Unmasked residual neuromuscular block after administration of vecuronium for days.

IMPLICATIONS: Significant neuromuscular block may be present in patients who have received vecuronium for days.

Neuromuscular effects of rapacuronium in pediatric patients during nitrous oxide-halothane anesthesia: comparison with mivacurium.

PURPOSE: To describe neuromuscular effects of rapacuronium in pediatric patients during N2O-halothane anesthesia and compare them with mivacurium in children. METHODS: 103 pediatric patients, seven days -12 yr, received rapacuronium or mivacurium during N2O-halothane anesthesia. Onset and recovery of block were measured using EMG (Datex). Block was compared between groups based on drug treatment and age. Children < two years received 1 or 2 mg x kg(-1) rapacuronium: 2-12 yr received either 2 mg x kg(-1) or 3 mg x kg(-1) rapacuronium, or 0.2 mg x kg(-1) mivacurium. RESULTS: There were no differences in onset (1.7+/-1.8 min) or maximum block (T1 2.4+/-8%) among neonates, infants, and toddlers after either dose of rapacuronium. There was no difference between 1 and 2 mg x kg(-1) of rapacuronium block at 60 sec. Train-of-four ratio (T4/T1) >0.7 occurred later after 2 mg x kg(-1) than 1 mg x kg(-1) in these patients (P<0.05). There was no difference in T25 among neonates, infants and toddlers for 1 mg x kg(-1) or 2 mg x kg(-1) doses. Rapacuronium, 3 mg x kg(-1), produced maximum block 1.5 min earlier than did mivacurium, 0.2 mg x kg(-1) (P<0.001). There was no difference in block at 60 sec, maximum block or time to maximum block between 2 and 3 mg x kg(-1) rapacuronium for children > two years of age. Maximum block occurred 1.0+/-0.5 min after 2 or 3 mg x kg(-1) when T1 was 0.2+/-1.1% of baseline. T25 and T4/T1 >0.7 occurred 10 to 11 min later after this dose of rapacuronium than after mivacurium. CONCLUSION: Rapacuronium produces block earlier than mivacurium. Recovery from rapacuronium block is dose related and slower than that following mivacurium during halothane anesthesia.

The incidence of tissue coring during the performance of caudal injection in children.

BACKGROUND AND OBJECTIVES: The performance of caudal injection (CI) has become a routine part of pediatric anesthesia. The intraoperative and immediate postoperative complications of CIs have been reported extensively. Although the long-term consequences of CI are unknown, they may include the development of epidermoid tumors in the spinal canal. Such tumors have been attributed to tissue coring (the process by which pieces of tissue are removed by a needle as it passes through the tissue) and the subdural deposition of such tissue. METHODS: In this study, we examine the internal needle of 20-gauge i.v. cannulae from 50 CIs for evidence of tissue coring. RESULTS: We found a total coring incidence of 54% (95% confidence interval = 40-68%). Epidermal tissue was present in 33% of the positive samples. Fat was present in 67% of the positive samples and bloody material in 26%. This study provides an estimate (with a 95% confidence interval) of the rate of coring during CI performed with hollow point needles. CONCLUSIONS: These findings suggest that technical modifications may improve patient safety. The results also have implications for long-term follow-up of caudal anesthetics. Techniques for reducing the incidence of tissue coring during the performance of CI are discussed.

Age related variability in the effects of mivacurium in paediatric surgical patients.

