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Central nervous system protein kinases are the intracellular effectors for many of the signal transduction pathways essential to neurotransmission. Although the in vitro activity of at least one of these important enzymes, protein kinase C, is diminished by therapeutic concentrations of ethanol and other central depressants, the relationship of this effect to intoxication in vivo is not known. If intoxication by ethanol involves central protein kinase inhibition, then other inhibitors of these enzymes should enhance ethanol's intoxicating potency. To test this hypothesis, we compared the median effective concentrations of ethanol and two other n-alkanols for loss-of-righting reflex in Rana pipiens tadpoles pretreated with staurosporine and in untreated controls. Alkanol concentrations were confirmed by gas chromatography and staurosporine concentrations by ultraviolet absorbance spectrophotometry. Results obtained with 650 animals demonstrate that pretreatment with staurosporine concentrations in the nanomolar range significantly decrease the median effective concentration for ethanol (56% of control; p < 0.001), butanol (38% of control; p < 0.001), and octanol (59% of control; p < 0.001). This finding supports that central protein kinase inhibition may be involved in the acute intoxicating effects of ethanol and other n-alkanols.

Protein kinase C, the intracellular effector for the inositol phosphate-mediated signal transduction pathway, plays a key role in neurotransmission in the central nervous system. Although the in vitro activity of protein kinase C is inhibited by therapeutic concentrations of volatile anesthetics, the relation of this effect to in vivo obtundation has not been established. If obtundation by volatile anesthetics involves protein kinase C inhibition, then an inhibitor of this enzyme should decrease the anesthetic requirement. To test this hypothesis, we compared the EC50s of halothane and diethylether for loss of the righting reflex in Rana pipiens tadpoles pretreated with Staurosporine and in untreated controls. Anesthetic concentrations were confirmed by gas chromatography and Staurosporine concentrations by ultraviolet absorbance spectropho-tometry. Results obtained in more than 1000 animals indicated that pretreatment with Staurosporine concentrations in the nanomolar range significantly decreased the EC50 for both halothane (68% of control; P < 0.035) and diethylether (41% of control; P < 0.001). This finding implies that protein kinase C inhibition may play a role in general anesthetic-induced obtundation.

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.

Somatomedin-C stimulates somatostatin release to a maximum of 390 percent of basal release during short-term (20-minute) incubation of rat hypothalamus. It has no effect on basal or stimulated growth hormone release from primary cultures of rat adenohypophyseal cells during a 4-hour incubation, but inhibits stimulated release by more that 90 percent after 24 hours. These findings suggest that somatomedin-C participates in the growth hormone negative feedback loop with an immediate effect on hypothalamic somatostatin and a delayed effect on the anterior pituitary.

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.