A randomized, double-blinded study of remifentanil versus fentanyl for tonsillectomy and adenoidectomy surgery in pediatric ambulatory surgical patients.

UNLABELLED: We compared, in a double-blinded manner, the anesthetic maintenance and recovery properties of remifentanil with a clinically comparable fentanyl-based anesthetic technique in pediatric ambulatory surgical patients. Anesthesia was induced with either halothane or sevoflurane and nitrous oxide and oxygen. Patients were randomized (computer generated) to receive either remifentanil or fentanyl in a blinded syringe with nitrous oxide and oxygen in one of four possibilities: halothane/remifentanil, halothane/fentanyl, sevoflurane/remifentanil or sevoflurane/fentanyl. In patients receiving remifentanil, a placebo bolus was administered, and a continuous infusion (0.25 microg. kg(-1). min(-1)) was begun. In patients receiving fentanyl, a bolus (2 microg/kg) was administered followed by a placebo continuous infusion. The time from discontinuation of the anesthetic to extubation, discharge from the postanesthesia care unit (PACU), and discharge to home, as well as pain scores, were assessed by a blinded nurse observer. Systolic blood pressure and heart rate were noted at selected times, and adverse events were recorded. Remifentanil provided faster extubation times and higher pain-discomfort scores. PACU and hospital discharge times were similar. There were no statistical differences among the groups for adverse events. There were statistically, but not clinically, significant differences in hemodynamic variables. We noted that continuous infusions of remifentanil were intraoperatively as effective as bolus fentanyl. Although patients could be tracheally extubated earlier with remifentanil, this did not translate to earlier PACU or hospital discharge times. In addition, remifentanil was associated with higher postoperative pain scores. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children. IMPLICATIONS: This is a study designed to examine the efficacy and safety of a short-acting opioid, remifentanil, when used in pediatric patients. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children.

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.

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.

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.

Pulmonary aspiration in pediatric patients during general anesthesia: incidence and outcome.

STUDY OBJECTIVES: To determine the incidence of, outcome of, and risk factors for anesthesia-related pulmonary aspiration in the predominantly pediatric population receiving anesthesia care. DESIGN: Using a clinical concurrent quality assessment system we developed, we used data stored in a custom-designed computerized database to initiate a retrospective review. Statistical relationships were analyzed by Fisher's exact test and binary logistic regression with commercially available software. SETTING: University-affiliated pediatric hospital. PATIENTS: All patients receiving anesthesia (n = 50,880) between April 1, 1988, and March 31, 1993. MEASUREMENTS AND MAIN RESULTS: Aspiration occurred in 52 (0.10% or 10.2 per 10,000) of the 50,880 general anesthesia cases. Aspirate was food or gastric contents in 25 cases (0.049% or 4.9 per 10,000), blood in 13 (0.026% or 2.6 per 10,000), and unknown material in 14 (0.0275% or 2.76 per 10,000). There were no deaths attributable to aspiration. Morbidity was confined to unanticipated hospital admission (n = 12), cancellation of the surgical procedure (n = 4), and intubation, with or without ventilation (n = 15). Aspiration occurred significantly more often in patients with greater severity of underlying illness (ASA physical status III or IV) (p = 0.0015), intravenous induction (p = 0.0054), and age equal to or greater than 6.0 years and less than 11.0 years (p = 0.0029). Emergency procedures had a marginally significant increased aspiration risk (p = 0.0527). CONCLUSIONS: The overall incidence of anesthesia-related aspiration in our series (0.10%) was twice that reported in studies of adults, and four times (0.25%) higher for those at highest risk (ASA physical status III or IV vs. physical status I or II). Anesthesia-related pulmonary aspiration was proven to be a rare event in this tertiary pediatric center and its consequences relatively mild. Because of the very low frequency and the lack of serious outcome after aspiration in ASA physical status I and II pediatric patients, it appears that routine prophylactic administration of histamine blockers or propulsive drugs in healthy pediatric patients is unwarranted.

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.

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.

Comparison of the neuromuscular effects of mivacurium and suxamethonium in infants and children.

We compared both the time course of neuromuscular blockade and the cardiovascular side-effects of suxamethonium and mivacurium during halothane and nitrous oxide anaesthesia in infants 2-12 months and children 1-12 years of age. Equipotent doses of mivacurium and suxamethonium were studied; 2.2 x ED95 was used in four groups of infants and children, while 3.4 x ED95 was used in two groups of children. Onset of neuromuscular block in infants was not significantly faster with suxamethonium than with mivacurium (P = 0.2). In all infants given suxamethonium, intubating conditions were excellent, while, in 6/10 infants given mivacurium, intubating conditions were excellent. Onset of complete neuromuscular block in children was significantly faster with suxamethonium, 0.9 min compared with mivacurium, 1.4 min (P < or = 0.05). Increasing the dose of suxamethonium or mivacurium in children to 3.4 x ED95 did not change the onset of neuromuscular block. Recovery of neuromuscular transmission to 25% of initial twitch height (T25) in infants and children was significantly faster after suxamethonium than after mivacurium, at 2.5 and 6 min, respectively (P < or = 0.05). In children given 3.4 x ED95 of suxamethonium or mivacurium, recovery from neuromuscular block was almost identical with the dose of 2.2 x ED95, with spontaneous recovery to T25 prolonged by only 0.5 min. No infant or child had hypotension after the mivacurium bolus dose.

