The effect of epidural administration of alfentanil on intra-operative intravenous alfentanil requirements during nitrous oxide-oxygen-alfentanil anaesthesia for lower abdominal surgery.

The effects of epidural administration of alfentanil on the intravenous alfentanil dose requirements and the plasma concentrations required to suppress responses to surgical stimulation during nitrous oxide-oxygen-alfentanil anaesthesia in 20 patients undergoing lower abdominal surgery were studied. Before induction of anaesthesia, patients in one group (E) received an epidural injection of 1 mg alfentanil, followed by an epidural infusion of alfentanil 0.2 mg.h-1 until skin closure, whilst patients in the other group (C, control) received a continuous infusion of sodium chloride via a sham catheter in order to blind the main investigator to the treatment. Anaesthesia was induced and maintained with nitrous oxide (66%) in oxygen and a 'target'-controlled intravenous infusion of alfentanil. During surgery, the 'target' alfentanil concentration was increased or decreased according to patients' responses. The number of responses to surgical stimulation was smaller in patients from group E (median 1, range 0-3) than in patients from group C (median 4, range 1-15; p < 0.005), even though the alfentanil intravenous infusion rates were smaller in group E [mean (SD): 1.6(0.5) micrograms.kg-1 min-1] than in group C [2.9(1.2) micrograms.kg-1 min-1, p < 0.02]. Both the lowest concentrations associated with no response [133(40) ng.ml-1] and the highest concentrations associated with a response [155(65) ng.ml-1] in group E were lower than those in group C [238(100) ng.ml-1, p < 0.01 and 334(163) ng.ml-1, p < 0.05, respectively]. We concluded that epidural administration of alfentanil reduces intravenous alfentanil requirements during nitrous oxide-oxygen-alfentanil anaesthesia for lower abdominal surgery. The results indicate a spinal mechanism of action of epidural alfentanil.

Plasma concentrations of alfentanil following epidural administration.

The plasma concentration-time profile of alfentanil following epidural administration was determined in eight patients undergoing lower abdominal surgery under nitrous oxide (66%)-oxygen (33%)-halothane (0.3%) anaesthesia, supplemented with intravenous sufentanil. Alfentanil (1 mg) was administered epidurally before induction of general anaesthesia. Blood samples for the determination of plasma alfentanil concentrations by capillary gas chromatography were collected at intervals until 12 h after the epidural injection. Peak plasma concentrations [mean (SD)] were 9.7 (2.3)ng.ml-1, and were attained in a median (range) time of 90 (30-120) min. The results suggest that alfentanil is slowly absorbed from the epidural space into the general circulation.

Pharmacokinetics of alfentanil after epidural administration. Investigation of systemic absorption kinetics with a stable isotope method.

BACKGROUND: The effects of epidurally administered alfentanil may be due in part to its uptake into the systemic circulation. Therefore we examined the systemic absorption kinetics after epidural injection of alfentanil. METHODS: Pharmacokinetics were determined using a stable isotope method in ten patients, undergoing lower abdominal surgery under general anesthesia. After epidural injection of 0.68 mg deuterium-labeled alfentanil (alfentanil-d5), 1 mg unlabeled alfentanil was administered over 1 h by an intravenous infusion. Blood samples were collected for 12 h. Concentrations of alfentanil and alfentanil-d5 were measured by a combination of gas chromatography and mass fragmentography. The systemic absorption profiles of alfentanil-d5 were determined by deconvolution of the plasma alfentanil-d5 concentrations with the biexponential unit disposition functions, derived from the intravenous data. In addition, data were analyzed by moment analysis. RESULTS: The mean (+/- SD) steady-state volume of distribution, total plasma clearance, elimination half-life and mean residence time, derived from the unlabeled alfentanil concentration-time data, were 43.2 +/- 19.5 1,418 +/- 129 ml/min, 119 +/- 34 min, and 103 +/- 26 min, respectively. The absorption of alfentanil-d5 was monophasic in most patients. The mean systemic availability and mean absorption time derived from the deconvolution data were 100 +/- 17% and 114 +/- 24 min. The values determined by moment analysis were 107 +/- 18% and 112 +/- 36 min, respectively. CONCLUSIONS: After epidural administration alfentanil is slowly absorbed into the general circulation. Resulting plasma concentrations are very low and do not contribute appreciably to the systemic opioid effect.

