Monitoring of neuromuscular transmission by electromyography (II)

The feasibility of the compound electromyogram (EMG) was evaluated during onset and recovery from pancuronium block in the tibialis anterior muscle of ten cats. The evoked EMG area, amplitude and duration of the total response and of the major negative deflection were evaluated and compared to the mechanomyogram during 0.1 Hz and train-of-four (TOF) stimulation. EMG areas and amplitudes were found to be linearly and similarly related to the mechanomyogram during onset and recovery. Slopes of the regression lines ranged between 1.00–1.02 and between 1.10–1.22 during onset and recovery, respectively, with high individual correlation coefficients (>0.95). The TOF ratio of the mechanomyogram was linearly related to the EMG TOF ratio during onset and to the square root of the EMG TOF ratio during recovery, with no differences between EMG areas and amplitudes, suggesting a higher initial recovery of the TOF ratio of the mechanomyogram during recovery. EMG duration increased as the level of block increased but was unsuitable for neuromuscular monitoring. Evaluation of the agreement between the two methods showed that the EMG may be from 15% below to 10% above the mechanomyogram during onset and from 40% below to 45% above the mechanomyogram during recovery, in spite of high correlation coefficients. In contrast, agreement between EMG parameters was found to be high. In conclusion, EMG is more reliable than the mechanomyogram for evaluation of neuromuscular transmission in the cat. EMG amplitudes and areas both reflect the degree of neuromuscular blockade equally well     

Die Wirkung des Alters auf Anschlagszeit und Erholung nach Atracurium,Rocuronium und Vecuronium

Elderly patients may show an age-related decline in physiologic functions, which may be responsible for the prolonged duration of some neuromuscular blocking agents. Previous studies have yielded conflicting results as to the effects of these drugs in the elderly. Methods. After obtaining informed consent and approval of the Ethics Committee, we compared onset and recovery times of single IV doses of atracurium, rocuronium, and vecuronium given to 108 patients divided into three groups according to age (18–50, 51–64, ≥65 years). Following oxazepam premedication and fentanyl and thiopentone induction, patients were randomly allocated to receive atracurium, rocuronium or vecuronium (0.5, 0.6, or 0.1?mg/kg, respectively) in ≤0.8?vol.% enflurane (end-tidal)-nitrous oxide anaesthesia. Muscular relaxation was assessed by electromyographic (EMG) recording of the adductor pollicis muscle after supramaximal single-twitch stimulation of the ulnar nerve every 10?s. Onset time and recovery to 25%, 75% and 90% of twitch control values (DUR25, 75, 90) were recorded. Creatinine clearance predicted from serum creatinine (C_cr) was correlated with recovery from neuromuscular block. Results. Onset time was not different among groups or relaxants. The results showed a prolonged duration of action for atracurium (DUR75, DUR90), rocuronium (DUR25, DUR75), and vecuronium (DUR25) in the elderly. A number of patients did not reach DUR75 or DUR90. There was a significant relationship between age and failure to return to control values during recovery from neuromuscular block, especially after atracurium and rocuronium. C_cr showed a negative correlation with age for all relaxants, but a negative significant correlation between C_cr and recovery was found only for rocuronium. Conclusions. This study suggests that onset time for atracurium, rocuronium and vecuronium is not age-dependent. Recovery was prolonged in the elderly for all three relaxants. This effect appears to be secondary to changes in body composition and function accompanying the aging process. Neither atracurium nor vecuronium depends significantly on the kidney for elimination, but the negative correlation between C_cr and rocuronium suggests an appreciable role for the kidney in the elimination of this relaxant. The long recovery times observed in this study could also be related to enflurane anaesthesia. We suggest that failure of EMG responses to return to baseline values during recovery from neuromuscular block may be related to age, especially for atracurium and rocuronium.     

