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)     

COMPARISON BETWEEN THE CONTINUOUS INFUSION OF VECURONIUM AND THE INTERMITTENT ADMINISTRATION OF PANCURONIUM AND VECURONIUM

The neuromuscular blocking effects of repeated bolus injectionsof pancuronium, or vecuronium, and of the continuous infusionof vecuronium have been compared in 36 patients by means ofevoked twitch tension Groups I and II received a loading dose(0.075 mg kg^–1) of pancuronium or vecuronium, respectively,followed by 0.015-mg kg^–1 maintenance doses when twitchtension had recovered to 25%. Group III received a 0.075-mgkg^–1 loading dose of vecuronium plus a continuous infusion(commenced simultaneously) delivering 0.075 mg kg^–1 h^–1.With repeated injections of pancuronium (group I) or vecuronium(group II), the durations of blockade to 25% recovery were 64and 25 min, respectively. Maintenance doses had to be injectedevery 42 min with pancuronium and every 12 min with vecuronium.The recovery times from 25% to 75% of control twitch tensionwere 44 v. 12 min. The continuous infusion of vecuronium (groupIII) produced consistent neuromuscular blockade at an averagelevel of 87% twitch depression. The times from the end of infusionto 25%, and from 25% to 75%, recovery averaged 20 and 26 min,respectively. These values did not correlate with the totaldose of vecuronium infused. For clinical practice, the suggestedloading dose is 1.5 times the ED₉₀ (= 0.07 mg kg^–1) followedby an infusion of the same dose per hour. The infusion shouldbe started within 10 min of the injection of the loading dose.     

RATE OF ONSET OF GOOD INTUBATING CONDITIONS, RESPIRATORY DEPRESSION AND HAND MUSCLE PARALYSIS AFTER VECURONIUM

The development of neuromuscular blockade of the adductor pollkismuscle following vecuronium 0.1, 0.15 and 0.2 mg kg^–1,was compared with the development of intubating conditions andrespiratory paralysis. From this relationship, the optimal timeafter injection required for ideal tracheal intubation was calculatedfor the three doses of vecuronium. The effects of these dosesof vecuronium on the onset, the duration of action and rateof recovery were studied. Vecuronium and "light" thiopentoneanaesthesia produced ideal intubation conditions only when completeneuromuscular blockade had been established for at least 30s.Intubation could be carried out with minimal reaction 3.3 and2.5 min after the injection of vecuronium 0.1 mg kg^–1and 0.2 mg kg^–1, respectively. Pancuronium 0.1 mg kg^–1produced good conditions about 3.8 min after injection. Suxamethonium1.5 mg kg^–1 (preceded by gallamine 20mg 2min earlier),produced excellent conditions in under 1 min. Hypopnoea occurredwhen the peripheral neuromuicular blockade was about 20–40%established with vecuronium or 50% established with pancuronium.Increasing the dose of vecuronium from 0.1 mg kg^–1 to0.2 mg kg^–1 prolonged significantly the duration of action(from 21 to 48 min) but did not shorten significantly the onsettime nor prolong the rate of recovery     

COMPARISON OF LARGE DOSE OF VECURONIUM WITH PANCURONIUM FOR PROLONGED NEUROMUSCULAR BLOCKADE

Dose-duration relationships for vecuronium were determined andthe duration of action produced by vecuronium 0.3 mg kg^–1shown to equal that of pancuronium 0.1 mg kg^–1. Usingthese doses, the neuromuscular blocking properties and cardiovasculareffects of the two drugs were compared. With large dose administrationof vecuronium (0.3 mg kg^–1), both the onset time (mean81 s) and the 25–75% recovery index (mean 13.9 min) wereabout one-half those associated with pancuronium (means 168.5s and 29.3 min, respectively). The duration of action until25% recovery was similar with both drugs. There was no evidenceof cardiovascular instability with the large dose of vecuronium.Heart rate, however, was significantly slower (range 89.7–94.2%of control) 2–20 min after the injection of vecuronium.Vecuronium 0.3 mg kg^–1 may have more favourable neuromuscularblocking effects than pancuronium 0.1 mg kg^–1 and maybe preferable to pancuronium when prolonged neuromuscular blockadeis required.     

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.      