PURPOSE: This study describes the effects of 0.3 mg.kg-1 mivacurium in 180 paediatric patients between the ages of one month and 13 yr. METHODS: Alternate patients at each of two geographic sites received nitrous oxide-halothane or nitrous oxide-opioid anaesthesia. Neuromuscular blockade was monitored by electromyography (Datex NMT). Blood pressure and heart rate were recorded from an automated oscillometer. Tracheal intubation was performed 90 sec after administration of mivacurium and conditions were judged by the Krieg scale. RESULTS: There was no difference in the time course of block between anaesthetics or geographic sites. The average time to 90% block and 25% recovery was 1.0 min and 8.0 min at one month vs 2.3 min and 9.8 min at 12.5 yr of age. Intubation conditions were better during opioid (excellent in 92%) than during halothane anaesthesia (excellent in 78%) (P = 0.03). Diaphragmatic movement was less frequent in younger patients (P < 0.001). Intubation conditions did not differ between the two geographic sites. In the first minute after mivacurium, systolic and diastolic blood pressures decreased (P < 0.001) to similar extents in all patients. A transient increase in the redness of the skin of the face, trunk, and/or arms was noted during both anaesthetics (28% of infants, and 61% of children over five yr of age). CONCLUSION: The time course of block produced by mivacurium is more rapid in younger paediatric patients. The time course of mivacurium does not have the transatlantic variation which has been observed for vecuronium. Physiological changes suggestive of histamine release were frequent. Intubation conditions were very likely to be acceptable 90 sec after 0.3 mg.kg-1 mivacurium.

Effects of cisatracurium in children during halothane-nitrous oxide anesthesia.

STUDY OBJECTIVE: To determine the neuromuscular blocking effect and recovery profile of cisatracurium besylate in children after administration of a bolus dose that was twice the estimated dose required to produce 95% of the maximum effect (2 x ED95; 0.08 mg/kg) followed by an infusion during halothane-nitrous oxide anesthesia. STUDY DESIGN: Open-label study. SETTING: Teaching hospital. PATIENTS: 30 male and female (ASA physical status I and II) patients, 2 to 10 years of age, scheduled for elective surgery of low to moderate risk. INTERVENTIONS: After induction of general anesthesia, patients received cisatracurium 0.08 mg/kg administered over 5 to 10 seconds. For surgical procedures requiring neuromuscular block for at least 60 minutes, a second bolus dose of cisatracurium 0.02 mg/kg was administered after the first response to a train-of-four stimuli (T1) recovered to 25% of baseline. When T1 was 5% of baseline after the second dose, a 3 microg/kg/min infusion of cisatracurium was initiated and titrated to maintain 89% to 99% block for the duration of the surgery. For procedures requiring neuromuscular block of less than 60 minutes, one or more maintenance doses of 0.02 mg/kg cisatracurium were administered when T1 was 25% of baseline after the preceding dose. In 10 patients, recovery was facilitated with edrophonium 1.0 mg/kg administered when T1 was 26% to 48% of the final baseline. MEASUREMENTS AND MAIN RESULTS: Evoked muscular response at the adductor pollicis was measured by electromyography. With 0.08 mg/kg, onset time (mean +/- SEM) was 4.1 +/- 0.4 minutes, and clinically effective duration was 27.3 +/- 0.9 minutes. Mean 5% to 95% and 25% to 75% recovery indices were 28.4 +/- 2. 7 minutes and 11.2 +/- 0.8 minutes, respectively. The mean infusion rate necessary to maintain 89% to 99% T1 suppression for 17 to 145 minutes was 1.7 microg/kg/min. After termination of infusion, the mean 5% to 95% and 25% to 75% recovery indices were similar to those after a single bolus dose, and time to 95% recovery was 30.4 +/- 3.0 minutes. After administration of edrophonium, full recovery (T4:T1 > or = 70%) occurred in 1.5 +/- 0.4 minutes. No clinically significant changes in heart rate or blood pressure were noted during the first 5 minutes after administration of cisatracurium 0.08 mg/kg. CONCLUSIONS: Cisatracurium provided maximal neuromuscular block, cardiovascular stability, and predictable recovery at the doses tested. In view of this finding, cisatracurium should be a useful intermediate-duration neuromuscular blocking drug for children during general anesthesia.

Intubation in children after 0.3 mg/kg of mivacurium.