Rocuronium in infants, children and adults during balanced anaesthesia

We studied 20 infants, 20 children and 20 adults during balanced anaesthesia to compare the neuromuscular blocking effects of rocuronium in these age groups. Neuromuscular function was recorded by adductor pollicis emg and a cumulative log-probit dose-response curve of rocuronium was established. Thereafter, full spontaneous recovery of the neuromuscular function was recorded. Onset time of the first dose of rocuronium was shorter in children than in infants or adults. The potency of rocuronium was greatest in infants and least in children; the ED₅₀ doses (mean ± SD) being 149 ± 36 μg˙kg^?1 in infants, 205 ± 52 μg˙kg^?1 in children and 169 ± 47 μg˙kg^?1 in adults (P<0.05 between infants and children) and the ED₉₅ doses being 251 ± 73 μg˙kg^?1, 409 ± 71 μg˙kg^?1 and 350 ± 77 μg˙kg^?1, respectively (P<0.05 between all groups). The emg recovery following an average 94.5 ± 4.8% neuromuscular blockade established by rocuronium was roughly similar in all study groups. Thus, one ED₉₅ dose of rocuronium, unlike vecuronium, acts as an intermediate-acting agent in all age groups.     

Differential effect of pancuronium at the adductor pollicis, the first dorsal interosseous and the hypothenar muscles. An electromyographic and mechanomyographic dose-response study

Cumulative dose-response curves were constructed from evoked compound electromyographic (EMG) recordings in man to compare the sensitivity to pancuronium of the adductor pollicis, the hypothenar and the first dorsal interosseous muscles. Also, the EMG and mechanomyography-based sensitivity of the adductor pollicis muscle were compared. The EMG and the mechanomyogram were evaluated in random sequence in each of 21 adult thiopental, fentanyl and diazepam anesthetized patients. The EMG-based ED50 were 36-38 micrograms.kg-1 with no differences between muscles. The EMG-based ED90 of the adductor pollicis and the hypothenar muscles were 62-65 micrograms.kg-1 compared to the 60 micrograms.kg-1 of the first dorsal interosseous muscle (P < 0.05). ED50 (34 micrograms.kg-1), and ED90 (56 micrograms.kg-1) obtained from the adductor pollicis mechanomyogram were significantly lower than those based on the EMG (P < 0.05). It is concluded that differences in sensitivity to pancuronium exist between the three muscles when evaluated from the EMG, and that the apparent sensitivity of a given muscle to a muscle relaxant may depend upon whether the response is evaluated using EMG or mechanomyography.     

ONSET AND RECOVERY OF ROCURONIUM (ORG 9426) AND VECURONIUM UNDER ENFLURANE ANAESTHESIA

We have studied the onset, duration of action and recovery indexof twice the ED₉₀ of rocuronium (Org 9426) (0.6 mg kg^–1)and of vecuronium (0.08 mg kg^–1) in patients during enf/uraneanaesthesia. Rocuronium had a significantly shorter mean onsettime of 1.8 (SD 0.4) min, compared with vecuronium 3.4 (0.8)min. Clinical duration (time for the first twitch in the train-of-fourto recover to 25% of control) was similar for both drugs (29(10) min vs 31 (12) min). Spontaneous recovery times (TOF ratio70%) did not differ significantly between rocuronium (47 (10)min) and vecuronium (44 (11) min). (Br. J. Anaesth. 1992;69:511–512)     

Nondepolarizing neuromuscular blocking drugs and train-of-four fade

The aim of this study was to examine differences in prejunctional effects of different relaxants by measuring the train-offour (TOF) fade during the onset and recovery of neuromuscular block. The relaxants studied were atracurium (225 μg · kg^?1), mivacurium (65 μg · kg^?1) rocuronium (300 μg · kg^?1)) and vecuronium (40 μg · kg^?1)). The TOF ratios were measured at approximate heights of T₁) (first response in the TOF) of 90, 75, 50, and 25%. The TOF fade (as shown by lower TOF ratios) increased with a decrease in the T₁) during onset of neuromuscular block. Although there was a slightly greater fade with atracurium and rocuronium during the onset of block, the differences among the relaxants were insignificant. It is concluded that the relative prejunctional effects of these relaxants are similar.     

