• Emily Brück, Anna Svensson-Raskh, Jacob W Larsson, April S Caravaca, Alessandro L Gallina, Michael Eberhardson, Peter V Sackey, and Peder S Olofsson.
• Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
• Acta Anaesthesiol Scand. 2021 Aug 1; 65 (7): 921-927.

PurposePhysical impairment after critical illness is recognized as a part of the post-intensive care syndrome (PICS). About one third of intensive care unit (ICU) survivors suffer from long-term physical disability, yet the underlying pathophysiological mechanisms remain poorly understood. The pro-inflammatory alarmin, high mobility group box 1 (HMGB1), promotes muscle dysfunction in experimental models, and HMGB1 stays elevated in some patients after ICU discharge. Accordingly, we investigated the relationship between HMGB1 plasma levels and physical performance in ICU survivors.MethodsProspective cohort study of 100 ICU survivors from the general ICU at the Karolinska University Hospital, Sweden. Patients returned for follow up at 3 (58 patients) and 6 months (51 patients) after ICU discharge. Blood samples were collected, and a 6-minute walk test (6-MWT), a handgrip-strength test (HST), and a timed-stands test (TST) were performed.ResultsCompared to reference values of the different physical tests, 16% of patients underperformed at all tests at 3 months and 12% at 6 months. All test results, except hand-grip strength left, improved significantly over the follow-up period (P < .05). There was no significant association between plasma HMGB1 levels at 3 and 6 months and scores on the three tests (6-MWT, TST, and HST) (P = .50-0.69).ConclusionIn this follow-up study of ICU survivors, we found no significant association between plasma HMGB1 levels and physical performance. Additional follow-up studies of HMGB1 plasma levels and muscle function in ICU survivors are still warranted.Editorial CommentHMGB-1, a marker of cell damage and activation, is known to increase in ICU patients. In study participants at 3- to 6-month post-ICU stay, HMGB-1 levels were still elevated, although no association to the primary outcome, physical performance, was found. Mechanisms for failure to recover physical performance post-ICU remain unclear, and investigations into cause of post-intensive care syndrome need to continue.Trial RegistrationsClinicalTrials.gov identifier NCT02914756.© 2021 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

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