Neuromuscular blocking effects of rocuronium during desflurane, isoflurane, and sevoflurane anaesthesia

Purpose

To determine the magnitude of the potentiation of rocuronium by desflurane, isoflurane and sevoflurane 1.5 MAC anaesthesia.

Methods

In a prospective, randomised, study in 80 patients, the cumulative dose-effect curves for rocuronium were determined during anaesthesia with desflurane, sevoflurane and isoflurane (with N₂O 70%, 15 min steady state) or total intravenous anaesthesia (TIVA) using propofol/fentanyl. Neuromuscular block was assessed by acceleromyography (TOF-Guard®) after train-of-four (TOF) stimulation of the ulnar nerve (2Hz every 12sec, 200 μsec duration), Rocuronium was administered in increments of 100 μg·kg^?1 until first twitch (T₁) depression > 95%.

Results

Rocuronium led to more pronounced T₁ depression with desflurane or sevoflurane anaesthesia than with TIVA. The ED₅₀ and ED₉₅ were lower during desflurane (95 ± 25 and 190 ± 80 μg·kg^?1) and sevoflurane (120 ±30 and 210 ± 40 μg·kg^?1) than with TIVA (150 ± 40 and 310 ± 90 μg·kg^?1) (P < .01), while the difference was not significant for isoflurane (130 ± 40 and 250 ± 90 μg·kg^?1). Following equi-effective dosing (T₁ > 95%) the duration to 25% T₁ recovery, recovery index (25/75), and TOF_0.70 was: 13.2 ± 1.8, 12.7 ± 3.4, and 26.9 ± 5.7 min during anaesthesia with desflurane; 15.5 ± 5.0, 11.4 ± 3.8, and 31.0 ± 6.0 min with sevoflurane; 13.9 ± 4.7, 10.7 ± 3.3, and 26.3 ± 8.9 min with isoflurane; and 13.9 ± 3.9, 11.3 ± 5.7, and 27.5 ± 8,2 min with TIVA anaesthesia (P: NS).

Conclusion

Interaction of rocuronium and volatile anaesthetics resulted in augmentation of the intensity of neuromuscular block but did not result in significant effects on duration of or recovery from the block.     

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.     

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.     

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.     

Reduced-dose rocuronium for day-case tonsillectomy in children where volatile anaesthetics are not used: operating room time saving

Objectives: Mivacurium, rocuronium, and vecuronium are neuromuscular blocking agents (NMB) commonly used in pediatric day‐case anesthesia. Mivacurium is the most appropriate NMB for short surgical procedures where NMB drugs were required but is not available in all countries. Aim: We evaluated the operating room time minimization after reduced‐dose rocuronium (0.45 mg·kg^?1) during elective day‐case tonsillectomy in children. Methods/Materials: One hundred and five children (6–9 years, ASA I/II status) scheduled for day‐case tonsillectomy were included in prospective, double blind clinical study. Children were randomly divided in three equal groups. All children were premedicated (midazolam 0.25 mg·kg^?1 orally, EMLA). Anesthesia was induced (2.5 mg·kg^?1) and maintained (0.1 mg·kg^?1·min^?2) by propofol and alfentanil (0.0015 mg·kg^?1·min^?1) and supplemented by inhalation mixture of 50% of O2/Air. Neuromuscular block was achieved by vecuronium (0.1 mg·kg^?1) (V) or rocuronium in standard (0.6 mg·kg^?1) (R) or reduced dose (0.45 mg·kg^?1) (LD). Neuromuscular transmission was monitored by acceleromyography. Time analysis of NMB drugs action was performed. Results: Time difference from the end of tonsillectomy to T90 neuromuscular block recovery was significantly shorter in LD Group (7.3 ± 0.41 min), (V = 15.9 ± 1.06, R = 16.0 ± 1.7 min) (P = 0.0011). The onset time of neuromuscular block was prolonged in LD Group (LD=3.1 ± 0.4, R = 1.3 ± 0.4, V = 2.2 ± 0.2 min) (P = 0.0039) without changing the intubating conditions. The maximum operation room time saving per each tonsillectomy was 37% in LD Group (Group V 21%, Group R 17%) (P = 0.0001). Low incidence of postoperative nausea and vomiting (PONV) 3–6% (0.4577) and good visual analog scale (VAS) score (≤2) (0.5969) were found in all study groups 12 h after surgery. Conclusions: Reduced‐dose rocuronium in addition with propofol and alfentanil in children where volatile anesthetics are not used effectively saves the operating room time during short elective surgical procedures, avoids delays in patient recovery, allows high level of acceptable intubating conditions, and improves the optimal surgical work. Low incidences of PONV as VAS score may achieved successfully.     

