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The effect of high-protein meal on the hepatic clearance (ClH) of intravenous lidocaine, because of its conceptual importance in understanding first-pass metabolic phenomena, was evaluated in nine healthy males. Our randomized crossover study demonstrated that mean ClH rose from 1245 to 1477 ml/min (P less than 0.03) as a result of the meal (i.e., mean area under the blood concentration-time curve decreased 20%). The magnitude of the change in clearance correlated weakly with fasting ClH (r = 0.54; slope = -0.037% per ml/min; intercept = 67.2%; P less than 0.15). In a separate study, it was observed that the meal did not influence lidocaine serum protein binding; the free fraction of lidocaine in samples drawn from the subjects in the fasting state averaged 0.305 +/- 0.027 while that from subjects who had eaten was 0.321 +/- 0.042. These data suggest that the mean clearance of lidocaine is increased by stimulation of hepatic blood flow rate. Furthermore, the magnitude of this increase is consistent with expectations based on a simple physiologic model. Thus, these data provide experimental support for the hypothesis that transient increases in splanchnic blood flow rate observed after a high-protein meal may explain apparent improvement of the oral bioavailability of model high intrinsic clearance drugs.

Four case histories are presented to illustrate that haemodynamic monitoring is a useful guide in the acute management of severe pre-eclampsia and eclampsia. The application of intensive monitoring and therapy to patients in the delivery room is both feasible and of great help to the clinician managing fluid therapy and/or anaesthesia.

A randomized double blind placebo controlled study of the efficacy, duration and safety of epidural morphine for the management of pain after Cesarean section is reported. Three similar groups of patients received either 0, 4 mg or 8 mg of morphine sulphate in 10 ml of normal saline through an epidural catheter at the completion of the operation. Compared to the saline controls, both the 4 mg and 8 mg epidural morphine groups had significant pain relief as judged by an analogue pain scale (p less than 0.001), the time to the first administration of narcotic analgesics (p less than 0.001) and the amount of supplemental analgesic required in the first 36 hours after operation (p less than 0.001). The side effects occurred in a dose-dependent fashion. Two patients who received epidural morphine 8 mg plus additional narcotic or antihistamine had reduced respiratory rates but were easily rousable. Our experience suggests that the epidural administration of morphine 4 mg may be a safe and reliable method of obtaining prolonged analgesia following Caesarean section.

The effect of lateral positioning and the volume of drug injected on the spread of epidural anaesthesia was assessed in 131 healthy parturients. Epidural injection for anaesthesia was done at the L3-4 interspace and a catheter was inserted into the epidural space after injection of the drug. The patients were randomly assigned to four groups. The doses used were 12 ml of bupivacaine 0.25 per cent and 6 ml of bupivacaine 0.5 percent. Patients were kept in the lateral position in which the block was done (Groups I and III) or turned to the opposite side after completion of the epidural injection (Groups II and IV). Sensory levels and maternal assessment of pain relief were determined fifteen to twenty minutes after injection. All assessments were done by a trained observer who did not know to what group the patient had been allocated. Maintenance of the lateral position after induction of epidural anaesthesia is compatible with satisfactory analgesia for labour. Twelve ml bupivacaine 0.25 per cent provides better analgesia than 6 ml bupivacaine 0.5 per cent although the same mass is injected. The quality of analgesia is improved by turning the patients to the contralateral side after injection of 12 ml bupivacaine 0.25 per cent.

The effects of enflurane analgesia (approximately 0.5%) were studied in 55 patients during the second stage of normal vaginal delivery and were compared with effects of nitrous oxide (approximately 40%) in 50 similar patients. The enflurane and oxygen mixture was rated satisfactory by 89% of the mothers and 80% of the anesthesiologists. These ratings did not differ significantly from those for nitrous oxide. Obstetricians, however, rated the enflurane and oxygen mixture superior. The newborns of mothers receiving both agents wee vigorous and comparable when assessed by Apgar scores and cord blood gas tensions. The estimate of blood loss was similar in both groups. Serum inorganic fluoride concentrations in the mother after anesthesia were not significantly increased from preanesthetic levels with either agent. There was no biochemical evidence of renal toxicity. In neonates of mothers given enflurane, the mean umbilical cord concentration of serum inorganic fluoride ions was 2.4 +/- 0.2 micromoles/L, a value well below that associated with nephrotoxicity.