kg^–1). During the first postoperative hour, childrenwere evaluated using a modified ‘objective pain scale’. Results: Only the 4 µg kg^–1 dose of clonidine was associatedwith a significant reduction in emergence agitation. Fewer childrenin the clonidine 4 µg kg^–1 group displayed agitation(25%) than in the midazolam group (60%) (P = 0.025). Incidenceof hypotension and bradycardia, time to first micturition andfirst drink did not differ among groups. Conclusions: In comparison with midazolam, clonidine 4 µg kg^–1reduced sevoflurane-induced emergence agitation without increasingpostoperative side-effects.     

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.     

Relation between fentanyl dose and predicted EC50 of propofol for laryngeal mask insertion

Background. This study sought to determine the effective concentrationfor 50% of the attempts to secure laryngeal mask insertion (predictedEC_50LMA) of propofol using a target-controlled infusion (Diprifusor^TM)and investigated whether fentanyl influenced these requiredconcentrations, respiratory rate (RR) and bispectral index (BIS). Methods. Sixty-four elective unpremedicated patients were randomlyassigned to four groups (n = 16 for each group) and given saline(control) or fentanyl 0.5, 1 or 2 µg kg^–1.Propofol target concentration was determined by a modificationof Dixon’s up-and-down method. Laryngeal mask airway insertionwas attempted without neuromuscular blocking drugs after equilibrationhad been established for >10 min. Movement was defined aspresence of bucking or gross purposeful muscular movement within1 min after insertion. EC_50LMA values were obtained by calculatingthe mean of 16 patients in each group. Results. Predicted EC_50LMA of the control, fentanyl 0.5, 1 and2 µg kg^–1 groups were 3.25 (0.20), 2.06 (0.55),1.69 (0.38) and 1.50 (0.54) µg ml^–1 respectively;those of all fentanyl groups were significantly lower than thatof control. RR was decreased in relation to the fentanyl doseup to 1 µg kg^–1. BIS values after fentanyl1 and 2 µg kg^–1 were significantly greaterthan in the control and 0.5 µg kg^–1 groups. Conclusions. A fentanyl dose of 0.5 µg kg^–1is sufficient to decrease predicted EC_50LMA with minimum respiratorydepression and without a high BIS value. Br J Anaesth 2004; 92: 238–41