[Sufentanil. An alternative to fentanyl/alfentanil?]

The introduction of the new opioid, sufentanil, into clinical practice should focus on the following questions: (1) What are the pharmacokinetic features of sufentanil that make it different from the well-established congeners alfentanil and fentanyl and open the way to new perspectives? and (2) Does sufentanil offer any particular advantages for specialised surgical procedures that make it the drug of first choice? Pharmacokinetics. Sufentanil is a potent analgesic with a very high receptor affinity and specificity, high lipid solubility, marked protein binding, and a shorter elimination half-life than fentanyl. Due to the high hepatic extraction ratio, metabolic degradation and elimination depend more on hepatic perfusion than on enzyme activity or renal clearance. However, changes in plasma protein concentration, volume of distribution, protein binding, or acid-base status may significantly alter the pharmacokinetic profile and prolong clinical effects. Pharmacodynamics. Several clinical trials have focused on the haemodynamic response to surgical manipulation, stress protection, induction time, and recovery time: 1. Induction of anaesthesia with low, medium, or high doses of sufentanil generally provide a stable haemodynamic profile comparable to that of fentanyl following intubation and surgical manipulation, even in cardiovascular risk patients. 2. Severe decreases in systolic blood pressure and bradycardia may occur in the dehydrated patient or in combination with vecuronium, however. 3. Despite some evidence of endocrinologic and metabolic stress protection in cardiac surgery in particular, an increase of hormonal stress parameters can only be ascertained prior to extracorporeal circulation. However, the clinical value of endocrinologic stress protection in terms of mortality and outcome has yet to be verified. 4. Induction time is significantly shorter with sufentanil compared to fentanyl, indicating a central sedative effect. 5. Despite experimental evidence of cerebral vasodilatation and increased intracranial pressure, there seems to be no disruption of cerebrovascular autoregulation in patients with normal intracerebral pressure. 6. Common side effects such as nausea, vomiting, and truncal rigidity occur in up to 30% of patients and are comparable to those after other opioids. 7. In the postoperative period the advantage of an intermediate elimination half-life seems to be out-weighed by the effects of volatile anaesthetics or sedatives on respiratory depression and postoperative recovery following balanced anaesthesia. 8. Epidural application of 10-50 micrograms sufentanil provides rapid and effective pain relief within 5-7 min for a period of 3-7 h. Doses of more than 50 micrograms seem to increase the risk of respiratory depression without further improvement of analgesia. Analgesia may be enhanced by combination with local anaesthetics or clonidine.(ABSTRACT TRUNCATED AT 400 WORDS)