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.     

Dose-response relationships for edrophonium antagonism of mivacurium-induced neuromuscular block during N2O-enflurane-alfentanil anaesthesia

The purpose of this study was to determine the dose-response relationships for edrophonium antagonism of mivacuriuminduced neuromuscular block. Seventy-five ASA I or II adults were given mivacurium 0.15 mg · kg^{? 1} followed by an infusion (7 μg · kg^{? 1} · min^{? 1}) during alfentanil-propofol-N₂O-enflurane anaesthesia. Train-of-four stimulation (TOF) was applied to the ulnar nerve every 20 sec and the response of the adductor pollicis was recorded (Relaxograph NMT-100. Datex, Helsinki, Finland). Mivacurium infusion was modified at five-minute intervals in order to keep the height of the first twitch in TOF (T₁) at 5% of its control value. At the end of surgery, edrophonium (0.0. 0.125, 0.25, 0.5. or 1.0 mg · kg^{? 1}) combined with glycopyrrolate (0.0, 0.0012, 0.0025, 0.005, or 0.01 mg · kg^{? 1}) were administered by random allocation. Edrophonium doses of 0.25, 0.5 and 1.0 mg · kg^{? 1} were different from placebo with regard to time to attain a TOF ratio (fourth twitch in TOF/ T,) = 0.7 (13.8 ± 4.5, 11.1 ± 3.5, 11.4 ± 3.0 vs 19.7 ± 4.7 min P < 0.05). Doses of 0.5 and 1.0 mg · kg^{? 1} permitted faster recovery time of T₁ from 10 to 95% (T_{10– 95}) than did placebo (7.5 ± 3.8,8.9 ± 3.5 vs 14.5 ± 5.0 min P < 0.05). Edrophonium 0.5 mg · kg^{? 1} was different from placebo with regard to recovery time of T₁ from 25 to 75% (T_{25– 75}) (3.3 ± 2.0 vs 6.7 ± 2.0 min P < 0.05). Only edrophonium 0.5 mg · kg^{? 1} provided faster recovery than placebo with regard to all three indices. It is concluded that edrophonium 0.5 + glycopyrrolate 0.005 mg · kg^{? 1} allow the fastest recovery from a mivacurium-induced block during enflurane-N₂O anaesthesia.     

The pharmacodynamics of rocuronium in pediatric patients anesthetized with halothane

The aim of this study was to determine the neuromuscular blocking potency of rocuronium (ORG 9426) in 4-to 14-year old children anesthetized with halothane. After induction of anesthesia, the ulnar nerve was stimulated with electrical impulses of 0.2 ms duration every 12 s and the force of contraction of the thumb (P) was continuously recorded. Doses of 0.12, 0.16, 0.20, and 0.24 mg·kg⁻¹ rocuronium were administered, in a randomized fashion, to 4 groups of 12 patients each. The ED₅₀, ED₉₀, and ED₉₅ of rocuronium determined from the log dose-probit regression lines were 0.18, 0.34, and 0.40 mg·kg⁻¹, respectively. To facilitate tracheal intubation, after the development of the maximal effect of the first dose, a variable second dose of rocuronium was administered to increase the total dose to 0.3 mg·kg⁻¹. If after the second dose P was greater than 10% of control, additional 0.025–0.1 mg·kg⁻¹ increments of rocuronium were administered until P became less than 10% of control. At this time the trachea was intubated. Muscular relaxation was maintained with 0.075, 0.1, or 0.125 mg·kg⁻¹ rocuronium, administered whenever P recovered to 25% of control. The clinical duration of these doses was 6.9±2.8, 6.1±0.4, and 8.1±0.6 min, respectively. On repeated administration of three 0.1 or 0.125 mg·kg⁻¹ doses, rocuronium showed little cumulative tendency. Time for spontaneous recovery of P from 25% to 75%, 8.4±0.39 min and from 10% to 90%, 16.19±0.15 min, of control, were relatively short. When at termination of anesthesia T4/T1 ratios were lower than 0.75, the residual neuromuscular block could be antagonized with 0.5 mg·kg⁻¹ edrophonium in 2 min. Rocuronium, 0.3 mg·kg⁻¹ caused a 13.5% increase of heart rate but had no effect on blood pressure. In conclusion, in 4 to 14-year-old children, rocuronium appears to have a more rapid onset and shorter duration of action than other steroid-type muscle relaxants. Presented in part at the Annual Meeting of the American Society of Anesthesiologists, San Francisco, October, 1991     

