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.     

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.     

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.     

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.     

A comparison of edrophonium and neostigmine for the antagonism of atracurium-induced neuromuscular block

Edrophonium, 0.5 mg/kg, or neostigmine, 0.05 mg/kg, was administered to groups of 20 patients each, for antagonism of atracurium-induced block at varying degrees of spontaneous recovery. Neuromuscular block was studied using train-of-four (TOF) stimulation. Adequate reversal of neuromuscular block (TOF ratio of 0.7) was achieved in all patients given neostigmine but only in 13 of the 20 given edrophonium. The onset of action of edrophonium (23 sec) was significantly more rapid than that of neostigmine (40 sec), as was the time taken to attain a TOF ratio of 0.7 in those in whom adequate antagonism was achieved (68 sec for edrophonium and 246 sec for neostigmine). Five of the seven patients in the edrophonium group who failed to be reversed adequately had shown three or fewer twitches to a TOF stimulation. It is concluded that edrophonium in a dose of 0.5 mg/kg does not consistently antagonize neuromuscular blockade induced by atracurium, particularly if all four responses to a TOF stimulation are not elicited prior to antagonism of the block.     

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.     

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)     

Neostigmine and edrophonium as antagonists of atracurium and pancuronium

Edrophonium 0.5 mg/kg or neostigmine 0.04 mg/kg were administered to two groups of 30 patients each for antagonism of atracurium- or pancuronium-induced neuromuscular block at 25% single twitch recovery. Neuromuscular block was studied using both single twitch and train-of-four (TOF) nerve stimulation. The times to 100% single twitch recovery were significantly more rapid for patients receiving edrophonium (P less than 0.01) in both groups (atracurium and pancuronium); the TOF ratios were similar for atracurium, but for pancuronium they were greater after neostigmine than after edrophonium, and only at 25 min were these ratios similar. It is concluded that edrophonium in a dose of 0.5 mg/kg antagonizes neuromuscular blockade induced by atracurium, as does neostigmine in a dose of 0.04 mg/kg, but the former does not consistently antagonize neuromuscular blockade induced by pancuronium even at 25% of single twitch recovery.     

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.     

DOSE-RESPONSE RELATIONSHIPS FOR NEOSTIGMINE ANTAGONISM OF VECURONIUM-INDUCED NEUROMUSCULAR BLOCK IN ADULTS AND THE ELDERLY

We have studied the dose-response relationship for neostigminein 36 adult (ages 18-50 yr) and 36 elderly (ages > 70 yr)subjects during antagonism of neuromuscular block induced byvecuronium. All patients received vecuronium 0.08 mg kg^–1and neuromuscular block was monitoredmechanomyo-graphicallyusing the train-of-four (TOF) mode of stimulation. Six patientsof each age group were allocated randomly to receive neostigmine5, 15, 25, 35 or 45 µg kg^–1 or saline at 10% recoveryof T1 (first response in the TOF). TOF ratios were recordedcontinuously over the next 10 min and the values at 1-min intervalsfrom 5 min onwards were used to construct the dose-responserelationships. There was a significant difference (P < 0,05)in the time to spontaneous recovery of T1 to 10% between theadults (24 (SD 5.5) min) and the elderly (33 (7.8) min). Dose-responsecurves for neostigmine were parallel in the two age groups,but those for the. elderly were significantly to the right ofthe curves for the adults. This sggests an apparently lesserrelative potency of neostigmine, or the requirement of a largerdose, in the elderly for attaining antagonism of a moderatelyintense vecuronium block at the same time as in adults.     

Neostigmine and edrophonium for reversal of pipecuronium neuromuscular blockade

Neostigmine 0.06 mg.kg-1 or edrophonium 1 mg.kg-1 were administered to two groups of 15 patients each for antagonism of pipecuronium-induced neuromuscular block at 20% spontaneous recovery of the first twitch (T1) of the train-of-four (TOF) stimulation. The mean onset of action (+/-SEM) of edrophonium (18.1 +/- 2.4 sec) was significantly more rapid (P less than 0.01) than that of neostigmine (47.6 +/- 4 sec), as were the times taken to attain a TOF ratio of 0.25 and 0.5. Nevertheless, the reversal time (time taken from the end of injection of the antagonist until TOF ratio value had reached 0.75) was significantly shorter (P less than 0.01) in the neostigmine than in the edrophonium group (499.3 +/- 62 vs 767 +/- 52 sec respectively). The TOF ratio ten minutes after reversal was greater in the neostigmine group than in the edrophonium group (P less than 0.01), 0.78 +/- 0.02 vs 0.68 +/- 0.02 min respectively. At that time, 33% (5 out of 15) and 80% (12 out of 15) patients failed to be reversed adequately (TOF ratio of 0.75) after neostigmine 0.06 mg.kg-1 and edrophonium 1 mg.kg-1, respectively. Administration of one additional dose (one-third of the initial dose) of the same antagonist resulted in adequate antagonism in the remaining five patients in the neostigmine group and in nine patients in the edrophonium group. Two such doses were required in the remaining three patients in the latter group. The mean total dose of neostigmine and edrophonium employed in this study was 0.067 +/- 0.002 and 1.3 +/- 0.05 mg.kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