VECURONIUM AND ATRACURIUM IN PATIENTS WITH END-STAGE RENAL FAILURE: A Comparative Study

Twenty patients with end-stage renal failure, undergoing kidneytransplantation, were assigned randomly to receive either vecuroniumor atracurium under evoked twitch tension control. The cumulative-dosetechnique was used to obtain 95% twitch depression (vecuronium:initial bolus 15 µg kg^–1, increments 6 µgkg^–1; atracurium: initial bolus 100 µg kg^–1,increments 40 µg kg^–1). Using ED₉₅ values derivedfrom the log-probit dose-response curves, vecuronium was 4.6times more potent than atracurium. The durations of action ofthe initial cumulativedoses (from end of injection of the lastincrement to 25% recovery) were 11.1± 3.3 min for vecuroniumand 16.2±3.9 min for atracurium (P < 0.05). In termsof duration of action of the maintenance doses (vecuronium one-quarterof the total incremental dose; atracurium one-third) some cumulationwas observed with vecuronium (interaction time x treatment;cumulation ratio 1.46 ±0.31 v. 0.98±0.10 for atracurium,P< 0.001). After 2 h of surgery, the mean recovery times(25% to 75% twitch height) did not differ (18.5±2.8 minand 16.7±4.4 min). It is concluded that vecuronium mightbe less safe than atracurium in patients with end-stage renalfailure undergoing prolonged operations.     

ATRACURIUM AND VECURONIUM: EFFECT OF DOSE ON THE TIME OF ONSET

The time intervals measured from the administrations of eitheratracurium or vecuronium to maximum or 95% neuromuscular blockade(T_max) were compared in 70 patients using the evoked compoundaction potential of the adductor pollicis muscle. Equipotentdoses, calculated from the relationship between dose and responsefor both drugs obtained in an earlier study, were compared.The doses of atracurium and vecuronium ranged from 0.135 to0.5 mg kg^–1 and from 0.02 to 0.1 mg kg^–1, respectively.The dose range for both drugs included the ED₅₀, ED₉₅ and thedose required to produce 100% blockade (ED_"100"). No significantchanges in mean T_max occurred for doses of atracurium in therange 0.135–0.2 mg kg^–1 and in the range 0.24–0.5mg kg^–1. Similarly, no change in T_max occurred at dosesof vecuronium in the range 0.02–0.05 mg kg^–1 and0.06–0.1 mg kg^–1. T_max, changed significantly inthe dose ranges atracurium 0.2–0.24 mg kg^–1 andVecuronium 0.05–0.06 mg kg^–1. There was no significantdifference in T_max when equipotent doses of atracurium and vecuroniumwere compared.     

TIME COURSE OF NEUROMUSCULAR EFFECTS AND PHARMACOKINETICS OF ROCURONIUM BROMIDE (ORG 9426) DURING ISOFLURANE ANAESTHESIA IN PATIENTS WITH AND WITHOUT RENAL FAILURE

We have studied the onset and duration of action and pharmacokineticsof rocuronium bromide (Org 9426) during anaesthesia with nitrousoxide, fentanyl and isoflurane after a single bolus dose ofrocuronium 0.6 mg kg^–1 in nine patients with chronic renalfailure requiring regular haemodialysis, and in nine healthycontrol patients. Blood samples were collected over 390 minand concentrations of rocuronium and its putative metabolitesmeasured using HPL C. Onset time for maximum block, durationof clinical relaxation (T1₂₅) and recovery index, were 61 (SD25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min and28 (12.3) min and 19 (8.8) min, respectively, for patients withand without renal failure. The time for TOF ratio to returnspontaneously to 0.7 was 99 (41.1) min and 73 (24.2) min, respectively,in the two groups. None of these differences was significant.The pharmacokinetic data were best described by a three-exponentialequation. There were significant differences between patientswith and without renal failure in the rates of clearance (2.5(1.1) ml kg^–1 min^–1 and 3.7(1.4) ml kg^–1 min^–1respectively) and the mean residence times (97.1 (48.7) minand 58.3(9.6) min) (P<0.05). The differences in other kineticparameters were not significant. We conclude that the effectsof rocuronium may be prolonged in patients with renal disease,because of a decreased clearance of the drug.     

COMPARISON OF ATRACURIUM AND VECURONIUM DURING ANAESTHESIA FOR LAPAROSCOPY

Atracurium 0.3 mg kg^–1 and vecuronium 0.06 mg kg^–1were compared directly in a double-blind randomized trial duringanaesthesia for laparoscopy in 57 healthy young women. The effectsof the drugs were monitored using a portable electromyograph.Both drugs provided adequate intubating conditions at 3 min,and prompt antagonism of paralysis after administration of neostigmine,but recovery was significantly faster with vecuronium (meantime to 20% recovery of control electromyographic response:vecuronium 15.1 min; atracurium 20.6 min (P < 0.001)). Atracuriumcaused a higher frequency of clinically observed allergoid reactions(21%) compared with vecuronium (3%).     

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.     

