Ethical considerations in conducting surgical research in severe complicated intra-abdominal sepsis

• Published in: World journal of emergency surgery Vol. 14; no. 1; p. 39
• Main Authors: Doig, Christopher J, Page, Stacey A, McKee, Jessica L, Moore, Ernest E, Abu-Zidan, Fikri M, Carroll, Rosemary, Marshall, John C, Faris, Peter D, Tolonen, Matti, Catena, Fausto, Cocolini, Federico, Sartelli, Massimo, Ansaloni, Luca, Minor, Sam F, Peirera, Bruno M, Diaz, Jose J, Kirkpatrick, Andrew W
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05-08-2019; BioMed Central; BMC
• Subjects: Analysis; Anesthesia; Antibiotics; Care and treatment; Clinical trials; Consent; Death; Delirium; Digestive System Surgical Procedures - education; Digestive System Surgical Procedures - ethics; Humans; Infection; Inflammation; Informed consent; Informed Consent - ethics; Informed Consent - standards; Intra-peritoneal sepsis; Laparotomy; Medical ethics; Medical law; Medical research; Mortality; Multiple organ dysfunction; Multiple organ failure; Open-abdomen; Patients' rights; Prospective Studies; Proxy; Randomized controlled trial; Research Design - standards; Retirement benefits; Review; Risk factors; Sepsis; Sepsis - surgery; Surgery; Waiver; Waiver; Intra-peritoneal sepsis; Open-abdomen; Multiple organ dysfunction; Consent; Randomized controlled trial
• ISSN: 1749-7922; 1749-7922
• DOI: 10.1186/s13017-019-0259-9

Severe complicated intra-abdominal sepsis (SCIAS) has high mortality, thought due in part to progressive bio-mediator generation, systemic inflammation, and multiple organ failure. Treatment includes early antibiotics and operative source control. At surgery, open abdomen management with negative-peritoneal-pressure therapy (NPPT) has been hypothesized to mitigate MOF and death, although clinical equipoise for this operative approach exists. The Closed or Open after Laparotomy (COOL) study (https://clinicaltrials.gov/ct2/show/NCT03163095) will prospectively randomize eligible patients intra-operatively to formal abdominal closure or OA with NPTT. We review the ethical basis for conducting research in SCIAS.
Research in critically ill incapacitated patients is important to advance care. Conducting research among SCIAS is complicated due to the severity of illness including delirium, need for emergent interventions, diagnostic criteria confirmed only at laparotomy, and obtundation from anaesthesia. In other circumstances involving critically ill patients, clinical experts have worked closely with ethicists to apply principles that balance the rights of patients whilst simultaneously permitting inclusion in research. In Canada, the Tri-Council Policy Statement-2 (TCPS-2) describes six criteria that permit study enrollment and randomization in such situations: (a) serious threat to the prospective participant requires immediate intervention; (b) either no standard efficacious care exists or the research offers realistic possibility of direct benefit; (c) risks are not greater than that involved in standard care or are clearly justified by prospect for direct benefits; (d) prospective participant is unconscious or lacks capacity to understand the complexities of the research; (e) third-party authorization cannot be secured in sufficient time; and (f) no relevant prior directives are known to exist that preclude participation. TCPS-2 criteria are in principle not dissimilar to other (inter)national criteria. The COOL study will use waiver of consent to initiate enrollment and randomization, followed by surrogate or proxy consent, and finally delayed informed consent in subjects that survive and regain capacity.
A delayed consent mechanism is a practical and ethical solution to challenges in research in SCIAS. The ultimate goal of consent is to balance respect for patient participants and to permit participation in new trials with a reasonable opportunity for improved outcome and minimal risk of harm.