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.     

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.     

ANTAGONISM OF ATRACURIUM-INDUCED NEUROMUSCULAR BLOCKADE BY NEOSTIGMINE OR EDROPHONIUM

Antagonism of atracurium-induced neuromuscular blockade by neostigmineor edrophonium has been studied using the tetanic (50 Hz) andtrain-of-four (2 Hz) or single twitch responses of the adductorpollicis muscle in 22 anaesthetized patients. A further ninepatients not given an anticholinesterase acted as a controlgroup. In two groups (six patients for each anticholinesterase)in whom antagonism was attempted at 95–98% blockade ofthe tetanic response, recovery of the tetanic response aftertwo or three doses of edrophonium 0.75 mg kg^–1 i.v. wasnot statistically different from that in the control group;recovery after two doses of neostigmine 2.5 mg i.v. was significantlyfaster (P < 0.001). Recovery of the single twitch responseafter antagonism with edrophonium, although longer than thatwith neostigmine (P < 0.01), was significantly shorter thanin the control group (P < 0.05). When edrophonium is givenat the commencement of recovery, the initial rapid antagonismof tetanic block is not sustained, whereas antagonism by neostigmineis more persistent and the recovery phase is significantly shortened.In a further two groups of patients (n = 5) given atracurium0.3 mg kg^–1 i.v. antagonism was not attempted until thepeak height of the tetanic contraction had reached approximately50% of the control value. It was found that recovery of thetetanic and train-of-four responses was significantly faster(P < 0.05–0.001) after antagonism with edrophonium0.75 mg kg^–1 i.v. than with neostigmine 2.5mg i.v. (approx.0.04 mg kg^–1). The train-of-four response recovered moreslowly than did the tetanic response after both agents (P <0.05–0.01). Department of Anaesthetics, University College Hospital, LondonWC1. ^*Clinical Investigation Department, Clinical and Applied researchDivision, The Wellcome Research Laboratories, Beckenham, Kent.     

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)     

ANTAGONISM OF VERCURONIUM-INDUCED NEUROMUSCULAR BLOCKADE WITH EDROPHONIUM OR NEOSTIGMINE

Antagonism of vecuronium-induced neuromuscular blockade wasattempted, at varying degrees of spontaneous recovery, withedrophonium 0.5 mg kg ^–1 or neostigmine 0.05 mg kg^–1in two groups of 20 patients. Neuromuscular blockade was monitoredusing a train-of-four (TOF) stimulation. Adequate antagonismof neuromuscular blockade, defined as a sustained TOF ratioof 0.7 or more, was attained in all 20 patients given neostigmineand in 13 out of 20 given edrophonium. Five of the remainingseven patients given edrophonium had shown three or less responsesto TOF stimulation before antagonism. While the time to onsetof the action of edrophonium (22 s) was not significantly shorterthan neostigmine (26 s), the time taken to attain a TOF ratioof 0.7 was significantly shorter with edrophonium (67 s comparedwith 194 s with neostigmine). It is concluded that edrophonium0.5 mg kg^–1 does not consistently antagonize vecuronium-inducedneuromusocular blockade, particularly if there are three orless responses to a TOF stimulation present before antagonism.     

Cholinesterase inhibitors do not prolong neuromuscular block produced by mivacurium

Cholinesterase inhibitors antagonize neuromuscular block producedby mivacurium, but some may also decrease its metabolism byinhibiting pseudocholinesterase. These opposing interactionswere examined in rats anaesthetized with pentobarbitone. Afterspontaneous recovery from an initial bolus dose of 0.03 mg kg^–1,mivacurium was infused to produce 80–90% block of gastrocnemiusmuscle twitch. After 15 min, the infusion was discontinued andsaline, edrophonium. pyridostigmine or neostigmine was administered.Fifteen minutes later, a second bolus dose of mivacurium wasgiven. Edrophonium, pyridostigmine and neostigmine reduced thesubsequent maximum block, compared with the change in salinecontrol, by 3%, 19% and 35%, respectively. Correspondingly,the time to recovery of T1 to 50% was decreased by 20%, 58%and 62%. In rats, acetylcholinesterase mediated antagonism ofneuromuscular block predominated over decreased pseudocholinesterasemediated metabolism, such that prior administration of a cholinesteraseinhibitor did not prolong the neuromuscular blocking effectsof mivacurium.     

