Frailty as a sequela of burn injury: a post hoc analysis of the “RE-ENERGIZE” multicenter randomized-controlled trial and the National Health Interview Survey
Authors: Panayi Adriana C. , Heyland Daren K. , Stoppe Christian , Jeschke Marc G. , Knoedler Samuel , Tapking Christian , Didzun Oliver , Haug Valentin , Bigdeli Amir K. , Kneser Ulrich , Orgill Dennis P. , Hundeshagen Gabriel 
Published: September 2024

Abstract
Background
With advancements in burn treatment and intensive care leading to decreased mortality rates, a growing cohort of burn survivors is emerging. These individuals may be susceptible to frailty, characterized by reduced physiological reserve and increased vulnerability to stressors commonly associated with aging, which significantly complicates their recovery process. To date, no study has investigated burns as a potential risk factor for frailty. This study aimed to determine the short-term prevalence of frailty among burn survivors’ months after injury and compare it with that of the general population.

Methods
A post hoc analysis was conducted on the Randomized Trial of Enteral Glutamine to Minimize the Effects of Burn Injury (RE-ENERGIZE) trial, an international randomized-controlled trial involving 1200 burn injury patients with partial- or full-thickness burns. Participants who did not complete the 36-Item Short Form Health Survey (SF-36) questionnaire were excluded. Data for the general population were obtained from the 2022 National Health Interview Survey (NHIS). Frailty was assessed using the FRAIL (Fatigue, Resistance, Ambulation, Illness, Loss of weight) scale. Due to lack of data on loss of weight, for the purposes of this study, malnutrition was used as the fifth variable. Illness and malnutrition were based on admission data, while fatigue, resistance, and ambulation were determined from post-discharge responses to the SF-36. The burn cohort and general population groups were matched using propensity score matching and compared in terms of frailty status. Within the burn group, patients were divided into different subgroups based on their frailty status, and the differences in their (instrumental) activities of daily living (iADL and ADL) were compared. A multivariable analysis was performed within the burn cohort to identify factors predisposing to frailty as well as compromised iADL and ADL.

Results
Out of the 1200 burn patients involved in the study, 600 completed the required questionnaires [follow-up time: (5.5 ± 2.3) months] and were matched to 1200 adults from the general population in the U.S. In comparison to the general population, burn patients exhibited a significantly higher likelihood of being pre-frail (42.3% vs. 19.8%, P < 0.0001), or frail (13.0% vs. 1.0%, P < 0.0001). When focusing on specific components, burn patients were more prone to experiencing fatigue (25.8% vs. 13.5%, P < 0.0001), limited resistance (34.0% vs. 2.7%, P < 0.0001), and restricted ambulation (41.8% vs. 3.8%, P < 0.0001). Conversely, the incidence rate of illness was observed to be higher in the general population (1.2% vs. 2.8%, P = 0.03), while no significant difference was detected regarding malnutrition (2.3% vs. 2.6%, P = 0.75). Furthermore, in comparison with robust burn patients, it was significantly more likely for pre-frail and frail patients to disclose compromise in ADL and iADL. The frail cohort reported the most pronounced limitation.

Conclusions
Our findings suggest a higher incidence of post-discharge frailty among burn survivors in the short-term following injury. Burn survivors experience compromised fatigue, resistance, and ambulation, while rates of illness and malnutrition were lower or unchanged, respectively. These results underscore the critical need for early identification of frailty after a burn injury, with timely and comprehensive involvement of a multidisciplinary team including burn and pain specialists, community physicians, physiotherapists, nutritionists, and social workers. This collaborative effort can ensure holistic care to address and mitigate frailty in this patient population.