This study examined the hypothesis that headache after general anesthesia is related to a caffeine withdrawal state. Two hundred eighty-seven patients undergoing minor elective procedures under general anesthesia were studied. Four to six hours after anesthesia each patient completed a questionnaire assessing his or her own alcohol, tobacco, and caffeine consumption, and the occurrence of postoperative side effects. A highly significant difference was found between the caffeine consumption of patients with and without preoperative (P = 0.0035) and postoperative (P less than 0.0001) headache. Logistic regression analysis of trend between headache and caffeine consumption suggested that with each 100-mg increase in caffeine consumption, there was a 12% increase in the odds of headache developing in the immediate preoperative period (P less than 0.0066) and a 16% increase in the odds of postoperative headache developing (P less than 0.0001). No relationship was found between headache and the patients' age, sex, usual frequency of headache, consumption of alcohol or nicotine, or the anesthetic agents or adjuvants used. It is concluded that postoperative headache is related to caffeine intake and that this relationship is explained, at least in part, by a perioperative caffeine withdrawal syndrome.

The hypokalaemic effects of equal doses (5 mg) of fenoterol, salbutamol, terbutaline and an equal volume of saline administered by nebulization were compared in eight healthy subjects. Plasma potassium was measured at 15-min intervals for 60 min and at 90 min, 2, 4 and 6 h following administration. Fenoterol, salbutamol and terbutaline all significantly decreased plasma potassium when compared to saline; however, the magnitude and duration of this effect differed between the active agents. Both fenoterol and terbutaline significantly reduced plasma potassium for 4 h whereas salbutamol was only different from 30 to 120 min. The maximum decrease occurred with fenoterol (-0.78 mmol/l), followed by terbutaline (-0.70 mmol/l) and salbutamol (-0.33 mmol/l). Both terbutaline and fenoterol had a significantly greater effect compared with salbutamol. When administered by nebulization fenoterol and terbutaline are likely to have a greater hypokalaemic effect than salbutamol and this effect is likely to be more long lasting.

No abstract

A double-blind crossover comparison of efficacy and recovery from midazolam 5 mg and diazepam (in propylene glycol) 10 mg was undertaken in eight volunteer subjects. It was found that midazolam was significantly more potent in this dose ratio than diazepam, helping to explain the finding of previous studies that the recovery from midazolam and diazepam in a 1:2 dose ratio is comparable.

Midazolam has a useful role as a premedicant, a sedative for minor surgical procedures and an induction agent. In comparison with diazepam in propylene glycol, the water-soluble midazolam produces a lower incidence of pain on injection and of thrombophlebitis [1], and has advantageous physicochemical and pharmacokinetic properties [2]. Although it has the shortest elimination half-life of all the commercially available benzodiazepines, clinical studies suggest that the recovery from equipotent doses of midazolam and diazepam is comparable [3-6]. The purpose of this study was to compare the efficacy and recovery characteristics of midazolam and diazepam following the administration of equipotent doses of each drug. SUBJECTS, MATERIALS AND METHODS Eight male volunteers in the age range 22-28 yr (mean 25±SD3yr; weight 75±11 kg; height 182 + 9 cm) were selected. All were healthy, were not receiving any psychotropic drugs and had been asked to refrain from ingesting alcohol for 24 h, or coffee for 6 h, before the study period. On each of two study days an 18-gauge cannula was inserted to a vein in the right antecubital fossa and physiological saline was infused at a constant rate. The volunteers then received diazepam in propylene glycol (Valium, Roche) 10 mg i.v., or midazolam (Hypnovel, Roche) 5 mg i.v. according to a random order crossover design. The midazolam was diluted in physiological saline to the same volume (2 ml) as the diazepam by an independent technician and injected by an anaesthetist not involved with data collection. Injections were given into the saline infusion and D. C.

No abstract

We have investigated the cardiovascular and metabolic effects of multiple inhaled doses of salbutamol and hexoprenaline in 12 healthy volunteers. They inhaled 200 micrograms of salbutamol or hexoprenaline at 15 min intervals for 60 min from a metered dose inhaler (total dose 1000 micrograms). We measured heart rate, blood pressure, total electromechanical systole (as a measure of inotropic response), QTc interval on the ECG, and plasma potassium at baseline, 10 min after each inhalation, and 30 and 60 min after the last inhalation. There was no difference in the effects of the two drugs on blood pressure, total electromechanical systole, or QTc interval. Salbutamol significantly increased heart rate compared with hexoprenaline. Hexoprenaline caused a significantly greater fall in plasma potassium compared with salbutamol.

The cardiovascular and metabolic effects of the long-acting beta 2-agonist formoterol were compared with those of salbutamol, fenoterol and placebo in 12 healthy volunteers, using a randomised, double-blind, cross-over design. On the study days, the subjects inhaled either formoterol (24 micrograms), salbutamol (400 micrograms), fenoterol (400 micrograms) or placebo, at 30 min intervals for five doses. Heart rate (HR) total electromechanical systole (Q-S2I) (a measure of inotropy), the corrected QT interval (QTc), systolic and diastolic blood pressure, plasma glucose and plasma potassium (K+) were measured prior to drug administration, 10 min after each inhalation and at 30 min intervals for 3 h after the last inhalation. All of the active agents significantly increased HR, QTc and plasma glucose, and decreased Q-S2I, diastolic blood pressure and plasma K+ compared to placebo. Fenoterol had a significantly greater maximum effect on HR, QTc and Q-S2I than either salbutamol or formoterol. Formoterol and fenoterol caused a similar maximum reduction in plasma K+, greater than that due to salbutamol. We conclude that formoterol is a more selective beta 2-agonist than fenoterol, and has similar cardiovascular effects to salbutamol when inhaled repeatedly by normal volunteers.