NEOSTIGMINE AND EDROPHONIUM ANTAGONISM OF MODERATE NEUROMUSCULAR BLOCK INDUCED BY PANCURONIUM OR TUBOCURARINE

Edrophonium and neostigmine are anticholin-esterase drugs usedcommonly to antagonize competitive neuromuscular block. Althoughit has a faster onset of action than neostigmine, edrophoniumis unreliable when used to antagonize deep neuromuscular block.We have compared the antagonist characteristics of these twodrugs when used to antagonize a moderate degree of pancuronium-or tubocurarine-induced neuromuscular block. Forty ASA I orII patients undergoing surgical procedures were allocated randomlyto receive either pancuronium 70 kg^-1 or tubo-curarine 0.5 mgkg^-1, and to receive either edrophonium 0.5 mg kg^-1 or neostigmine0.05 mg kgr^-1. Antagonism was attempted when the first responseto train-of-four (TOF) stimulation recovered spontaneously to25% of the control height. Neuromuscular function was monitoredusing the evoked integrated electromyogram of the first dorsalinterosseous muscle of the hand. Adequate recovery was definedas the achievement of a TOF ratio of 0.70 or greater. Only sevenof 20 patients who received edrophonium demonstrated adequaterecovery 30 min after antagonism. Under the conditions describedin this study, edrophonium 0.5 mg kg7 was less effective asan antagonist than neostigmine 0.05 mg kg^-1. (Br. J. Anaesth.1993; 70: 160–162)     

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     

ELECTRICAL AND MECHANICAL RESPONSES AFTER NEUROMUSCULAR BLOCKADE WITH VECURONIUM, AND SUBSEQUENT ANTAGONISM WITH NEOSTIGMINE OR EDROPHONIUM

Six unpremedicated patients who had given their informed consentwere given vecuronium 0.08 mg kg^–1 before elective surgery.Recovery from neuromuscular blockade was measured electricallyand mechanically. Neuromuscular blockade was antagonized 1 hafter the administration of vecuronium with two doses of neostigmine2.5 mg (three patients) or edrophonium 0.5 mg kg^–1 (threepatients). Although the onset of initial recovery was similar,subsequent recovery was faster when meassured electrically (EMG)than when measured mechanically. Recovery appeared to be fasterin younger patients. Reintroduction of neuromuscular blockadeoccurred after the second dose of neostigmine 2.5 mg, givento antagonize the block. This did not occur after either doseof edrophonium 0.5 mg kg^–1. ^*University College and Middlesex Hospitals, Mortimer Street,London W1 7PN. Department of Anesthesiology, U.C.L.A. Medical School, Los Angeles,U.S.A.     

ANTAGONISM OF VECURONIUM AND ATRACURIUM: COMPARISON OF NEOSTIGMINE AND EDROPHONIUM ADMINISTERED AT 5% TWITCH HEIGHT RECOVERY

In 39 healthy patients antagonism, by neostig-mine 0.07 mg kg^–1or edrophonium 0.8 mg kg^–1, of neuromuscular blockadeinduced by vecuronium or atracurium, was compared. Reversalwas attempted when the height of the single twitch (TH) hadrecovered spontaneously to 5% of the control value. The evokedresponses, initially single twitch, then train-of-four (TOF)were observed until the TOF ratio was 70%. Induced recoveryfrom TH 5% to 25% was shorter following edrophonium than followingneostigmine with both vecuronium (P < 0.05) and atracurium(P < 0.05). The recovery indices and times until TH was 75%of control and until the TOF ratio was 70% were not different.The time from a TH of 75% to a TOF ratio of 70% was shorterfollowing neostigmine than following edrophonium with both vecuronium(P < 0.01) and atracurium (P < 0.01). Edrophonium hada much more variable effect on vecuronium than on atracurium.These results show that although the onset of action of edrophoniumwas faster than that of neostigmine, this did not lead to afaster clinical recovery, and antagonism by edrophonium maybe delayed in a number of patients if vecuronium is the neuromuscularblocker.     