STUDY OBJECTIVE: To distinguish among potential predictors of early, easy intubation in children, including apnea, neuromuscular block at two sites, and time, after administration of 0.3 mg/kg of mivacurium. DESIGN: Prospective, randomized study. SETTING: Operating rooms of Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania. PATIENTS: 60 ASA physical status I and II children aged 2 through 7 years, scheduled for elective surgical procedures requiring endotracheal intubation. INTERVENTIONS AND MEASUREMENTS: After premedication with midazolam, general anesthesia was induced with halothane and nitrous oxide, and patients were randomly assigned to one of four groups. Mivacurium 0.3 mg/kg was given and tracheal intubation was begun 45 seconds after its injection, or when apnea, block of the orbicularis oculi, (OO) or block of the adductor pollicis (AP) was noted. Intubation conditions were evaluated by an experienced endoscopist. MAIN RESULTS: The first clinical event after administration of mivacurium 0.3 mg/kg was apnea at 43 seconds (median) (average 48 seconds, SEM 2 seconds) after injection. The difference in the time at which neuromuscular block occurred at the AP (median 75 seconds) (average 77 seconds, SEM 2 seconds) and the OO (median 63 seconds) (average 68 seconds, SEM 4 seconds) was statistically, but not clinically, significantly different. All nine intubations that were begun at least 90 seconds after administration of mivacurium resulted in good or excellent intubation conditions, as did 30 of the 51 intubations started earlier. CONCLUSIONS: In children, there is no advantage to monitoring neuromuscular function at the OO rather than the AP. After administration of 0.3 mg/kg of mivacurium, a 90-second interval before the start of intubation was a better predictor of good intubation conditions during halothane anesthesia (1% inspired) than were changes in evoked neuromuscular function.

Decreasing morbidity following laryngotracheal reconstruction in children.

Our objectives are to report (1) methods for decreasing infectious complications and excessive weakness associated with the period of sedation and neuromuscular blockade (NMB) following single-stage laryngotracheal reconstruction (SSLTR); (2) an association between gastroesophageal reflux (GER) and subglottic stenosis (SGS); (3) results of 21 SSLTRs and 15 two-stage LTRs (TSLTRs). A retrospective chart review was performed for the period January, 1990-August, 1995, including 36 patients who had 38 LTRs for SGS and/or posterior glottic stenosis at a tertiary care center. Our most recent post-SSLTR protocol included: (1) prophylactic antimicrobials (clindamycin plus antipseudomonal agents = C + A); (2) GER treatment; (3) titrated infusion NMB with daily recovery of neuromuscular function; (4) avoidance of prolonged simultaneous administration of NMB and corticosteroids. Patients who had prophylactic antimicrobials (C + A) during intubation following SSLTR had fewer (1/13, 8%) postoperative infectious complications than patients who received other/no antibiotics (4/8, 50%) (P < 0.05). Avoidance of prolonged simultaneous administration of NMB and corticosteroids and use of titrated infusion of NMB with daily recovery of neuromuscular function was associated with less weakness following extubation (0/11, 0% vs. 4/6, 66%) (P < 0.002). Of 26 patients tested for GER, 21 (81%) had at least one positive test, suggesting a significant association between GER and SGS (P < 0.05). The overall success rate for LTR was 33/36 or 92%. SSLTR had a 95% success rate while two-stage LTR had an 87% success rate, although two revisions were required. Prophylactic antimicrobials, improved postoperative management and GER treatment allowed successful LTRs with decreased infectious complications and less weakness.

Recovery from doxacurium infusion administered to produce immobility for more than four days in pediatric patients in the intensive care unit.

Doxacurium was administered by titrated infusion to 14 pediatric patients for 4.7-12.3 days after laryngotracheal reconstruction to produce minimum spontaneous movement and less than five posttetanic movements of the first toe after stimulation of the posterior tibial nerve. Recovery was documented by stimulation of the ulnar nerve with 2 Hz for 2 s (train-of-four [TOF]) at intervals of 1 min and measurement of the ratio of the fourth to the first response (TOF ratio) at the adductor pollicis. During spontaneous recovery, the TOF ratio was between 0.4 and 0.7 for 0.6-3.3 h, mean (SEM) 2.2 (0.31) h. The TOF ratio equaled 1 between 4.7 and 23.0 h, mean (SEM) 11.0 (2.1) h after termination of doxacurium infusion. In six of the patients, weakness and decreased coordination were noted for a few days to weeks postoperatively. There were no complications related to impairment of upper airway function or ventilation in those patients who had recovery of neuromuscular transmission to the extent of TOF ratio equal to 1 prior to extubation or in those patients in whom weakness or lack of coordination was noted after tracheal extubation.

