Effect of epidural liposomal morphine on the postoperative stress response in humans

Abstract

O-26 Introduction: The prolonged release of morphine from high load liposomal formulations provides significant analgesia following neuraxial application. We investigated in this double-blind, randomized placebo-controlled trial whether such formulations were efficient for obtunding the postoperative stress response. Methods: The protocol was approved by the University Ethics Committee. Forty patients, ASA class II-III, scheduled for abdominal surgery, received a single epidural injection of 7 mL of either placebo (PL), plain morphine (1 mg mL−1, MOR), liposomal morphine 1 mg mL−1 (LIP1) or liposomal morphine 2 mg mL−1 (LIP2) after operation. All patients used i.v. PCA fentanyl for analgesia. Arterial samples were taken before anaesthesia and postoperatively before and at 4 and 24 h after drug administration. Catecholamine assays were performed using HPLC and results analysed with two-way ANOVA tests. Results: All groups (n = 10 per group) were comparable for age, weight, gender and pre-operative values of catecholamines. The epinephrine levels increased 6-fold in all groups after surgery. Concentrations decreased by 50% 4 h after drug application in the MOR and LIP1 groups and returned to preoperative values in the LIP2 group (P < 0.01). The norepinephrine levels remained higher in the PL group than in the MOR and LIP1 groups, and were lowest in the LIP2 group (PL: 612 (163, SEM) pg mL−1; LIP2: 397 (38) pg mL−1, P < 0.05) at 24 h. No difference was found between the MOR and LIP1 groups (MOR: 531 (61, SEM) pg mL−1; LIP1: 494 (59, SEM) pg mL−1). Conclusion: The neuraxial administration of a liposomal formulation with high morphine load (2 mg mL−1) provided a quicker return of epinephrine concentrations to preoperative values, and decreased the rise of norepinephrine concentrations after operation compared to the use of plain morphine or i.v. PCA fentanyl.