A Comparison of Targinact vs. Oxycodone on Gut Function After Colorectal Surgery
A Comparison of Targinact vs. Oxycodone on Gut Function After Colorectal Surgery
Two key requirements for discharge from hospital after major abdominal surgery are adequate
 oral analgesia and resumption of oral nutrition. Up to 40% of patients suffer delayed
 discharge after abdominal surgery due to delayed return of gut function, manifesting as
 nausea, vomiting, constipation and abdominal distension. Opiates and their derivatives are
 the mainstay of postoperative analgesic regimens after abdominal surgery and are highly
 effective in achieving adequate pain control. However, opioids cause impaired gut function by
 reducing normal forward propulsion and increasing gut spasm. Opioid receptor blockers such as
 Alvimopan counteract these effects and can accelerate postoperative gut recovery but are
 expensive and cause cardiac complications; alternative painkillers such as non-steroidal
 anti-inflammatories are less effective than opioids and have been linked with increased risk
 of anastomotic leaks.

 Targinact is a combination of prolonged release opioid analgesic (oxycodone hydrochloride)
 and naloxone hydrochloride (an opioid receptor blocker). The formulation of the product
 confines the naloxone action to the gut to reduce the unwanted side-effects on gut function.
 Targinact has been shown in patients with chronic severe pain to provide comparable analgesia
 to other opioid analgesics whilst reducing the unwanted side-effect of constipation.

 The Investigators wish to test the hypothesis that Targinact will provide adequate analgesia
 after colonic resection with reduced postoperative gastrointestinal dysfunction. The surgical
 procedure chosen to test this hypothesis is laparoscopic segmental colectomy, a consistently
 reproducible intervention with a postoperative gut dysfunction rate of up to 40% (prospective
 data from the Edinburgh Colorectal Unit). The main outcome of the study will be return of
 normal gut function at the time of planned discharge (Day 3).
Study hypothesis: Targinact is effective as oral analgesia after major colorectal surgery and
 is associated with less gut dysfunction than Oxycodone.

 Up to 40% of patients suffer delayed return of gut function after elective colorectal
 surgery, leading to prolonged hospital stay and higher inpatient costs. For the patient, this
 is characterised by a variety of symptoms including nausea and vomiting, delayed ability to
 regain normal oral intake, abdominal discomfort/distension and constipation. Although
 post-operative gut dysfunction tends to resolve spontaneously in 3-7 days, both symptoms and
 supportive treatment (nasogastric tube insertion, repeated venous cannulation for intravenous
 fluid administration etc) are unpleasant.

 Elective colorectal surgery is a common hospital intervention hence a reduction in the
 prevalence of post-operative gut dysfunction would be expected to benefit a large number of
 patients with attendant reduction in health service costs. The objective aligns well with the
 current national dissemination of Enhanced Recovery after Surgery programmes by the UK
 Department of Health and Scottish Government.

 Post-operative gut dysfunction is multifactorial. Opioid analgesics are contributory and all
 Enhanced Recovery after Surgery (ERAS) programmes emphasise strategies to minimise systemic
 opioid use (eg using regional or local anaesthetic techniques).

 Targinact has not been evaluated in the setting of short-term post operative analgesia in
 colorectal surgery but offers the potential to achieve effective analgesia with a lower
 incidence of gut dysfunction and therefore an important role within the ERAS program after
 colorectal surgery. Oxycodone is currently the oral opioid analgesic of choice in our unit
 and most patients are prescribed a combination of oxycodone and oxynorm as step-down
 analgesia following cessation of systemic or epidural analgesia, often in combination with
 fentanyl patches.

 Data will be collected from patient hospital records and questionnaires administered by the
 principal investigator and research study nurse.

 Multiple measures will be employed to record both presence of good function and absence of
 dysfunction.

 -  Time to first flatus

 -  Time to first bowel movement

 -  Time from surgery to cessation of iv fluids

 -  Total dose of rescue antiemetic (protocol ondansetron not included)

 -  Reinstitution of iv fluids (Y/N) Quantity of laxative used

 -  Measurement of oral nutritional intake:

 Preoperative intake will be recorded by means of a recall diary. Postoperative oral intake
 will be recorded by the participant using a food diary for 7 days from the date of surgery.
 Energy intake will then be estimated using CompEat Pro® forWindows® (Nutrition Systems,
 Banbury, UK). Time to attain and maintain 80% of normal solid food intake and the percentage
 Recommended Nutritional Intake (RNI) achieved on days 1-3 and days 5-7 after surgery will be
 used in comparisons between study groups.

 -  Validated nausea and vomiting score (Miles and Wengritzky)

 -  Presence of abdominal distension (Y/N)

 -  13C Stable Isotope Gastric Empyting Breath Test to measure gastric motility on the
 second postoperative morning. The technique has been previously used in the Edinburgh
 Department of Surgery and validated to be a reproducible and accurate measurement of
 upper GI motility.

 Additional data to be recorded:

 -  Patient demographics, co morbidity, regular medications

 -  Pre op bowel function questionnaire

 -  Postoperative nausea and vomiting prediction data (Apfel score)

 -  Day 3 achievement of discharge criteria (pain controlled by oral analgesia, tolerating
 adequate oral diet and fluids, independently mobile and willing to go home) Y/N

 -  30-day/Inpatient mortality

 -  Duration of hospital admission

 -  Complications (recorded by organ system and severity as assessed by Clavien/Dindo scale)

 -  Unscheduled readmissions to hospital within 30 days of discharge

 -  Patient-reported outcome questionnaire
Inclusion Criteria:

 -  Patients scheduled for elective laparoscopic segmental colectomy at the Colorectal
 Surgery Unit, Western General Hospital, Edinburgh.

 Exclusion Criteria:

 -  Pregnancy Age <18 years Patients lacking capacity to give informed consent. Severe
 liver dysfunction (Child's A or greater) Patients participating in another therapeutic
 clinical trial Contraindication to oxycodone, naloxone or Targinact Pre-existing
 dependence on opioid analgesia (current medications will be checked prior to
 discussing consent) Pre-existing use of opioid analgesia for chronic pain (current
 medications will be checked prior to discussing consent) Patients with rectal cancer
 Plan to form any stoma during procedure