Implications for post critical illness trial design: sub-phenotyping trajectories of functional recovery among sepsis su
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RESEARCH
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Implications for post critical illness trial design: sub-phenotyping trajectories of functional recovery among sepsis survivors Zudin A. Puthucheary1,2*, Jochen S. Gensichen3,4,5, Aylin S. Cakiroglu6, Richard Cashmore2, Lara Edbrooke7,8, Christoph Heintze9, Konrad Neumann10, Tobias Wollersheim11, Linda Denehy7,8 and Konrad F. R. Schmidt3,5,9
Abstract Background: Patients who survive critical illness suffer from a significant physical disability. The impact of rehabilitation strategies on health-related quality of life is inconsistent, with population heterogeneity cited as one potential confounder. This secondary analysis aimed to (1) examine trajectories of functional recovery in critically ill patients to delineate sub-phenotypes and (2) to assess differences between these cohorts in both clinical characteristics and clinimetric properties of physical function assessment tools. Methods: Two hundred ninety-one adult sepsis survivors were followed-up for 24 months by telephone interviews. Physical function was assessed using the Physical Component Score (PCS) of the Short Form-36 Questionnaire (SF-36) and Activities of Daily Living and the Extra Short Musculoskeletal Function Assessment (XSFMA-F/B). Longitudinal trajectories were clustered by factor analysis. Logistical regression analyses were applied to patient characteristics potentially determining cluster allocation. Responsiveness, floor and ceiling effects and concurrent validity were assessed within clusters. Results: One hundred fifty-nine patients completed 24 months of follow-up, presenting overall low PCS scores. Two distinct sub-cohorts were identified, exhibiting complete recovery or persistent impairment. A third sub-cohort could not be classified into either trajectory. Age, education level and number of co-morbidities were independent determinants of poor recovery (AUROC 0.743 ((95%CI 0.659–0.826), p < 0.001). Those with complete recovery trajectories demonstrated high levels of ceiling effects in physical function (PF) (15%), role physical (RP) (45%) and body pain (BP) (57%) domains of the SF-36. Those with persistent impairment demonstrated high levels of floor effects in the same domains: PF (21%), RP (71%) and BP (12%). The PF domain demonstrated high responsiveness between ICU discharge and at 6 months and was predictive of a persistent impairment trajectory (AUROC 0.859 (95%CI 0.804–0.914), p < 0.001). (Continued on next page)
* Correspondence: [email protected] 1 William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK 2 Critical Care and Perioperative Medicine Research Group, Adult Critical Care Unit, Royal London Hospital, London E1 1BB, UK Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long
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