Table: Values: mean±SD *sig diff: P<0.05; **P=0.08 Gp n Age (yr) Wt (kg) GA (min) Miv (μg. kg–1.min–1) T1% at end surgy Iso 4 3.5±2.5 14.3±3.3 78.3±19.2 0 80-100 Pro 4 1.6±0.6 11.8±1.4 88.5±14.0 1.1±0.9** 78-100 711 ABSTRACTS OF PAPERS Anaesthesia and Intensive Care, Vol. 25, No. 6, December 1997 Compared with nonpregnant women, the ED50s and ED95s of isoflurane for hypnosis were 32% and 31% less in the pregnant group respectively. BIS was lower in the pregnant women at each isoflurane concentrations (P<0.05). The BIS value (BIS50 (95% CI)) at which 50% of the patients respond to verbal command was 86 (84-87) in the nonpregnant group and it was similar to that of the pregnant patients, 85 (84-86). The hypnotic requirement of isoflurane in the early pregnancy is 32% less than that of the matched controls. This is reflected by the changes in BIS.

We compared the potency and duration of action of rocuronium in Chinese and Caucasian patients during general anesthesia. Thirty-six women (18 Caucasian and 18 Chinese) and 36 children (18 Caucasian and 18 Chinese) were evaluated during the administration of propofol/fentanyl anesthesia. Patients in each age group were randomized into three subgroups to receive single doses of 0.06, 0.12, or 0.18 mg/kg rocuronium (adults) or 0.12, 0.18, or 0.24 mg/kg rocuronium (children). Neuromuscular blockade was assessed by electromyography of the adductor pollicis after train-of-four (TOF) stimulation of the ulnar nerve. Dose response curves were constructed when maximum neuromuscular depression of the first twitch of the train (T-1) was obtained. A second bolus dose of rocuronium was then administered to a total dose of 0.6 mg/kg. The times of spontaneous recovery to T-1 10%, 25%, and 90% of control and to TOF 0.25, 0.50, and 0.70 were recorded. For both adults and children, recovery occurred later in Chinese than in Caucasian patients (P < 0.05 for T-1 of 10%, 25%. 75%, and 90% and TOF to 0.7). The 50% effective dose was smaller in Chinese adults (125 +/- 63 vs 159 +/- 66 g/kg) and Chinese children (171 +/- 43 vs 191 +/- 46 mug/kg) than in Caucasian adults and children, but the difference was not statistically significant. In adults, time to 25% T-1 recovery was 43 +/- 13 min in Chinese patients and 33 +/- 10 min in Caucasian patients (P < 0.05). The corresponding values were more rapid for children: 30 +/- 10 and 24 +/- 6 min (P < 0.05). We conclude that the recovery from rocuronium neuromuscular blockade was longer in Chinese compared with Caucasian patients and in adults compared with children.

UNLABELLED: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.

The purpose of this study was to compare the mivacurium infusion requirements and neuromuscular recovery in adults and children during propofol/opioid and sevoflurane anesthesia.Seventy-five adult and 75 pediatric patients were randomized to receive propofol/opioid 0.5 or 1.0 minimum alveolar anesthetic concentration (MAC) (age-related) sevoflurane anesthesia. Plasma cholinesterase (PChE) activity was measured. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation every 10 s and adductor pollicis electromyography. A bolus of 2 x the 95% effective dose of mivacurium (0.25 mg/kg) was followed by an infusion titrated to maintain 90%-95% blockade. Mivacurium doses were recorded every 5 min. At the end of surgery, the infusion was stopped, and recovery from mivacurium was monitored until TOF >or=to0.7. PChE concentrations were within the normal range (adults 4-12 KU/L, children 6-16 KU/L) and correlated with mivacurium dose. Mivacurium infusion rates were higher in children than in adults: at 30 min, the rates in children were 13.1 +/- 6.4, 8.1 +/- 4.7, and 5.2 +/- 2.9 [micro sign]g [center dot] kg-1 [center dot] min-1 at 0, 0.5, and 1.0 MAC sevoflurane, respectively; the corresponding rates in adults were 5.9 +/- 3.1, 4.3 +/- 1.7, and 2.9 +/- 0.7 [micro sign]g [center dot] kg-1. min-1 (P < 0.01). Sevoflurane decreased mivacurium requirements, maximal decreases at 45 min in children and 10 min in adults, and delayed neuromuscular function recovery. Children recovered twice as quickly as adults, achieving TOF >or=to 0.7 at 9.8 +/- 2.5, 11.4 +/- 2.8, and 19.6 +/- 6.3 min compared with 19.9 +/- 5.4, 26.4 +/- 8.3, and 32.9 +/- 9.8 min in adults (P < 0.0001). In conclusion, mivacurium requirements were correlated with PChE, were greater in children than in adults, and were reduced by sevoflurane. Neuromuscular recovery occurred more rapidly in children and was delayed by sevoflurane. Implications: The mivacurium infusion requirement to maintain constant 90%-95% neuromuscular block during anesthesia is correlated with plasma cholinesterase activity. It is increased in children and reduced by the inhaled anesthetic sevoflurane. Despite the larger dose administered to children, recovery from block occurred more rapidly in children than in adults and was delayed by sevoflurane. (Anesth Analg 1998;87:772-8)

