Does Postoperative Administration of Oral Oxycodone With/Without Naloxone, Reduce the Duration of Epidural Analgesia in Patients Undergoing Cystectomy Without Impairing Its Benefits? A Randomized, Double Blind Controlled Trial

Background

Cystectomy with pelvic lymph node dissection and urinary diversion is major abdominal surgery, which is associated with a high incidence of postoperative complications. Gastrointestinal complications are frequent and perioperative techniques aiming at an early return of bowel function are to be pursued.The rationale for this patients population (i.e. cystectomy patient with ileal urinary derivation) is that they are at high risk for postoperative complications (around 50%) and specially gastrointestinal (8-20%). There is a need for improvement in the postoperative setting aiming to reduce complications and costs.

Optimal postoperative pain management is one of the key factors leading to enhanced recovery after surgery. The perioperative use of thoracic epidural analgesia (TEA) for major abdominal surgery is established, not only because of its excellent analgesic properties, but also because TEA reduces the postoperative stress response, accelerates the return of bowel function, and lowers postoperative morbidity and mortality. However, TEA is associated with additional costs, need for close monitoring and nursing. Once successfully established, TEA requires constant attention from skilled nurses and anaesthetists often from an acute pain service to achieve and maintain optimal analgesia. Attention must also be directed to limiting or avoiding side-effects such as hypotension or motor block, which will reduce the benefits of the technique by preventing the patient from mobilizing effectively after operation.In addition each supplemental day with an indwelling TEA catheter increases the risk of infection, which is associated with a high morbidity. The mean length of stay of the TEA catheter in cystectomy patients at the investigators' institution is 6 days. If the risk of epidural infection is low (estimated 1:2000 in Switzerland, this risk increases the longer the epidural catheter is left in place. It is recommended to re-assess the risk/benefit ratio of TEA after 4 days, if not sooner. Therefore, it is important to develop strategies that reduce the duration of TEA without impairing the benefits. Enhanced recovery after surgery protocols, which have been established for colorectal surgery in the last 10 years, recommend removing the TEA catheter in the morning of postoperative day (POD) 2, which does not impair the return of the gastrointestinal function. However, while this approach is well established for colorectal surgery, there is less evidence for small bowel surgery or cystectomy with urinary diversion.

Systemic analgesics with prolonged-release oral formulation like oral oxycodone (Oxycontin®) or combined drug mixture (oral oxycodone/naloxone (Targin®)) could be a valuable alternative pain treatment as a second analgesic step, starting on POD 3, so that the epidural catheter could be removed earlier without impairing postoperative enhanced recovery including return of the bowel function. Both oxycodone and naloxone orally administered are a recognized and accepted treatment option.The selected dosages of both orally administered drugs are in accordance with the literature and follow the recommendation of the manufacturers. In addition the dosages reflect the clinical practice of the investigators' institution. These drugs are daily used in a clinical setting in their pain service. The implementation of a placebo controlled group is considered as a gold standard approach in a randomized controlled trial aiming to assess the benefit of a drug for a specific indication. In addition, a rescue pain medication is implanted in the protocol. Rescue medication for breakthrough pain will be additional epidural boluses of 5 ml, limited to maximum one bolus per h. In case of persistent pain, orally administered of 5 mg oxycodone every 4-6 hours will be allowed by the ward nurses.

The investigators expect, by administering oxycodone/naloxone in the early postoperative period to reduce the length of TEA without impairing the return of the bowel function. This could reduce the risk induced by the prolonged TEA (i.e. local infection, malfunction) and costs (pain service). This can result in the implementation in the future of a new postoperative analgesia concept with the early postoperative administration of an oral pain killer, reducing the length of epidural analgesia without impairing the enhanced recovery.