Antagonism of pancuronium- and pipecuronium-induced neuromuscular block

We have compared the antagonism of neuro muscular block producedby pipecuronium with pancuronium in 80 anaesthetized surgicalpatients using mechanomyography and electromyography. Pancuronium0.1 mg kg or pipecuronium 0.07 mg kg^–1 was given afterinduction of anaesthesia and neuromuscular block was adjustedto 75% twitch depression at the time of antagonism. The followingregimens were used: edrophonium 0.5 and 1.0 mg kg^–1, neostigmine0.04 mg kg^–1 pyridostigmine 0.3 mg kg^–1 and edrophonium0.25 mg kg^–1 with pyridostigmine 0.15 mg kg^–1. Antagonismwas evaluated also by the head lift test. There was no differencebetween the reversibility of neuromuscular block produced bypancuronium or pipecuronium. Edrophonium produced a significantlyfaster antagonism than neostigmine or pyridostigmine but onsetof action was not significantly faster than that of edrophoniumwith pyridostigmine. All regimens produced 100% (or near 100%)antagonism of twitch response within 15 min. However, TOF fadeantagonism was more complete with pyridostigmine, neostigmineand edrophonium 1.0 mg kg^–1 than with edrophonium 0.5mg kg^–1. The head lift test indicated somewhat less antagonismwith edrophonium 0.5 and 1.0 mg kg^–1. Using five monitoringmethods, the rank order of reversal potency was: pyridostigmine neostigmine > edrophonium 1.0 mg kg^–1 edrophonium+ pyridostigmine > edrophonium 0.5 mg kg^–1.     

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.     

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)     

Pharmacodynamics and pharmacokinetics of an infusion of Org 9487, a new short-acting steroidal neuromuscular blocking agent

We have evaluated in 10 anaesthetized patients the time courseof action, infusion requirements, reversibility and pharmacokineticsof Org 9487. Org 9487 was administered as a bolus dose of 1.5mg kg^–1 followed by an infusion to maintain a block of75–85% for 60 min. After recovery from the bolus dose,a mean dose of Org 9487 3.4 (SD 1.0) mg kg^–1 h^–1was administered to maintain a mean neuromuscular block of 83(3)%. During the final 15 min of infusion, the infusion requirementswere 2.5 (1.1) mg kg^–1 h^–1 In the five patientswho were allowed to recover spontaneously, a TOF ratio of 0.7was reached 37.9 (12.4) min after stopping the infusion of Org9487. In the five patients who received neostigmine, a TOF ratioof 0.7 was reached after 14.5 (6.1) min. Plasma clearance was8.5 (30%) ml kg^–1 min^–1. Volume of distributionat steady state was 293 (55%) ml kg^–1 Terminal half lifeand mean residence time were 71.7 (34%) and 33.4 (31%) min,respectively. The concentration of the 3-OH metabolite remainedrelatively low. Urinary excretion of Org 9487 and its metaboliteswas 22% in 24 h. In conclusion, a 1-h infusion of the short-actingdrug Org 9487 changed its time course characteristics graduallyfrom that of a short-acting neuromuscular blocking agent tothat of a neuromuscular blocker with an intermediate durationof action.     

ANTAGONISM OF MODERATE DEGREES OF VECURONIUM-INDUCED NEUROMUSCULAR BLOCK BY SMALL DOSES OF NEOSTIGMINE

We have studied the influence of a reduced dose of neostigmineon recovery from vecuroniuminduced neuromuscular block in 26adult patients, using electromyographic responses to train-of-four(TOF) stimulation. Neostigmine 10, 20 or 40 µg kg^–1was administered when the first response had recovered spontaneouslyto 5–10% or 40–50% of control. Antagonism was acceptedas adequate when the first response reached 90% of control andthe TOF ratio reached 0.7. At both degrees of spontaneous recovery,neostigmine 40 µg kg^–1 evoked the most rapid antagonism.Clinical recovery was satisfactory with no differences betweengroups. Block produced by neostigmine was not observed. Thepattern of recovery of the single response and the TOF ratiowas not altered by neostigmine in the range of doses studied.We suggest that the dose of neostigmine should not be reducedbelow 40 µ kg^–1, even when all responses of theTOF are present. ^* present address: Royal Perth Hospital, Western Australia     