Efficacy of epidurally administered sufentanil versus bupivacaine during thoracic surgery. A randomised placebo-controlled double-blind study.

The efficacy of thoracic epidural sufentanil 50 micrograms was compared with bupivacaine 0.5% with adrenaline 5 micrograms.ml-1 (dose 40 mg) or saline, in 30 patients (n = 10 in each group) undergoing lateral thoracotomy. Sufentanil, bupivacaine or saline was administered epidurally after induction of anaesthesia with sufentanil 1 microgram.kg-1 and thiopentone 2-5 mg.kg-1. Anaesthesia was maintained with nitrous oxide 66% and halothane 0.3%. Supplementary sufentanil 25 micrograms was given whenever the systolic arterial blood pressure increased more than 15 mmHg above the pre-operative value, whenever heart rate exceeded 90 beat.min-1 in the absence of hypovolaemia, or when other autonomic or somatic signs occurred. Fewer patients in the epidural sufentanil (n = 4, p < 0.005) and bupivacaine (n = 1, p < 0.001) groups required supplementary sufentanil compared to the placebo group, in which all patients needed supplementary sufentanil, but there was no statistical difference between the sufentanil and bupivacaine groups. One or more hypotensive episodes occurred in five patients in the sufentanil group, in all patients in the bupivacaine group and in no patient in the placebo group, and the differences were significant (p < 0.02).

An intra-operative comparison of lumbar with thoracic epidural sufentanil for thoracotomy.

The efficacy of thoracic epidural sufentanil 50 micrograms was compared with lumbar epidural sufentanil 50 micrograms in 30 patients (n = 15 in each group) undergoing lateral thoracotomy. Sufentanil was administered epidurally after induction of anaesthesia with sufentanil 1 microgram.kg-1 and thiopentone 2-5 mg.kg-1 intravenously. Anaesthesia, nitrous oxide 66%, halothane 0.3% and sufentanil 25 micrograms intravenously were given whenever the systolic arterial blood pressure increased more than 15 mmHg above the preoperative value and heart rate exceeded 90 beat.min-1 in the absence of hypovolaemia, or when other autonomic or somatic signs were seen. Four patients in the thoracic epidural group and five in the lumbar epidural group needed supplementary sufentanil. Six patients in the thoracic epidural group and three in the lumbar epidural group each had a single hypotensive episode. Lumbar and thoracic epidural sufentanil are equally effective in contributing to intra-operative analgesia for lateral thoracotomy.

Preoperative interpleural administration of sufentanil or bupivacaine reduces intraoperative intravenous sufentanil requirements during thoracotomy.

The efficacy of interpleural administration of sufentanil, 50 micrograms, was compared with that of 150 mg of bupivacaine, 0.5%, with epinephrine, 5 micrograms/mL, or saline, in 30 patients (N = 10 in each group) undergoing lateral thoracotomy. Sufentanil, bupivacaine, or saline was administered interpleurally after induction of anesthesia with sufentanil, 1 microgram/kg intravenously, and thiopental, 2 to 5 mg/kg. Anesthesia was maintained with nitrous oxide, 66%, and halothane, 0.3% inspired concentration. Supplementary intravenous sufentanil, 25 micrograms, was given whenever the systolic arterial blood pressure increased more than 15 mmHg above the preoperative value, heart rate exceeded 90 beats/min in the absence of hypovolemia, or when other autonomic or somatic signs of inadequate anesthesia occurred. The additional intravenous sufentanil requirement and the incidence of hypotension were compared between the groups. All patients in the placebo group needed supplementary sufentanil. Significantly fewer patients in the interpleural sufentanil (N = 1, P < 0.0002) and bupivacaine (N = 1, P < 0.0002) groups required supplementary sufentanil compared to the placebo group (N = 10). The time from interpleural administration of the study drug to the first administration of postoperative analgesic was significantly longer (P < 0.001) in the sufentanil group (228 +/- 72 min) and bupivacaine group (242 +/- 76 min) compared to the placebo group (141 +/- 50 min). It was concluded that interpleural administration of either sufentanil or bupivacaine contributes to intraoperative analgesia during thoracotomy.