Exploring genetic risk for catatonia in a genome wide association study and polygenic risk score analysis.

BACKGROUND: Catatonia is an under-recognized disorder characterized by psychomotor (increased, decreased, or abnormal) changes, affective symptoms, and disturbance of volition, which may arise in the setting of decompensated psychiatric or non-psychiatric medical disorders. Genetic studies of catatonia are limited, and to the best of our knowledge no prior genome wide association studies of catatonia have been performed to date. METHODS: First we performed a genome wide association study of catatonia regardless of etiology (psychiatric or non-psychiatric). Secondarily we evaluated whether there was an elevated genetic risk profile for predisposing psychiatric disorders (schizophrenia spectrum disorder, bipolar affective disorder, etc.) in patients with catatonia. We used a matched case control design and applied polygenic risk scores to evaluate for a shared polygenetic contribution to catatonia from common psychiatric phenotypes that show a high prevalence of catatonia in their decompensated states. RESULTS: Anxiety, bipolar affective disorder, schizophrenia spectrum disorder and cross disorder polygenic risk scores were significantly associated with catatonia case status in both unadjusted and adjusted logistic regression models for the European Ancestry set even after correcting for multiple comparisons. Depression, Alzheimer's, Autism Spectrum Disorder and Obsessive Disorder polygenic risk scores were not significantly associated with catatonia status in participants of European Ancestry. In the African Ancestry set, no psychiatric polygenic risk scores were significantly associated with catatonia status in either the unadjusted or adjusted regression models. CONCLUSIONS: Even after controlling for relevant covariates, anxiety, bipolar affective disorder, schizophrenia spectrum disorder and cross disorders were significantly associated with catatonia status suggesting that there might be a shared genetic risk for those disorders amongst patients with catatonia.

In-hospital catatonia, delirium, and coma and mortality: Results from the delirium and catatonia prospective cohort investigation.

BACKGROUND: Catatonia, a form of acute brain dysfunction typically linked with severe affective and psychotic disorders, occurs in critical illness with delirium and coma. Delirium and coma are associated with mortality, though catatonia's relationship with mortality is unclear. We aim to describe whether catatonia, delirium, and coma are associated with mortality. METHODS: We enrolled a convenience cohort of critically ill adults (N = 378) at an academic medical center. We assessed catatonia, delirium, and coma using the Bush-Francis Catatonia Rating Scale, the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation-Sedation Scale, respectively. We tested the associations between previous day brain dysfunction state occurrence with in-hospital and one-year mortality using multivariable time-dependent risk models. Additionally, we tested the association between brain dysfunction duration and one-year mortality. RESULTS: Catatonia was not associated with death on the day after diagnosis during hospitalization, and neither previous catatonia occurrence nor duration was associated with one-year mortality. Delirium was not associated with death on any day following diagnosis during hospitalization, and neither previous delirium occurrence nor duration was associated with one-year mortality. The occurrence of coma was associated with death on any day after diagnosis during hospitalization (HR 2.30,CI 1.19-4.44,p = 0.014), as well as through one year following hospital discharge (HR 1.68,CI 1.09-2.59,p = 0.02). CONCLUSIONS: Coma, but neither catatonia nor delirium, was associated with future day in-hospital and one-year mortality. More research is needed to understand catatonia's clinical impact. Delirium results differ from existing literature likely due to cohort demographics and size. Coma results highlight the prognostic significance of suppressed arousal while critically ill.

Why We Must Prevent and Appropriately Manage Delirium.

Delirium is common and increases in prevalence with age and medical complexity. A form of acute brain dysfunction, its presence is associated with significant morbidity, such as cognitive impairment, decreased mobility, depression, and institutionalization, as well as mortality. Many organizations have developed clinical protocols to prevent and treat delirium and what are called "cognitive-friendly" policies to care for elderly patients.

Mitigating neurological, cognitive, and psychiatric sequelae of COVID-19-related critical illness.