Administration of atropine and onset of neuromuscular block produced by atracurium in infants.

In this prospective study we tested the hypothesis that atropine administration, which is known to increase heart rate and cardiac output in infants, will result in a faster onset of neuromuscular block with atracurium. Thirty infants scheduled for elective surgery had anaesthesia induced with nitrous oxide and halothane. Fifteen patients were given atropine and 15 patients acted as controls. All the infants were given atracurium 0.5 mg.kg-1, and neuromuscular block was recorded with the Datex 221 neuromuscular transmission monitor. Although atropine caused an increase in heart rate compared to the control group (median 164 [range 151-182] vs 120 [98-160]min-1 P < 0.0001), there was not a statistically significant difference in the onset of neuromuscular block between the two groups. We conclude that onset of neuromuscular block after atracurium is determined mainly by noncirculatory factors and less by the circulation time to the muscle. The effect of atropine on the time course of neuromuscular block might be different with faster acting neuromuscular blockers.

Spontaneous versus edrophonium-induced recovery from paralysis with mivacurium.

This study compared spontaneous with edrophonium-induced recovery of neuromuscular transmission (NMT) after mivacurium infusion. During nitrous oxide-narcotic-propofol anesthesia, the electromyogram (EMG) of the adductor pollicis (AP) was recorded and the movement of the first toe in response to stimulation of the posterior tibial nerve was noted. Mivacurium infusion was titrated to produce posttetanic count of 1-5 at the toe and absence of NMT at the AP. Thirty children were assigned to three groups on the basis of age. Edrophonium, 1 mg/kg, with atropine 10 micrograms/kg, was given after the mivacurium infusion when NMT of the AP was 1% or 10% of baseline. In the third group, spontaneous recovery was observed. Edrophonium given when NMT was 11% +/- 1% SEM produced the most rapid recovery, 7.5 +/- 0.6 min to a train-of-four (TOF) ratio (T4/T1) of 0.9 and the shortest interval from T4/T1 of 0.4-0.9, when residual block was likely to be underestimated, 4.8 +/- 0.6 min. Edrophonium given when block was greater produced recovery of the T4/T1 to 0.4 in 2.8 +/- 0.7 min, but the time from then to T4/T1 = 0.9 was 7.9 +/- 1.1 min, as long as during spontaneous recovery. Spontaneous recovery to T4/T1 = 0.9 occurred 12.9 +/- 0.7 min after the first measurable AP EMG. There was no significant relationship between duration of infusion, which ranged from 16 to 135 min, and time to appearance of AP EMG after the infusion, which averaged 3.1 +/- 0.5 min. We recommend that administration of edrophonium to induce reversal of mivacurium be delayed until two responses to a TOF stimuli are observed because this will produce the most rapid recovery and decrease the interval in which residual block may be underestimated.

Combinations of high-dose vecuronium and mivacurium provide similar paralysis and intubation conditions to succinylcholine in paediatric patients.

This randomized blinded study tested the hypothesis that equipotent doses of vecuronium and mivacurium given in combination could achieve onset times to 90% neuromuscular block (B90) and intubation scores similar to succinylcholine. Thirty children were randomly assigned to one of three groups as follows. Group Sux received a single dose (1 mg.kg-1) of succinylcholine followed by normal saline. Group V1M1 received 0.08 mg.kg-1 of vecuronium followed by 0.1 mg.kg-1 of mivacurium. Group V2M2 received 0.16 mg.kg-1 of vecuronium followed by 0.2 mg.kg-1 of mivacurium. Anaesthesia consisted of propofol, fentanyl, and nitrous oxide. Neuromuscular response was monitored by adductor pollicis electromyography (Datex NMT). Sixty s after administration of the first injection, the laryngoscopy began, with the anaesthesiologist scoring the ease of intubation on a four category scale as excellent, good, poor, or inadequate. Time from injection to B90 was 39 (2.6)s after succinylcholine, which was not significantly different from 48 (3.5)s after vecuronium 0.16 mg.kg-1 and mivacurium 0.2 mg.kg-1 (V2M2). Mean time to B90 for group V1M1 was 64 (4.7)s, which was significantly different from that in group Sux. The intubation score was 'excellent' for all patients in groups Sux and V2M2 and for only seven of ten patients in group V1M1. Only combination of vecuronium (0.16 mg.kg-1) and mivacurium (0.2 mg.kg-1) provided rapid onset of neuromuscular blockade and excellent intubating conditions comparable to succinylcholine 1 mg.kg-1. This combination did result in prolonged recovery times.