Residual paralysis induced by either vecuronium or rocuronium after reversal with pyridostigmine

We investigated postoperative residual curarization after administration of either vecuronium or rocuronium with reversal by pyridostigmine in 602 consecutive patients without perioperative neuromuscular monitoring. On arrival in the recovery room, neuromuscular function was assessed both by acceleromyography in a train-of-four (TOF) pattern and also clinically by the ability to sustain a head-lift for >5 s and the tongue-depressor test. Postoperative residual curarization was defined as a TOF ratio <0.7. One fifth of 602 patients (vecuronium, 24.7%; rocuronium, 14.7%) had a TOF <0.7 in the recovery room. There were no significant differences in the TOF ratios between 10 mg and 20 mg of pyridostigmine. The patients with residual block had several associated factors: the absence of perioperative neuromuscular monitoring, the use of pyridostigmine, which is less potent than neostigmine, a larger dose of vecuronium, shorter time from the last neuromuscular blocker to TOF monitoring, or peripheral cooling. We conclude that significant residual neuromuscular block after vecuronium or rocuronium was not eliminated even with reversal by a large dose of pyridostigmine. IMPLICATIONS: Without monitoring, the significant residual neuromuscular block after vecuronium or rocuronium is not eliminated even by reversal with a large dose of pyridostigmine and can still be a problem in the recovery room.     

Neuromuscular effects of 600 μg·kg−1 of rocuronium in infants during nitrous oxide-halothane anaesthesia

Rocuronium bromide (Zemuron) is a new steroidal nondepolarizing neuromuscular blocking drug. We were interested in determining the effect of a bolus of rocuronium in infants during halothane anaesthesia as we did previously in older children. Eighteen infants (2-11 months) received a bolus of 600 μg·kg^?1, which is equal to twice the dose of rocuronium estimated to produce 95% depression of neuromuscular function (ED₉₅) in children (2-12 yr). Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Time (mean ± SEM, range) from administration of 600 μg·kg^?1 rocuronium to 90% (B₉₀) and 100% (B₁₀₀) neuromuscular block was 37 ± 2 (20-60) s and 64 ± 10 (20-180) s, respectively. The time to recovery of neuromuscular transmission to 10% (T₁₀) was 35.3 ± 3.0 (20.7-57.8) min and to 25% of baseline (T₂₅) was 41.9 ± 3.2 (24.3-67.7) min. The recovery index (T₂₅-T₇₅) was 26.6 ± 2.7 (11.7-44.5) min, and the time to recovery of the train-of-four ratio (T₄/T₁) ± 0.75 was 82.1 ± 6.9 (53.2-138.3) min. The plasma concentration of rocuronium when T₁ had recovered to about 30% was 654 ± 34 (417-852) ng·ml^?1 which is similar to that observed in children. Six-hundred μg·kg^?1 of rocuronium has a rapid onset of effect in infants and prolonged duration of action in infants compared to children.     

Interaction between rosuvastatin and rocuronium in rat sciatic-gastrocnemius nerve-muscle preparation

Purpose

Long-term use of rosuvastatin may be associated with myotoxicity. Statins are one of the groups commonly found to be associated with neuromuscular weakness. The present study was designed to investigate the interaction between rosuvastatin and rocuronium in vivo by using a sciatic-gastrocnemius nerve-muscle preparation of rat.

Methods

In our study groups, animals received rosuvastatin 2 mg/kg for 14 and 28 days. Train of four (TOF) stimulation was applied to the sciatic nerve, and gastrocnemius muscle contractions were recorded in Wistar albino rats. Intravenous infusion of rocuronium was given until the twitch responses were abolished. We ultimately compared the effective dose required for a desired effect in 95% of the population (ED₉₅), duration 25 %, deep block, recovery index, and time for returning of TOF ratio to 0.9 between the active control and study groups.

Results

Chronic administration of rosuvastatin at a dose of 2 mg/kg for 28 days significantly reduced the ED₉₅ of rocuronium as compared to the active control group. Deep block and duration 25 % were increased by 3.5 and 2.5 times, respectively, compared to the active control group. The spontaneous recovery of neuromuscular block was delayed, as evidenced by the prolonged recovery index and increase in time required for a return of the TOF ratio to 0.9.

Conclusion

The neuromuscular blocking potency of rocuronium is increased and recovery is delayed in rats that pre-treated with rosuvastatin.     