Despite advances in the treatment and mitigation of critical illness caused by infection with SARS-CoV-2, millions of survivors have a devastating, post-acute infection syndrome known as long COVID. A large proportion of patients with long COVID have nervous system dysfunction, which is also seen in the distinct but overlapping condition of post-intensive care syndrome (PICS), putting survivors of COVID-19-related critical illness at high risk of long-lasting morbidity affecting multiple organ systems and, as a result, engendering measurable deficits in quality of life and productivity. In this Series paper, we discuss neurological, cognitive, and psychiatric sequelae in patients who have survived critical illness due to COVID-19. We review current knowledge of the epidemiology and pathophysiology of persistent neuropsychological impairments, and outline potential preventive strategies based on safe, evidence-based approaches to the management of pain, agitation, delirium, anticoagulation, and ventilator weaning during critical illness. We highlight priorities for current and future research, including possible therapeutic approaches, and offer considerations for health services to address the escalating health burden of long COVID.

Thinking Clearly: The History of Brain Dysfunction in Critical Illness.

Brain dysfunction during critical illness (ie, delirium and coma) is extremely common, and its lasting effect has only become increasingly understood in the last two decades. Brain dysfunction in the intensive care unit (ICU) is an independent predictor of both increased mortality and long-term impairments in cognition among survivors. As critical care medicine has grown, important insights regarding brain dysfunction in the ICU have shaped our practice including the importance of light sedation and the avoidance of deliriogenic drugs such as benzodiazepines. Best practices are now strategically incorporated in targeted bundles of care like the ICU Liberation Campaign's ABCDEF Bundle.

The effect of telemental versus in-person mental health consults in the emergency department on 30-day utilization and processes of care.

OBJECTIVES: We sought to characterize how telemental health (TMH) versus in-person mental health consults affected 30-day postevaluation utilization outcomes and processes of care in Veterans presenting to the emergency department (ED) and urgent care clinic (UCC) with acute psychiatric complaints. METHODS: This exploratory retrospective cohort study was conducted in an ED and UCC located in a single Veterans Affairs system. A mental health provider administered TMH via iPad. The primary outcome was a composite of return ED/UCC visits, rehospitalizations, or death within 30 days. The following processes of care were collected during the index visit: changes to home psychiatric medications, admission, involuntary psychiatric hold placement, parenteral benzodiazepine or antipsychotic medication use, and physical restraints or seclusion. Data were abstracted from the Veterans Affairs electronic health record and the Clinical Data Warehouse. Multivariable logistic regression was performed. Adjusted odds ratios (aORs) with their 95% confidence intervals (95% CIs) were reported. RESULTS: Of the 496 Veterans in this analysis, 346 (69.8%) received TMH, and 150 (30.2%) received an in-person mental health evaluation. There was no significant difference in the primary outcome of 30-day return ED/UCC, rehospitalization, or death (aOR 1.47, 95% CI 0.87-2.49) between the TMH and in-person groups. TMH was significantly associated with increased ED/UCC length of stay (aOR 1.46, 95% CI 1.03-2.06) and decreased use of involuntary psychiatric holds (aOR 0.42, 95% CI 0.23-0.75). There were no associations between TMH and the other processes-of-care outcomes. CONCLUSIONS: TMH was not significantly associated with the 30-day composite outcome of return ED/UCC visits, rehospitalizations, and death compared with traditional in-person mental health evaluations. TMH was significantly associated with increased ED/UCC length of stay and decreased odds of placing an involuntary psychiatric hold. Future studies are required to confirm these findings and, if confirmed, explore the potential mechanisms for these associations.

Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors: A Secondary Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Randomized Clinical Trial.

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.

Malignant Catatonia: A Review for the Intensivist.