NEUROMUSCULAR BLOCKING EFFECTS OF VECURONIUM AND PANCURONIUM DURING HALOTHANE ANAESTHESIA

The neuromuscular blocking properties of vecuronium (Org NC45) and pancuronium were compared in 40 patients during halothaneanaesthesia. Onset time was found to be dose-dependent, butno significant difference was found between the two drugs. Theduration of action of vecuronium was significantly shorter thanpancuronium. Times to 90 recovery of twitch height followingvecuronium 0.03 mg kg^–1 and 0.057 mgkg^–1 were 32.0min and 44.9 min, respectively, compared with 72.9 min and 124.7min following equipotent doses of pancuronium (0.042 mg kg^–1and 0.08 mg kg^–1). Recovery indices following both dosesof vecuronium (10.0 min and 11.8 min) were significantly shorterthan after pancuronium (31.0 min and 46.9 min). The reversaltimes of vecuronium (times from 10 to 90 twitch height recovery)were significantly shorter than those of pancuronium (7.9 minand 7.3 min, respectively, compared with 17.1 min and 17.7 min).     

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)     

PHARMACOKINETICS AND PHARMACODYNAMICS OF VERCURONUIUM IN PATIENTS WITH CHOLESTASIS

pharmacokinetics and pharmacodynamics of vecuronium were studiedin nine surgical patients with cholestasis, and in 14 patientswithout hepatic or renal disease. After the administration ofvecuronium 0.2 mg kg^–1 the plasma concentration of vecuroniumand the degree of neuromuscular blockade were measured. Theplasma clearance of vecuronium was decreased significantly (P< 0.01) from 4.30± 1.56 ml min^–1 kg^–1(mean±SD) in normal patients to 2.36± 0.80 mlmin^–1 kg^–1 in patients with cholestasis. The eliminationhalf-life was of 58±22 min in normal patients and wasprolonged to 98±57 min (P < 0.05) in patients withcholestasis. The total apparent volume of distribution was unchangedin patients with cholestasis. A prolonged neuromuscular blockadeinduced by vecuronium was observed in patients with cholestasis:the duration of effect from injection to 75% recovery of thetwitch height was prolonged from 74 ± 19 min in normalpatients to 111 ± 13 min in patients with cholestasis.The plasma concentration corresponding to 50% recovery fromparalysis did not differ significantly between the two groups.Vecuronium has a prolonged effect in patients with cholestasiswhich is caused by a delay in its elimination.     

ATRACURIUM, VECURONIUM AND PANCURONIUM IN END-STAGE RENAL FAILURE: Dose-Response Properties and Interactions with Azathioprine

Dose-response relations for atracurium, vecuronium and pancuroniumwere determined in patients in end-stage renal failure for theinitial neuromuscuiar blockade (using three cumulative doses)and for the maintenance of stable 90% response (during continousinfusion). All measurements were during renal transplant surgery,and the interaction of azathioprine on neuromuscuiar blockadewas estimated. Mean ED₉₅ doses were (µg kg^–1): atracurim375.6, vecuronium 67.2, pancuronium 86.6; the intial blockaderequired significantly larger doses than in normal patients(37%, 20% and 45%, respectively, using ED₅₀ values). Mean infusionrates for 90% sustained blockade in renal failure were (µgkg^–1h^{– 1}): atracurium 409.4, vecuronium 78.3, pancuronium14.2. The atracurium dose was not influenced by renal function,wheread vecuronium and pancuronium requirements were significantlyreduced by 23.2 % and 61.5%, respectively, compared with normalpatients (Previous study). Azathioprine was injected at therate of 1 mg kg–¹ min–¹ for 3 min at stable 90%neuromuscuiar blockade with constant-rate infusion of the neuromuscuiarblocking drug. This produced a relatively small and transientantagonism of blockadelprobably of negligible clinical significance.     

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.     

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.     

Duration of exposure to sevoflurane affects dose-response relationship of vecuronium

The purpose of this study was to quantify the relationship betweenthe dose–response curve of vecuronium and duration ofexposure to an end-tidal concentration of 1.7% sevoflurane in67% nitrous oxide and oxygen. Forty adult patients, in groupsof 10, were allocated randomly to receive vecuronium by a cumulativedose method at intervals of 15 min (group 15), 30 min (group30), 60 min (group 60) or 90 min (group 90) after starting inhalationof sevoflurane. Neuromuscular function was monitored by acceleromyographictrain-of-four (TOF) responses of the adductor pollicis muscleto ulnar nerve stimulation. Dose–response curves wereconstructed by least-squares regression analysis and the effectivedoses of vecuronium (ED₅₀, ED₉₀ and ED₉₅) were estimated andcompared between groups. Mean (SEM) ED₅₀, ED₉₀ and ED₉₅ were16.8 (0.5), 32.6 (1.7) and 40.9 (2.4) µg kg^–1, respectively,in group 15; 10.6 (1.0), 20.8 (1.7) and 26.2 (2.2) µgkg^–1, respectively, in group 30; 11.2 (1.1), 21.7 (1.6)and 27.3 (1.8) µg kg^–1, respectively, in group 60;and 11.0 (1.1), 21.7 (1.6) and 27.5 (1.9) µg kg^–1,respectively, in group 90. The values obtained in group 15 weresignificantly higher than those in the other three groups (P<0.05).The results indicate that the duration of sevoflurane anaesthesiainfluences the dose–response of vecuronium and 30 mininhalation of 1.7% end-tidal concentration is sufficient toachieve a stable potentiating effect. Br J Anaesth 2000; 85: 732–4 ^* Corresponding author     