USE OF MIVACURIUM CHLORIDE BY CONSTANT INFUSION IN THE ANEPHRIC PATIENT

Twenty anephric and 20 healthy patients received a bolus doseof mivacurium 150 fig kg–1 When the first EMG response(T1) of the train-of-four had recovered to 5% of control (TO),an infusion of mivacurium 10 ng kg–1 min–1was startedand adjusted to keep T1 at 5% Ten patients in each group weregiven neostigmine 35 pg kg–1 when the infusion was stoppedwhen T1/TO had recovered to 20% in the others recovery was spontaneous.After the bolus dose of mivacurium, mean (SD) depression ofT1 was greater in the anephric group than in the normal group(98.4 (3.5) vs 96.8 (4.4)%; P < 0.07; and recovery of T1/T0to 5% was slower (15.3 (6.9) vs 9.8 (3.5) min; P < 0.01).Anephric patients required a slower infusion rate (6.3 (1.9)vs 10.4 (2.8) ng kg–1 min–1; P < 0.001) Neostigminehastened recovery of both T1/T0 and T4/T1 in both groups. Spontaneousrecovery of T1/T0 (from 25% to 75%) after the infusion was alsoslower in anephric patients (12.2 (8.2) vs 7.7 (1.2) min; P< 0.05). Plasma cholinesterase activity was less in the anephricgroup (785 (207) vs 943 (217) µu litre^–1; P <0.05) and there was a (negative) correlation overall betweencholinesterase activity and time to 5% recovery of T1/T0 afterthe bolus dose (r = –0.42; P < 0.02). We conclude thatpatients with chronic renal failure may require a reduced doseof mivacurium.     

Neuromuscular and haemodynamic effects of mivacurium in elderly and young adult patients

We have studied the neuromuscular effects of mivacurium andchanges in heart rate and arterial pressure in 40 elderly (aged70 yr) and 20 young adult (aged 18–40yr) patients anaesthetizedwith thiopentone, fentanyl, nitrous oxide in oxygen and halothane.Neuromuscular block was monitored by train-of-four (TOF) stimulationof the ulnar nerve and recording of the force of contractionof the adductor pollicis muscle using a force displacement transducerand a neuromuscular function analyser (Myograph 2000, BiometerLtd). Twenty elderly and 10 young adults received single closesof mivacurium 0.15 mg kg^–1 and spontaneous recovery wasrecorded. The other 20 elderly and 10 adults received the samedose but an infusion was started at T1 (first response in TOF)of 10% and the block maintained at this level. Haemodynamiceffects were studied after administration of mivacurium over15 or 5 s in elderly (n=10 each) and over 5 s in adult (n=10)patients. Onset of maximum block occurred at a mean time of122 (sd 32) and 125 (49) s in elderly and young adults, respectively.Recovery of T1 to 25% occurred in 22.0 (5.7) and 17.2 (4.4)min, and T1 to 90% in 32.8 (6.9) and 24.4 (5.8) min in elderlyand adult subjects, respectively. Recovery of the TOF ratioto 0.7 occurred in 32.8 (7.1) and 26.0 (15.0) min in the elderlyand young subjects, respectively (all P<0.05 between youngand elderly). Mean mivacurium requirements by continuous infusionfor maintenance of 90% block were 3.67 and 5.50 ng kg^–1min^–1 in elderly and the young adults, respectively (P< 0.05). In the elderly, neuromuscular effects were prolongedby approximately 30% and infusion requirements reduced by 38%.Residual neuromuscular block was antagonized easily with edrophoniumor neostigmine. Except for small changes in systolic arterialpressure, mivacurium exhibited good haemodynamic stability inboth groups. Cutaneous flushing was observed in six elderly(1 5%) and six young adults (30%).     