Catatonia is a clinical syndrome characterized by psychomotor, neurological and behavioral changes. The clinical picture of catatonia ranges from akinetic stupor to severe motoric excitement. Catatonia can occur in the setting of a primary psychiatric condition such as bipolar disorder or secondary to a general medical illness like autoimmune encephalitis. Importantly, it can co-occur with delirium or coma. Malignant catatonia describes catatonia that presents with clinically significant autonomic abnormalities including change in temperature, blood pressure, heart rate, and respiratory rate. It is a life-threatening form of acute brain dysfunction that has several motoric manifestations and occurs secondary to a primary psychiatric condition or a medical cause. Many of the established predisposing and precipitating factors for catatonia such as exposure to neuroleptic medications or withdrawal states are common in the setting of critical illness. Catatonia typically improves with benzodiazepines and treatment of its underlying psychiatric or medical conditions, with electroconvulsive therapy reserved for catatonia refractory to benzodiazepines or for malignant catatonia. However, some forms of catatonia, such as catatonia secondary to a general medical condition or catatonia comorbid with delirium, may be less responsive to traditional treatments. Prompt recognition and treatment of catatonia are crucial because malignant catatonia may be fatal without treatment. Given the high morbidity and mortality associated with malignant catatonia, intensivists should familiarize themselves with this important and under-recognized condition.

In-Hospital Depressed Level of Consciousness and Long-Term Functional Outcomes in ICU Survivors.

OBJECTIVES: Among critically ill patients, acutely depressed level of consciousness is associated with mortality, but its relationship to long-term outcomes such as disability and physical function is unknown. We investigated the relationship of level of consciousness during hospitalization with long-term disability and physical function in ICU survivors. DESIGN: Multi-center observational cohort study. SETTING: Medical or surgical ICUs at five U.S. centers. PATIENTS: Adult survivors of respiratory failure or shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Depressed level of consciousness during hospitalization was defined using the Richmond Agitation Sedation Scale (RASS) score (including all negative scores) by calculating the area under the curve using linear interpolation. Sedative-associated level of consciousness was similarly defined for all hospital days that sedation was received. We measured disability in basic activities of daily living (BADLs), instrumental activities of daily living (IADLs), discharge destination, and self-reported physical function. In separate models, we evaluated associations between these measures of level of consciousness and outcomes using multivariable regression, adjusted for age, sex, race, body mass index, education level, comorbidities, baseline frailty, baseline IADLs and BADLs, hospital type (civilian vs veteran), modified mean daily Sequential Organ Failure Assessment score, duration of severe sepsis, duration of mechanical ventilation, and hospital length of stay. Of the 1,040 patients enrolled in the ICU, 781 survived to hospital discharge. We assessed outcomes in 624 patients at 3 months and 527 patients at 12 months. After adjusting for covariates, there was no association between depressed level of consciousness (total or sedation-associated) with BADLs or IADLs at either 3- or 12-month follow-up. There was also no association with self-reported physical function at 3 or 12 months or with discharge destination. CONCLUSIONS: Depressed level of consciousness, as defined by the RASS, was not associated with disability or self-reported physical function. Future studies should investigate additional modifiable in-hospital risk factors for disability and poor physical function following critical illness.

Advanced Age Is Associated With Catatonia in Critical Illness: Results From the Delirium and Catatonia Prospective Cohort Investigation.

Introduction: Catatonia, characterized by motor, behavioral and affective abnormalities, frequently co-occurs with delirium during critical illness. Advanced age is a known risk factor for development of delirium. However, the association between age and catatonia has not been described. We aim to describe the occurrence of catatonia, delirium, and coma by age group in a critically ill, adult population. Design: Convenience cohort, nested within two clinical trials and two observational cohort studies. Setting: Intensive care units in an academic medical center in Nashville, TN. Patients: 378 critically ill adult patients on mechanical ventilation and/or vasopressors. Measurements and Main Results: Patients were assessed for catatonia, delirium, and coma by independent and blinded personnel, the Bush Francis Catatonia Rating Scale, the Confusion Assessment Method for the Intensive Care Unit (ICU) and the Richmond Agitation and Sedation Scale. Of 378 patients, 23% met diagnostic criteria for catatonia, 66% experienced delirium, and 52% experienced coma during the period of observation. There was no relationship found between age and catatonia severity or age and presence of specific catatonia items. The prevalence of catatonia was strongly associated with age in the setting of critical illness (p < 0.05). Delirium and comas' association with age was limited to the setting of catatonia. Conclusion: Given the significant relationship between age and catatonia independent of coma and delirium status, these data demonstrate catatonia's association with advanced age in the setting of critical illness. Future studies can explore the causative factors for this association and further elucidate the risk factors for acute brain dysfunction across the age spectrum.

