Intravenous ketorolac tromethamine versus morphine sulfate in the treatment of immediate postoperative pain.

Intravenous ketorolac tromethamine was compared with morphine sulfate for the relief of moderate to severe postoperative pain and for side effects in 125 women undergoing major abdominal gynecologic surgery. Patients were randomly assigned to receive an initial intravenous dose of ketorolac 10 mg, ketorolac 30 mg, morphine 2 mg, or morphine 4 mg, administered in a double-blind fashion. No other narcotics were administered in the 3 hours preceding the first dose of study drug. A second dose was administered on request, but no sooner than 15 minutes after the initial dose. Patients who required additional analgesia within the 6-hour observation period were remedicated with a backup analgesic and withdrawn from the study. Pain scores and side effect evaluations were performed at baseline, 30 minutes, 1 hour, and then hourly for up to 6 hours or until the subject terminated the study. No significant differences among the treatments were noted in terms of area under the time-effect curves for pain intensity differences or pain relief. In each treatment group, 70-80% of patients withdrew within 1 hour and approximately 90% within 3 hours of the initial drug dose because of inadequate analgesia. With the dosage regimens used, neither drug adequately controlled moderate to severe pain in the immediate postoperative period. Patients receiving ketorolac experienced significantly less drowsiness than those given morphine, and some subjects in each experienced nausea. No serious adverse effects were reported.

Reversible resistance to the renal action of parathyroid hormone in man.

1. Normal subjects showed a highly reproducible, rapid increase in plasma adenosine 3':5'-cyclic monophosphate (cyclic AMP) after an intravenous injection of 200 MRC units of highly purified bovine parathyroid hormone. 2. No significant increase in plasma cyclic AMP was observed after administration of bovine parathyroid hormone to patients with severe chronic renal failure. 3. Even when renal function was not impaired, some patients with primary hyperparathyroidism, who had high concentrations of endogenous parathyroid hormone, showed resistance to bovine parathyroid hormone and when this was injected intravenously it caused only a small increase in plasma cyclic AMP. This resistance was reversible since there was marked improvement in the response after parathyroidectomy, when endogenous parathyroid hormone concentration had fallen. 4. It was possible to reproduce this resistance to the hormone by intravenous infusion of bovine parathyroid hormone into normal subjects. When the hormone (1000 MRC units) was infused over 2 h, after an initial increase there was a progressive decline in plasma cyclic AMP concentration and a fall in urinary cyclic AMP excretion. The response to a standard test stimulus (200 MRC units of bovine parathyroid hormone given as a rapid intravenous injection) was examined at intervals after 1000 units of bovine parathyroid hormone had been infused. Initially, the response was severely impaired; at 4 h, partial recovery had occurred and, 24 h after the infusion, recovery of the response was complete. The resistance was therefore reversible. Infusion of the amino-terminal peptide, fragment 1-34, gave the same effect as infusion of intact hormone. Region-specific assays for the hormone were used to show that the concentration of immuno-assayable hormone remained high during the infusions. 5. The mechanism of this reversible resistance to parathyroid hormone remains to be elucidated; it seems unlikely that circulating hormone fragments could account for the prolonged impairment in the responsiveness to the intact hormone. It is possible that alteration in the formation, intracellular degradation or, perhaps, release of cyclic AMP from the cells, is the cause. Changes in the characteristics of the hormone receptor sites might also explain the phenomenon.