S429 Introduction: Sevoflurane, like isoflurane and desflurane [1,2], is expected to decrease mivacurium requirements and prolong recovery. This study compared mivacurium infusion rates and recovery characteristics in adults and children during propofol/narcotic and sevoflurane anesthesia. Methods: After informed consent, 75 adult (20-65 yr) and 75 pediatric (2-12 yr), ASA 1-2, elective surgical patients were randomized to 3 groups to receive anesthesia with propofol/narcotic, 0.5 or 1.0 MAC sevoflurane. Blood was sampled for plasmacholinesterase estimation, and EMG neuromuscular monitoring (Datex Relaxograph: TOF every 10 sec, adductor pollicis) before mivacurium 0.25 mg/kg i.v. bolus. Mivacurium infusion commenced at 10 [micro sign]g/kg/min and was titrated to maintain 90-95% block. Rates were recorded every 5 min. At the end of surgery, the infusion was stopped and spontaneous recovery from mivacurium blockade monitored until TOF 0.7 was achieved. Results: Neither adults nor children showed demographic differences among groups. Plasmacholinesterase concentrations were normal (adults 4-12, children 6-16 KU/L). Mivacurium infusion rates, twice as high in children as in adults, decreased over time, and in proportion to sevoflurane concentration. Recovery was prolonged, but children recovered twice as quickly as adults (Table 1).Table 1Discussion: Sevoflurane halved mivacurium infusion requirements and doubled recovery times. Higher doses were needed in children, but recovery was faster than in adults. Mivacurium rates continued to decrease and, at 45 min, sevoflurane equilibration was incomplete at the neuromuscular junction.

Midazolam has GABAergic effects in children that may modify propofol-induced involuntary movements, yet delay recovery. In a double-blind, randomized study, 24 children (2-7 yr of age, ASA physical status I or II) undergoing short surgical procedures received midazolam 0.5 mg/kg (Group M) or placebo (Group P) per os 20-30 min before propofol anesthesia (5 mg/kg intravenously followed by an infusion). Blind observers scored sedation and anxiety levels (scale 1-4) before premedication, at separation from parents, and at induction of anesthesia. Induction and emergence were videotaped, and body movements were recorded. During recovery, times to eye opening and maximum Steward (SS = 6) and Vancouver Sedative Recovery (VSRS = 22) scores were noted. Parents were questioned about side effects that may have occurred during the following week. Both groups were similar in age, sex, weight, timing of premedication, propofol dose, and duration of surgery. The incidence of involuntary movements did not differ between groups but was higher at induction (79%) than on emergence (25%) (P < 0.05). Anxiety and sedation scores were similar in Group P and Group M, but recovery took longer after midazolam, with eye opening (mean +/- SD) 24 +/- 7 vs 43 +/- 18 min, maximum SS (median and range) 27 (13-37) vs 55 (24-138) min, and maximum VSRS 51 (30-100) vs 80 (50-130) min. Children returned to normal activity in 1 (0-5) day, and none exhibited neurological complications. We conclude that an oral premedicant dose of midazolam prolongs recovery from anesthesia in children without affecting dystonic movements after propofol. (Anesth Analg 1997;85:50-4)