Duration of action of an equipotent dose of vecuronium in infants and in children

During general anaesthesia without any volatile anaesthetic agents, ten infants and ten children received incremental doses of vecuronium to achieve a 95% neuromuscular block. Thereafter, the thenar electromyographic response was allowed to recover spontaneously. Total dose of vecuronium to establish a 95.0 ± 0.5% (mean ± SEM) neuromuscular block was 66% greater for children than for infants (73 ± 4 vs. 44 ± 4 μg·kg^?1, P < 0.0001). However, recovery index and time to complete recovery of the neuromuscular function were 88 and 89% longer, respectively, in infants than in children (P < 0.0001). These results of the effect of an equipotent dose of vecuronium in infants and in children confirm that vecuronium is a long acting neuromuscular blocking agent in infants.     

Mivacurium in infants and children

Mivacurium is the only available short-acting nondepolarizing muscle relaxant in clinical use. It is a bis-quaternary benzylisoquinolinium ester hydrolysed by plasma-cholinesterase into inactive compounds. The ED₅₀ and ED₉₅ in children are about 50 μg·kg^?1 and 90 μg·kg^?1 respectively. In infants, they have a tendency to be lower. A standard intubating dose of 0.25 mg·kg^?1 causes complete neuromuscular depression in 1.5–2 min, recovery to 5% in 6–10 min, and complete recovery in 15–20 min. The recent tendency is to use 0.3 mg·kg^?1 to obtain better intubating conditions with slight prolongation of effect. Since the recovery profile of mivacurium is independent of the dose and duration, it is most suitable for administration by continuous infusion. The infusion requirement in children is 10–16 μg·kg^?1 min^?1, which is about twice that of adults. Cutaneous flushes from histamine release are commonly seen with the larger doses of mivacurium; however, the associated hypotensive effects are minimal and counteracted by the tracheal intubation. The duration of action of mivacurium is prolonged in patients with cholinesterase deficiency. Mivacurium's neuromuscular effects can be satisfactorily antagonized by edrophonium or neostigmine.     

Recovery of neuromuscular function after atracurium and pancuronium maintenance of pancuronium block

The study was undertaken to determine whether a neuromuscular blockade induced with pancuronium but maintained with atracurium was associated with a shorter time to complete recovery after administration of neostigmine than if the blockade was maintained with pancuronium alone. Anaesthesia consisted of thiopentone, N₂O/O₂/enflurane and fentanyl, and the neuromuscular blockade, induced by pancuronium 0.1 mg · kg^?1 was monitored by the force of contraction of adductor pollicis during major abdominal surgery lasting 2–5 hr. In 24 patients — Group 1 — atracurium 0.07 mg · kg^?1 was repeated when the first twitch of the train-of-four (TOF) returned to 25% of control (T₁/ TC 25). In 28 patients — Group 2 — pancuronium 0.015 mg · kg^?1 was given at similar recovery of T₁/ TC. At the end of surgery, neostigmine 0.07 mg · kg^?1 and glycopyrrolate 0.015 mg · kg^?1 were given to reverse the residual neuromuscular blockade which was indicated by a T₁/TC of less than 25% in all patients. The time from injection of the reversal drugs to a TOF ratio of 70% was similar in both groups (Group 1, 11.6 ± 7.6 min; Group 2, 10.1 ± 6 min; P = NS), but the recovery index was smaller in Group 2 (Group 1, 4 ± 2.6 min; Group 2, 2.61 ± 1.2 min; P < 0.05). Furthermore, there was no difference between groups in the duration of action of each redose. The study showed that when compared with pancuronium, equipotent doses of atracurium were not associated with (a) a shorter time to complete recovery from a neuromuscular blockade induced with pancuronium or (b) a shorter duration of action.     

