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Analgesic and hemodynamic effects of intrathecal clonidine as the sole analgesic agent during first stage of labor: a dose-response study.

BACKGROUND: Intrathecal clonidine produces dose-dependent postoperative analgesia and enhances labor analgesia from intrathecal sufentanil. The authors evaluated the dose-response potency of intrathecally administered clonidine by itself during first stage of labor with respect to analgesia and maternal and fetal side effects. METHODS: Thirty-six parturients requesting labor analgesia were included in this prospective, randomized, double-blind study. Parturients with < 6 cm cervical dilatation received either 50, 100, or 200 microg intrathecal clonidine. The authors recorded visual analog pain score (VAPS), maternal blood pressure and heart rate, ephedrine requirements, and sedation at regular intervals and fetal heart rate tracings continuously. Duration of analgesia was defined as time from intrathecal clonidine administration until request for additional analgesia. RESULTS: Clonidine produced a reduction in VAPS with all three doses. The duration of analgesia was significantly longer in patients receiving 200 microg (median, 143; range, 75-210 min) and 100 microg (median, 118; range, 60-180 min) than 50 microg (median, 45; range, 25-150 min), and VAPS was lower in the 200-microg than in the 50-microg group. In the 200-microg group, hypotension required significantly more often treatment with ephedrine than in the other groups. No adverse events or fetal heart rate abnormalities occurred. CONCLUSIONS: Fifty to 200 microg intrathecal clonidine produces dose-dependent analgesia during first stage of labor. Although duration and quality of analgesia were more pronounced with 100 and 200 microg than with 50 microg, the high incidence of hypotension requires caution with the use of 200 microg for labor analgesia.

Adult↗

Patient-controlled analgesic therapy, Part III: pharmacokinetics and analgesic plasma concentrations of ketobemidone.

The effects of anaesthesia and surgery on the pharmacokinetics of ketobemidone were studied in 12 patients. Plasma ketobemidone concentrations were assayed with a mass-fragmentographic method. The peroperative Vd(area) was 5.9 +/- 2.6L/kg and the terminal half-life was 3.9 +/- 1.7 h. In the postoperative period Vd(area) decreased to 3.7 +/- 0.4L/kg and the terminal half-life to 2.1 +/- 0.4 h. Plasma clearance (Clp) did not change significantly, peroperative Clp being 18 +/- 4.3 ml/min/kg and postoperative Clp being 22 +/- 7.5 ml/min/kg. The pharmacokinetics of ketobemidone were not influenced by the addition of a spasmolytic agent in the commercial combination ketobemidone preparation 'Ketogin'. Postoperative pain was relieved in 15 patients by patient-controlled intravenous administration of ketobemidone by means of a programmable drug injector. The mean ketobemidone consumption was 2.3 +/- 0.8 mg/h, which produced a mean plasma concentration of 28 +/- 11 mg/ml. Pseudosteady-state plasma concentrations of ketobemidone were established with a mean minimum effective concentration (MEC) of 25 +/- 11 ng/ml. Ketobemidone 'plain' and 'Ketogin' did not differ significantly in these respects. Analgesia was considered by all patients to be satisfactory.

Abdomen↗

Patient-controlled analgesic therapy, Part IV: pharmacokinetics and analgesic plasma concentrations of morphine.

The influence of anaesthesia and surgery on the pharmacokinetics of morphine was studied in 10 patients. Plasma concentrations of morphine were assayed by gas chromatography with electron capture detection. All patients were studied on the day of surgery and again 3 to 7 days later. Mean +/- SD for peroperative Vd(area) was 6.3 +/- 3.6 L/kg and for the terminal half-life was 3.8 +/- 2.3 h. In the postoperative period, Vd(area) decreased to 3.7 +/- 1.4L/kg and the terminal half-life to 2.2 +/- 1.1 h. Plasma clearance (Clp) remained constant, peroperative Clp being 20 +/- 7.0 ml/min/kg and postoperative Clp 21 +/- 6.0 ml/min/kg. Postoperative pain was relieved by patient-controlled administration of intravenous doses of morphine by means of a programmable drug injector. The mean morphine consumption was 2.6 +/- 1.2 mg/h, which produced a mean plasma concentration of 21 +/- 12 ng/ml with a calculated mean minimum effective concentration (MEC) of 16 +/- 9 ng/ml. In 1 patient, temporary hypercapnia was seen during a period of hypovolaemia. Analgesia was considered satisfactory by all patients.

Abdomen↗