LAUSR

Necrotising soft-tissue infections (NSTIs) include necrotising forms of fasciitis, myositis and cellulitis and are potentially lifethreatening infections that frequently require intensive care level treatment, extensive surgical debridement, broad spectrum antibiotics and a multispecialty and multidisciplinary approach to care. The estimated incidence of NSTI is 3.5 cases per 100 000 persons and the mortality rate for NSTI varies widely, but is generally reported to be in the range of 20–30%. Hyperbaric oxygen treatment (HBOT) is offered as an adjunctive treatment for NSTI in some centres and has been since the 1960s when Brummelkamp first proposed it could treat anaerobic infections. The proposed physiologic mechanisms supporting the use of HBOT in NSTI are attractive – increased tissue oxygen tension (which both reduce tissue oedema via an osmotic effect and also salvage critically ischaemic areas), potentiation of antibiotic efficiency, improved white cell killing efficacy and anti-inflammatory effects. A number of non-randomized observational studies suggest that HBOT may be beneficial in the treatment of NSTI while other studies report no change in mortality with HBOT. There are no randomized controlled trials (RCTs) evaluating this question at the time of writing; however, the recommendation from a 2014 Cochrane review was that an RCT would be the best course of action to evaluate the effectiveness of HBOT for NSTI. In planning for an RCT of HBOT for NSTI, there are multiple considerations to be taken into account. Given the low incidence of NSTI, a multi-centre or multi-national study is required for adequate power. Surgical and antibiotic approaches would need to be standardized. Given the heterogeneity of the condition (both in severity and anatomical area affected), a multiple stratification approach would be necessary and would further increase the number of participants required. Engagement from all stakeholders would be essential for the success of any future RCT. Also importantly, the ethics of the trial must be considered and in particular, the ethics of randomizing patients away from a treatment, which is routine practice in many centres. The idea of collective or clinical equipoise was argued by Benjamin Freedman in 1987; a concept requiring genuine uncertainty about a treatment within the expert medical community in order for the randomization of patients within a clinical trial to be considered ethical. This definition was further sharpened in 2011 to ‘a state of genuine agnosticism or conflict in the expert medical community about the net preferred medically established procedure for the condition under study’. Johnson, et al.’s ethometric study was an effort to quantify clinical equipoise and the thresholds at which a study may be considered ethical or unethical. They concluded that trials are perceived to be unethical when equipoise is disturbed beyond 70:30, for example if 70% of experts favour a treatment, then 50% of subjects would prefer that the treatment is used rather than be tested in a trial. Johnson suggests that if experts are completely agnostic, or individually equipoised, their votes should be divided and added equally to each side. In order to assess clinical equipoise regarding the use of HBOT in NSTI and to gauge what proportion of an expert group would be prepared to participate in an RCT examining this, we developed an anonymous survey that was distributed to key stakeholders in the care of patients with NSTI at our organization. HBOT is used more frequently for management of NSTI at Alfred Health than any other centre in Australasia (Table S1). The survey was developed and study data were collected and managed using research electronic data capturetools hosted at Alfred Health. It was distributed via email to specialist staff at Alfred Health: 34 plastic and reconstructive and general surgeons, 33 intensivists, 41 infectious disease physicians and five hyperbaric physicians. Participants were asked to provide the following: their specialty, their response to the statement that HBOT has a role in patients with NSTI and whether or not they would be prepared to participate in an RCT to investigate this. The survey was kept brief to aid response rates. Protocol for the survey was reviewed and approved by The Alfred Hospital Research and Ethics Committee (project number 307/20).