Mivacurium chloride and myasthenia gravis

We describe the successful use of the short-acting, non-depolarizingneuromuscular blocking agent, mivacurium, in a patient withmyasthenia gravis taking pyridostigmine 120 mg four times daily.Increased sensitivity to mivacurium was demonstrated using train-of-fourmonitoring. A dose of 0.5 times the recommended ED₉₅ (3.0 mg)resulted in 93% block of T1. Spontaneous recovery was prolongedwith a recovery index (25%–75% T1) of 20.5 min. Residualblock was antagonized without difficulty using neostigmine 2.5mg. We discuss the relationship between plasma cholinesterase,acetylcholinesterase and anticholinesterase drugs. (Br. J. Anaesth.1994; 72: 468–469)     

Optimum dose of neostigmine at two levels of atracurium-induced neuromuscular block

There is controversy about the optimum dose of neostigmine forantagonizing neuromuscular block. We have studied 57 patientsundergoing gynaecological surgery to establish a dose-responserelationship when neostigmine was given to antagonize atracurium-inducedblock. Anaesthesia was induced with thiopentone and fentanyland maintained with nitrous oxide and enflurane in oxygen andneuromuscular block was produced with a bolus of atracurium0.5 mg kg–1. At the time of antagonism of block, threegroups received neostigmine 20, 40 or 80 µg kg–1at 5–10% recovery of the compound muscle action potentialof the adductor pollicis (profound block) and three groups receivedone of these doses at 40–50% neuromuscular recovery (lightblock). At profound block, antagonism was prolonged by reducingthe dose of neostigmine from 40 µg kg–1 to 20 µgkg–1, but not shortened by increasing the dose from 40µg kg–1 to 80 µg kg–1. At light block,there was no significant difference between the three groupsin the time taken to reach a train-of-four ratio of 0.7. Therewas little benefit in increasing the dose of neostigmine from40 µg kg–1 to 80 µg kg–1 when antagonizingprofound neuromuscular block. When light block was antagonized,neostigmine 20 µg kg–1 was the optimum dose. Wesuggest that smaller doses of neostigmine than are given commonlyproduce adequate antagonism of atracurium-induced neuromuscularblock. (Br. J. Anaesth. 1994; 72: 82–85)     

COMPARISON OF MIVACURIUM AND SUXAMETHONIUM ADMINISTERED BY BOLUS AND INFUSION

Mivacurium chloride is a new, short-acting non-depolarizingneuromuscular blocking agent presently undergoing clinical evaluation.The neuromuscular effects of mivacurium and suxamethonium givenby bolus and infusion were compared in adult patients duringnitrous oxide-oxygen-oploid anaesthesia. Neuromuscular blockwas monitored by recording the compound electromyogram of theadductor pollicis muscle resulting from supramaximal train-of-fourstimuli applied to the ulnar nerve. Time to onset of completeblock and recovery to T₅ were significantly shorter for suxamethoniumthan for mivacurium (1.0 (0.1) v. 2.5 (0.3) min and 6.4 (0.7)v. 17.5 (1.8) min; mean (SEM)). Conditions for tracheal intubationwere similar in the two groups although intubation was performed0.75–1.3 min later following mivacurium. The infusionrate required to maintain neuromuscular block was 88.6 (10.4)µg kg^–1 min^–1 for suxamethonium and 7.8 (1.2)µg kg^–1 min^–1 for mivacurium. There was asignificant negative correlation between recovery to T₅ andinfusion rate for mivacurium and for suxamethonium. It was equallyeasy to titrate the in fusion rate to the desired degree ofblock in each group. The recovery index (T₂₅–T₇₅) afterthe infusion stopped was similar in patients who received mivacuriumand those who received suxamethonium.     

