Intrathecal opioids decrease bladder function by causing dose-dependent suppression of detrusor contractility and decreased sensation of urge. Recovery of normal lower urinary tract function is significantly faster after intrathecal sufentanil than after morphine, and the recovery time is clearly dose dependent.

We have studied the plasma concentrations (Cp) and pharmacokinetics of sufentanil injected i.v. (IVS), intradurally (IS) or extradurally (ES) under general anaesthesia in 31 patients undergoing major abdominal surgery. Sufentanil appeared in plasma very rapidly and Cpmax was also attained rapidly after both extradural and intrathecal injection. Apart from the first 2 min after injection, Cp after ES and IVS were comparable until the end of the study. Cp after ES was greater than after IS up to 0.25 h. Cp after IS was significantly greater than that after ES at 1 h and 2.5 h, and was also greater than that after IVS at 3 h. At tracheal extubation there was no difference in Cp between groups. Peak Cp values were significantly different between ES and IS, but the times taken to reach Cpmax were comparable. Plasma pharmacokinetics after ES and IS were similar. The plasma mean residence time and volume of distribution of sufentanil at steady state after ES and IS were significantly different in comparison with those after IVS.

We studied the effect of large-dose intrathecal sufentanil (ITS) for major abdominal surgery on the hormonal stress response. Forty patients were randomly allocated to receive either IV sufentanil (IVS) or 150 microg of ITS as part of general anesthesia. In the IVS group, adrenocorticotropic hormone (ACTH) and cortisol concentrations were larger than baseline and the ITS group, 60 min after incision and at skin closure. Plasma concentrations of cortisol and ACTH were not different from baseline in the ITS group during surgery. Six hours after skin closure, cortisol concentrations were larger than baseline in both groups. Twenty-four and 48 h after skin closure, ACTH and cortisol values were similar between groups. Norepinephrine concentrations increased after surgery in both groups. Blood glucose levels increased in both groups during and after surgery. Pain scores and morphine consumption during the first 48 h after surgery were lower in the ITS group. The data show that large-dose ITS prevents the intraoperative hormonal stress response in comparison with balanced anesthesia. We speculate that this is due to the highly specific binding of sufentanil to spinal and supraspinal receptors. This technique improves postoperative analgesia when compared with balanced anesthesia.

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The pharmacokinetics of intradural morphine used for major abdominal surgery were evaluated. Lumbar spinal fluid and plasma concentrations were measured at intervals after morphine 0.05 mg/kg had been injected intradurally in 21 patients scheduled for elective abdominal aortic surgery. The CSF morphine concentrations were fitted by a biexponential function. A non-compartmental model based on statistical moment theory was used for calculating the intradural morphine disposition. Mean residence time was 137 +/- 54.9 minutes, mean initial volume of distribution 15 +/- 5.49 ml, mean volume of distribution at steady-state 42 +/- 18.25 ml and mean clearance 0.34 +/- 0.18 ml/min (0.02 +/- 0.01 L/h). The moments of the morphine concentration-time curves and the pharmacokinetic parameters varied between the patients. They were not significantly different with regard to morphine dosage, or patient sex or age. Free morphine could not be detected in plasma. Morphine-3-glucuronide appeared in plasma at 5 minutes, increased to a maximum at 240 minutes and fell below the detection limit at about 16 hours after morphine administration. Possible clinical causes of interindividual variations in the CSF morphine concentrations and the pharmacokinetics of intradural morphine are discussed.