Intubating conditions and neuromuscular block after divided dose mivacurium or single dose rocuronium

Purpose

To evaluate the tracheal intubating conditions and neuromuscular blocking charactenstics of divided dose mivacurium or single dose rocuronium.

Methods

Thirty-two patients undergoing elective surgery were studied. Anaesthesia was with propofol 2 mg · kg^?1, followed by an infusion of l50 μg · kg^?1 · min^?1. Patients were randomized to receive either mivacurium-0.15 mg · kg^?1 followed 30 sec later by 0.1 mg · kg^?1, or rocuronium-0.9 mg · kg^?1, followed 30 sec later by placebo. Tracheal intubating conditions were assessed 90 sec after the initial dose of relaxant by an anaesthetist who was unaware of patient group. The electromyographic (EMG) response of the first dorsal interosseus muscle to ulnar nerve train-of-four was measured.

Results

Successful tracheal intubation was performed in all patients after both mivacurium and rocuronium. Intubating conditions (jaw relaxation, open visible vocal cords) were judged to be good-excellent in all but one patient before insertion of the tracheal tube. However, patients receiving mivacunum were more likely to experience coughing and bucking after tracheal tube insertion (10/16 patients) than those receiving rocuronium (3/16 patients, P < 0.05). No patient in the rocuronium group experienced moderately vigorous coughing and bucking after insertion of the tracheal tube vs six patients in the mivacurium group (P < 0.05). Time to 10 and 25% recovery of neuromuscular function was faster (P < 0.05) after divided dose mivacunum (20 ± 1 and 23 ± 1 min, respectively) than after rocuronium (45 ± 5 and 57 ± 8 min, respectively).

Conclusion

The results suggest that, during conditions of the study, divided dose mivacurium is not recommended for a 90-sec tracheal intubation in patients where moderate coughing and bucking is deemed unacceptable.     

Different priming techniques,including mivacurium,accelerate the onset of rocuronium

Different priming sequences of equipotent doses of rocuronium and mivacurium on the onset of maximum neuromuscular block and intubating conditions were compared with those obtained after succinylcholine. During thiopentone-fentanylnitrous oxide anaesthesia, 70 patients were randomly assigned into seven groups. Group I received mivacurium 0.15 mg · kg^?1 as a single bolus dose. Group II received a priming dose of mivacurium 0.015 mg · kg^?1 followed three minutes later by mivacurium 0.135 mg · kg^?1. Group III received rocuronium 0.6 mg · kg^?1 as a single bolus dose, and Group IV received an initial dose of rocuronium 0.06 mg · kg^?1 followed by rocuronium 0.54 mg · kg^?1. Group V received a priming dose of mivacurium 0.015 mg · kg^?1 followed by rocuronium 0.54 mg · kg^?1. Group VI received an initial dose of rocuronium 0.06 mg · kg^?1 followed by mivacurium 0.135 mg · kg^?1. Group VII received succinykholine 1.0 mg · kg^?1. Groups I, III, and VII received a placebo injection before the administration of the neuromuscular blocking drug. Additional thiopentone 2 mg · kg^?1 iv was given 30 sec before intubation. Onset times (mean (95% confidence interval)) after priming a rocuronium block with either rocuronium (73 (57–90) sec) or mivacurium (58 (47–69) sec) were similar to those after succinykholine (54 (40–68) sec), and were shorter (P < 0.01) than that observed in other groups. Intubating conditions were not different between the groups. The duration of neuromuscular block was shortest with succinykholine. It is concluded that priming a rocuronium block with either mivacurium or rocuronium resulted in a neuromuscular block comparable to that of succinykholine in both the onset of action and intubating conditions.     