ANTAGONISM OF INTENSE ATRACURIUM-INDUCED NEUROMUSCULAR BLOCK IN CHILDREN

Antagonism of intense neuromuscular block induced by atracurium0.5 mg kg^–1 was attempted in four groups of six childrenusing one of two doses of neostigmine (0.05 mg kg^–1 and0.1 mg kg^–1) or of edrophonium (0.5 mg kg^–1 and1.0 mg kg^–1) when the first twitch of the post-tetaniccount (PTC1) was 10% of control. For comparison with normalpractice, a fifth group received neostigmine 0.05 mg kg^–1when the first twitch of the train-of-four was 10% of control.Total recovery time from PTC1 10% to a train-of-four ratio of0.8 was not reduced by early administration of the anticholinesterases,compared with conventional administration of neostigmine atT1 10%. However, recovery from intense block was faster afterneostigmine than edrophonium (P < 0.01). Doubling the dosesof the anticholinesterases did not reduce the recovery timeand had the effect of increasing variability. We conclude thatthere is no clinical advantage in attempting to antagonize intenseneuromuscular block in children using normal or increased dosesof neostigmine or edrophonium.     

Effects of cholinesterase inhibitors on the neuromuscular blocking action of suxamethonium

Prolonged neuromuscular block occurs when suxamethonium is givenafter neostigmine or pyridostigmine; however, studies of edrophoniumand suxamethonium have yielded conflicting results. We havestudied, therefore, interactions between suxamethonium and allthree anticholinesterases in rats anaesthetized with pentobarbitone.After recovery from an initial bolus of suxamethonium, saline,edrophonium, pyridostigmine or neostigmine was administeredand a second dose of suxamethonium was then given. All threeanticholinesterases prolonged the duration of neuromuscularblock (90% suppression to 50% twitch recovery) to 127(SEM 9)%,127(10)% and 138 (11)% of baseline for edrophonium, pyridostigmineand neostigmine, respectively. Recovery index (25% to 75% twitchrecovery) was increased also to 125 (9)%; 149 (10%) and 185(15)% of baseline, respectively for the three drugs. Presented in part at the 1992 annual meetings of the AmericanSociety of Anesthesiologists and the California Society of Anesthesiologists.     

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.     

Mivacurium in the myasthenic patient

We have used mivacurium in four myasthenic patients presentingfor thymectomy. Supramaximal single twitch stimulation was appliedto the ulnar nerve at the wrist and the force of contractionof the adductor pollicis was measured. After an initial bolusdose of 30 µg kg^–1 (approximately one-fifth of thenormal intubating dose), we observed a mean 37.5 (SEM 5.6)%reduction in evoked twitch tension. Neuromuscular block wasincreased with incremental doses and maintained with repeatbolus doses of 15 µg kg^–1 at 25% recovery. The intervalbetween maintenance bolus doses remained constant (mean 5.9(0.7) min). Spontaneous offset was rapid with a mean recoveryindex (T25-T75) of 11.9 (2.1) min. Provided anticholinesterasetherapy is withheld in the immediate preoperative period, mivacuriumwould appear to be a safe and appropriate neuromuscular blockerin this variably sensitive group of patients. The cumulativedose required to establish full neuromuscular block varied between60 and 90 µg kg^–1 A maintenance infusion, commencingat 3 µg kg^–1 min^–1 is recommended, guidedby neuromuscular monitoring. Present address: Department of Anaesthesia, Chase Farm Hospital,The Ridgeway, Eafield, Middlesex EN2 8JL Present address: Department of Anaesthesia, St Mary's Hospital,London Present address: Department of Anaesthesia, Queen ElizabethHospital, Birmingham     

DETERMINANTS OF THE REVERSAL TIME OF COMPETITIVE NEUROMUSCULAR BLOCK BY ANTICHOLINESTERASES

We have assessed, in 200 patients, the determinants of the reversaltime of competitive neuromuscular block by anticholinesterasewhen alcuronium and atracurium neuromuscular block were antagonizedby neostigmine 0.04 and 0.08 mg kg^–1 and edrophonium 0.5and 1.0 mg kg^–1. A biexponential relationship was foundbetween the reversal time (time from injection of anticholinesteraseto a train-of-four ratio of 70%) and the degree of neuromuscularblock at reversal (all groups; F ratio, P < 0.05). Reversaltime was determined by two processes: direct antagonism by theanticholinesterase and spontaneous recovery of the neuromuscularblocking agent, with the latter becoming the major determinantat profound levels of neuromuscular block (0–10% of controltwitch height). Neostigmine, in the doses studied, appearedto have a higher "ceiling" of neuromuscular block which it completelyantagonized, although edrophonium had a more rapid onset ofaction. The reversal time for alcuronium became progressivelylonger relative to atracurium as neuromuscular block increasedbecause of the slower spontaneous recovery rate. Avoidance ofprofound neuromuscular block at the completion of surgery isrequired to ensure reliable antagonism of the block within 5–10min by an anticholinesterase. Neostigmine 0.08 mg kg^–1was found to be the most effective agent in antagonizing profoundneuromuscular block.     

