Efficacy of target controlled infusion of alfentanil for patient controlled postoperative analgesia

M.C.O. Van den Nieuwenhuyzen, F.H.M. Engbers, A.G. Burm, A.A. Vletter, J.W. van Kleef, R.H.W.M. van den Hoogen, J.G. Bovill. Departments of Anesthesiology, Leiden University Medical Centre, Diaconessenhuis Leiden, Leiden, The Netherlands

 

Introduction

The concept of target controlled infusion (TCI) for intraoperative drug administration has been well documented. However, it has been hardly investigated in the postoperative period.^1,2 TCI allows more complex infusion regimens, aimed at providing optimal pain relief with minimal side effects. This study examined the efficacy of target controlled infusion of alfentanil for patient-controlled postoperative analgesia (PC-TCIA).

 

Methods

With institutional approval and informed consent, 50 ASA I and II patients, 18-65 yrs, who underwent major orthopedic (n=25) or gynecological (n=25) surgery, were studied. Anesthesia was induced and maintained with O₂ in air, propofol, sufentanil and pancuronium. Postoperatively when patients reported pain the PC-TCIA was started with a target concentration (C_T)=20 ng/ml. Every 5 min the C_T was increased by 10 ng/ml according to the patient's response. When the patient was oriented and C_T had not been changed for 30 min the patient was allowed to self activate the system. The increase in C_T was then changed to 5 ng/ml with a lockout of 5 min. When an unrewarded demand was followed by a rewarded demand within the next 5 min, C_T  was increased by 10 ng/ml, 2 or more unrewarded demands followed by a rewarded demand within the next 5 min increased C_T  by 20 ng/ml. The maximum C_T was 150 ng/ml. When PC-TCIA had not been activated for 1 h, the C_T was automatically decreased by 10% or at least 5 ng/ml every h. The study was ended 72 h postoperatively or when C_T < 5 ng/ml for 4 hours. Respiratory rate (RR) and oxygen saturation (SaO₂) were continuously monitored, the number of demands recorded, pain scores assessed with a Visual Analogue Scale, level of sedation and side effects were hourly recorded. Arterial blood samples for the determination of the plasma concentration of alfentanil were obtained every 15 min during the loading period, hourly until 22 PM on the day of surgery and every 4 hours thereafter. The bias and inaccuracy for the system were assessed by the median performance error (MDPE) and median absolute performance error (MDAPE)². Statistical analysis was done using the unpaired t-test and Mann-Whitney U-test, where appropriate. P<0.05 was regarded significant. Data are presented as mean±SD or median (95% confidence interval of the median).

 

Results

Demographic data as well as duration of surgery and all variables presented below did not differ between the ortho and gyn patients. Onset of postoperative pain was 37±30 min after the end of anesthesia. In 5 patients the study was prematurely ended, because of inadequate analgesia (n=2), respiratory depression (n=1), excessive nausea (n=1) and patient withdrawal (n=1). Onset of satisfactory analgesia (VAS<3.0 or asleep) was within 15 (10-25) min. Postop-erative alfentanil consumption was 1.1±0.8 mg/h, resp. The mean time in the study was 53±20 h. The percentage of time in the study with satisfactory analgesia was 91% (85-95). 24 patients reached the maximum C_t during the study. Frequently noted side effects were nausea and vomiting; 27 patients needed an anti-emetic. Respiratory depression (RR<8, SaO₂<90%) occurred in 1 patient, and 2 patients complained of itching. Excessive sedation did not occur. 1022 blood samples of 45 patients were analysed. MDPEs were resp. 6 (ortho) and 4% (gyn) and MDAPEs were 34% and 33%.

 

Conclusion

PC-TCIA with the settings used in this study, results in a fast onset of analgesia and relieves postoperative pain effectively. Although the incidence of side effects was high, patients were generally satisfied with the analgesic regimen.

 

References

Clin Pharmacokinet 20:319-330,1991 2. Anesthesiology 79:481-492,1993.