Prolonged mivacurium infusion in young and elderly adults

Purpose

This study was designed to evaluate phanmacodynamically and phamnacokinetically if the cis-cis isomer of mivacurium contributed to neuromuscular block during prolonged infusions lasting more than four hours in young adult and elderly (> 60 yr) patients.

Methods

The mechanomyogramic neuromuscular response of the adductor pollicis was recorded in 32 adults 18–59 yr. and 19 elderly (> 60 yr.) patients dunng N₂O:O₂:opioid anaesthesia. The mivacurium infusion rate was adjusted to maintain single twitch depression at 95 ± 4% of control. Blood samples were taken every 30 min to determine the plasma concentration of cis-cis isomer of mivacurium. At the end of the surgical procedure, patients were allowed to recover spontaneously to at least 25% of control twitch response.

Results

The mean mivacurium infusion requirement to maintain 97 ± 1 (mean ± SD)% depression of the twitch response was 6.0 ± 0.4 μg· kg^?1· min^?1 in young adults, and 4.3 ± 0.3 μg· kg^?1· min^?1 in elderly patients (P < 0.001). The infusion requirement in patients with low plasma cholinesterase activity was the lowest 2.4 ± 1.2 μg· kg^?1· min^?1. Plasma cis-cis isomer concentrations reached peak levels within one-two hours and remained relatively constant throughout the duration of infusion even in patients with tow cholinesterase activity. There was no relationship between duration of infusion, plasma concentrations of cis-cis isomer and the early recovery indices of mivacurium (up to 25%). Neuromuscular transmission recovered adequately with or without antagonism in all patients.

Conclusion

When the mivacurium infusion was titrated to maintain 95 ± 4% twitch depression, the plasma concentration of the cis-cis isomer did not increase during prolonged infusions (four hours) and neuromuscular transmission recovers satisfactorily.     

Edrophonium requirements for reversal of deep neuromuscular block following infusion of mivacurium

Mivacurium is a new non-depolarizing muscle relaxant consisting of three stereoisomers. The two active isomers (cis-trans andtrans-trans) undergo rapid metabolism by plasma cholinesterase (t_1/2 β<2 min). Due to its rapid elimination, the need for reversal of mivacurium-induced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the current investigation was to establish the lowest effective dose of edrophonium required to reverse deep mivacurium-induced neuromuscular block. One hundred ASA Class I and II patients undergoing outpatient surgery in two teaching institutions were studied in this randomized, placebo-controlled double-blind trial. Under balanced propofol/nitrous oxide/alfentanil anaesthesia, a continuous infusion of mivacurium was adjusted to maintain between 5– 10% of control T₁ amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal saline (Group PLAC), edrophonium 0.125 mg · kg^{? 1} (Group EDR- 1), 0.25 mg · kg^{? 1} (Group EDR- 2), or 0.50 mg · kg^{? 1} (Group EDR- 3), in addition to a corresponding dose of atropine. 4Spontaneous recovery, from a T₁ response of<10% to a TOF ratio ≥0.7, required 13.5 ± 2.6 min (PLAC Group). In comparison, patients in the EDR- 1 group required 9.2 ± 2.6 min (P < 0.01). Higher doses of edrophonium conferred no advantage. Four patients (4%) had not achieved a TOF ratio of ≥ 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbers and cholinesterase levels consistent with an E^UE^A genotype, whereas the two patients with delayed recovery in the EDR- 1 group had characteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg · kg^{? 1}) hastens reversal of deep mivacurium-induced neuromuscular block by approximately four minutes, and that edrophonium doses exceeding 0.125 mg · kg^{? 1} provide no additional benefit. Heterozygous patients with atypical plasma cholinesterase levels, as well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular block, but the block is easily reversed with edrophonium.     

