Award Title: CAMELOT - Continuous rectus sheath Analgesia in eMErgency LaparOTomy: Multi-centre, randomised sham-controlled trial of rectus sheath catheter-delivered local anaesthetic infusion compared with usual care in patients undergoing emergency bowel surgery
Funder: Department of Health and Social Care

Abstract: BACKGROUND_x000D_
In the UK around 30,000 patients a year undergo an operation called an emergency laparotomy to treat life-threatening conditions. A large vertical cut is made in the abdomen when patients are asleep under general anaesthesia. Good pain relief after surgery will help patients feel better and recover quicker. Because of the high level of pain experienced by many patients, opioid based painkillers such as morphine are often given, using patient-controlled analgesia (PCA) pumps. However, morphine can cause serious side effects such as breathing problems, nausea and vomiting, and delayed bowel movement, which can slow patient recovery. Rectus sheath catheters (RSCs) are a newer way of providing pain relief, where two thin tubes (catheters) are inserted on either side of the wound during the operation. Local anaesthetic is injected slowly into the catheters to numb the nerves and reduce pain for about three days. Small studies suggest that RSCs may provide effective pain relief, reduce the use of morphine, and help patient recovery. Potential disadvantages are that RSCs take time to insert and are expensive. More work is needed to understand whether there are any unwanted effects with RSCs. _x000D_
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AIM_x000D_
Our study will find out whether adding RSCs to standard PCA provides better pain relief, fewer side effects and complications, and greater satisfaction for patients undergoing emergency laparotomy. It will also determine whether they are safe and cost-effective._x000D_
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METHODS_x000D_
We will recruit 750 patients over three years in 15 hospitals. Patients will be randomly assigned to one of two groups: one group will have RSCs plus standard PCA, and the other will have standard PCA only. In the PCA only group, identical-looking catheters will be attached on the skin surface, but no local anaesthetic will be given. This means that patients will report their pain without knowing which group they are in. We will compare the two groups using the Overall Benefit of Analgesia Score (OBAS). This measures pain scores, opioid side effects and patient satisfaction, and will be completed daily for five days after surgery. We will also compare the speed of patients’ recovery from surgery and look for relevant complications such as breathing problems. We will check for long-term pain six months after surgery, measure NHS costs and impact on patients’ return to activities (e.g. work). _x000D_
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PATIENT AND PUBLIC INVOLVEMENT_x000D_
Our patient co-applicant is an important team member and will be supported by a patient advisory group of six individuals with experience of emergency laparotomy as a patient or carer. They emphasised the critical importance of pain management to patients going through this surgery and recommended a patient rating of pain control as the most important measure to use in the trial. They also advised on suitable consent and follow-up processes, and will have ongoing input during the trial. Two patient representatives will contribute to trial oversight as members of a steering committee. _x000D_
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DISSEMINATION_x000D_
Study results will be published in research journals and presented at conferences. We will use our close links with key organisations to include the study findings in clinical guidelines. We will also share our findings with participants and the public through patient meetings, newsletters and social media.

Lay Abstract: BACKGROUND: In the UK over 30,000 patients/year undergo emergency laparotomy surgery. Severe post-operative pain is common after this operation. Small studies suggest that rectus sheath catheters (RSCs) may provide effective pain relief, reduce morphine use and aid recovery, but they have not been investigated in a large randomised controlled trial (RCT)._x000D_
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AIM: To compare the clinical and cost-effectiveness of RSC vs. standard analgesia for patients undergoing emergency laparotomy surgery._x000D_
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DESIGN: Multi-centre, pragmatic, parallel group, superiority randomised sham-controlled trial with blinding of patients and outcome assessors; an internal pilot phase to determine feasibility of recruitment and protocol adherence; patient follow-up for 6 months._x000D_
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SETTING: Acute surgical services in NHS hospitals._x000D_
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POPULATION: Adults 18 years or over, undergoing emergency laparotomy surgery via a midline incision and eligible for inclusion in the National Emergency Laparotomy Audit._x000D_
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EXCLUSIONS: Clinician or patient refusal, planned epidural anaesthesia, contraindications to RSC including allergy to local anaesthetic (LA), anatomical factors making RSC insertion impossible._x000D_
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INTERVENTION: Insertion of RSCs with constant infusion of LA for 72 hours from the end of surgery._x000D_
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COMPARATOR: Sham RSCs with inactive infusion device in place for 72 hours from the end of surgery._x000D_
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USUAL CARE: All participants will be given standard analgesia including opioid-based patient-controlled analgesia in addition to the RSC/sham RSC._x000D_
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OUTCOME MEASURES: _x000D_
Primary: mean Overall Benefit of Analgesia Score (OBAS) on postoperative days 1-5._x000D_
Secondary: Postoperative complications including pulmonary, surgical site infections and intervention complications; time to return of bowel function; time to 1st mobilisation; pain intensity at rest and on movement at 24, 48 and 72 hours; postoperative opioid use; mortality at 30 and 90 days; chronic postoperative pain; health-related quality of life; length of stay in critical care and in hospital; cost effectiveness._x000D_
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SAMPLE SIZE: 750 participants (375 per group), which will provide 90% power to detect a 15% relative reduction in mean OBAS assuming a standard deviation (on the logarithmic scale) of 0.65, 5% statistical significance and allowing for 10% missing data._x000D_
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ANALYSIS: The primary analyses will be by intention to treat and results will be reported in line with the CONSORT guidelines. The economic evaluation will be conducted from an NHS perspective at 6 months_x000D_
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PROJECT TIMETABLE: Target randomisation rate: 2 patients/centre/month across 15 centres. Study duration 56 months: 8-mths set up, 36-mths recruitment (12-mths internal pilot, 24-mths main trial), 6-mths follow-up on all participants; 6-mths analysis and report_x000D_
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EXPERTISE: The multidisciplinary team includes patients, anaesthetists, surgeons, pain nurse, statistician, health economist, trialists/methodologists and a UKCRC-registered clinical trials unit._x000D_
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ANTICIPATED IMPACT AND DISSEMINATION: Our national survey has confirmed only limited uptake of RSC into routine emergency laparotomy care. If shown to be superior, we will work closely with our stakeholders to impact clinical guidance and bring RSC into routine practice. Results will be rapidly disseminated through a variety of media, publication in peer-reviewed journals and conference presentations. The CAMELOT patient advisory group will advise on dissemination to relevant patient groups.

Research Activity Codes: 6.1 PHARMACEUTICALS;6.4 SURGERY
Health Categories: NEUROLOGICAL