The analgesic efficacy of dexmedetomidine (DEX)--a novel alpha 2-adrenoceptor agonist--was studied in man. Single intravenous doses of fentanyl (FEN; 2 micrograms/kg), DEX (0.25, 0.50 and 1.0 micrograms/kg) and placebo were administered to 5 healthy male volunteers in a double-blind, crossover study in randomized order. The analgesic effect of the different treatments was measured by determining the time course of pain threshold with dental dolorimetry and by quantitating subjective pain induced by a standard ischemic pain stimulus on the upper arm using a visual analogue scale (VAS). The drugs were generally well tolerated. FEN and DEX both had analgesic effects on ischemic pain, which was seen as a statistically significant decrease in subjective VAS ratings. FEN appeared to be more effective than DEX; the difference was not, however, statistically significant. Neither of the drugs affected the pain threshold measurements.

To evaluate the usefulness of intravenous patient-controlled analgesia (PCA) fentanyl for labour analgesia, its effectiveness for maternal pain and safety for the fetus and newbom.Methods: Twenty primigravidas were randomised to receive intravenous PCA fentanyl or epidural analgesia for labour pain. Maternal pain, heart rate and arterial oxyhaemoglobin saturation (Sp02) were monitored. Fetal and neonatal monitoring induded cardiotocogram (CTG), APG/~ neurological scoring and static-charge-sensitive bed (SCSB) recording for 12 hr postnatally with ECG and SpOr Fentanyt concentrations and pH of umbilical artery and vein were analysed. l~sull~: Ini~ally, epidural analgesia was more effective (P = 0.0 I), and three patients in the fentanyl group were given epidural due to unsatisfactory pain relief. Overall satisfaction for analgesia did not differ between the groups. Maternal side-effects were more frequent in the fentanyl group (dizziness and tiredness most often, P = 0.0001 ). Severe sideeffects were not reported. In CTG there were no differences between groups. All the newboms were healthy, APGAR and pH were normal. Naloxone was not used. Neurological scoring was similar in both groups. In 12 hr monitoring heart rate, breathing frequency and movement time were similar in both groups, but SpO~ was lower in the fentanyt group (P < 0.00 I). Umbilical cord fentanyt concentrations were low or beyond the detection limit. Cx)nd~ion: Intravenous fentanyl can be used for labour analgesia with the doses reported here as an altemative to epidural analgesia. However, the fetus and neonate must be appropriately monitored. Naloxone and oxygen should be available if neonatal distress occurs.Obj~cis : ~aluer rimportance de I'analg&ie intraveineuse auto-contr61& (PCA) au fentanyl en analg~sie obst~tri-cale en tenant compte de son efl~cacitE et de la s&uritE foeto-matemelle. M~J~xlm : Vingt primipares ont Et6 assign&s al6atoirernent ~ recevoir soit du fentanyl intraveineux en PCA soit une analgEsie Epidurale dans le but de soulager la douleur de I'accouchement. La douleur maternelle, la fr~luence cardiaque et la saturation art&ielle (SpO2) ont EtE not&~s. Le monitorage foetal et n~natal inclualt la cardiotocographie (CTG), le score d'APGAFL r~valuation neurologique et I'enregistrement au lit sensible ~ la statique (SCSB) pendant 12 h apr~s la nalssance avec I'I~CG ET la SpO 2. La concentration de fentanyt et le pH de rart&e et de la veine ombilicales Kent mesur~s, ]L~ultats : Initialement, I'analg~sie Epidurale s'est av&& plus ef~ce (P = 0,0 I) et trois pa~entes clu groupe fentanyl ont dO accepter une analg&ie Epidurale ~ cause du manque de soulagement. La satisfaction globale en rapport avec t'analg~'ie n'a pas diffEr~ entre les groupes. Des effets maternels secondaires sans gravit~ sont survenus plus souvent dans le groupe fentanyt (surtout des &ourdissements et de la fatigue, P = 0,0001). Le CTG n'a pas r~vEIE de differences intergroupes. Tousles enfants sont n8 en 10on ~at avec des scores d'APGAR et des pH normaux. On n'a pas ...

1 The ability of atipamezole, a specific and selective a2-adrenoceptor antagonist, to reverse the pharmacological effects induced by the a2-adrenoceptor agonist dexmedetomidine was studied in six healthy male volunteers. Each volunteer received in four sessions in a randomized and single-blind manner three different doses (6.7,ug kg-1, 27 ,ug kg-' and 67 ,ug kg-') of atipamezole or saline placebo as 5 min i.v. infusions preceded by a fixed i.v. dose of dexmedetomidine (0.67 ,ig kg-').2 Dexmedetomidine caused profound sedation, with the subjects actually falling asleep. This was effectively reversed by the two highest doses of atipamezole. 3 Dexmedetomidine reduced salivary flow on average by 70%. A rapid and full reversal of this effect was seen after the highest dose of atipamezole. 4 Hypotension induced by dexmedetomidine was also effectively antagonized by atipamezole. Bradycardia was very modest after dexmedetomidine in this study, and thus no reversal of a2-adrenoceptor agonist-induced bradycardia could be demonstrated. 5 Plasma noradrenaline concentrations were reduced by 80% by dexmedetomidine. This was effectively antagonized by atipamezole, and the highest dose caused a 50% overshoot in plasma noradrenaline concentrations over the basal levels. 6 It is concluded that the effects of dexmedetomidine are effectively reversible by atipamezole. A dose ratio of 10: 1 for atipamezole: dexmedetomidine was clearly insufficient for this purpose, but ratios in the range of 40 : 1 to 100 : 1 were found to be effective in the current experimental situation.

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