BACKGROUND:Reversal of neuromuscular blockade induced with pancuronium, d-tubocurarine, or doxacurium is achieved using smaller doses of neostigmine in adults than in children. Also, pancuronium- and doxacurium-induced blockade is reversed with smaller doses of edrophonium in children than in adults. The purpose of this study was to compare the spontaneous and neostigmine- and edrophonium-assisted recovery of mivacurium-induced neuromuscular block in adults and children. METHODS:Fifty-four adults, aged 40.1 +/- 10.9 yr, and 54 children, aged 4.9 +/- 0.7 yr, physical status ASA 1-2, were studied during propofol/fentanyl/nitrous oxide anesthesia. A Datex relaxograph was used to monitor the electromyographic response of the adductor pollicis to train-of-four stimulation of the ulnar nerve every 10 s. After induction of anesthesia, 0.2 mg x kg(-1) intravenous mivacurium was administered followed by an infusion to maintain 90-95% T1 block. At the end of surgery, one of four doses of neostigmine (5, 10, 20, and 50 micrograms x kg(-1)) or edrophonium (100, 200, 400, and 1,000 micrograms x kg(-1)) or placebo was given, by random allocation, when T1 had recovered to 10%. Values of T1 and train-of-four were measured for 10 min. RESULTS:Spontaneous recovery proceeded more rapidly in children than in adults. At 10 min, T1 had recovered to 97 +/- 2% (SD) in children compared with 69 +/- 11% in adults and train-of-four to 84 +/- 5% versus 30 +/- 13% (P<0.0001). In children, 10 min after reversal, recovery of T1 and train-of-four was not different from control after edrophonium and was enhanced only by the larger doses of neostigmine. In adults, recovery was accelerated by both edrophonium and neostigmine. Five minutes after reversal, recovery was improved by either drug in adults and in children. CONCLUSIONS:Spontaneous recovery from mivacurium- induced neuromuscular block is more rapid in children than in adults. Ten minutes after attempted reversal, recovery is accelerated by edrophonium and usually by neostigmine in adults but not in children. Thus, when reversal is required, edrophonium may be preferred to neostigmine.

BACKGROUND:The rapid recovery from mivacurium- induced neuromuscular block has encouraged omission of its reversal. The purpose of this study was to determine, in children and in adults, whether failure to reverse mivacurium neuromuscular block was associated with residual neuromuscular block on arrival in the postanesthesia care unit. METHODS:In 50 children, aged 2-12 yr, and 50 adults, aged 20-60 yr, anesthesia was induced and maintained with propofol and fentanyl, and neuromuscular block was achieved by an infusion of mivacurium, to maintain one or two visible responses to train-of-four (TOF) stimulation of the ulnar nerve. At the end of surgery, mivacurium infusion was stopped, and 10 min later, reversal was attempted with saline or 0.5 mg x kg(-1) edrophonium by random allocation. On arrival in the postanesthesia care unit, a blinded observer assessed patients clinically and by stimulation of the ulnar nerve with a Datex electromyogram in the uncalibrated TOF mode. RESULTS:Children arrived in the postanesthesia care unit 8.2 +/- 3-4 min after reversal of neuromuscular block and showed no sign of weakness, either clinically or by TOF stimulation. Although TOF ratio was greater in children who had received edrophonium (1.00 +/- 0.05 vs. 0.93 +/- 0.01, P<0.01), TOF was >0.7 in all children. Adults arrived in the postanesthesia care unit 12.9 +/- 5.3 min after reversal of neuromuscular block(P<0.01 vs. children). Six in the saline group demonstrated weakness (two required immediate reversal of neuromuscular block, and TOF was <0.7 in four others), compared with TOF <0.7 in only one of the edrophonium group (P<0.05). CONCLUSIONS:This study demonstrated that, in adults, failure to reverse mivacurium neuromuscular block was associated with an increased incidence of residual block. Such weakness was not observed in children receiving similar anesthetic and neuromuscular blocking regimens.