Synergism between atracurium and mivacurium compared with that between vecuronium and mivacurium.

Synergism exists between some combinations of nondepolarizing muscle relaxants. To test the possibility of synergism between mivacurium and atracurium or vecuronium, 60 children anesthetized with propofol-alfentanil-N2O-O2 were randomized to one of five groups. Three groups of 10 patients each received an ED50 dose of a parent drug atracurium (A), vecuronium (V), or mivacurium (M), respectively, and two other groups of 15 patients each received a single-dose combination of atracurium with mivacurium (cAM) or vecuronium with mivacurium (cVM). Dose combinations constituted 0.5 times an ED50 dose of each drug. Neuromuscular response was monitored by adductor pollicis electromyogram (EMG). Maximum neuromuscular block (NMB) established by a single parent drug did not differ between the groups or from 50% NMB. It averaged 5.03 +/- 0.12 probits (51.2% NMB). On the contrary, maximum NMB established by the two-dose combinations, cAM or cVM, was significantly more than NMB produced by either single parent drug of the particular combination (cAM vs A or M; P = 0.0035, and cVM vs V or M; P = 0.0004) without a statistically significant difference between groups cAM and cVM. Maximum NMB established by combinations averaged 6.15 +/- 0.21 probits (87.5% NMB). The onset of maximum NMB for mivacurium was significantly faster compared to that for atracurium or for vecuronium (2.8 +/- 0.3 vs 5.7 +/- 0.4 or 4.0 +/- 0.3 min, respectively; P = 0.0001). Our results indicate that both drug combinations are synergistic even though only vecuronium is markedly different in its molecular structure from mivacurium.

Dose response of succinylcholine at the adductor pollicis of children with cerebral palsy during propofol and nitrous oxide anesthesia.

Children with cerebral palsy may be resistant to paralysis induced by nondepolarizing neuromuscular blocking drugs. Potency of a bolus of succinylcholine in children with cerebral palsy has not been studied previously. Therefore, we measured the response of the adductor pollicis to succinylcholine in children with cerebral palsy anesthetized with propofol and nitrous oxide. Forty children between the ages of 2 and 10.2 yr with spastic quadriplegic cerebral palsy were randomly assigned to receive 100, 175, 250, or 375 micrograms/kg of succinylcholine during anesthesia with propofol and nitrous oxide. The ulnar nerve was stimulated with a train-of-four supramaximal stimulus every 10 s and the compound electromyogram of the adductor pollicis recorded by a Datex NMT monitor. Plasma cholinesterase activity was measured in all patients with three different substrates (propionylthiocholine, benzoylcholine, and succinylcholine). Dibucaine number was also determined using inhibition of benzoylcholine degradation. ED50 of succinylcholine was 146.8 micrograms/kg with 95% confidence intervals of 111.4-193.7 micrograms/kg. ED95 of succinylcholine was 360.5 micrograms with 95% confidence intervals of 273.3-475.5 micrograms/kg. We conclude that children with cerebral palsy are slightly sensitive to succinylcholine, but probably not sufficiently to be clinically important.

Frequency of train-of-four stimulation influences neuromuscular response.

We have compared the effects of two different frequencies of train-of-four stimulation of the ulnar nerve (2-Hz stimulation once every 10 or 20 s) on onset time and potency of atracurium, vecuronium and mivacurium during balanced anaesthesia. The adductor pollicis EMG was recorded simultaneously in both hands of 24 children aged 2-12 yr. After administration of an ED50 dose of each blocker, onset times were mean 21 (SEM 10) s shorter (P < 0.05) and decreases in neuromuscular function were 22 (3)% greater (P < 0.001) in the hand which was stimulated once every 10 s. We conclude that it is not possible to compare potency estimates of neuromuscular blocking agents if different stimulation patterns have been used.