TOF count at corrugator supercilii reflects abdominal muscles relaxation better than at adductor pollicis

Background: A recovery profile from neuromuscular block similar to thatof abdominal (AB) muscles, but different to that of the adductorpollicis (AP) muscle, has been demonstrated at the corrugatorsupercilii (CSC) muscle. We hypothesized that neuromusculartransmission (NMT) monitoring of CSC might provide useful informationon AB relaxation compared with AP. We compared the visual estimationof NMT at CSC and AP with electromyographic measurements ofAB during recovery from a vecuronium block. Methods: Ten adult patients were studied during balanced anaesthesia.After induction of anaesthesia and tracheal intubation withoutneuromuscular blocking agents, supramaximal stimulations wereapplied to three nerves: left 10th intercostal, ulnar, and facial.Electromyographic activity (EMG) of AB was measured (ABEMG).After a bolus dose of vecuronium 0.1 mg kg^–1, an independentobserver blinded to the EMG measurements counted visually detectabletrain-of-four (TOF) responses at CSC and AP. Values of ABEMGassociated with 1 to 4 TOF responses at CSC and AP were compared.Values are means (SD). Results: Reappearance of the first and second TOF responses at CSC occurredsignificantly (P < 0.05) earlier and at lower ABEMG recoverythan that of AP [35 (8) and 41 (9) min vs 51 (10) and 56 (12)min; and 17 (8) and 26 (9)% vs 56 (10) and 75 (11)%, respectively]. Conclusions: We demonstrated that the TOF response count at the CSC, comparedwith the AP, allowed a better quantification of the degree ofAB muscle relaxation during recovery from vecuronium block.     

Effects of vecuronium and rocuronium in antagonistic laryngeal muscles and the anterior tibial muscle in the cat

BACKGROUND: Adequate vocal cord paralysis and full recovery of laryngeal muscle function are important when muscle relaxants are used perioperatively. This study was designed to compare the effects of vecuronium and rocuronium at the vocal cord abductor and adductor muscles and the anterior tibial muscle in cats. METHODS: Twelve adult cats were studied under pentobarbitone-N2O/O2-anesthesia. After supramaximal electrical stimulation of the peroneal nerve and the recurrent laryngeal nerve (0.1 Hz and intermittent train-of-four) evoked electromyographic responses were obtained from the anterior tibial muscle, the posterior cricoarytenoid muscle (vocal cord abductor) and two vocal cord adductor muscles, the lateral cricoarytenoid and the vocal muscle. Six cats received bolus doses of increasing size of vecuronium (ED90 22.5 microg x kg(-1)) and six cats rocuronium (ED90 90 microg x kg(-1)). RESULTS: Equipotent doses of vecuronium and rocuronium caused a similar degree of paralysis in all muscles (vecuronium ED90: 70% blockade at the posterior cricoarytenoid, 83% at the lateral cricoarytenoid, 84% at the vocal muscle and 90% at the anterior tibial muscle; rocuronium ED90: 71% at the posterior cricoarytenoid, 67% at the lateral cricoarytenoid, 78% at the vocal muscle and 90% at the anterior tibial muscle; vecuronium 2 x ED90: 93% blockade at the posterior cricoarytenoid, 95% at the lateral cricoarytenoid, 97% at the vocal muscle and 99% at the anterior tibial muscle; rocuronium 2 x ED90: 89% blockade at the posterior and lateral cricoarytenoid, 93% at the vocal muscle and 100% at the anterior tibial muscle). Onset time was significantly shorter at the posterior cricoarytenoid muscle (290 s) compared to the lateral cricoarytenoid muscle (400 s) after vecuronium ED90 and to the vocal muscle (150 s versus 210 s) after rocuronium ED90. Compared to the anterior tibial muscle (interval 25-75%: 6.5 min after vecuronium 2 x ED90 and 3.3 min after rocuronium 2 x ED90 and to the posterior cricoarytenoid muscle (interval 25-75%: 7 min after vecuronium 2 x ED90 and 4.3 min after rocuronium 2 x ED90), recovery of laryngeal adductor muscle function was markedly delayed with both neuromuscular blocking drugs (interval 25-75% at the lateral cricoarytenoid and vocal muscle: 14 min and 15.8 min after vecuronium 2 x ED90 and 10.3 min and 11.6 min after rocuronium 2 x ED90 respectively). CONCLUSION: In cats, the time course of neuromuscular blockade after vecuronium and rocuronium differs in antagonistic laryngeal muscles. The protective laryngeal function of glottis closure recovers later than vocal cord abduction after both vecuronium and rocuronium.     

Comparison of neuromuscular effects, efficacy and safety of rocuronium and atracurium in ambulatory anaesthesia

Purpose

To compare the neuromuscular effects, efficacy, and safety of equi-effective doses of rocuronium and atracurium in ambulatory female patients undergoing surgery.