ANTAGONISM OF PROFOUND NEUROMUSCULAR BLOCKADE INDUCED BY VECURONIUM OR ATRACURIUM: Comparison of Neostigmine with Edrophonium

The effectiveness of neostigmine 0.07mg kg^–1 and edrophonium0.8 mg kg^–1 as antagonists of profound neuromuscular blockadeinduced by vecuronium 0.1 mg kg^–1 or atracurium 0.5 mgkg^–1 was studied in 59 healthy patients. The antagonistswere administered 5 min after total ablation of the twitch responseand the end-point of recovery was a train-of-four ratio of 70%.In 30 patients given vecuronium the mean time to reach thispoint (duration TOF₇₀) was 66.7min in the control group (noantagonist), 43.5 min in the group given neostigmine and 59.8min in the group given edrophonium. The duration TOF₇₀ was shorterin the neostigmine group than in the control {P < 0.01) andedrophonium (P<0.01) groups. The duration TOF₇₀ did not differfrom control in the edrophonium group. In 29 patients givenatracurium, the durations TOF₇₀ were 66.4, 44.1 and 54.9 minin the control, neostigmine and edrophonium groups, respectively.The durations TOF₇₀ in the neostigmine (P < 0.01) and edrophonium(P < 0.01), groups were shorter than control. The durationTOF₇₀ of the neostigmine group was shorter than in the edrophoniumgroup (P < 0.01). These results show that pro-found neuromuscularblockade cannot be rapidly antagonized by either of these twoagents, but if reversal is required under these circumstances,neostigmine would be the more effective drug. ^*The initial results from the vecuronium group were presentedat the 4th Ludwig Boltzmann Symposium, Vienna, 1984.     

EFFECTS OF NEOSTIGMINE AND EDROPHONIUM ON HUMAN ERYTHROCYTE ACETYLCHOLINESTERASE ACTIVITY

Erythrocyte acetylcholinesterase (AChE) activities in vivo weremeasured over 60 min using a spectrophotometric method afteradministration of neostigmine or edrophonium for antagonismof pancuronium-induced neuromuscular block in 31 patients. ErythrocyteAChE activities decreased to 11.3 (SD 1.2) % and 11.4 (0.8)% of baseline values (P < 0.001) within 2 min, then recoveredslowly and were 43.2 (6.2) % and 27.9 (2.9) % (P < 0.001)60 min after administration of neostigmine 0.036 mg kg^–1and 0.071 mg kg^–1, respectively. However, the enzyme activityafter edrophonium 1.43 mg kg^–1 did not change significantlyover 60 min. The results suggest that mechanisms other thanAChE inhibition may be responsible for the anti- curare effectof edrophonium     

DIURETIC-INDUCED HYPOKALAEMIA, PANCURONIUM NEUROMUSCULAR BLOCKADE AND ITS ANTAGONISM BY NEOSTIGMINE

The effect of hypokalaemia on a neuromuscular blockade inducedby pancuronium and its antagonism by neostigmine was studiedin the cat anterior tibialis-peroneal nerve preparation usingthe constant infusion of pancuronium technique. Hypokalaemiawas induced by chronic administration of chlorothiazide. Theinfusion rate of pancuronium required to maintain a 90% depressionof twitch tension was reduced from 0.72 ±0.06 µgkg^–1 min^–1 in the cats with a normal serum concentrationof potassium (K⁺ = 4.4±0.2 mmol litre^–1; n = 7)to 0.41±0.07 µg kg^–1 min^–1 in the hypokalaemiccats (K⁺ = 2.3±0.1 mmol litre^–1; n = 8). The doseof neostigmine necessary for 50% antagonism of the pancuronium-induceddepression of twitch tension (ED₅₀) was 10.0 µg kg^–1in the cats with a normal potassium concentration and 18.5 µgkg^–1 in hypokalaemic cats. We conclude that hypokalaemiadecreases the dose of pancuronium required for neuromuscularblockade and increases the dose of neostigmine required forantagonism of the block.     

