Report of the Society for Pediatric Anesthesia 13th annual meeting.
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Anesthesia↗
Biomedical subjects
N Goudsouzian
Publications and source records attributed to N Goudsouzian.
Intramuscular rocuronium in infants and children: a multicenter study to evaluate tracheal intubating conditions, onset, and duration of action.
BACKGROUND: This multicenter, assessor-blinded, randomized study was done to confirm and extend a pilot study showing that intramuscular rocuronium can provide adequate tracheal intubating conditions in infants (2.5 min) and children (3 min) during halothane anesthesia. METHODS: Thirty-eight infants (age range, 3-12 months) and 38 children (age range, 1 to 5 yr) classified as American Society of Anesthesiologists physical status 1 and 2 were evaluated at four investigational sites. Anesthesia was maintained with halothane and oxygen (1% end-tidal concentration if <2.5 yr; 0.80% end-tidal concentration if >2.5 yr) for 5 min. One half of the patients received 0.45 mg/kg intravenous rocuronium. The others received 1 mg/kg (infants) or 1.8 mg/kg (children) of intramuscular rocuronium into the deltoid muscle. Intubating conditions and mechanomyographic responses to ulnar nerve stimulation were assessed. RESULTS: The conditions for tracheal intubation at 2.5 and 3 min in infants and children, respectively, were inadequate in a high percentage of patients in the intramuscular group. Nine of 16 infants and 10 of 17 children had adequate or better intubating conditions at 3.5 and 4 min, respectively, after intramuscular rocuronium. Better-than-adequate intubating conditions were achieved in 14 of 15 infants and 16 of 17 children given intravenous rocuronium. Intramuscular rocuronium provided > or =98% blockade in 7.4+/-3.4 min (in infants) and 8+/-6.3 min (in children). Twenty-five percent recovery occurred in 79+/-26 min (in infants) and in 86+/-22 min (in children). CONCLUSIONS: Intramuscular rocuronium, in the doses and conditions tested, does not consistently provide satisfactory tracheal intubating conditions in infants and children and is not an adequate alternative to intramuscular succinylcholine when rapid intubation is necessary.
Androstanols↗
Potentiation of mivacurium by rocuronium is age- and time-dependent: a study in children, adolescents, and young and elderly adults.
Potentiation occurs when the steroidal muscle relaxant, rocuronium, is coadministered with the benzylisoquinolinium relaxant, mivacurium. The effect of time and age on this interaction was evaluated in four predetermined groups: children, adolescents, young adults, and elderly adults (15 per group) by monitoring the ulnar nerve-evoked force of contraction of the adductor pollicis (twitch response). During recovery from paralysis induced by 800 micrograms/kg of rocuronium, an infusion of mivacurium was started and maintained for at least 90 minutes to retain the twitch response at 1% to 9% of baseline tension (95 +/- 4% paralysis). Rocuronium at 600 micrograms/kg induced greater than 95% paralysis in 57 of the 60 patients within 2.2 +/- 0.4 (mean +/- SE) minutes. The period of recovery from rocuronium-induced paralysis to 5% of baseline twitch height was longest in the elderly (30.1 +/- 2.9 minutes) and shortest in the adolescents (16.5 +/- 2.4 minutes). The mivacurium infusion requirements to maintain 95 +/- 4% paralysis was highest in children and progressively increased with time. In young and elderly adults, the infusion rates remained lower than that of children and did not change with time. The incidence of satisfactory spontaneous recovery within 20 minutes (train-of-four ratio > 75%) was the highest in children, followed by adolescents and young adults, and was least in the elderly. The residual neuromuscular effect of rocuronium on the subsequent mivacurium infusion was most pronounced in the elderly, followed by young adults, then adolescents, and was least in children.
Adolescent↗
Prolonged mivacurium infusion in young and elderly adults.
PURPOSE: This study was designed to evaluate pharmacodynamically and pharmacokinetically 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 during 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 micrograms.kg-1.min-1 in young adults, and 4.3 +/- 0.3 micrograms.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 micrograms.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 low 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.
Adolescent↗
Pseudocholinesterase-mediated hydrolysis is superior to neostigmine for reversal of mivacurium-induced paralysis in vitro.
