Opioids are the cornerstone medication for the treatment of moderate to severe pain. However, analgesic opioid requirements and the propensity to suffer from aversive opioid effects, including fatal respiratory depression and addiction, vary widely among patients. The factors underlying the substantial response variance remain largely unknown and need clarification for using opioids more effectively in appropriately selected patients. This ongoing study takes advantage of the twin paradigm to estimate the genetic and environmental contributions to inter-individual differences in opioid responses. Evidence of significant heritability will justify more detailed and extensive genomic studies. The enrollment target is 80 monozygotic and 45 dizygotic twin pairs who undergo a target-controlled infusion of the opioid alfentanil and saline placebo in sequential but randomized order. In a laboratory-type setting, well-defined pharmacodynamic endpoints are measured to quantify pain sensitivity, analgesic opioid effects, and aversive opioid effects including respiratory depression, sedation and reinforcing affective responses. First results obtained in 159 participants provide evidence for the feasibility and utility of this interventional study paradigm to estimate familial aggregation and heritability components of relevant drug effects. Areas highlighted in this report include recruitment strategies, required infrastructure and personnel, selection of relevant outcome measures, drug infusion algorithm minimizing pharmacokinetic variability, and considerations for optimizing data quality and quantity without hampering feasibility. Applying the twin paradigm to complex and potentially harmful studies comprehensively characterizing pharmacological response profiles is without much precedent. Methods and first results including heritability estimates for heat and cold pain sensitivity should be of interest to investigators considering similar studies.

Background and objective: The addition of alfentanil or atracurium to lidocaine solution for intravenous regional anaesthesia of the arm may have advantages with respect to improved muscle relaxation and better analgesia. The study investigates these possibilities.

Methods: We investigated 33 patients. Plain lidocaine solution was administered to Group 1 (n = 11). Alfentanil (0.5 mg) and atracurium (3 mg) were added to the lidocaine solution in Groups 2 (n = 11) and 3 (n = 11), respectively. The onset of sensory and motor block, intra- and postoperative pain scores, and the duration of postoperative analgesia were evaluated.

Results: There was a significant difference in the speed of the onset of sensory block in the hand, but not at the tourniquet site. The onset of the motor block, intra- and postoperative pain scores, and the duration of postoperative analgesia were similar in all groups.

Conclusions: No clinical benefits of adding alfentanil or atracurium to lidocaine solution for intravenous regional anaesthesia of the arm could be shown.

Background and objective: The effects of remifentanil, alfentanil and fentanyl were compared on cardiovascular responses to laryngoscopy and endotracheal intubation in morbidly obese patients.

Methods: Eighty morbidly obese ASA I–II patients were included in the study. Patients were randomly divided into four groups to receive either 1 μg kg−1 fentanyl (Group F), 10 μg kg−1 alfentanil (A), 1 μg kg−1 followed by an infusion of 0.5 µg kg min−1 remifentanil (R) or saline (P). The patients corrected weight was used to calculate the drug doses. Body mass indices (range) were: 54.3 ± 7.37 (49–78.4), 55.67 ± 7.44 (48.5–78.4), 53.17 ± 5.36 (48.1–63.2), and 56.3 ± 6.09 (46.6–67.7) kg m−2, in Groups F, R, A and P respectively. Systolic, diastolic and mean arterial pressures and heart rate were measured non-invasively at three time points, which were 2 min before induction, 2 min after induction and 2 min after endotracheal intubation.

Results: After induction of anaesthesia, arterial pressures decreased significantly in all groups, but the decrease was more pronounced in Groups A and R. After induction, heart rate decreased significantly in all groups except in Group P. After intubation, haemodynamic responses were similar in the remifentanil, fentanyl and alfentanil groups and were within normal limits. In Group P, arterial pressures and heart rates were significantly higher.

Conclusions: Alfentanil, fentanyl and remifentanil in the doses described had similar effects in controlling the haemodynamic response to tracheal intubation in ASA I–II morbidly obese patients.