Pseudodelirium: Psychiatric Conditions to Consider on the Differential for Delirium.

OBJECTIVE: The phenotypes of several psychiatric conditions can very closely resemble delirium; the authors describe such presentations as pseudodelirium. However, because the clinical management of these conditions differs markedly from that of delirium, prompt differentiation is essential. The authors provide an educational review to assist clinicians in identifying and managing psychiatric conditions that may be especially challenging to differentiate from delirium. METHODS: Based on clinical experience, the authors identified four psychiatric conditions as among the most difficult to differentiate from delirium: disorganized psychosis, Ganser syndrome, delirious mania, and catatonia. An overview of each condition, description of clinical features, differentiation of specific phenotypes from delirium, and review of clinical management are also provided. RESULTS: The thought and behavioral disorganization in disorganized psychosis can be mistaken for the clouded sensorium and behavioral dysregulation encountered in delirium. The fluctuating alertness and apparent confusion in Ganser syndrome resemble delirium's altered arousal and cognitive features. As its name suggests, delirious mania presents as a mixture of hyperactive delirium and mania; additional features may include psychosis, autonomic activation, and catatonia. Both delirium and catatonia have hypokinetic and hyperkinetic variants, and the two syndromes can also co-occur. CONCLUSIONS: The clinical presentations of several psychiatric conditions can blend with the phenotype of delirium, at times even co-occurring with it. Detailed evaluation is often required to differentiate such instances of pseudodelirium from delirium proper.

Association of Delirium during Critical Illness With Mortality: Multicenter Prospective Cohort Study.

BACKGROUND: The temporal association of delirium during critical illness with mortality is unclear, along with the associations of hypoactive and hyperactive motoric subtypes of delirium with mortality. We aimed to evaluate the relationship of delirium during critical illness, including hypoactive and hyperactive motoric subtypes, with mortality in the hospital and after discharge up to 1 year. METHODS: We analyzed a prospective cohort study of adults with respiratory failure and/or shock admitted to university, community, and Veterans Affairs hospitals. We assessed patients using the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the intensive care unit (ICU) and defined the motoric subtype according to the corresponding Richmond Agitation-Sedation Scale if delirium was present. We used Cox proportional hazard models, adjusted for baseline characteristics, coma, and daily hospital events, to determine whether delirium on a given day predicted mortality the following day in patients in the hospital and also to determine whether delirium presence and duration predicted mortality after discharge up to 1 year in patients who survived to hospital discharge. We performed similar analyses for hypoactive and hyperactive subtypes of delirium. RESULTS: Among 1040 critically ill patients, 214 (21%) died in the hospital and 204 (20%) died out-of-hospital by 1 year. Delirium was common, occurring in 740 (71%) patients for a median (interquartile range [IQR]) of 4 (2-7) days. Hypoactive delirium occurred in 733 (70%) patients, and hyperactive occurred in 185 (18%) patients, with a median (IQR) of 3 (2-7) days and 1 (1-2) days, respectively. Delirium on a given day (hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.32-6.21; P = .008), in particular the hypoactive subtype (HR, 3.35; 95% CI, 1.51-7.46; P = .003), was independently associated with an increased risk of death the following day in the hospital. Hyperactive delirium was not associated with an increased risk of death in the hospital (HR, 4.00; 95% CI, 0.49-32.51; P = .19). Among hospital survivors, neither delirium presence (HR, 1.01; 95% CI, 0.82-1.24; P = .95) nor duration (HR, 0.99; 95% CI, 0.97-1.01; P = .56), regardless of motoric subtype, was associated with mortality after hospital discharge up to 1 year. CONCLUSIONS: Delirium during critical illness is associated with nearly a 3-fold increased risk of death the following day for patients in the hospital but is not associated with mortality after hospital discharge. This finding appears primarily driven by the hypoactive motoric subtype. The independent relationship between delirium and mortality occurs early during critical illness but does not persist after hospital discharge.

