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Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown. Objectives: To compare the effects of lower (90% [range, 88–92%]), intermediate (94% [range, 92–96%]), and higher (98% [range, 96–100%]) oxygen-saturation targets on long-term outcomes. Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction. Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91–96%), 95% (93–97%), and 97% (95–99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92–2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62–1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83–1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life. Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes. [ABSTRACT FROM AUTHOR]

Background: We sought to identify potentially modifiable in‐hospital factors associated with global cognition, post‐traumatic stress disorder (PTSD) symptoms, and depression symptoms at 12 months. Methods: This was a multi‐center prospective cohort study in adult hospitalized patients with acute COVID‐19. The following in‐hospital factors were assessed: delirium; frequency of in‐person and virtual visits by friends and family; and hydroxychloroquine, corticosteroid, and remdesivir administration. Twelve‐month global cognition was characterized by the MOCA‐Blind. Twelve‐month PTSD and depression were characterized using the PTSD Checklist for the DSM‐V and Hospital Anxiety Depression Scale, respectively. Findings: Two hundred three patients completed the 12‐month follow‐up assessments. Remdesivir use was associated with significantly higher cognition at 12 months based on the MOCA‐Blind (adjusted odds ratio [aOR] = 1.98, 95% CI: 1.06, 3.70). Delirium was associated with worsening 12‐month PTSD (aOR = 3.44, 95% CI: 1.89, 6.28) and depression (aOR = 2.18, 95% CI: 1.23, 3.84) symptoms. Multiple virtual visits per day during hospitalization was associated with lower 12‐month depression symptoms compared to those with less than daily virtual visits (aOR = 0.40, 95% CI: 0.19, 0.85). Conclusion: Potentially modifiable factors associated with better long‐term outcomes included remdesivir use (associated with better cognitive function), avoidance of delirium (associated with less PTSD and depression symptoms), and increased virtual interactions with friends and family (associated with less depression symptoms). [ABSTRACT FROM AUTHOR]

Introduction: Millions of Americans are admitted to the intensive care unit (ICU) per year. Many survivors of the ICU will experience posttraumatic stress disorder (PTSD); although volumetric hippocampal and amygdala studies have been conducted in other trauma survivors (i.e., veterans), the association between PTSD symptoms and hippocampal and amygdala volumes in ICU survivors has not been described. We hypothesize that the severity of posttraumatic stress symptoms in ICU survivors is associated with lower volumes of both the hippocampus and amygdala at 3 and 12 months. Methods: Secondary analysis of the VISIONS study, a prospective sub-study of the BRAIN-ICU cohort, which included survivors of critical illness. The PTSD Checklist Specific was used at 3 and 12 months to evaluate the ICU as a traumatic experience. A Philips Achieva 3T MRI scanner was used to scan patients at both discharge and 3 months. To compare median brain volumes at discharge and 3 months for those with and without PTSD symptomatology, we used a Kruskal–Wallis (KW) test. Results: At 3 month follow up, three patients had PTSD symptomatology and N = 1 at 12 month follow up. There was no difference between median brain volumes (hippocampus or amygdala) between individuals with PTSD symptomatology at either 3 or 12 months (p -values > 0.05). Discussion: Although our study did not reveal significant differences in brain volumes between PTSD patients and non-PTSD patients, sample size was a major limitation and larger scale studies should be undertaken to elucidate possible neurobiological markers of PTSD in ICU survivors. [ABSTRACT FROM AUTHOR]

Importance: Sepsis is associated with long-term cognitive impairment and worse psychological and functional outcomes. Potential mechanisms include intracerebral oxidative stress and inflammation, yet little is known about the effects of early antioxidant and anti-inflammatory therapy on cognitive, psychological, and functional outcomes in sepsis survivors., Objective: To describe observed differences in long-term cognitive, psychological, and functional outcomes of vitamin C, thiamine, and hydrocortisone between the intervention and control groups in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized clinical trial., Design, Setting, and Participants: This prespecified secondary analysis reports the 6-month outcomes of the multicenter, double-blind, placebo-controlled VICTAS randomized clinical trial, which was conducted between August 2018 and July 2019. Adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction who survived to discharge or day 30 were recruited from 43 intensive care units in the US. Participants were randomized 1:1 to either the intervention or control group. Cognitive, psychological, and functional outcomes at 6 months after randomization were assessed via telephone through January 2020. Data analyses were conducted between February 2021 and December 2022., Interventions: The intervention group received intravenous vitamin C (1.5 g), thiamine hydrochloride (100 mg), and hydrocortisone sodium succinate (50 mg) every 6 hours for 96 hours or until death or intensive care unit discharge. The control group received matching placebo., Main Outcomes and Measures: Cognitive performance, risk of posttraumatic stress disorder and depression, and functional status were assessed using a battery of standardized instruments that were administered during a 1-hour telephone call 6 months after randomization., Results: After exclusions, withdrawals, and deaths, the final sample included 213 participants (median [IQR] age, 57 [47-67] years; 112 males [52.6%]) who underwent long-term outcomes assessment and had been randomized to either the intervention group (n = 108) or control group (n = 105). The intervention group had lower immediate memory scores (adjusted OR [aOR], 0.49; 95% CI, 0.26-0.89), higher odds of posttraumatic stress disorder (aOR, 3.51; 95% CI, 1.18-10.40), and lower odds of receiving mental health care (aOR, 0.38; 95% CI, 0.16-0.89). No other statistically significant differences in cognitive, psychological, and functional outcomes were found between the 2 groups., Conclusions and Relevance: In survivors of sepsis, treatment with vitamin C, thiamine, and hydrocortisone did not improve or had worse cognitive, psychological, and functional outcomes at 6 months compared with patients who received placebo. These findings challenge the hypothesis that antioxidant and anti-inflammatory therapy during critical illness mitigates the development of long-term cognitive, psychological, and functional impairment in sepsis survivors., Trial Registration: ClinicalTrials.gov Identifier: NCT03509350.