Clinical pharmacology of mivacurium in pediatric patients less than off years old during nitrous oxide-halothane anesthesia.

We determined the dose-response relationship of mivacurium in infants 2-6 and 7-11 mo of age during nitrous oxide-halothane anesthesia. The neuromuscular and cardiovascular effects of a bolus dose of mivacurium larger than the ED95 in infants and young children from 2-23 mo of age were observed. The infusion rate of mivacurium required to maintain approximately 95% neuromuscular block was determined. There was no significant difference between the estimated dose-response relationship in infants 2-6 mo and that in infants 7-11 mo. The ED50 and ED95 were 44 micrograms/kg and 85 micrograms/kg for infants 2-11 mo (n = 70), r = 0.53. A bolus dose of 150 micrograms/kg mivacurium in infants (2-6 mo) produced 100% depression of the initial twitch height (T1) in 8 out of 9 infants and 85% depression in 1 infant. The time to onset of maximum block was 1.6 +/- 0.3 (0.7-2.7) (mean, SEM [range]) min, and time to recovery to 25% of T1 (T25) was 7.5 +/- 0.7 (5.5-11) min after 150 micrograms/kg in these patients. A bolus dose of 200 micrograms/kg mivacurium in infants and young children (7-23 mo) produced 100% depression of T1 in 14 of 17 patients, 97% depression in 2, and 90% depression in 1. The time to onset of maximum block was 1.5 +/- 0.1 (0.8-3) min and T25 was 10.3 +/- 1.5 (4.8-30.5) min after 200 micrograms/kg in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of bolus administration of ORG-9426 in children during nitrous oxide-halothane anesthesia.

ORG-9426 is a new steroidal nondepolarizing neuromuscular blocking drug. We determined the dose-response relationship of ORG-9426 in 62 children (aged 1-5 yr) during nitrous oxide-halothane anesthesia by means of log-probit transformation and least-squares linear regression of the initial dose and response. Twelve additional patients received a bolus of 600 micrograms/kg (2 X the dose estimated to produce 95% depression of neuromuscular function [ED95]) of ORG-9426. 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. To determine the dose-response relationship, patients randomly received initial bolus doses of 120 (n = 15), 160 (n = 16), 200 (n = 16), or 240 (n = 15) micrograms/kg ORG-9426. The resulting dose estimated to produce 50% depression of neuromuscular function (ED50) and ED95 were 179 and 303 micrograms/kg, respectively. Time from administration of 600 micrograms/kg to onset of 90% and 100% neuromuscular block was 0.8 +/- 0.1 (0.5-1.3) and 1.3 +/- 0.2 (0.7-2.8) min. The time to recovery of neuromuscular transmission to 25% (T25) was 26.7 +/- 1.9 (17.2-39.0) min. The recovery index (T25-75) was 11.0 +/- 1.6 (6.0-22.8) min, and the time to complete recovery of the magnitude of the fourth response to a train-of-four stimuli divided by the magnitude of the first response (T4/T1) greater than or equal to 0.75 was 41.9 +/- 3.2 (26.5-57.7) min.(ABSTRACT TRUNCATED AT 250 WORDS)

Mivacurium infusion during nitrous oxide-isoflurane anesthesia: a comparison with nitrous oxide-opioid anesthesia.

STUDY OBJECTIVE: To determine the potentiation of the neuromuscular blockade induced by a titrated infusion of mivacurium in the presence of isoflurane versus a nitrous oxide (N2O)-opioid anesthesia. DESIGN: An open-label, controlled study. SETTING: The inpatient anesthesia service of two university medical centers. PATIENTS: Thirty adults divided into two groups. INTERVENTION: An intravenous infusion of mivacurium during anesthesia with N2O-opioid or N2O-isoflurane. MEASUREMENTS AND MAIN RESULTS: A neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. The mivacurium infusion rate was significantly less in the presence of isoflurane [4.0 +/- 0.8 micrograms/kg/min (mean +/- SEM)] than during N2O-opioid anesthesia (6.4 +/- 0.6 micrograms/kg/min). The recovery rates did not differ between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 of at least 0.75 occurred in an average of 17.9 +/- 1.5 minutes, with a mean recovery index (T25-75) of 6.0 +/- 0.7 minutes. CONCLUSION: Isoflurane anesthesia reduces the infusion rate of mivacurium required to produce about 95% depression of neuromuscular function.

