Analgesia for major minimally invasive abdominal surgery: A randomised controlled trial of Intrathecal Morphine (The AIM study)

Analgesia for major minimally invasive abdominal surgery: A randomised controlled trial of Intrathecal Morphine (The AIM study)


CIA: Dr Katrina Pirie

Project summary

To conduct a multicentre, randomised controlled trial evaluating whether a single pre-operative spinal injection of intrathecal morphine (ITM) improves the quality of recovery for patients after minimally invasive (laparoscopic or robotic assisted) major abdominal surgery.
Primary Aim: To compare the quality of recovery between the ITM and control groups on post-operative day 1.
Secondary Aims: To compare cumulative opioid consumption, dynamic pain scores, and rest pain scores in the ITM and control groups, up to post-operative day 3.
Tertiary Aims: To compare functional recovery, incidence of opioid related side-effects, Days Alive and at Home up to 30 days after surgery (DAH30), post-operative adverse events up to Day 30, ongoing opioid use at 90 days post- operatively, and patient and health care worker satisfaction levels.

Major abdominal surgery is common, encompassing a broad range of surgical subspecialities and patient populations. It is associated with significant morbidity, commonly including wound infections, post-operative deconditioning from the catabolic surgical stress-response, ileus, venous thromboembolism, and pulmonary complications. The incidence of these common post-operative complications can be reduced with effective analgesia. Suboptimal post-operative pain management also negatively affects the quality of life and functional recovery, is a risk factor for persistent post-surgical pain and for long-term opioid use. The requirement for high doses of opioids post-operatively may also increase the risk of opioid dependence. Up to 10% of opioid-naïve patients continue to use opioids beyond 90 days after a range of major and minor surgeries, with a substantial burden of morbidity and cost/risk to the community. Opioid-sparing techniques in open and laparoscopic abdominal surgery are associated with early mobilisation, fewer complications, faster return of bowel function and shorter hospital stay. The adverse effects of epidurals (higher failure rate, hypotension associated with local anaesthetic use) and inconsistent findings of patient outcome benefits have resulted in a decline in popularity for epidural regional anaesthesia and therefore our increased interest in the use of ITM. Less invasive (e.g., laparoscopic, or robotic- assisted) surgical techniques are increasingly utilised for major abdominal surgery which minimise the surgical stress response, expedite post-operative recovery and improve patient satisfaction. A recent meta-analysis concluded that epidural analgesia offers no clinical benefit within enhanced recovery after surgery (ERAS) protocols in laparoscopic surgery.

Our feasibility study demonstrated successful recruitment of patients and excellent protocol adherence by the clinicians and suggested a more favourable post-operative recovery with ITM than in the control group. However, ITM is not devoid of limitations or adverse effects, and is supported by relatively small, single centre studies. Therefore, we require a large definitive trial to direct clinicians working with this expanding patient population having minimally invasive abdominal surgery.

The use of ITM, as an opioid-sparing strategy during minimally invasive major abdominal surgery, will: Primary Hypothesis: Enhance quality of recovery of patients after minimally invasive major abdominal surgery. Secondary Hypothesis: Improve pain control, functional recovery, opioid-sparing, with an equivalent safety profile.

This randomised controlled, double-blind multicentre trial will be conducted across multiple tertiary centres including The Alfred Hospital and Peter MacCallum Cancer Centre, with additional sites recruited subject to grant funding. We will recruit 280 patients, given a sample size calculation of 262 (see section 9.3 – power analysis).
Eligibility criteria include: Adults scheduled for elective laparoscopic or robot-assisted major abdominal surgery with a predicted surgical time of ³2 hours. Ineligibility criteria include: A contra-indication to neuraxial injection; inability to complete the quality of recovery questionnaire (QoR-15) or pain scores; chronic pain with pre-operative baseline opioid use; decline to participate in the study, or inability to consent. Written informed consent will be obtained from all patients. On the day of surgery, patients will be randomly assigned using an electronic randomisation tool to receive either spinal with 200mcg ITM with local anaesthetic (Intervention Group) or a sham injection of subcutaneous saline in the lumbar region (Control Group) both conducted with full sterile precautions. Intravenous fentanyl can be administered during induction and intra-operatively based on haemodynamic changes suggestive of pain. Patients in both cohorts will have intravenous fentanyl patient-controlled analgesia for 24 hours following ITM or until the oral route is available. Multimodal analgesia will be encouraged peri-operatively. All other aspects of intra- operative care will be at the discretion of the treating anaesthetist, who is unblinded to patient allocation. The patient and research staff conducting data collection remain blinded for the duration of the trial.

Likely benefits
We anticipate improved quality of recovery, reduced opioid consumption and opioid-related side- effects, and high patient and health care worker satisfaction in the intervention group. Given the expanding indications for minimally invasive surgery this research proposal has a high degree of clinical relevance globally.

Chief investigators

Dr Katrina Pirie, Professor Paul Myles, Alfred Hospital
Professor Wendy Brown, Monash University, Melbourne.



The project was awarded A$89,920 (including scholarship) funding through the ANZCA research grants program for 2024.   

Last updated 10:55 15.12.2023