SOME ACTIONS OF ORG NC45 AND OF EDROPHONIUM IN THE ANAESTHETIZED CAT AND IN MAN

Some actions of the muscle relaxant drug Org NC45 on the tibialisanterior muscle of cats under barbiturate—chloralose anaesthesiahave been studied. Its effects were characteristic of a neuromuscularblocking agent that acts predominantly, although not necessarilyexclusively, by blocking postiunctional cholinoceptors. It wasconfirmed that one of the important features of the action ofOrg NC 45 is that, despite its high potency, its offset of actionis unusually rapid. The pronounced antagonism of the block followingan interposed tetanus suggested that Org NC 45 is more easilydisplaced from the endplate cholinoceptors than are rubocuranneor pancuronium, and this led to the idea, confirmed by experiment,that edrophonium would be a more effective antagonist of OrgNC45 than of most other neuromuscular blocking drugs. Edrophoniumwas about 12 times less potent than neostigmine m antagonizingOrg NC 45. However, with equipotent antagonistic doses, edrophoniumrestored transmission to control (as measured by the train-of-fourtest) at least twice as rapidly as neostigmine and, more importantly,edrophonium had a much weaker effect than neostigmine on thecardiac vagus. The results obtained in cats with edrophoniumwere essentially confirmed in preliminary studies on nine anaesthetizedpatients. In these studies, a dose of edrophonium 0.5mgkg^–1i.v. was found to produce adequate and rapid antagonism of OrgNC45, and because of the relatively weak side-effects of edrophonium,it was necessary, about 30 s before edrophonium, to administeronly 0.6 mg of atropine (about 9 µkg^–1 ), whichis half the dose commonly used when neostigmine is the reversalagent. These preliminary observations in man suggest that edrophoniummay be the reversal agent of choice for Org NC 45.     

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)     

Edrophonium and plasma cholinesterase activity

Plasma cholinesterase activity was estimated following administration of edrophonium 0.5 or 1.0 mg X kg-1 given for antagonism of atracurium-induced neuromuscular block. There was no inhibition of enzyme activity for up to three hours following edrophonium administration. This is in contrast to profound and prolonged inhibition of enzyme activity seen following neostigmine and pyridostigmine.     

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.     

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     

COMPARISON OF NEUROMUSCULAR BLOCK IN THE DIAPHRAGM AND HAND AFTER ADMINISTRATION OF TUBOCURARINE, PANCURONIUM AND ALCURONIUM

The onset and offset of neuromuscular block in the diaphragmand in the adductor pollicis muscle were recorded using unilateralsupramaximal stimulation of phrenic and ulnar nerves. Thirtypatients were allocated randomly to receive tubocurarine 0.4–0.5mg kg^–1, pancuronium 0.07–0.08 mg kg^–1 oralcuronium 0.2–0.3 mg kg^–1. In all cases the onsetof neuromuscular block occurred in the diaphragm before adductorpollicis, and spontaneous recovery was evident first in thediaphragm. There was a correlation between the time of spontaneousreappearance of twitch in the diaphragm and in the adductorpollicis only in the patients who received pancuronium (r =0.97, P < 0.05 for reappearance of the first twitch of thetrain-of-four of each muscle). The duration of paralysis inthe diaphragm was less than 5 min in five patients who receivedtubocurarine and in one who received alcuronium; this correspondedto a period of paralysis in the adductor pollicis muscle ofmore than 25 min in each case.     

COMPARISON OF THE TRAIN-OF-FOUR FADE PROFILES PRODUCED BY VECURONIUM AND ATRACURIUM

In this double-blind study, we have allocated randomly 40 ASAI-III patients to one of four groups. After a standard anaestheticinduction, patients received vecuronium 0.08 mg kg^–1 or0.10 mg kg^–1, or atracurium 0.4 mg kg^–1 or 0.5 mgkg^–1. Using an electromyogram (Datex Relaxograph) thetrain-of-four (TOF) response was measured during onset of andrecovery from neuromuscular block. A greater degree of fadeof TOF was observed with atracurium during onset of neuromuscularblock than with equivalent doses of vecuronium. During recoveryof neuromuscular transmission, vecuronium was associated withmore fade than atracurium. The differences in the TOF profilesof these two drugs may be important when judging the adequacyof antagonism of neuromuscular block using the TOF response.