BACKGROUND: The metabolic hydrolysis of mivacurium (and succinylcholine) is markedly impaired in the presence of hereditary or acquired defects of pseudocholinesterase. Clinical reports are conflicting as to the utility of anticholinesterases, in the reversal of mivacurium paralysis. In the current study, the role of exogenous cholinesterases and/or of anticholinesterase, neostigmine, in the reversal of deep mivacurium-induced paralysis, was studied. The rat phrenic-diaphragm preparation, in a fixed volume of Krebs solution, was chosen to eliminate the confounding effects on the dissipation of neuromuscular effects caused by hydrolysis, elimination, and redistribution of the drug. METHODS: In the phrenic-diaphragm preparation, mivacurium was administered to obtain >90% single twitch inhibition. Single twitch responses (0.1 Hz) were monitored for 60 min, after which the response to train-of-four stimulation was tested. The reversal of mivacurium by 0.5, 1.0, or 2.0 units/ml of (true) acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase and by neostigmine, 0.1, 1.0, or 10.0 micrograms/ml tested. The efficacy of human plasma cholinesterase, 1 unit/ml in combination with each of the above neostigmine concentrations, also was examined. The reversal of succinylcholine-induced paralysis by the acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase (1 unit/ml) alone and in the presence of neostigmine (10.0 micrograms/ml) was additionally tested as a positive control. A train-of-four ratio > 0.75 was considered adequate reversal. RESULTS: Acetylcholinesterase was a poor hydrolyzer of mivacurium, as bioassayed by reversal of paralysis. Bovine pseudocholinesterase in concentrations of 0.5 and 1.0 units/ml did not effectively reverse single twitch and train-of-four responses by 60 min, but bovine pseudocholinesterase (2 units/ml) and all concentrations of human plasma cholinesterase did. Neostigmine alone, tested at all concentrations, was an incomplete reversal drug. Clinical or therapeutic concentrations (0.1 and 1.0 micrograms/ml) of neostigmine did not, but pharmacologic concentrations (10 micrograms/ml) interfere with the efficacy of human plasma cholinesterase (1 unit/ml). Bovine pseudocholinesterase and human plasma cholinesterase equally reversed the effects of succinylcholine but acetylcholinesterase did not, whereas the addition of 10 micrograms/ml neostigmine to the enzymes inhibited the reversal of succinylcholine. CONCLUSIONS: Human plasma cholinesterase will reverse mivacurium more effectively than bovine pseudocholinesterase, but both will effectively reverse succinylcholine. Acetylcholinesterase has no effects on either relaxant. The anticholinesterase neostigmine was an incomplete reversal drug. Pharmacologic concentrations of anticholinesterases do, while clinical or therapeutic concentrations do not, completely inhibit the metabolic activity of pseudocholinesterases.
Animals↗
Mivacurium infusion requirements following vecuronium: different response between adults and children.
The mivacurium infusion requirements following vecuronium were evaluated in 15 adults and 15 children in an open prospective clinical study. This study was undertaken to elucidate whether potentiation of effect occurred when a mivacurium infusion was administered after vecuronium was used for the facilitation of tracheal intubation. The adult patients were anaesthetized with N2O:02, propofol and fentanyl, the children with halothane (1%) N2O:O2. Vecuronium 100 micrograms.kg-1 was administered during stimulation of the ulnar nerve with train-of-four stimuli at 0.1 Hz. The force of contraction of adductor pollicis was recorded. Upon recovery of the twitch response from vecuronium, a mivacurium infusion was started at 4 micrograms.kg-1.min-1, thereafter adjustments were made to maintain the first twitch of the train-of-four (T1) at 1-10% of control. The mean (+/- SE) initial infusion requirements in children of mivacurium was 4.3 (0.4) micrograms.kg-1.min-1 which increased linearly (P < 0.001) over the next 90 min to 10 micrograms.kg-1.min-1. In adults the infusion requirement was lower than in children and remained at approximately 3 micrograms.kg-1.min-1 over the next 75 min. At the end of the surgical procedure, the children recovered faster than the adults with no child requiring reversal. Because of prolonged recovery ( > 20 min), seven adults required reversal with 15-70 micrograms.kg-1 neostigmine. Mivacurium infusion requirements following vecuronium are higher in children than adults. Potentiation of the effects of mivacurium were seen when vecuronium preceded mivacurium. This potentiation of effect lasted longer in adults than in children.
Adolescent↗
Neuromuscular blocking agents of intermediate duration in children.
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Androstanols↗
Dose-response to pancuronium in identical twins.