Determination of the pharmacodynamic interaction of propofol and dexmedetomidine during esophagogastroduodenoscopy in children

Objectives: Propofol is a sedative‐hypnotic drug commonly used to anesthetize children undergoing esophagogastroduodenoscopy (EGD). Dexmedetomidine is a highly selective alpha‐2 adrenergic receptor agonist that has been utilized in combination with propofol to provide anesthesia. There is currently no information regarding the effect of intravenous dexmedetomidine on the propofol plasma concentration–response relationship during EGD in children. This study aimed to investigate the pharmacodynamic interaction of propofol and dexmedetomidine when used in combination for children undergoing EGD. Methods: A total of 24 children undergoing EGD, ages 3–10 years, were enrolled in this study. Twelve children received dexmedetomidine 1 μg·kg^?1 given over 10 min as well as a continuous infusion of propofol delivered by a computer‐assisted target‐controlled infusion (TCI) system with target plasma concentrations ranging from 2.8 to 4.0 μg·ml^?1 (DEX group). Another group of 12 children undergoing EGD also received propofol administered by TCI targeting comparable plasma concentrations without dexmedetomidine (control group). We used logistic regression to predict plasma propofol concentrations at which 50% of the patients exhibited minimal response to stimuli (EC₅₀ for anesthesia). Results: The EC₅₀ ± se values in the control and DEX groups were 3.7 ± 0.4 μg·ml^?1 and 3.5 ± 0.2 μg·ml^?1, respectively. There was no significant shift in the propofol concentration–response curve in the presence of dexmedetomidine. Conclusion: The EC₅₀ of propofol required to produce adequate anesthesia for EGD in children was unaffected by a concomitant infusion of dexmedetomidine 1 μg·kg^?1 given over 10 min.     

Edrophonium antagonism of vecuronium at varying degrees of fourth twitch recovery

The purpose of this study was to determine the optimal dose of edrophonium needed for successful antagonism (train-of-four ratio, or T₄/T₁ > 0.7) of vecuronium-induced blockade when all four twitches were visible in response to indirect train-offour (TOF) stimulation. Forty patients, scheduled for elective surgical procedures not exceeding 120 min, received vecuronium, 0.08 mg · kg^?1, during thiopentone-N₂O-isoflurane anaesthesia. Train-of-four stimulation was applied every 20 sec and the force of contraction of the adductor pollicis muscle was recorded. Increments of vecuronium, 0.015 mg · kg^?1, were given as required. At the end of surgery, and provided that neuro-muscular activity had recovered to four visible twitches, edrophonium, 0.1 mg · kg^?1, was given. Two minutes later, edrophonium, 0.1 mg · kg^?1, was given if T₄/T₁ did not reach 0.7. After another two minutes, edrophonium, 0.2 mg · kg^?1, was given if T₄/T₁ did not reach 0.7 or more. Finally, if T₄/ T₁ was still < 0.7, a dose of 0.4 mg · kg^?1 was given. Seventeen patients (42.5%) required 0.1 mg · kg^?1 of edrophonium for successful reversal, sixteen patients (40%) needed a cumulative dose of 0.2 mg · kg^?1 and six patients (15%) required 0.4 mg · kg^?1. Only one patient received 0.8 mg · kg^?1. There was a good correlation between T₄/ T₁ two minutes after the first dose of edrophonium and pre-reversal T₄/T₁ (r = 0.6; P = 0.00014). All patients with pre-reversal T₄/ T₁ > 0.23 required at most 0.2 mg · kg^?1 of edrophonium for successful reversal. We conclude that when all four twitches are clearly visible following train-of-four stimulation, small doses of edrophonium (0.1-0.2 mg · kg^?1) might be sufficient to antagonize vecuronium neuromuscular blockade.     

Détermination de la courbe dose-effet du vécuronium chez l'homme anesthésié

Dose-response curves have been determined in 37 healthy subjects, after injection of a single bolus of Organon NC 45 (vecuronium or Norcuron®). The doses used were 0.0125, 0.025, 0.037 and 0.05 mg · kg^?1. The ulnar nerve was stimulated at the wrist and the force of thumb adduction measured. No premedication was used. Anesthesia was induced with thiopentone and fentanyl, and maintained by a nitrous oxide/oxygen mixture under controlled ventilation. Paco₂ was 37 ± 0.5 mmHg and temperature 36.8 ± 0.1 °C. The effective doses (ED) were : ED₅₀ at 0.024 mg · kg^?1, ED₉₀ at 0.034 mg · kg^?1 and ED₉₅ at 0.037 mg · kg^?1. At 0.05 mg · kg^?1, the degree of twitch inhibition was 99.2 ± 0.6 %, the delay of maximum effect was 7.7 ± 1.4 min, and the length of action (up to 90 % recovery) was 27.2 ± 2.3 min. Vecuronium is therefore a potent neuromuscular blocking agent with a relatively short duration of action.     

