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A simple, manually controlled infusion scheme for continuous administration of propofol was derived by simulation of a computer algorithm designed to achieve a predetermined blood concentration of propofol within 2 minutes and to maintain a constant blood level for the duration of surgery. The manual infusion scheme for a target blood propofol concentration of 3 micrograms/ml, consisted of a loading dose of 1 mg/kg followed immediately by an infusion of 10 mg/kg/hour for 10 minutes, 8 mg/kg/hour for the next 10 minutes and 6 mg/kg/hour thereafter. An overall mean blood propofol concentration of 3.67 micrograms/ml was achieved within 2 minutes and maintained stable for the subsequent 80-90 minutes of surgery. The decrease of systolic and diastolic arterial pressures at induction was much less than that previously described after larger induction doses of propofol and there was a negligible haemodynamic response to laryngoscopy and intubation or to the subsequent surgery. The quality of induction and maintenance of anaesthesia was satisfactory in every patient.

Despite adverse side effects, phenoxybenzamine has been widely used for the preoperative management of patients with pheochromocytoma. Doxazosin, a specific a 1-adrenoceptor antagonist, has a pharmacologic profile more suited to controlling blood pressure in such patients. A sequential study of 35 patients with pheochromocytoma encompassed a definite and prescribed change in preoperative drug management from phenoxybenzamine to doxazosin. Hemodynamic, pharmacologic, and biochemical indicators of a- and b-adrenoceptor blockade were measured before, during, and after anesthesia and surgery in 8 patients pretreated with phenoxybenzamine and 27 patients pretreated with doxazosin. Doxazosin (2-16 mg/day) was as effective as phenoxybenzamine in controlling arterial pressure and heart rate before and during surgery, but doxazosin caused fewer undesirable side effects both before and after surgery. Following phenoxybenzamine therapy substantial a 1-adrenoceptor blockade, detected as a right shift of phenylephrine dose-response curves, persisted for more than 2 days postoperatively, whereas after doxazosin it was undetectable on the first postoperative day. Doxazosin provided safe, efficacious pre- and perioperative control of arterial pressure. In patients with predominantly norepinephrine-secreting tumors, pretreatment 24-hour urinary norepinephrine excretion gave an indication of the daily doxazosin requirement.

SummaryThe efficacy and safety of remifentanil and alfentanil for patients undergoing major abdominal surgery were compared. Premedicated patients received a loading dose of remifentanil (1.0 mg.kg ¹1 ; n ¼ 116) and a continuous infusion of 0.5 mg.kg ¹1 .min ¹1 , or a loading dose of alfentanil (25 mg.kg ¹1 ; n ¼ 118) and a continuous infusion of 1.0 mg.kg ¹1 .min ¹1 . Propofol was administered (10 mg every 10 s) until loss of consciousness. Patients' lungs were ventilated with 66% nitrous oxide and 0.5% (end-tidal) isoflurane in oxygen. The study drug infusion rate was reduced by 50% 5 min after intubation. Alfentanil was discontinued 15 min before the end of surgery, whereas remifentanil was continued in the immediate postoperative period at a reduced dose. Responses to intubation (28%) and skin incision (17%) occurred approximately twice as often in the alfentanil group (15% and 8%; p ¼ 0.014 and p ¼ 0.037, respectively). More patients receiving alfentanil had one or more responses to surgery (72% vs. 57%; p ¼ 0.016). The time to spontaneous respiration, adequate respiration, response to verbal command and time to recovery room discharge were similar. However, owing to decreased variability, the time to extubation was shorter with remifentanil than with alfentanil (p ¼ 0.048). There was a similar overall incidence of adverse events in both groups, 82% and 75% of patients, respectively. Adverse events associated with remifentanil were rapidly controlled by dose reductions. The incidence of intra-operative hypotension and bradycardia was higher in the remifentanil group (p Յ 0.033). An initial remifentanil infusion rate of 0.1 mg.kg ¹1 .min ¹1 titrated to individual need provided postoperative pain relief in the presence of adequate respiration in 71% of patients. When using remifentanil in the immediate postoperative setting, rapid administration of bolus doses and infusion rate increases resulted in a relatively high incidence of muscle rigidity, respiratory depression and apnoea. Changing the postoperative regimen to avoid rapid changes in remifentanil blood concentration resulted in more effective analgesia and dramatically reduced the incidence of adverse events during this period. In patients undergoing major abdominal surgery, remifentanil appears to offer superior intra-operative haemodynamic stability during stressful surgical events compared with alfentanil without compromising recovery from anaesthesia. Remifentanil can be administered as a postoperative analgesic agent at a starting dose of 0.1 mg.kg ¹1 .min ¹1 ; however, it should only be used in the presence of adequate supervision and monitoring of the patient. Administration of bolus doses is not recommended in this setting.

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