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     

EDROPHONIUM ANTAGONISM OF ATRACURIUM DURING ENFLURANE ANAESTHESIA

To determine the influence of enflurane on the ability of edrophoniumto antagonize atracurium block, dose—response curves wereconstructed for edrophonium in the presence of 0%, 1% and 2%enflurane, and for 2% enflurane discontinued at the time ofadministration of edrophonium. One hundred ASA Physical StatusI or II patients (four groups of 25), selected randomly andundergoing elective surgery, received atracurium 0.5 mg kg^–1,with thio-pentone, nitrous oxide and enflurane. Supplementarydoses of fentanyl were given if needed. Train-of-four (TOF)stimulation was applied every 12 s, and the force of contractionof the adductor pollicis muscle was recorded. When first twitchheight (T1) had recovered spontaneously to 10 % of initial value,edrophonium 0.1, 0.2, 0.4 or 1 mg kg^–1 was administeredby random allocation. Enflurane concentrations remained constant,except that enflurane was discontinued in 50% of the patientswho had received 2% enflurane. Monitoring was continued forat least 10 min, at which time T1 and TOF ratio (T4/T1) weremeasured. The ED₈₀ for T1 recovery depended on the dose of enflurane:0.08 (SEM 0.03), 0.21 (0.06) and 0.42 (0.18) mg kg^–1 for0%, 1% and 2% enflurane, respectively (P < 0.005). With enflurane2% discontinued, the ED₈₀ was 0.095 (0.050) mg kg^–1 (P< 0.02 compared with 2% enflurane). The ED₅₀ for TOF responseswere 0.13 (0.05), 0.46 (0.10) and 1.04 (0.38) mg kg^–1for 0%, 1% and 2% enflurane, respectively (P < 0.001). With2% enflurane discontinued, the ED₅₀ for TOF was 0.17 (0.12)mg kg^–1 (P < 0.05 compared with 2% enflurane). It isconcluded that, even when given at the same degree of spontaneousrecovery, the effect of edrophonium is markedly attenuated byenflurane.     

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.     

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.     

Dose-response relationships for edrophonium and neostigmine antagonism of atracurium and cisatracurium- induced neuromuscular block

PURPOSE: To study the dose-response relationships for neostigmine and edrophonium during antagonism of neuromuscular block induced by atracurium and cisatracurium. METHODS: One hundred and twenty eight, ASA group 1 or 2 adults were given either 0.5 mg x kg(-1) atracurium or 0.1 mg x kg(-1) cisatracurium during fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. The neuromuscular block was measured by an acceleration-responsive transducer. Responses were defined in terms of percent depression in the first twitch (T1) and train-of-four (TOF) response. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg x kg(-1)) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg x kg(-1)) was administered by random allocation. Neuromuscular function in another sixteen subjects was allowed to recover spontaneously. RESULTS: At five minutes, unlike edrophonium, neostigmine was equally effective against atracurium and cisatracurium with respect to T1 recovery. The neostigmine T1-ED50 was 10.3 +/- 1.06 (SEM) microg x kg(-1) after atracurium and 11.2 +/- 1.06) microg x kg(-1) after cisatracurium. The edrophonium ED50 was 157 +/- 1.07 microg x kg(-1) with atracurium and 47.4 +/- 1.07 microg x kg(-1) with cisatracurium, giving a neostigmine:edrophonium potency ratios of 15.2 +/- 1.7 and 4.2 +/- 0.41 (P < 0.001) for atracurium and cisatracurium, respectively. At 10 min neostigmine was 13 +/- 1.4 times as potent as edrophonium for achieving 50% TOF recovery after atracurium paralysis. After cisatracurium the potency ratio was 11.8 +/- 1.3 (NS). CONCLUSIONS: Although there were differences at five minutes, neostigmine:edrophonium potency ratios at 10 min, were similar in both relaxants studied.     

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.     

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.     

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