Reversal of doxacurium and pancuronium neuromuscular blockade with neostigmine in children

Recovery after doxacurium and pancuronium neuromuscular blockade and their acceleration by neostigmine have not been compared in children. Therefore, 60 paediatric surgical patients aged 2–10 yr (ASA 1–2) were studied. They were randomized to receive doxacurium 30 μg · kg^?1 or pancuronium 70 μg · kg^?1 iv during propofol, fentanyl, isoflurane and nitrous oxide anaesthesia. Electromyographic (EMG) responses of the adductor pollicis to train-of-four (TOF) stimulation of the ulnar nerve were recorded every ten seconds using a Datex NMT monitor. Six patients in each relaxant group received neostigmine (0, 5, 10, 20 or 40 μg · kg^?1) with atropine by random allocation when first twitch height (T_I) had recovered to 25% of control. Spontaneous recovery after ten minutes was similar following doxacurium (mean ± SEM values of 45.0 ± 3.9 vs 49.5 ± 10.0 % for T_I and 25.2 ± 3.8 vs 14.8 ± 3.6% for TOF ratios). Dose-responses to neostigmine were calculated from the log dose vs logit of T_I or TOF ratio after ten minutes. Neostigmine-assisted recovery was not different in the two groups, with ED₇₀ and ED₉₀ doses for T_I of 14.3 ± 1.8 and 25.7 ± 2.7 μg·kg^?1 for doxacurium and 12.5 ± 1.7 and 25.3 ± 2.3 μg· kg^?1 for pancuronium. Time to recovery of TOF ratio to 70% after neostigmine 40 ng · kg^?1 was 2.3 ± 1.0 and 4.2 ± 1.7 min (P = NS) following pancuronium and doxacurium, respectively. Adjusted recovery due to neostigmine alone (spontaneous recovery subtracted from the total) required two to three times higher doses of neostigmine. Thus, in children, the spontaneous recovery and reversal of neuromuscular blockade is similar with doxacurium and pancuronium. However, compared with previous adult studies, they recover twice as quickly from doxacurium neuromuscular blockade and neostigmine antagonism is achieved at 25–50% of the adult doses.     

Pharmacodynamics of doxacurium during cardiac surgery with hypothermic cardio-pulmonary bypass

Purpose

To determine the characteristics of neuromuscular block produced by two and three times the 95% effective dose (ED₉₅) of doxacurium in patients undergoing coronary artery surgery with hypothermic cardiopulmonary bypass.

Methods

In a prospective non randomized study, ten patients received doxacurium 0.05 mg·kg^?1 (Group 1) and ten others received 0.075 mg · kg^?1 (Group 2) with midazolam and sufentanil. The mechanomyographic response of the adductor pollicis muscle after supramaximal train-of-four (TOF) stimulation of the ulnar nerve was recorded intraoperatively and postoperatively. Additional doxacurium (10% of the initial dose) was administered until sternal closure whenever the first twitch (T₁) had recovered to 25% of control.

Results

The onset time (time to maximal T₁ depression) of doxacurium was 390 ± 148 sec in Group 1 and 370 ± 74 sec in Group 2 (P = 0.71). The clinical duration of neuromuscular block (time to 25% T₁ recovery) was 165 ± 90 min in Group 1 and 258 ± 86 min in Group 2 (P = 0.03). On arrival to recovery room the mean T₁ was 57 ± 23% in Group 1 and 24 ± 21% in Group 2(P = 0.003); the mean T₄/T₁ ratio was 0.25 ± 0.15 for five patients of Group 1 with four responses to TOF stimulation and 0.10 for the only patient of Group 2 with four twitches.

Conclusion

In contrast with findings in patients without cardiac disease, this study shows comparable onset times of doxacurium with doses of two and three times ED₉₅. The clinical duration of doxacurium is 60 to 100% longer than previously reported in noncardiac surgery.