Background. Increasing age appears to be associated with a slower onset of neuromuscular blockade, but such an effect has not been studied with the same doses of the same drugs across pediatric and adult age groups.Methods. The authors measured the evoked compound action potential of the adductor pollicis muscle in response to 0.1-Hz stimulation of the ulnar nerve, during fentanyl-thiopental-oxygen anesthesia, in 160 patients aged 1-3 yr, 3-10 yr, 20-40 yr, or 60-80 yr. Subparalyzing doses of vecuronium (0.03 mg/kg) or succinylcholine (0.3 mg/kg), or paralyzing doses of vecuronium (0.1 mg/kg) or succinylcholine (1.0 mg/kg), were administered to ten patients in each age group.Results: Onset time, defined as the time from injection to maximum depression of response with a subparalyzing dose or the time from injection to ablation of visible response with a paralyzing dose, varied with age in all groups (P < 0.001). For 0.3 mg/kg succinylcholine, it increased from 49 +/- 6 s in 1-3-yr-old patients, to 104 +/- 9 s in 60-80-yr-old patients (P < 0.00001). For 0.03 mg/kg vecuronium, onset time was 3.6-5.9 times longer than for succinylcholine, increasing from 219 +/- 15 s in 3-10-yr-old patients to 473 +/- 30 s in 60-80-yr-old patients (P < 0.00001 by linear regression). For paralyzing doses, succinylcholine 1.0 mg/kg had an onset time of 58 +/- 7 s and 95 +/- 7 s, in 1-3-yr-old and 60-80-yr-old patients, respectively (P < 0.001). For 0.1 mg/kg vecuronium, onset time varied between 125 +/- 19 s in 1-3-yr-old patients to 295 +/- 31 s in 60-80-yr-old patients (P < 0.00001), and was 2.1-3.3 times longer than 1 mg/kg succinylcholine.Conclusions. Increasing age is associated with slower onset for both succinylcholine and vecuronium. When equipotent, subparalyzing doses of succinylcholine and vecuronium are compared, onset time is 4.5 times as long with vecuronium.

After anesthesia employing nondepolarizing muscle relaxants, 30%-40% of adult patients demonstrate residual paralysis with a train-of-four ratio less than 70%, but it is not known if the same is true for children. This study was designed to investigate neuromuscular transmission in 91 ASA physical status I or II day-care children (aged 0-10 yr) after halothane anesthesia in which pancuronium (n = 34), atracurium (n = 32), or vecuronium (n = 25) was administered. Peripheral nerve stimulation was used clinically to assess neuromuscular blockade during surgery. In the recovery room, the evoked response of the adductor pollicis muscle was measured by train-of-four stimulation of the ulnar nerve. This measurement was made (mean +/- SEM) at 18.0 +/- 1.5, 15.0 +/- 1.3, and 15.0 +/- 1.7 min after pharmacologic antagonism with 0.02 mg/kg atropine and 0.06 mg/kg neostigmine in the pancuronium, atracurium, and vecuronium groups, respectively. There were no differences in the ages of the patients in the three groups at 4.3 +/- 0.4, 4.0 +/- 0.4, and 5.0 +/- 0.5 yr, with 17 children less than 2 yr. Recovery from neuromuscular blockade in all three groups was almost complete. The train-of-four ratio (height of fourth twitch compared with the first) was similar in patients who had received pancuronium (96.7% +/- 0.9%), atracurium (95.5% +/- 0.9%), or vecuronium (96.3% +/- 1.3%). Therefore, postoperative muscle weakness or respiratory impairment is unlikely in pediatric day-care surgical patients more than 2 yr old when these anesthetic techniques are used.

Wiesel, Saul MD, FRCPC; Bevan, Joan C. MD, FFARCS; Samuel, Jacob MB, FFARCS; Donati, Francois PhD, MD, FRCPC Author Information

The increases in tension at the masseter and adductor pollicis muscles following succinylcholine, 1 mg.kg-1, during halothane anaesthesia were measured in eight children, 3-10 yr, with strabismus. The results were compared with those obtained in a control group of general surgical patients. Supramaximal train-of-four (TOF) stimulation was applied to the ulnar nerve and the nerve to the masseter simultaneously. Jaw closure was measured by a force transducer system. In all patients, succinylcholine caused an increase in resting tone at the jaw and at the thumb. In the strabismus group, the magnitude of this increase was 55.7 +/- 23.2 g, mean +/- SD, at the jaw and 11.3 +/- 5.6 g at the thumb. This was not significantly different from the values obtained in controls, 45.3 +/- 33.4 g and 7.9 +/- 4.2 g, respectively. The duration of the phenomenon was 1-2 min in both muscles studied, and was not statistically different in the strabismus group. Time to complete neuromuscular blockade was significantly faster at the masseter, 31 +/- 6 sec--control groups; 39 +/- 11 sec--strabismus group, than at adductor pollicis, 61 +/- 34 sec--control groups; 75 +/- 28 sec--strabismus group (P less than 0.05 and 0.013 respectively). It is concluded that succinylcholine causes similar increases in jaw tension and comparable degrees of neuromuscular blockade in patients undergoing strabismus surgery as in other children.

