Delirium is characterized by an acutely altered mental status accompanied by reductions in cognitive function and attention. Delirium in septic patients, termed sepsis-associated delirium (SAD), differs in several specific aspects from the other types of delirium that are typically encountered in intensive care units. Since sepsis and delirium are both closely associated with increased morbidity and mortality, it is important to not only prevent but also promptly diagnose and treat SAD. We herein reviewed the etiology, pathogenesis, risk factors, prevention, diagnosis, treatment, and prognosis of SAD, including coronavirus disease 2019 (COVID-19)-related delirium. Delirium by itself not only worsens long-term prognosis, but it is also regarded as an important factor affecting the outcome of post-intensive care syndrome. In COVID-19 patients, the difficulties associated with adequately implementing the ABCDEF bundle (Assess, prevent, and manage pain; Both spontaneous awakening and breathing trials: Choice of analgesia and sedation; Delirium assess, prevent, and manage; Early mobility and exercise; Family engagement/empowerment) and the need for social isolation are issues that require the development of conventional care for SAD.

Introduction: Post-intensive care syndrome (PICS) is an emerging problem in critically ill patients and the prevalence and risk factors are unclear in patients with severe coronavirus disease 2019 (COVID-19). This multicenter prospective observational study aimed to investigate the prevalence and risk factors of PICS in ventilated patients with COVID-19 after ICU discharge. Methods: Questionnaires were administered twice in surviving patients with COVID-19 who had required mechanical ventilation, concerning Barthel Index, Short-Memory Questionnaire, and Hospital Anxiety and Depression Scale scores. The risk factors for PICS were examined using a multivariate logistic regression analysis. Results: The first and second PICS surveys were obtained at 5.5 and 13.5 months (mean) after ICU discharge, with 251 and 209 patients completing the questionnaires and with a prevalence of PICS of 58.6% and 60.8%, respectively, along with the highest percentages of cognitive impairment. Delirium (with an odds ratio of (OR) 2.34, 95% CI 1.1–4.9, and p = 0.03) and the duration of mechanical ventilation (with an OR of 1.29, 95% CI 1.05–1.58, and p = 0.02) were independently identified as the risk factors for PICS in the first PICS survey. Conclusion: Approximately 60% of the ventilated patients with COVID-19 experienced persistent PICS, especially delirium, and required longer mechanical ventilation.

Nafamostat mesylate (NM) is a synthetic serine protease inhibitor that can be used as an anticoagulant during blood purification in critically ill patients, as well as a treatment for disseminated intravascular coagulation. Although NM has been reported to reduce the risk of bleeding during blood purification, its effect on survival outcomes of patients who received blood purification treatments is unclear. We hypothesized that administration of NM during blood purification can reduce mortality in patients with sepsis. A post hoc analysis was conducted on a nationwide retrospective registry that included data from 3195 sepsis patients registered at 42 intensive care units throughout Japan. We evaluated the effect of NM on hospital mortality and bleeding complications using propensity score matching in 1216 sepsis patients who underwent blood purification in the intensive care unit (ICU). Two-hundred-and-sixty-eight pairs of propensity score-matched patients who received NM and conventional therapy were compared. Hospital and ICU mortality rates in the NM group were significantly lower than those in the conventional therapy group. However, rates of bleeding complications did not differ significantly between the two groups. These data suggest that administration of NM improved the survival outcomes of sepsis patients who underwent blood purification in the ICU.

Background/Objectives: This study investigated the prevalence of functional impairments and the effects of long COVID on long-term functional impairments in patients with severe COVID-19. Methods: We conducted a nationwide multicenter cohort study in collaboration with nine hospitals, collecting data using self-administered questionnaires from participants aged 20 years or older who were diagnosed with COVID-19, admitted to the intensive care unit (ICU) between April 2021 and September 2021, and discharged alive. Questionnaires regarding daily life, sequela, and functional impairments were mailed to patients in August 2022. The effects of long COVID on functional impairments were examined using a multivariate logistic regression analysis. Results: The survey was completed by 220 patients, with a mean of 416 days after discharge. Among respondents, 20.5% had physical impairments (n = 45), 35.0% had mental disorders (n = 77), and 42.7% had either (n = 94). Furthermore, 77.7% had long COVID (171/220), and the most common symptom was dyspnea (40.0%). The multivariate analysis showed that fatigue/malaise, upper respiratory tract symptoms, myalgia, muscle weakness, decreased concentration, sleep disorder, brain fog, and dizziness were risk factors for functional impairments at one year. Conclusions: Many patients with severe COVID-19 admitted to the ICU still suffered from post-intensive care syndrome even after one year, which manifested in combination with direct symptoms of the original disease, such as long COVID.

