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Background Recent evidence is consistent with the view that volatile anesthetics interact directly with excitable membrane-bound channel proteins. If these agents interact directly with chiral centers in the neuronal cell membrane, then their effects should be stereoselective. Using rat brain membranes enriched in gamma-aminobutyric acid type A (GABAA) receptors, we investigated the hypothesis that the permeability response of this well-characterized central nervous system channel protein to stereoisomers of isoflurane is stereoselective. Methods Rat brain synaptic microvesicles were prepared by differential centrifugation. Agonist-stimulated 36Cl- flux through membrane-bound GABAA receptors was assayed in the presence of (+)- and (-)-isoflurane and compared with control conditions. Results Both isomers increased the potency and efficacy of GABA; however, (+)-isoflurane was significantly more potent and efficacious than the (-)-isomer. For example, the (+)-isomer (140 microM) reduced the median effective concentration of GABA from 12.7 +/- 1.0 to 5.4 +/- 0.5 microM, whereas the (-)-isomer reduced it to 9.6 +/- 1.0 microM (P < 0.001). The (+)-isomer also was 1.6 times as potent as the (-)-isomer in augmenting 5 microM GABA-gated flux (79 +/- 11 vs. 130 +/- 17 microM, respectively; P = 0.01). In addition, the (+)-isomer produced significantly greater maximal enhancement of flux (9.4 +/- 0.4 vs. 7.0 +/- 0.3 nmol.mg-1.3 s-1; P < 0.001). Conclusions Isoflurane's effects on GABA-gated chloride flux were stereoselective. This result supports direct interaction with a stereoselective site, possibly the GABAA channel protein itself, rather than a nonspecific perturbation of the surrounding membrane lipid. In addition, these findings, from a functional assay using mammalian brain, agree with recent observations in invertebrate ion channels and mammalian neuronal cell cultures.

The neuromuscular effects of the combined administration of pancuronhim and dimethyltubocurarine were evaluated in children undergoing reconstructive surgery (n = 6), or the skin grafting of acute burn wounds: body surface area (BSA) burns less than 40% (n =5); and BSA burns greater than 40% (n =6). A dose of pancuronium 0.005 mg kg−1 was considered to be equipotent with dimethyitubocurarine 0.02 mg kg−1, and each dose was defined as being equal to 1 relaxant equivalent (RE). Incremental doses of the combination of pancuronium and dimethyltubocurarine were administered until a 95% depression of twitch height was achieved (ED95). These results were compared with previously published data for pancuronium and dimethyltubocurarine alone. The mean ED95 of the combination in the control population (reconstructive surgery) was 5.1 RE, compared with 10.8 RE and 10.0 RE for pancuronium and dimethyltubocurarine, respectively, administered alone. In the acutely burned population, the mean ED95 for the combination was 9.9 and 15.9 RE, respectively, compared with 26 RE for pancuronium alone in burned patients. In all groups of patients, significantly less total drug was required when the combined therapy was used.

To determine whether prematurely born infants with a history of idiopathic apneic episodes are more prone than other infants to life-threatening apnea during recovery from anesthesia, the authors prospectively studied 214 infants (173 full term, 41 premature) who received anesthesia. Fifteen premature infants had a preanesthetic history of idiopathic apnea. Six of these required mechanical ventilation because of idiopathic apneic episodes during emergence from anesthesia. Two were ventilated for other reasons, and seven recovered normally. Infants ventilated for apnea were younger (postnatal age 1.6 +/- 1.2 months, mean +/- SD; conceptual age 38.6 +/- 3.0 weeks) than those who recovered normally (postnatal age 5.6 +/- 2.7 months; conceptual age 55.1 +/- 11.3 weeks) (P less than 0.01). No other premature or full-term infant was ventilated because of postoperative apneic episodes. The authors conclude that anesthetics may unmask a defect in ventilatory control of prematurely born infants younger than 41-46 weeks conceptual age who have a preanesthetic history of idiopathic apnea.

Expired carbon dioxide measurements (PeCO2) were used (1) to assess the adequacy of initial alveolar ventilation, and (2) to document intraoperative airway events and metabolic trends. Three hundred and thirty-one children were studied. Thirty-five intraoperative events were diagnosed by continuous PeCO2 monitoring; 20 were potentially life-threatening problems (malignant hyperthermia, circuit disconnection or leak, equipment failure, accidental extubation, endobronchial intubation, or kinked tube); only two of these were also diagnosed clinically. The duration of anaesthesia may be a factor: 3.9 hours for cases with events vs. 2.5 hours for cases without events (p less than 0.002). There was a higher incidence of hypercarbia (peak expired PeCO2 greater than or equal to 50) in children who were not intubated (29 per cent) compared to those who had an endotracheal tube in place (12 per cent) (p = 0.0001). Hypocarbia (peak expired PeCO2 less than or equal to 30) was more frequent in intubated cases (11 per cent) than in unintubated cases (three per cent) (p = 0.03). There was a high incidence of hypocarbia in infants less than one year of age (p = 0.02). We conclude: (1) life-threatening airway problems are common during anaesthesia in paediatric patients; (2) quantitative measurement of PeCO2 provides an early warning of potentially catastrophic anaesthetic mishaps; (3) the incidence of events increases with duration of anaesthesia.