The choice of hypnotics and opioids for rapid-sequence induction, and the use of premedication, is influenced by the choice of the muscle relaxant. Anaesthetic agents have a major influence on the quality of intubation when rapid-sequence induction is achieved without a muscle relaxant. Premedication is important, along with a high dose of propofol (2.5 mg kg−1 or more) and a short-acting opioid such as alfentanil (30–40 μg kg−1) or remifentanil (up to 4 μg kg−1). It has also been demonstrated that i.v. lidocaine can improve intubating conditions. When a muscle relaxant is used, the choice of the anaesthetic agents depends on the onset of action of the relaxant. With a rapid-acting compound such as rocuronium at a dose of 0.6 mg kg−1, the hypnotic agents need to be supplemented with only a small dose of opioids, e.g. alfentanil 10–20 μg kg−1. When succinylcholine, rocuronium 1.0 mg kg−1 or rapacuronium 1.5 mg kg−1 are used, excellent intubating conditions may be obtained by relatively smaller doses of hypnotic agents even without opioids; however, haemodynamic and intraocular pressure changes are better controlled when small doses of opioids are administered.

The direct cardiac effects of morphine, alfentanil, ketamine, etomidate, thiopentone, midazolam and propofol were measured in isolated Wistar rat hearts. Experiments were performed using a multiple conlumnar Langendorff apparatus and the hearts were perfused with a modified Tyrode solution under constant pressure. Each drug was applied from a different column in rising concentrations at 5-min intervals. Dose ranges were chosen to compare effects at sub-clinical, clinically relevant and more than clinical concentrations. Six rat hearts were chosen at random for each drug. Only thiopentone reduced contractile force at a clinically relevant concentration: measured as g contractility per g heart weight−1 (mean±standard deviation), base-line contractility was 8.8±2.4, and contractility at 10−4 mol litre−1 thiopentone was 7.1±1.5 (P<0.01). Alfentanil was the only drug to have no significant effect on the isolated heart at any concentration. Propofol was not cardiodepressant at clinically relevant concentrations, but had a lower therapeutic range than the other drugs.

Patient-controlled sedation (PCS) has been used during many different surgical procedures, both alone and as an adjunct to local or regional anaesthesia. Sedation with an admixture of propofol and alfentanil during transvaginal oocyte retrieval has been used successfully in this unit and this study was performed to assess the degree of patient acceptance of patient-controlled sedation, as other studies have indicated that self-administration of sedation may confer additional benefits on the patient, unrelated to the choice of sedation agent.

An admixture of 50 mL propofol 1% with alfentanil 2 mg was loaded into a Graseby 3300 patient-controlled analgesia pump and administered as increments of 0.3 mL with a zero lock-out interval. This method of sedation provided safe and highly satisfactory sedation for this group of patients with 55 of 56 patients indicating that they would opt for this type of sedation again. There was a very low incidence of over-sedation, and this sedation method is likely to produce a relaxed and co-operative patient for a wide variety of surgical procedures.

The relation between intra-operative gas exchange and post-operative oxygen saturation was examined using pulse oximetry (SpO2) 30 h after anaesthesia for upper abdominal surgery. The inspired oxygen partial pressure (PIO2) was varied during anaesthesia to produce a plot of PIO2 vs. SpO2. Gas exchange during anaesthesia was inferred from the relation between PIO2 and SpO2 which was described by its lateral and vertical displacement away from the position of a standard oxygen dissociation curve. With patients breathing air, the SpO2 was measured over a 10-min period at 30 h after surgery. The correlation coefficient of the lateral displacement with post-operative SpO2 was 0.7, and that of the vertical displacement with post-operative SpO2 was 0.66. The correlation coefficient of intra-operative SpO2 at PIO2=21 kPa with post-operative SpO2 was 0.69. It can be concluded that gas exchange abnormalities during anaesthesia deduced from the displacement of the PIO2 vs. SpO2 curve correlate with SpO2 30 h post-operatively and may help to identify patients at risk of post-operative hypoxaemia.

One hundred and one women (ASA grades I and II) were anaesthetized for routine gynaecological surgery using an intravenous (i.v.) anaesthetic technique combining propofol and alfentanil. The patients were allocated randomly into groups. Group one received 33% oxygen in nitrous oxide and group two received 33% oxygen in air (total i.v. anaesthesia). The group receiving nitrous oxide required significantly less (P < 0.05) of the propofol and alfentanil mixture to maintain anaesthesia and this was found to reduce the mean cost of anaesthesia by £1.70, (P < 0.05). There was no significant difference in the incidence of post-operative complications between the two groups. We suggest that nitrous oxide may be used to reduce the cost of total i.v. anesthesia with propofol and alfentanil without causing any increase in post-operative morbidity in patients undergoing routine gynaecological surgery.