Objectives: To investigate the prevalence of long-term mental disorders in caregivers of ICU sepsis survivors and examine associations with post-intensive care syndrome (PICS) in patients. Design: Prospective observational study. Setting: Twenty-one mixed ICUs. Patients: Caregivers (the next of kin) of the patients diagnosed with sepsis between November 2020 and April 2022. Interventions: None. Measurements and Main Results: Caregivers and patients were assessed at 3, 6, and 12 months after hospital discharge by telephone and mail. The primary outcome was caregiver mental disorders (mental post-intensive care syndrome-family [PICS-F]). Mixed-effects logistic regression analyses were performed to evaluate the association between caregiver PICS-F and patient PICS. Ninety-four caregiver-patient dyads were analyzed. Caregivers were a median of 67 years old (55–79 yr old), 31 (33.0%) were male, and 41 (43.6%) were spouses. Patients were a median of 74 years old (69–82 yr old), and 54 (57.4%) were male. The prevalence of mental PICS-F did not decrease from 3 to 12 months (43% vs. 42%, respectively), whereas the presence of PICS symptoms in patients decreased from 82% to 62%. In mixed-effects logistic regression, the presence of PICS symptoms in patients was significantly associated with PICS-F (adjusted odds ratio, 3.00; 95% CI, 1.54–5.88; p < 0.01). Among the individual patient PICS domains, only mental PICS was significantly associated with PICS-F (3.71; 2.03–6.77; p < 0.01), whereas physical and cognitive impairments in patients were not. Conclusions: The prevalence of mental PICS-F in caregivers of ICU sepsis survivors was frequent and long-lasting over the first year after hospital discharge. Since it was most strongly associated with patients’ mental disorders rather than physical or cognitive impairments, the mental PICS domain in patients may be an important indicator of PICS-F and should be considered in future studies.

OBJECTIVE: Return-to-work varies among previously employed patients after critical illness. Social determinants of health (SDH) may play a role in this variation. We compared patient characteristics and explored the association between SDH and long-term joblessness among patients who experienced severe COVID-19. DESIGN: A secondary analysis of a prospective nationwide database. SETTINGS: The COVID-19 Recovery Study II (CORES II) study, a nationwide prospective observational study in Japan that examined long-term symptoms and social status over two years following hospitalization. PATIENTS: We included adults hospitalized with severe COVID-19 between April 1 and September 30, 2021, who were employed before hospitalization. SDH included education history and pre-hospitalization employment status. MEASUREMENTS AND MAIN RESULTS: The primary outcome was joblessness at the first- and second-year follow-ups. We used generalized estimating equations for the main analysis to examine longitudinal associations between SDH and joblessness, with the SDH variables entered into the model as separate categorical variables. Of 3297 hospitalized patients, 337 met inclusion criteria. At the first-year follow-up, 275 had returned to work, whereas 62 (18.4%) remained jobless. At the second-year follow-up, 242 (82.3 %) had returned to work, and 52 (17.7%) remained jobless. Patients who were jobless at the first-year follow-up showed more persistent symptoms and greater physical and mental impairment compared with those who returned to work. Among SDH factors, non-permanent employment was associated with joblessness over the 2-year follow-up period (odds ratio 2.35; 95% CI [1.26–4.40]) compared with permanent employment. Education history was not associated with joblessness at the first- or second-year follow-ups. CONCLUSIONS: Non-permanent employment was associated with joblessness during the pandemic after hospitalization for severe COVID-19. Pre-hospitalization employment status may be relevant to long-term social recovery after critical illness.