Post partum phaeochromocytoma.

A case of phaeochromocytoma which presented post partum is reported. Uneventful pregnancy and delivery of a healthy infant were followed by acute respiratory and cardiovascular deterioration of the mother. Despite intervention our patient died 36 h after first presentation. Diagnosis of phaeochromocytoma was confirmed post mortem.

Morphine-6-glucuronide: effects on ventilation in normal volunteers.

The respiratory responses to intravenous morphine sulphate (0.12 mg/kg), morphine-6-glucuronide (M6G: 0.03 mg/kg) and placebo were assessed in 6 healthy volunteers, using a single blind randomised crossover design. Five of these subjects underwent an additional study of M6G at 0.06 mg/kg. Respiratory rate, minute volume and end-tidal CO2 were continuously measured using a low resistance non-rebreathing circuit, a mass spectrometer and a dry gas meter. The ventilatory responses to CO2 exposures (5.5% for 4 min) were assessed 40 and 20 min before, and 20, 40 and 80 min after drug administration. Following placebo and M6G (at both doses) no change in end-tidal CO2 occurred whilst the subjects were breathing air, whereas following morphine a significant rise was seen (P less than 0.05). Morphine reduced the ventilatory response to 5.5% CO2 at all times tested (P less than 0.05) and M6G (at both doses) reduced the response to CO2 at 20 and 40 min after administration, but to a lesser degree than did morphine (P less than 0.05).

Disposition of morphine-6-glucuronide and morphine in healthy volunteers.

The pharmacokinetics and subjective side effects of i.v. morphine sulphate 120 micrograms kg-1 and morphine-6-glucuronide (M6G) 30 micrograms kg-1 were determined in six healthy volunteers, using a placebo-controlled, single-blind randomized crossover design. Five of these volunteers underwent an additional (non-randomized) study of M6G 60 micrograms kg-1. Subjective side effects were similar following both drugs, but of shorter duration following M6G. Morphine was not detected after administration of M6G. For M6G 30 micrograms kg-1 the mean (SD) volume of distribution, elimination half-life and clearance were 29.38 (18.36) litre, 2.05 (1.2) h and 187.81 (37.41) litre h-1, respectively. These values were not significantly different from those obtained for M6G 60 micrograms kg-1. In all subjects the volumes of distribution and clearances were significantly smaller for M6G than for morphine, but the elimination half-lives were similar.

Analgesic efficacy and CSF pharmacokinetics of intrathecal morphine-6-glucuronide: comparison with morphine.

The analgesic efficacy and CSF pharmacokinetics of intrathecal morphine sulphate and morphine-6-glucuronide (M6G) were compared in a single-blind crossover study. Lumbar intrathecal catheters were sited in three patients with chronic cancer pain, and morphine sulphate 500 micrograms or M6G 500 micrograms given via the catheter on separate days. CSF was sampled for 24 h following drug administration and analysed for morphine and M6G by high pressure liquid chromatography. The mean (SD) requirement for patient controlled analgesia with pethidine was 393.3 (227.4) mg/24 h during the morphine limb of the trial and 226.7 (113.6) mg/24 h during the M6G limb. M6G was not detected in CSF following administration of morphine. Fitting of CSF concentrations to triexponential curves revealed mean (SD) alpha, beta and gamma half-lives of 13.2 (7.4), 54.9 (31.5) and 222.5 (100) min for morphine and 11.2 (2.4), 67.3 (49.9) and 619.3 (629.7) min for M6G.