Pain and reward in emergency surgery trials

“They’re called ‘trials’ for a reason” a very experienced clinical academic once told me during a difficult oversight meeting for a study I was leading. This randomised controlled trial (RCT) of an intervention used during emergency bowel surgery was struggling with recruitment rates after the pandemic and we were discussing ways to get things back on track. With some intensive efforts from all involved – and a fair amount of stress - we did manage to finish participant recruitment. Unperturbed, I even took on co-leadership of another emergency perioperative trial, CAMELOT, exploring rectus sheath catheter infusions for post-laparotomy analgesia.

Many of those interested in research and quality improvement for patients undergoing emergency surgery have felt compelled by the obvious health burden: 30,000 emergency laparotomy cases each year in the UK, with a 10% mortality rate at one month after surgery. The latter seems to have stubbornly plateaued after an initial improvement soon after our national audit rolled out. Yet most perioperative research is still directed at those undergoing elective surgery, with much lower overall risks. This is clearly a patient group that remains under-served, and with a lot to gain from even small improvements in postoperative outcomes. But formally evaluating new treatments in this setting is not without challenge.

As in any acute care setting, potential participants will need the interventions being tested at any hour of the day or night. Very few hospitals can provide research delivery team support outside core hours. The urgent nature of this surgical pathway - in patients who may be critically unwell - shrinks the time window for enrolment and reduces the capacity of patients and clinicians to focus on anything other than immediate clinical care. Furthermore, clinicians may have a prior view on the intervention that is strong enough to deter them from allowing the randomisation system to dictate what happens.

This issue of lacking equipoise is both interesting and frustrating for trialists. Widespread practice variability around a particular treatment suggests that equipoise exists at a community level. Individual-level equipoise is a different thing though. Two clinicians may have strongly held but divergent beliefs even when definitive evidence on an aspect of care is lacking. Surgery and anaesthesia are “craft” specialties with many technique-based approaches. Perioperative care is littered with complex interventions, in stark contrast to pharmacological treatments in other specialties that enter practice with a more straightforward evidence-based journey. New perioperative techniques that appear rational and that bring the instant gratification of an apparent improvement in patient health during early postoperative recovery can take hold rapidly with the backing of only low-quality evidence. But not all the effects of our interventions are visible to the naked eye. Without structured, objective assessment of large numbers of cases, and the magic confounder-limiting effect of randomisation, we should be open to the possibility that certain areas of our practice might be no better, or even worse, than a reasonable alternative.

Overcoming these barriers was a priority when we were planning the CAMELOT trial. Our team includes academic anaesthetists, surgeons, statisticians, methodologists, health economists and of course patients and public members with experience of being on the receiving end of emergency laparotomy care. Their views echoed what we had seen in previous emergency trials, that patients often have mental capacity to make decisions about taking part in research but can feel overwhelmed by events or overloaded with information. Together we designed a layered consent process that invites verbal consent before surgery with simple written information.

Acknowledging the limitations of research delivery team coverage, we have always strongly encouraged clinicians to get trained as local investigators in return for recognition for their contribution in publications. This has been particularly successful in CAMELOT sites with highly motivated residents taking part in the excellent NIHR Associate Principal Investigator Scheme. Nevertheless, given the demands of busy on-call clinical duties, expectations should be realistic. We see most participant recruitment during core hours, supported by the research teams, and we set achievable recruitment targets with sites.

Managing a “complex intervention” in a trial is a balance between simplifying where possible while ensuring the quality of the intervention implementation. One advantage of testing interventions already used in clinical practice is that there is already a degree of familiarity among clinicians. We invested in high-quality training materials and a quality assurance package. We are also updating our processes to allow ultrasound-guided catheter insertion by anaesthetists as an alternative to the usual placement by surgeons. This will help CAMELOT to be representative of current practice and support post-trial adoption of the findings. Meanwhile, additional training is provided in setting up the control group, who receive sham catheters on the skin surface, with dressings, a deactivated pump and giving set mimicking the real thing. All patients receive opioid patient-controlled analgesia, and multi-modal analgesics chosen by their care team, which can include spinal anaesthesia/analgesia.

Finally, equipoise was one of the biggest considerations during trial setup. In some hospitals the routine use of rectus sheath catheters is so firmly established that randomising half of patients to the control group was not thought feasible. We therefore had careful pre-trial discussions with interested sites at earlier stages of adoption. Local conversations with all stakeholders were encouraged to make sure the trial would be supported by a majority, and on the whole, this is working out well.

It is unrealistic to expect universal equipoise among all clinicians, and we have given careful thought to how it can be encouraged. It seems clear that confronting colleagues with data (or the lack of it) in an effort to persuade them is rarely effective on its own and can risk entrenching positions. Enquiring conversations with space for colleagues to voice concerns can be more productive, and foster a greater understanding of patient-centred choice and safety in research. More widely, in the last couple of decades, large scale multicentre perioperative trials have become more common. Clinicians are being increasingly exposed to trials while providing patient care, and at an earlier point in their careers. This will only help to demystify trial concepts (e.g. that patients may remain in a trial as part of the intention-to-treat population even if trial care did not perfectly follow the protocol) and get colleagues used to the slightly strange idea that part of their patient care will be decided by a randomisation system.

CAMELOT is now over halfway to its sample size target of around 700 participants. While any research in this challenging setting will be hard work for all involved, the potential impact of an improved postoperative analgesia strategy for this patient group could be huge. If your hospital is not yet taking part, we would love to hear from you. If your hospital is helping recruitment, we are very grateful and hope you can contribute whatever you can to the spirit of equipoise, to the expansion of clinician-investigator numbers, and to the normalisation of interventional research as part of perioperative care.

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For more information on the CAMELOT trial see: https://www.bristol-trials-centre.bristol.ac.uk/studies/camelot-continuous-rectus-sheath-analgesia-in-emergency-laparotomy/

Contact the trial team at Camelot-trial@bristol.ac.uk