Methods

Forty-one patients undergoing laparoscopic gynaecological surgery were randomized to receive 2 × ED₉₀ rocuronium (0.6 mg·kg^?1; n = 20) or atracurium (0.5 mg·kg^?1; n = 21) during intravenous propofol/alfentanil anaesthesia with N₂O/O₂ ventilation. Neuromuscular block was measured with a mechanomyogram eliciting a train-of-four (TOF) response at the wrist. Intubation conditions 60 sec after administration of muscle relaxant and immediate cardiovascular disturbances or adverse events during the hospital stay were noted by blinded observers.

Results

Compared with atracurium, rocuronium was associated with a shorter onset time (59.0 ± 22.2vs 98.6 ± 41.4 sec;P < 0.001) and clinical duration of action (33.3 ± 7.1vs 44.7 ± 7.2 min;P < 0.001), but longer spontaneous recovery index (9.6 ± 2.41vs 6.9 ± 1.89 min;P = 0.023) and a similar time to spontaneous recovery to TOF 70%; 53 ± 6.31vs 59.2 ± 7.59 min;P =0.139). Tracheal intubation was accomplished in < 90 sec in all patients receiving rocuronium but in only 14 of 21 patients receiving atracurium. The incidence of adverse events and the cardiovascular profiles for the two drugs were similar, although one patient receiving atracurium experienced transient flushing of the head and neck.

Conclusion

Rocuronium has minimal side effects, provides conditions more suitable for rapid tracheal intubation, and is associated with a shorter clinical duration than atracurium. Once begun, the spontaneous recovery profile of rocuronium is slightly slower than that of atracurium.     

Smoking increases the requirement for rocuronium

Purpose

To compare the potency of rocuronium in non-smokers and smokers during general anaesthesia.

Methods

In a randomized, open clinical study, 40 patients, 17–62 yr of age, were anaesthetized with propofol, alfentanil and nitrous oxide in oxygen. After obtaining individual dose-response curves for rocuronium, bolus doses of rocuronium were given to maintain neuromuscular block at 90–99% for 60 min. Evoked adductor pollicis electromyography (EMG) was used to monitor neuromuscular block.

Results

The ED₉₅ values (± SEM) for rocuronium were 460.5 ± 28.9 and 471.5 ± 22.1 μg·kg^?1 for nonsmokers and smokers, respectively (P:NS). However, doses of rocuronium to maintain 90–99% neuromuscular block (± SEM) were 620.1 ± 46.7 and 747.4 ± 56.0 μg·kg^?1·hr^?1 for non-smokers and smokers, respectively (P = 0.0504).

Conclusion

The results may indicate increased metabolism of rocuronium in smokers rather than increased requirement of rocuronium at the receptor site.     

Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children.

We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Implications: These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.     

Pharmacodynamic behaviour of rocuronium in the elderly

This study compared the potency and time course of action of rocuronium (ORG 9426) in elderly and young patients during nitrous oxide-opioid anaesthesia. One hundred ASA physical status I– II patients (60, âgéd 65–80 yr, and 40, âgéd 20–45 yr) were studied by measuring the force of contraction of the adductor pollicis in response to train-of-four stimulation of the ulnar nerve. After induction of anaesthesia with thiopentone and maintenance with N₂O/O₂ and fentanyl, rocuronium 120,160, 200, or 240 μg · kg ^?1 was administered to determine dose-response curves. When maximum block had been obtained,further rocuronium to a total of 300 μg · kg ^?1 was given. Additional doses of 100 μg · kg^?1 were administered when the first twitch height (T₁) had recovered to 25% control. At the end of surgery neuromuscular blockade was allowed, whenever possible, to recover spontaneously until T₁ was 90% of control before administration of neostigmine. There was no difference in the potency of rocuronium in the elderly and the younger patients. The ED₅₀ was 196 ±8 (SEE for the mean) in elderly,vs 215 ±17 iμg · kg ^{? 1} in young patients (NS). When individual cumulative dose-response curves were constructed, the ED₅₀ was 203 ± 7(SEM) and 201 ± 10 μg · kg ^{? 1} in the elderly and the young respectively (NS). However, the onset of maximum neuromuscular block was slower in the elderly 3.7 ±1.1 (SD) vs 3.1 ± 0.9 min, P < 0.05). The time to 25% T ₁ recovery was longer in the elderly (11.8 ± 8.1 vs 8.0 ± 6.5 min,P <0.05) as was the recovery index, time from 25 to 75% T₁ recovery (15.5 ± 6.2 vs 11.2 ± 4.9 min, P< 0.05). The duration of neuromuscular block after each maintenance dose was longer in the elderly (P <0.01) and increased gradually with time. It is concluded that rocuronium is an intermediate-acting neuromuscular blocking drug with a similar potency in elderly and young patients, but the onset and recovery of neuromuscular blockade are slower in the elderly.     