COMPARISON OF THE NEUROMUSCULAR BLOCK INDUCED BY MIVACURIUM, SUXAMETHONIUM OR ATRACURIUM DURING NITROUS OXIDE-FENTANYL ANAESTHESIA

We compared the neuromuscular and cardiovascular changes followingadministration of mivacurium 0.15, 0.20 and 0.25 mg kg^–1,suxamethonium 1.0 mg kg^–1 or atracurium 0.5 mg kg^–1i.v. in 41 (ASA physical status I or II) patients during nitrousoxide—fentanyl anaesthesia. Mean onset times for totalablation of twitch response for mivacurium 0.15, 0.20 and 0.25mg kg^–1, were 2.5, 2.4 and 2.7 min, respectively, similarto that for atracurium (2.5 min), but longer than for suxamethonium(1.1 min) (P < 0.05). Mean times from administration of druguntil twitch response recovered to 10% of control were shorterfor each dose of mivacurium (15.6, 18.0 and 20.6 min, respectively)than for atracurium (40.0 min) and longer than for suxamethonium(7.7 min) (P < 0.05). Mean infusion rate required to maintaintwitch response at 5±4% control was 6.7 µg kg^–1min^–1 for mivacurium and 6.3 µg kg^–1 min^–1for atracurium. Following neostigmine 0.045 mg kg^–1, meantimes for twitch tension to recover from 10% to 90% of controlwere similar for mivacurium (9.7 min) and atracurium (10.5 min).Transient decreases in mean arterial pressure (> 20%) wereobserved in seven of 15 patients who received the two higherdoses of mivacurium. Presented in part at the Annual Scientific Meeting of the AmericanSociety of Anesthesiologists, San Francisco, October 1988.     

Mivacurium-induced prolonged neuromuscular block

We report a case of prolonged neuromuscular block after administrationof mivacurium 0.2 mg kg^–1 to a 16-yr-old patient wherethe duration of block was 2.5 h. The interesting points in thiscase were that the patient had homozygous atypical plasma cholinesterasedeficiency (both parents had a normal phenotype) following livertransplantation. Investigations showed low plasma cholinesteraseactivity (343 iu litre^–1 normal 600–1400) and dibucainenumber was 25 (normal 76–83). Despite possessing atypicalenzyme normally associated with markedly prolonged durationof suxamethonium, on two occasions the patient received suxamethoniumand responded normally. This had not previously been reported.The patient demonstrated prolonged block with mivacurium asa result of atypical enzyme (despite normal metabolism of suxamethonium).     

Recovery characteristics after early administration of anticholinesterases during intense mivacurium-induced neuromuscular block