The effect of succinylcholine on baseline tension and evoked twitch height was measured at the masseter and the adductor pollicis muscles in ten adults undergoing elective surgery. During thiopental-nitrous oxide-enflurane (end-tidal concentration less than 0.25%) anesthesia, supramaximal stimulation was applied to both the ulnar nerve and the nerve to the masseter. Baseline tension and the isometric force of contraction were measured at the jaw and the thumb. Cumulative dose-response relationships were obtained by giving succinylcholine in incremental doses (initial dose, 0.10 mg/kg, followed by 0.05- or 0.1-mg/kg increments, depending on response). An infusion was started after the maximum effect of the first dose, at a rate adjusted to compensate for the rapid metabolism of the drug. There was no difference between the sensitivity of the masseter and the adductor pollicis. The ED50 values were (mean +/- SEM) 0.11 +/- 0.01 mg/kg at both muscles. The ED90 values were 0.17 +/- 0.02 mg/kg at the masseter and 0.16 +/- 0.01 mg/kg at the adductor pollicis. Onset of action was more rapid at the masseter. In six of the ten patients, baseline tension at the jaw was found to increase by a mean of 80 +/- 24 g (range 25-188 g). It is concluded that in adults, masseter neuromuscular blockade can be achieved with succinylcholine doses approximately equal to those required to block the adductor pollicis. In addition, the drug may cause increased tension in the muscles of the jaw.

Double-burst stimulation (DBS), a new technique to evaluate neuromuscular function, consists of two 50-Hz trains of 60-ms duration and 750 ms apart. DBS was compared with train-of-four (TOF) stimulation in 21 children aged 3-10 yr, during halothane anesthesia. On one arm the ulnar nerve was stimulated supramaximally with TOF stimulation every 12 s and the force of the evoked contraction of the adductor pollicis measured with an FTO3 force transducer and recorded on paper. Atracurium (0.4-0.5 mg.kg-1) was administered. During recovery from neuromuscular blockade, TOF stimulation was interrupted periodically and DBS substituted. The same stimulation patterns were applied to the ulnar nerve of the other arm simultaneously, and the clinical anesthesiologist was asked to estimate the degree of fade with both. There was good correlation between the measured TOF ratio (ratio of fourth to first response) and DBS ratio (ratio of second to first response). The TOF and DBS ratios above which fade could no longer be appreciated manually were (mean +/- SEM) 0.44 +/- 0.03 and 0.67 +/- 0.04 (P = 0.0002). Corresponding ranges were 0.3-0.8 for TOF and 0.4-0.9 for DBS, but DBS fade was always apparent if TOF fade could be detected. Therefore, in children, DBS is more sensitive than is TOF stimulation for the clinical assessment of recovery from neuromuscular blockade.

We have studied the effect of prior administration of non-depolarizing neuromuscular blocking drugs on suxamethonium-induced increases in masseter muscle tension in 21 children aged 3-10 yr, anaesthetized with nitrous oxide and halothane using supramaximal stimulation of the ulnar nerve and the nerve to masseter. Resting tension and isometric force of contraction were measured in the adductor pollicis and masseter muscles. A sub-paralysing dose of tubocurarine 0.05 mg kg-1, a paralysing dose of atracurium 0.5 mg kg-1 or saline was given, followed 3 min later by suxamethonium 1 mg kg-1. Onset times of suxamethonium and atracurium block were shorter in the masseter than in the adductor pollicis muscle. When preceded by a sub-paralysing dose of tubocurarine, suxamethonium produced an increase in masseter tension (47 (SEM 15) g) similar to that produced by suxamethonium alone (59 (13) g). Prior administration of a paralysing dose of atracurium almost abolished this increase in tension (2.5 (2.5) g) (P less than 0.05 vs saline). The tension increase in adductor pollicis was 0, 3.2 (2.2) and 5.9 (1.1) g in the atracurium, tubocurarine and saline groups, respectively. Tubocurarine and atracurium prevented muscle fasciculations in all patients. It was concluded that increased muscle tone is a normal response to suxamethonium and is greater in the masseter than adductor pollicis. Sub-paralysing doses of non-depolarizing neuromuscular blockers have little effect, in contrast with paralysing doses. This suggests that the effect is mediated via postsynaptic receptors.

Summary A case report is presented of a patient receiving chronic phenytoin therapy who demonstrated resistance to pancuronium by increased hourly requirements. Stable neuromuscular blockade was achieved by atracurium infusion at normal rates. Possible explanations for the differences in response to the two non‐depolarizing muscle relaxants are discussed.