Acceleromyography and mechanomyography for establishing potency of neuromuscular blocking agents: a randomized-controlled trial

Background: Acceleromyography (AMG) is increasingly being used in neuromuscular research, including in studies establishing the potency of neuromuscular blocking and reversal agents. However, AMG is insufficiently validated for use interchangeably with the gold standard, mechanomyography (MMG) for this purpose. The aim of this study was to compare AMG and MMG for establishing dose–response relationship and potency, using rocuronium as an example. Methods: We included 40 adult patients in this randomized‐controlled single‐dose response study. Anaesthesia was induced and maintained with propofol and opioid. Neuromuscular blockade was induced with rocuronium 100, 150, 200 or 250 μg/kg. Neuromuscular monitoring was performed with AMG (TOF‐Watch^® SX) with pre‐load (Hand Adapter) at one arm and MMG (modified TOF‐Watch^® SX) on the other, using 0.1 Hz single twitch stimulation. Dose–response relationships were determined for both recording methods using log (dose) against probit (maximum block). The obtained slopes of the regression lines, ED₅₀, ED₉₅ and the maximum block were compared. Results: The ED₅₀ and ED₉₅ [95% confidence interval (CI)] for AMG were 185 μg/kg (167–205 μg/kg) and 368 μg/kg (288–470 μg/kg), compared with 174 μg/kg (159–191 μg/kg) and 338 μg/kg (273–418 μg/kg) for MMG. There were no statistically significant biases in maximum block, ED₅₀, ED₉₅ or slopes obtained with the two methods. Conclusion: Our results indicate that any possible difference between AMG and MMG is so small that it justifies AMG to be used for establishing the potency of neuromuscular blocking agents. However, the wide CIs show that we cannot rule out a 13% higher ED₅₀ and a 26% higher ED₉₅ for AMG.     

Neuromuscular effects of rocuronium in children during halothane anaesthesia

Rocuronium bromide, a nondepolarizing muscle relaxant has been shown to have a short onset and intermediate duration of action in adults and young children. We evaluated onset time, intubating conditions, as well as duration of action of rocuronium in children ages four to 12 years during nitrous oxide-halothane anaesthesia. Following a stable recording of train-of-four (TOF) impulses at the ulnar nerve, patients were given rocuronium 600 μg˙kg^?1 intravenously. We found that the time to 90% and 100% neuromuscular (N-M) block of the (TOF) was 51 ± 18 s and 66 ± 32 s respectively. Intubation was achieved at 94 ± 31 s and rated as good or excellent in all cases. Time to recovery of N-M transmission to 25%, 75% and 90% of control was 29 ± 8 min, 42 ± 14 min and 46 ± 16 min respectively. Heart rate increased ～12 BPM after drug injection, while the blood pressure remained unchanged. From our data we conclude that, as in other age groups, rocuronium has a rapid onset, intermediate duration of action in children 4–12 years of age, and appears devoid of significant side effects.     