Pharmacologic Management of Intensive Care Unit Delirium: Clinical Prescribing Practices and Outcomes in More Than 8500 Patient Encounters.

BACKGROUND: Pharmacologic agents are frequently utilized for management of intensive care unit (ICU) delirium, yet prescribing patterns and impact of medication choices on patient outcomes are poorly described. We sought to describe prescribing practices for management of ICU delirium and investigate the independent association of medication choice on key in-hospital outcomes including delirium resolution, in-hospital mortality, and days alive and free of the ICU or hospital. METHODS: A retrospective study of delirious adult ICU patients at a tertiary academic medical center. Data were obtained regarding daily mental status (normal, delirious, and comatose), pharmacologic treatment, hospital course, and survival via electronic health record. Daily transition models were constructed to assess the independent association of previous day mental status and medication administration on mental status the following day and in-hospital mortality, after adjusting for prespecified covariates. Linear regression models investigated the association of medication administration on days alive and free of the ICU or the hospital during the first 30 days after ICU admission. RESULTS: We identified 8591 encounters of ICU delirium. Half (45.6%) of patients received pharmacologic treatment for delirium, including 45.4% receiving antipsychotics, 2.2% guanfacine, and 0.84% valproic acid. Median highest Richmond Agitation-Sedation Scale (RASS) score was 1 (0, 1) in patients initiated on medications and 0 (-1, 0) for nonrecipients. Haloperidol, olanzapine, and quetiapine comprised >97% of antipsychotics utilized with 48% receiving 2 or more and 20.6% continued on antipsychotic medications at hospital discharge. Haloperidol and olanzapine were associated with greater odds of continued delirium (odds ratio [OR], 1.48; 95% confidence interval [95% CI], 1.30-1.65; P < .001 and OR, 1.37; 95% CI, 1.20-1.56; P = .003, respectively) and increased hazard of in-hospital mortality (hazard ratio [HR], 1.46; 95% CI, 1.10-1.93; P = .01 and HR, 1.67; 95% CI, 1.14-2.45; P = .01, respectively) while quetiapine showed a decreased hazard of in-hospital mortality (HR, 0.58; 95% CI, 0.40-0.84; P = .01). Haloperidol, olanzapine, and quetiapine were associated with fewer days alive and free of hospitalization (all P < .001). There was no significant association of any antipsychotic medication with days alive and free of the ICU. Neither guanfacine nor valproic acid were associated with in-hospital outcomes examined. CONCLUSIONS: Pharmacologic interventions for management of ICU delirium are common, most often with antipsychotics, and frequently continued at hospital discharge. These medications may not portend benefit, may introduce additional harm, and should be used with caution for delirium management. Continuation of these medications through hospitalization and discharge draws into question their safety and role in patient recovery.

Worse Than Death: Survey of Public Perceptions of Disability Outcomes After Hypothetical Traumatic Brain Injury.

OBJECTIVE: The aim of this study was to determine the health utility states of the most commonly used traumatic brain injury (TBI) clinical trial endpoint, the Extended Glasgow Outcome Scale (GOSE). SUMMARY BACKGROUND DATA: Health utilities represent the strength of one's preferences under conditions of uncertainty. There are insufficient data to indicate how an individual would value levels of disability after a TBI. METHODS: This was a cross-sectional web-based online convenience sampling adaptive survey. Using a standard gamble approach, participants evaluated their preferences for GOSE health states 1 year after a hypothetical TBI. The categorical GOSE was studied from vegetative state (GOSE2) to upper good recovery (GOSE8). Median (25th percentile, 75th percentile) health utility values for different GOSE states after TBI, ranging from -1 (worse than death) to 1 (full health), with 0 as reference (death). RESULTS: Of 3508 eligible participants, 3235 (92.22%) completed the survey. Participants rated lower GOSE states as having lower utility, with some states rated as worse than death, though the relationship was nonlinear and intervals were unequal between health states. Over 75% of participants rated a vegetative state (GOSE2, absence of awareness and bedridden) and about 50% rated lower severe disability (GOSE3, housebound needing all-day assistance) as conditions worse than death. CONCLUSIONS: In the largest investigation of public perceptions about post-TBI disability, we demonstrate unequally rated health states, with some states perceived as worse than death. Although limited by selection bias, these results may guide future comparative-effectiveness research and shared medical decision-making after neurologic injury.