REPETITIVE ADMINISTRATION OF PANCURONIUM AND VECURONIUM (Org NC 45, NORCURON) IN PATIENTS UNDERGOING LONG LASTING OPERATIONS

Fifty-one patients undergoing surgical procedures which requiredat least 2 h of anaesthesia were randomly divided into two groupsreceiving either pancuronium or vecuronium (Org NC 45) as amuscle relaxant under evoked twitch tension control. In theabsence of halogenated inhalation anaesthetics, both drugs wereadministered by initial bolus injection of 0.1 mg kg^–1,followed by increments of 0.025 mg kg^–1 when twitch heighthad recovered to 25% of control. In all cases the initial doseproduced total neuromuscular blockade and satisfactory intubationconditions within 2–4min. The time of onset was slightlyshorter with vecuronium than with pancuronium. The mean durationfrom the end of injection to 25% recovery of the initial aridthe maintenance doses was three and four tunes longer with pancuroniumthan with vecuronium, respectively. The average drug requirementper hour to maintain at least 75% block was one maintenancedose of pancuronium 0.025mg kg^–1 and four maintenancedoses of vecuronium 0.1 mg kg^–1. The overall recoverytime (25% to 75% twitch height) irrespective of the number ofmaintenance doses was 40±14min with pancuronium and 15±8minwith vecuronium (mean±SD). Some cumulation was observedwith pancuronium, particularly in terms of prolonged recoverytime. With vecuronium, both duration of action of maintenancedoses and recovery time did not depend on the number of maintenancedoses. In both groups of patients no cardiovascular or otherside-effects were observed. It is concluded that vecuroniumis a true intermediate-acting non-depolanzing muscle relaxant.Its lack of cumulation favours the maintenance of profound neuromuscularblockade until close to the end of operation without the riskof an unduly long recovery time.     

COMPARISON OF CUMULATIVE AND SINGLE BOLUS DOSE TECHNIQUES FOR DETERMINING THE POTENCY OF VECURONIUM

The potency of vecuronium was determined using single bolusdose administrations of 10–50 µg kg^–1in 28patients anaesthetized with thiopentone, nitrous oxide, oxygenand fentanyl. The results were compared with those previouslyobtained using a cumulative dose technique in a comparable groupof 10 patients. The 50% and 95% blocking doses (ED₅₀and ED₉₅)of vecuronium were found to be 23.1 and 39.6 µg kg^–1,respectively. These were significantly lower than the 30.5 and56.7µg kg^–1 obtained previously using the cumulativedose technique. We recommend the use of single bolus dose methodof determining potency for relatively shorter-acting drugs likevecuronium.     

EFFECT OF H2-RECEPTOR ANTAGONIST PRETREATMENT ON VECURONIUM- AND ATRACURIUM-INDUCED NEUROMUSCULAR BLOCK

Seventy-two patients were studied in a double-blind randomizedcontrolled design to assess the effects of oral administrationof cimetidine 400 mg, ranitidine 150 mg or placebo 90 min beforeanaesthesia on the neuromuscular blocking effects of atracurium0.45 mg kg^–1 or vecuronium 0.08 mg kg^–1. The timesto reappearance of T1 (first response in the train-of-four stimulation)and its recovery to 25% of control were 22.5 (SD) 5.2 and 30(7.1) min, 30 (10) and 43 (15.4) min, and 25.8 (4.1) and 34(6.2) min, respectively in the vecuronium groups pretreatedwith placebo, cimetidine and ranitidine, the times followingcimetidine pretreatment being prolonged significantly (P <0.05). The respective recovery indices (times for 25–75%recovery of T1) in these three groups were 11.0 (3.5), 17.4(6.8) and 13.0 (3.9) min. There were no significant differencesin any of the variables following ranitidine pretreatment andeither neuromuscular blocker or following cimetidine pretreatmentand atracurium.