Vecuronium infusion requirements in children during halothane-narcotic-nitrous oxide, isoflurane-narcotic-nitrous oxide, and narcotic-nitrous oxide anesthesia.

We were interested in determining the infusion rate of vecuronium required to maintain approximately 95% neuromuscular blockade in children during halothane-narcotic-nitrous oxide (0.8% end-tidal concentration), isoflurane-narcotic-nitrous oxide (1.0% end-tidal concentration), or narcotic-nitrous oxide anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity (Datex NMT) of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Effective vecuronium infusion requirements averaged 1.5 +/- 0.1 micrograms.kg-1.min-1 (mean +/- SEM) during isoflurane-narcotic-nitrous oxide anesthesia, 1.9 +/- 0.1 micrograms.kg-1.min-1 during halothane-narcotic-nitrous oxide anesthesia, and 2.4 +/- 0.3 micrograms.kg-1.min-1 during narcotic-nitrous oxide anesthesia. Infusion requirements significantly decreased after the first 30 min of infusion in the presence of both potent inhalation anesthetics, but did not change with time during narcotic-nitrous oxide anesthesia. There was no evidence of decreasing infusion requirements during prolonged vecuronium infusion (2.5 h). There was no difference in the rate of spontaneous or pharmacologically induced recovery between anesthetic groups. The mean recovery index (T25-75) after termination of the infusion was 13.7 min.

Mivacurium infusion requirements in pediatric surgical patients during nitrous oxide-halothane and during nitrous oxide-narcotic anesthesia.

We were interested in determining the infusion rate of mivacurium required to maintain approximately 95% neuromuscular blockade during nitrous oxide-halothane (0.8% end-tidal) or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity (Datex NMT) of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Mivacurium steady-state infusion requirements averaged 315 +/- 26 micrograms.m-2.min-1 during nitrous oxide-halothane anesthesia and 375 +/- 19 micrograms.m-2.min-1 (mean +/- SEM) during nitrous oxide-narcotic anesthesia. Higher levels of pseudocholinesterase activity were generally associated with a higher mivacurium infusion requirement. During both anesthetics, younger age was associated with a higher infusion requirement when the infusion requirement was calculated in terms of micrograms.kg-1.min-1. This difference was not present when the infusion rate was calculated in terms of micrograms.m-2.m-1. There was no evidence of cumulation during prolonged mivacurium infusion. There was no difference in the rates of spontaneous or reversal-mediated recovery between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 greater than or equal to 0.75 occurred in 9.8 +/- 0.4 min, with a recovery index, T25-75, of 4.0 +/- 0.2 min (mean +/- SEM). In summary, pseudocholinesterase activity is the major factor influencing mivacurium infusion rate in children during nitrous oxide-narcotic or nitrous oxide-halothane (0.8% end-tidal) anesthesia.

Isoflurane for refractory status epilepticus: a clinical series.

General anesthesia has been recommended to control convulsive status epilepticus that is refractory to conventional anticonvulsant therapy. Halothane has been the recommended agent, but without experimental justification. Isoflurane, which has no reported organ toxicity and produces electrographic suppression at clinically useful concentrations in normal humans, should be a better volatile anesthetic for this purpose. The efficacy and safety of isoflurane administered to control convulsive status epilepticus were assessed on 11 occasions in nine patients in seven North American hospitals. Isoflurane, administered for 1-55 h, stopped seizures in all patients and was able to be titrated to produce burst-suppression patterns on electroencephalograms. Blood pressure support with iv fluids and/or pressor infusions was required in all of the patients. Seizures resumed upon discontinuation of isoflurane on eight of 11 occasions. Six of the nine patients died. The three survivors sustained cognitive deficits. In one patient urine fluoride concentrations were elevated, although not to nephrotoxic levels. These cases suggest that isoflurane 1) is an effective, rapidly titratable anticonvulsant; 2) does not reverse underlying causes of the refractory seizures; and 3) usually necessitates hemodynamic support with fluids and/or pressors. Isoflurane may be administered for seizures, but only when iv agents in anesthetic doses are ineffective or produce unacceptable side effects.

Comparison of mivacurium and suxamethonium administered by bolus and infusion.