The dose-response to pancuronium was determined in identical twins within an hour with the same anesthetic technique. The dose-response curves did not differ from parallelism, but one infant was more sensitive to pancuronium than the other. The recovery rates were also different. The variation in the dose response to pancuronium seems to extend to identical twins.
Anesthesia, Intravenous↗
Continuous infusion of atracurium in children.
Atracurium infusion requirements were determined in 28 children anesthetized with N2O:O2 narcotic, N2O:O2 halothane (1% inspired), and N2O:O2 enflurane (2% inspired). When the patient was recovering from a bolus dose of 0.4 mg/kg atracurium, a continuous infusion of atracurium was started and the rate was adjusted to maintain 90-99% muscle twitch depression. Patients receiving enflurane anesthesia required atracurium at an infusion rate of 4.9 +/- 0.3 micrograms X kg-1 X min-1 which was a significantly lower rate (P = 0.0001) than those anesthetized with halothane (8.3 +/- 0.4 micrograms X kg-1 X min-1) or with N2O:O2 and narcotic (9.3 +/- 0.5 micrograms X kg-1 X min-1). At the onset of neuromuscular blockade, the twitch response disappeared faster after train-of-four stimulation repeated every 10 s than after single twitch rates of stimulation at 0.1 Hz. In children, during halothane anesthesia after 0.4 mg/kg atracurium, the response of the adductor of the thumb was ablated in 2.0 +/- 0.3 min with train-of-four stimulation, and in 3.7 +/- 0.4 min with single twitch stimulation. The authors recommend the use of a nerve stimulator during continuous infusion of atracurium because of the marked interpatient differences in infusion-rate requirements.
Anesthesia↗
Pharmacokinetics and pharmacodynamics of atracurium during isoflurane anesthesia in normal and anephric patients.
We compared the pharmacokinetics and pharmacodynamics of atracurium in eight normal and eight anephric patients during isoflurane anesthesia. Plasma concentrations were measured by high performance liquid chromatography after a single injection of 0.5 mg/kg, and neuromuscular effects were evaluated by the single twitch method. With regard to pharmacokinetic or pharmacodynamic parameters, we found no statistically significant differences between normal and anephric patients. We conclude that during isoflurane anesthesia, anephric patients distribute and eliminate atracurium much as normal patients do.
Anesthesia, General↗
Neuromuscular effects of atracurium in infants and children.
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Adolescent↗
End-tidal CO2 monitoring. Its use in the diagnosis and management of malignant hyperthermia.
Two cases of malignant hyperthermia are described where the earliest sign was a rise in the end-tidal CO2 concentration. This led to nearly immediate detection and adequate treatment with sodium dantrolene. These cases demonstrate the efficacy of monitoring end-expired CO2 concentrations in patients at risk from malignant hyperthermia, as well as a means for following the adequacy of treatment.
Carbon Dioxide↗
The dose-response effects of oral cimetidine on gastric pH and volume in children.
The effects of preanesthetic oral cimetidine on gastric fluid pH and volume were studied in 97 infants and children. A dose-response curve was constructed using doses of 2.5, 5.0, 7.5, and 10 mg/kg. The ED50 of cimetidine that produces pH values higher than 2.5 was 3.0 mg/kg, and the ED95 was 7.5 mg/kg. Cimetidine exponentially reduced the volume of gastric fluid. Cimetidine was most effective between one and four hours after oral administration. In children who are at high risk of pulmonary aspiration, we recommend that oral cimetidine, 7.5 mg/kg, be given 1-3 hours preoperatively in order to protect the lungs from the accidental aspiration of acidic gastric secretions.
Adolescent↗
Haemodilution in an eight-month-old infant.
Transient haemodilution was carried out in an 8-month-old infant whose parents were Jehovah's Witnesses during an abdominoperineal pull-through procedure. Adult ACD blood packs were altered to suit the needs of the child. With judicious fluid management, the child was extubated and did well postoperatively.
Blood Transfusion, Autologous↗
Reaction to ketamine: anaphylactoid or anaphylactic?
A 3-year-old child developed extensive macular rash after ketamine. The mechanism of this reaction was investigated by the Prausnitz-Kutzner (P-K) test. It demonstrated that the histamine release was not the result of an anaphylactic reaction, but rather a direct pharmacological effect of the drug. The result suggests that this child can receive ketamine in the future without any severe manifestations. The mechanisms of histamine release are discussed and the treatment of its clinical manifestations is reviewed.
Anaphylaxis↗