Comparison of rectal to intramuscular administration of midazolam and atropine for premedication of children.

The effectiveness of midazolam and atropine as anaesthetic premedication was investigated, comparing rectal to intramuscular administration. A total of 202 children varying in age from 10 months to 9 years, who had been admitted to the Day Surgery Department for short ENT procedures, were assigned to one of two groups on a random basis. The first group (n = 102) was given 0.5 mg/kg midazolam and 0.05 mg/kg atropine as a rectal solution 30 to 75 min prior to induction, while the second group (n = 100) was given 0.15 mg/kg midazolam and 0.02 mg/kg atropine as an intramuscular injection 20 to 60 min prior to induction. The levels of sedation and salivation were compared, as was the degree of tolerance to intravenous induction. The parents of children older than 3 years of age were given a questionnaire designed to determine the degree of amnesia. We found this combination of drugs to be effective in the relief of anxiety, the inhibition of salivary secretion and the promotion of memory loss, regardless of the route of administration. We feel that rectal administration is preferable because it is not associated with pain or anxiety.

Comparison of metabolites in skeletal muscle biopsies from normal humans and those susceptible to malignant hyperthermia.

In earlier work on malignant hyperthermia (MH) susceptible pigs the concentration of muscle metabolites differed from that found in normal control pigs. Therefore, in the present study these metabolites were measured in human muscle biopsies to find out whether normal individuals could be discriminated from MH-susceptible persons. Analysis of skeletal muscle metabolites was performed on skeletal muscle obtained from humans (n = 68) being screened to exclude or confirm susceptibility to MH. Three groups were identified based on the reaction pattern of a skeletal muscle sample exposed in vitro to caffeine or halothane 1% plus caffeine: 1) MH susceptible (MHS; n = 19); 2) normal humans, (controls; n = 31); and 3) intermediate-reaction type (K-type:n = 18). No significant differences were found in metabolite levels of phosphocreatine (normal, MHS, and K-type: 13.20 vs. 13.74 vs. 14.42 nmol/mg wet weight, respectively), creatine (16.30 vs. 16.94 vs. 15.06 nmol/mg wet weight, respectively), adenosine triphospate (3.75 vs. 3.98 vs. 3.89 nmol/mg wet weight, respectively) and lactate (3.73 vs. 3.65 vs. 3.79 nmol/mg wet weight, respectively). It is concluded that analysis of skeletal muscle metabolites cannot be used as a screening test to confirm or exclude MH susceptibility in humans.

In vivo induced malignant hyperthermia in pigs. I. Physiological and biochemical changes and the influence of dantrolene sodium.

The effects of an induced malignant hyperthermia (MH) crisis have been studied in the intact pig. Both physiological and biochemical changes in skeletal muscle were studied. MH was induced with 3% halothane plus a bolus injection of succinylcholine. In the prechallenge period a significant difference was observed in the concentration of certain muscle metabolites, comparing the MH-susceptible (MH+) with the non-susceptible (MH-) pigs. A lower level was measured for phosphocreatine (PCr), inosine monophosphate (IMP) and an increased level of lactate and creatine (Cr) in the susceptible pigs (MH+). The challenge caused a significant reduction of the level of PCr and adenosine in MH+ pigs, compared to the prechallenge period. After administration of dantrolene sodium, a significant decrease was measured in the level of lactate, compared to the prechallenge period as well as during the challenge. In contrast, in the control pigs no significant changes were observed in muscle metabolites, either after induction of MH or after the administration of dantrolene sodium. Enzyme activity determinations of muscle adenylate kinase and adenosine monophosphate (AMP)-deaminase did not show any difference in activity either before or during the MH crisis or after treatment with dantrolene sodium. The earliest physiological change during an induced MH crisis in our study was the rapid increase of the end-tidal CO2. Within 5 min after MH induction, end-tidal CO2 was doubled. It is concluded that the monitoring of the end-tidal CO2 is essential to diagnose MH at a very early stage.

In vivo induced malignant hyperthermia in pigs. III. Localization of calcium in skeletal muscle mitochondria by means of electronmicroscopy and microprobe analysis.

Biceps femoris muscle biopsies of malignant hyperthermia susceptible (MH+) and non-susceptible (MH-) Dutch Landrace pigs were studied ultrastructurally, and exchangeable calcium was demonstrated, using the antimonate precipitation technique in combination with electron probe x-ray microanalysis. Biopsies were taken before and during the administration of halothane-plus-succinylcholine and after dantrolene sodium treatment of the animals. MH+ muscle, taken before the MH triggering, showed a high proportion (about 35%) of cells with supercontraction. Both MH+ and MH- muscle had broad but nearly identical ranges of cell diameter. Core-like structures were occasionally present in muscle from MH+ pigs. Muscle mitochondria from the MH+ pigs accumulated large amounts of calcium in their matrix compartment during the halothane-plus-succinylcholine induced MH crisis. This calcium loading in the course of time caused swelling and structural damage to the mitochondria. Skeletal muscle mitochondria from MH- pigs did not show such a reaction pattern on challenge with halothane and succinylcholine. It is concluded that in MH+ pigs the challenge brings about an increase in myoplasmic free calcium, which is predominantly due to calcium influx from the extracellular fluid. This rise in cytosolic calcium causes the mitochondria to accumulate the cation in an energy-dependent way. These findings are discussed in relation to the diverging halothane and caffeine contraction responses of aerobic type I and anaerobic type II muscle fibres.

In vivo induced malignant hyperthermia in pigs. II. Metabolism of skeletal muscle mitochondria.

The biochemical characteristics of skeletal muscle mitochondria of malignant hyperthermia (MH) susceptible Dutch Landrace pigs have been investigated before and during an MH attack, induced in vivo by halothane plus succinylcholine. The muscle homogenates have a decreased capacity to synthesize ATP and creatine phosphate during the MH period. Muscle mitochondria prepared from susceptible pigs in an MH period consume less oxygen than do mitochondria isolated before the attack, or mitochondria from control pigs during the challenge. The oxidative phosphorylation is not uncoupled during the critical period. The production of CO2 indicates that the in vitro measured capacity of the MH muscle mitochondria correctly reflects the in vivo condition during the MH attack. The restricted synthesis may be caused by a factor, finding expression in the mitochondria themselves, and obtained or activated during the MH attack.