Depression predicts long-term cognitive impairment in survivors of critical illness.

INTRODUCTION: Intensive care unit (ICU) survivorship is associated with long-term cognitive impairment (LTCI). Our work has found post-ICU depression in up to 30% and posttraumatic stress disorder (PTSD) in up to 10% of ICU survivors. We hypothesized that post-ICU depression and PTSD are independently associated with LTCI in ICU survivors. METHODS: This is a five-center nested prospective cohort of critically ill patients admitted to medical and surgical ICUs who underwent neuropsychological assessments at 3 and 12 months posthospital discharge. Our primary outcome was global cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Trail Making Test, Part B, a test of executive functioning, at 3- and 12-month follow-up. Our independent variables were Beck Depression Inventory II and the PTSD Checklist-Specific Version measured at 3 and 12 months. We performed multivariable linear regression models controlling for covariates such as age, years of education, preexisting cognitive impairment, comorbidities, ventilator days, hypoxemia episodes, and days of delirium or coma. RESULTS: Of 1,047 patients in the combined cohort, 679 were alive and available for follow-up at 3 months. A total of 590 (87%) ICU survivors completed at least one 3-month assessment, and of the 554 who survived to 12 months, 519 (94%) completed both a 3- and 12-month assessment with a median age of 61 years (52-70 years) and mean daily Sequential Organ Failure Assessment score of 6 (4-8), 520 (88%) were mechanically ventilated, and 420 (71%) were with delirium. Of these, 113 (19%) had PTSD and 187 (32%) had depression at 3 months with similar rates at 12 months. Depression at 3 months was associated with lower 3-month RBANS (coefficient, -2.25; -3.10 to -1.39) and lower Trails B scores at both 3 months (odds ratio, 0.69; 0.56-0.85) and 12 months (odds ratio, 0.66; 0.52-0.84). Posttraumatic stress disorder at 3 months had no association with RBANS or Trails B scores at 3 or 12 months. CONCLUSION: Early post-ICU depression, but not PTSD, is independently associated with coexisting LTCI, even when controlling for past ICU delirium. Treatment for early depression represents a novel intervention area for LTCI prevention in ICU survivors. LEVEL OF EVIDENCE: Prognostic/epidemiological, level III.

Publisher Correction: Delirium.

An Erratum to this paper has been published: https://doi.org/10.1038/s41572-020-00236-z.

Delirium.

Delirium, a syndrome characterized by an acute change in attention, awareness and cognition, is caused by a medical condition that cannot be better explained by a pre-existing neurocognitive disorder. Multiple predisposing factors (for example, pre-existing cognitive impairment) and precipitating factors (for example, urinary tract infection) for delirium have been described, with most patients having both types. Because multiple factors are implicated in the aetiology of delirium, there are likely several neurobiological processes that contribute to delirium pathogenesis, including neuroinflammation, brain vascular dysfunction, altered brain metabolism, neurotransmitter imbalance and impaired neuronal network connectivity. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) is the most commonly used diagnostic system upon which a reference standard diagnosis is made, although many other delirium screening tools have been developed given the impracticality of using the DSM-5 in many settings. Pharmacological treatments for delirium (such as antipsychotic drugs) are not effective, reflecting substantial gaps in our understanding of its pathophysiology. Currently, the best management strategies are multidomain interventions that focus on treating precipitating conditions, medication review, managing distress, mitigating complications and maintaining engagement to environmental issues. The effective implementation of delirium detection, treatment and prevention strategies remains a major challenge for health-care organizations globally.

The Association Between Brain Volumes and Posttraumatic Stress Disorder in Intensive Care Unit Survivors: A Preliminary Study.

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.