Plasma HMGB1 levels and physical performance in ICU survivors.

PURPOSE: Physical 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. METHODS: Prospective 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. RESULTS: Compared 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). CONCLUSION: In 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 COMMENT: HMGB-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 REGISTRATIONS: ClinicalTrials.gov identifier NCT02914756.

Lack of clinically relevant correlation between subjective and objective cognitive function in ICU survivors: a prospective 12-month follow-up study.

BACKGROUND: Cognitive impairment and psychological distress are common in intensive care unit (ICU) survivors. Early identification of affected individuals is important, so intervention and treatment can be utilized at an early stage. Cognitive Failures Questionnaire (CFQ) is commonly used to screen for subjective cognitive function, but it is unclear whether CFQ scores correlate to objective cognitive function in this population. METHODS: Between 2014 and 2018, 100 ICU survivors aged 18-70 years from the general ICU at the Karolinska University Hospital, Solna, were included in the study. Out of these, 58 patients completed follow-up at 3 months after ICU discharge, 51 at 6 months, and 45 at 12 months. Follow-up included objective cognitive function testing using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and subjective cognitive function testing with the self-rating Cognitive Failures Questionnaire (CFQ), as well as psychological self-rating with the Post-Traumatic Stress Symptoms Scale-10 (PTSS-10) and Hospital Anxiety and Depression Scale (HADS). RESULTS: The prevalence of cognitive impairment as measured by four selected CANTAB tests was 34% at 3 months after discharge, 18% at 6 months, and 16% at 12 months. There was a lack of significant correlation between CANTAB scores and CFQ scores at 3 months (r = - 0.134-0.207, p > 0.05), at 6 months (r = - 0.106-0.257, p > 0.05), and at 12 months after discharge (r = - 0.070-0.109, p > 0.05). Correlations between CFQ and PTSS-10 scores and HADS scores, respectively, were significant over the follow-up period (r = 0.372-0.710, p ≤ 0.001-0.023). In contrast, CANTAB test scores showed a weak correlation with PTSS-10 and HADS scores, respectively, at 3 months only (r = - 0.319-0.348, p = 0.008-0.015). CONCLUSION: We found no clinically relevant correlation between subjective and objective cognitive function in this cohort of ICU survivors, while subjective cognitive function correlated significantly with psychological symptoms throughout the follow-up period. Treatment and evaluation of ICU survivors' recovery need to consider both subjective and objective aspects of cognitive impairment, and subjective reports must be interpreted with caution as an indicator of objective cognitive function.

Early psychological screening of intensive care unit survivors: a prospective cohort study.

BACKGROUND: A majority of patients survive their episode of critical illness but up to 30% of patients suffer from psychological problems such as post-traumatic stress, anxiety and depression in the year after intensive care unit (ICU) stay. A method to identify discharged patients at risk for adverse psychological outcome would be helpful in the triage for ICU follow-up and could enable early intervention. The aim of this study was to evaluate whether early screening with validated questionnaires after ICU discharge can identify patients at risk for symptoms of post-traumatic stress, anxiety and depression 3 months after ICU stay. METHODS: We performed a prospective observational cohort study in the general ICU at the Karolinska University Hospital Solna, Stockholm, Sweden. All adult patients surviving ≥ 24 hours in the ICU in a 9-month period were eligible for inclusion. Patients with mental disability, serious auditory and visual disorder, aphasia or who were unable to understand Swedish were excluded. One hundred and thirty-two patients were included and visited by a follow-up nurse within 1 week after ICU discharge. The Hospital Anxiety and Depression Scale (HADS) and the Post-Traumatic Stress Symptoms Checklist-10 (PTSS-10) were administered. Three months after ICU discharge the patients received the same questionnaires by postal mail. We assessed the predictive values of the questionnaires using the area under the receiver operating characteristic curve (AUROC). For correlation calculations, we used Spearman's rank correlation coefficient. Negative and positive predictive values for each questionnaire were calculated. RESULTS: Eighty-two patients returned the follow-up questionnaires. We found correlation between early and late scores and reasonable predictive precision regarding 3-month outcomes, with an AUROC of 0.90 for PTSS-10 part B, 0.80 for the HADS anxiety subscale and 0.75 for the HADS depression subscale. CONCLUSIONS: Symptoms of post-traumatic stress, anxiety and depression assessed 1 week after ICU stay correlate with 3-month psychological outcome. The HADS and PTSS-10 may be useful aids to identify ICU survivors at high risk for clinically significant symptoms of post-traumatic stress, anxiety and depression 3 months post ICU stay.

The impact of sepsis, delirium, and psychological distress on self-rated cognitive function in ICU survivors-a prospective cohort study.

BACKGROUND: Many intensive care unit (ICU) survivors develop psychological problems and cognitive impairment. The relation between sepsis, delirium, and later cognitive problems is not fully elucidated, and the impact of psychological symptoms on cognitive function is poorly studied in ICU survivors. The primary aim of this study was to examine the relationship between sepsis, ICU delirium, and later self-rated cognitive function. A second aim was to investigate the association between psychological problems and self-rated cognitive function 3 months after the ICU stay. METHODS: Patients staying more than 24 h at the general ICU at the Karolinska University Hospital Solna, Stockholm, Sweden, were screened for delirium with the Confusion Assessment Method-ICU (CAM-ICU) during their ICU stay. Sepsis incidence and severity were recorded. Three months later, 216 patients received the Cognitive Failures Questionnaire (CFQ), Hospital Anxiety and Depression Scale (HADS), and Post-Traumatic Stress Symptoms-10 (PTSS-10) questionnaires via postal mail. RESULTS: One hundred twenty-five patients (60%) responded to all questionnaires. Among respondents, the incidence of severe sepsis or septic shock was 42%. The overall incidence of delirium was 34%. Patients with severe sepsis/septic shock had a higher incidence of delirium, with an odds ratio (OR) of 3.7 (95% confidence interval (CI), 1.7-8.1). Self-rated cognitive problems 3 months post-ICU were found in 58% of the patients. We did not find any association between sepsis or delirium and late self-rated cognitive function. However, there was a correlation between psychological symptoms and self-rated cognitive function, with the strongest correlation between PTSS-10 scores and CFQ scores (r = 0.53; p < 0.001). CONCLUSIONS: ICU delirium is more common in severely septic/septic shock patients. In our cohort, neither severe sepsis nor ICU delirium was associated with self-rated cognitive function 3 months after the ICU stay. Ongoing psychological symptoms, particularly post-traumatic stress was associated with worse self-rated cognitive function. Psychological symptoms need to be taken into account when assessing cognitive function in ICU survivors.