Mivacurium chloride is a new, short-acting nondepolarizing neuromuscular blocking agent presently undergoing clinical evaluation. The neuromuscular effects of mivacurium and suxamethonium given by bolus and infusion were compared in adult patients during nitrous oxide-oxygen-opioid anaesthesia. Neuromuscular block was monitored by recording the compound electromyogram of the adductor pollicis muscle resulting from supramaximal train-of-four stimuli applied to the ulnar nerve. Time to onset of complete block and recovery to T5 were significantly shorter for suxamethonium than for mivacurium (1.0 (0.1) v. 2.5 (0.3) min and 6.4 (0.7) v. 17.5 (1.8) min; mean (SEM]. Conditions for tracheal intubation were similar in the two groups although intubation was performed 0.75-1.3 min later following mivacurium. The infusion rate required to maintain neuromuscular block was 88.6 (10.4) micrograms kg-1 min-1 for suxamethonium and 7.8 (1.2) micrograms kg-1 min-1 for mivacurium. There was a significant negative correlation between recovery to T5 and infusion rate for mivacurium and for suxamethonium. It was equally easy to titrate the infusion rate to the desired degree of block in each group. The recovery index (T25-T75) after the infusion stopped was similar in patients who received mivacurium and those who received suxamethonium.

Clinical pharmacology of mivacurium chloride (BW B1090U) in children during nitrous oxide-halothane and nitrous oxide-narcotic anesthesia.

We determined the dose-response relationships of mivacurium (BW B1090U) in children (2-10 years) during nitrous oxide-halothane anesthesia (0.8% end-tidal) and during nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relationships, for each anesthetic background four subgroups of nine patients received single bolus doses of 20-120 micrograms/kg mivacurium. The ED50 and ED95 (estimated from linear regression plots of log-dose vs. probit of effect) were 52 micrograms/kg and 89 micrograms/kg during halothane anesthesia and 62 micrograms/kg and 103 micrograms/kg during narcotic anesthesia. Nine additional patients in each anesthetic group received 250 micrograms/kg mivacurium. Three of the 18 patients given 250 micrograms/kg mivacurium developed cutaneous flushing; in one of these mean arterial pressure decreased 32% for less than 1 minute; no significant changes in heart rate occurred. With the increase in mivacurium dose from 120 micrograms/kg to 250 micrograms/kg the times to onset of 90% and maximum neuromuscular block decreased by 0.5 to 1 minute, and the times to recovery of neuromuscular transmission to 5% (T5) or 25% (T25) increased by 2-4 minutes. The recovery index (T25-75) in patients anesthetized with halothane was 4.3 +/- 1.5 minute (mean +/- SD); the time to complete recovery (T4:1 greater than or equal to 0.75) was 19.8 +/- 7.4 minutes.

Mivacurium chloride (BW B1090U)-induced neuromuscular blockade during nitrous oxide-isoflurane and nitrous oxide-narcotic anesthesia in adult surgical patients.

The neuromuscular and cardiovascular effects of mivacurium were studied in 90 adult patients during nitrous oxide-oxygen-isoflurane (n = 45, ISO group) and nitrous oxide-oxygen-narcotic (n = 45, BAL group) anesthesia. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relations, three subgroups of nine patients in the ISO group received mivacurium doses of 0.025, 0.03, and 0.04 mg/kg, respectively. Similarly, three subgroups of nine patients in the BAL group received mivacurium doses of 0.03, 0.04, and 0.05 mg/kg, respectively. The ED50 and ED95 of mivacurium in each group were estimated from linear regression plots of log dose vs probit of maximum percentage depression of neuromuscular function. The estimated ED50 values for the ISO and BAL groups were 0.029 and 0.041 mg/kg, respectively. The estimated ED95 values for the ISO and BAL groups were 0.045 and 0.058 mg/kg, respectively. Recovery indexes were measured in 26 patients who received ED95 or greater doses of mivacurium in either the ISO or BAL groups. The recovery index was shorter in the BAL group (5.5 +/- 1.6 minutes [n = 10]), than in the ISO group (7.4 +/- 3.0 minutes [n = 16]). The addition of isoflurane (0.5-0.75% end-tidal concentration) to nitrous oxide-narcotic anesthesia augments the degree of neuromuscular blockade from a given dose of mivacurium and also prolongs the recovery index.

Clinical pharmacology of doxacurium chloride (BW A938U) in children.

The neuromuscular effects of doxacurium were studied in 26 children during halothane-nitrous oxide-oxygen anesthesia. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate the cumulative dose-response relation, nine patients received incremental doses of doxacurium (2.5-10 micrograms/kg); nine patients received 27.5 micrograms/kg (the estimated ED95); eight patients received 50 micrograms/kg (1.8 X ED95). The ED25, ED50, ED75, and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 11.5, 14.8, 19.0, and 27.3 micrograms/kg, respectively. Clinical duration (T25) was 27.8 +/- 10.3 (mean +/- SD) minutes at 1 X ED95 and 50.6 +/- 15.6 minutes at 1.8 X ED95. Time to recovery of the train-of-four ratio to 0.75 was 63.1 +/- 32.9 minutes at 1 X ED95 and 108.5 +/- 25.7 minutes at 1.8 X ED95. There were no significant changes in heart rate or mean arterial pressure after bolus administration of any dose of doxacurium.