The time course of recovery after early administration of anticholinesterasesduring intense mivacurium-induced block was evaluated by recordingthe mechanomyographic response of the adductor pollicis to post-tetaniccount (PTC) and train-of-four (TOF) ulnar nerve stimulation.Seventy-two adult patients receiving thiopentone, fentanyl,nitrous oxide, isoflurane anaesthesia and mivacurium 0.15 mgkg^–1 were allocated randomly to one of six equal groupsaccording to the type of anticholinesterase and intensity ofblock at which antagonism was attempted. Groups 1, 3 and 5 receivedneostigmine 0.07 mg kg^–1, while groups 2, 4 and 6 receivededrophonium 1 mg kg^–1. At the time of administration ofantagonist there was no response to PTC in groups 1 and 2, aPTC of 1 or more was detectable in groups 3 and 4 and the firsttwitch of the TOF (T1) had recovered to 10% in the conventionalantagonism groups (5 and 6). The longest clinical duration (CD)values (time from administration of mivacurium to T1 25%) wereencountered in groups 1, 5 and 6 and were 17.4 (7.9), 19.7 (3.4)and 21.4 (4.8) min, respectively. CD was reduced significantlyin groups 2, 3 and 4 and values were 13.9 (3.5), 13.7 (3.5)and 13.8 (3.3) min, respectively. Recovery indices (Rl) (timeinterval between T1 25% and 75%) were 13.8 (7.3), 6.3 (1.4),4.6 (1.8), 6.0 (2.1), 3.7 (2.2) and 4.8 (3.1) min in groups1–6, respectively and was prolonged with neostigmine antagonismat PTC 0 (group 1). Reversal time (RT) (time between administrationof antagonist and TOF 0.70) was 34.9 (16.6) min in group 1 whoreceived neostigmine at PTC 0 and was prolonged markedly comparedwith all other groups. Antagonism with edrophonium at PTC 0(group 2) was associated with an RT of 16.7 (5.1) min and wassignificantly longer compared with the conventional antagonismgroups only. Reversal times were similar in groups 3–6.Total recovery times (TRT) (time between administration of mivacuriumand TOF 0.70) were 41.5 (16.6), 23.2 (5.2), 23.2 (5.3), 24.1(4.5), 26.8 (4.8) and 28.5 (9.1) min in groups 1–6, respectively,and was markedly prolonged in group 1 only. In summary, administrationof neostigmine during intense mivacurium block, not responsiveto TOF and PTC stimulation was associated with marked delayin recovery, possibly because of inhibition of plasma cholinesterase.At this intensity of block, edrophonium was preferable. It isadvisable to wait for a detectable PTC before attempting antagonismof an intense mivacurium block. After detection of PTC, neostigmineor edrophonium antagonism reduced the clinical duration butnot the total recovery time compared with conventional reversaladministered at T1 10%.     

NEUROMUSCULAR AND CARDIOVASCULAR EFFECTS OF MIVACURIUM CHLORIDE (BWB1090U) DURING NITROUS OXIDE-FENTANYL-THIOPENTONE AND NITROUS OXIDE-HALOTHANE ANAESTHESIA

Seventy-two adult surgical patients were studied to compareneuromuscular and cardiovascular effects of mivacurium chlorideduring nitrous oxide-fentanyl-thiopentone (BAL group) or nitrousoxide-halothane (HAL group) anaesthesia. Eighteen patients inthe BAL group received an initial bolus of mivacurium, eitherthe ED₂₅ (n = 9) or the ED50 (n = 9) (0.03 and 0.05 mg kg^–1).These doses were based on the assumption that the slope of thedose-response curve during nitrous oxide-opioid anaesthesiawould be approximately the same as the slope of the neuromuscularresponse from the first human studies with mivacurium. Twenty-sevenadditional patients were allocated to subgroups of nine patientsto receive mivacurium 0.04. 0.08 or 0.15 mg kg^–1. Twenty-sevenpatients in the HAL group were allocated also to subgroups ofnine patients to receive mivacurium 0.03, 0.04 or 0.15 mg kg^–1.During stable anaesthesia, mean endtidal halothane concentrationswere maintained at 0.49±0.01%. The estimated ED₅₀, ED₇₅and ED₉₅ for BAL and HAL groups were 0.039, 0.05 and 0.073 mgkg^–1 and 0.040, 0.053 and 0.081 mg kg^–1, respectively.Halothane did not potentiate maximum block or time to maximumblock. Halothane did affect spontaneous recovery. With the 0.15-mgkg^–1 dose, time to 95% recovery was prolonged significantlyin the HAL group (30.0 (SEM 1.4) min) compared with the BALgroup (24.1 (1.5) min). Recovery index from 25% to 75% recoverywas also prolonged significantly in the HAL group (7.0 (0.4)min) compared with the BAL group (5.4 (0.4) min). There wereno significant haemodynamic changes in groups given mivacuriumdoses up to and including 2 x ED₉₅ by bolus i.v. administration ^*Department of Anesthesia, University of Iowa Hospitals andClinics, Iowa City, Iowa 52242, U.S.A.     

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