Beeinflussung der Pharmakodynamik von Rocuronium durch Cimetidin

Cimetidine is a commonly used H₂-receptor antagonist that has been recommended for the prevention of acid aspiration syndrome and has been shown to potentiate vecuronium-induced neuromuscular block. The present study was designed to investigate the influence of a single IV dose of cimetidine on the neuromuscular effects of rocuronium, an analogue of vecuronium with a short onset time. Methods. Twenty adults aged 18–65 years were included in the study with their informed consent and approval of the Ethics Committee. Following oxazepam premedication, 10 patients were randomly allocated to receive cimetidine 400 mg IV 30 min before anaesthesia. After fentanyl and thiopentone induction, single-twitch stimulation of the ulnar nerve was performed every 10 s. Following stabilisation of control responses, patients received rocuronium 0.6 mg/kg for intubation. Anaesthesia was maintained with enflurane ≤0.8 vol.% (end-tidal) and 65% nitrous oxide. Onset time and recovery times to 25% and 75% of the twitch control values were recorded. Results. Onset and recovery times did not differ between groups. Conclusions. The results of the present study demonstrate that cimetidine does not increase the duration of rocuronium neuromuscular blockade. Inhibition of the cytochrome P450 system or a direct effect at the neuromuscular junction have been suggested as the mechanisms of drug interaction associated with cimetidine. Impairment of hepatic microsomal drug metabolism results in a prolonged duration of action of vecuronium, which appears to be eliminated primarily via the liver. Data on the elimination pathway of rocuronium in humans are not available. The fact that cimetidine does not alter the recovery from rocuronium-induced neuromuscular block confirms a previous suggestion that rocuronium may not be eliminated principally by the liver. A direct effect of cimetidine on the neuromuscular junction could not be confirmed by this study. Therefore, cimetidine can be given as premedication without a risk of prolonged rocuronium block.     

Postoperative residual block after intermediate-acting neuromuscular blocking drugs

The frequency and duration of postoperative residual neuromuscular block on arrival of 150 patients in the recovery ward following the use of vecuronium (n = 50), atracurium (n = 50) and rocuronium (n = 50) were recorded. Residual block was defined as a train-of-four ratio of <0.8. An additional group of 10 patients received no neuromuscular blocking drugs during anaesthesia. The incidence of postoperative residual neuromuscular block was 64%, 52% and 39% after the use of vecuronium, atracurium and rocuronium, respectively. Similar numbers of patients were not able to maintain a sustained head or leg lift for 5 s on arrival in the recovery ward. The mean [range] times to attaining a train-of-four ratio of > or =0.8 after arrival in the recovery ward were 9.2 [1-61], 6.9 [1-24] and 14.7 [1.5-83] min for vecuronium, atracurium and rocuronium, respectively. None of the 10 patients who did not receive neuromuscular blocking drugs had train-of-four ratios <0.8 on arrival in the recovery ward. It is concluded that a large proportion of patients arrive in the recovery ward with a train-of-four ratio <0.8, even with the use of intermediate-acting neuromuscular blocking drugs. Although the residual block is relatively short lasting, it may occasionally be prolonged, requiring close observation and monitoring of such patients in the recovery ward.     

The Pharmacodynamics of Vecuronium in Chronic Renal Failure Patients: The Impact of Different Priming Doses

Purpose: The concept of priming was introduced to facilitate a faster onset of nondepolarizing neuromuscular blocker for endotracheal intubation. Vecuronium is still very much in use for most chronic renal failure patients posted for renal transplantation. The aim of this study was to examine the pharmacodynamics of vecuronium without and with preceding different small doses. Methods: One hundred chronic renal failure patients were assigned into four groups according to the used vecuronium priming regimen. The first control group (V₀-group), where no priming dose was given. The other three priming groups (V₁₀- , V₁₅- , and V₂₀-groups), where 10%, 15%, and 20% of ED₉₅ of vecuronium were administrated 5 min prior to the remaining intubating dose (2 × ED₉₅) of vecuronium. Neuromuscular blockade was measured via acceleromyographic response of the ulnar nerve. Train-of-four (TOF) ratio was measured every minute during priming interval. Any unpleasant symptoms during precurarization were recorded. Lag time and onset time (from injection of intubating dose) were recorded. Endotracheal intubation condition was scored blindly. The duration and recovery times were also recorded. Results: The significant higher incidence of symptoms of paresis was encountered in V₂₀-group in comparison with other two priming groups. TOF ratio started to decrease significantly at the first minute in V₂₀-group, at the second minute in V₁₅-group, and at the third minute in V₁₀-group, till the fourth minute in the priming interval. Although TOF ratio was still above 0.90 in V₁₀-group, it was below 0.80 in V₂₀-group. Priming groups did not show significant intergroup difference in onset time. However, duration and recovery times were significantly longer in priming groups in comparison with V₀-group without priming. Conclusion: Priming the chronic renal failure patients with 10% of ED₉₅ vecuronium dose acquit the best pharmacodynamics with the fewest signs of muscle weakness. Larger vecuronium priming doses are unfavorable and convey no more clinical utility.