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.

Delirium, depression, and long-term cognition.

OBJECTIVES: We examined whether preadmission history of depression is associated with less delirium/coma-free (DCF) days, worse 1-year depression severity and cognitive impairment. DESIGN AND MEASUREMENTS: A health proxy reported history of depression. Separate models examined the effect of preadmission history of depression on: (a) intensive care unit (ICU) course, measured as DCF days; (b) depression symptom severity at 3 and 12 months, measured by the Beck Depression Inventory-II (BDI-II); and (c) cognitive performance at 3 and 12 months, measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) global score. SETTING AND PARTICIPANTS: Patients admitted to the medical/surgical ICU services were eligible. RESULTS: Of 821 subjects eligible at enrollment, 261 (33%) had preadmission history of depression. After adjusting for covariates, preadmission history of depression was not associated with less DCF days (OR 0.78, 95% CI, 0.59-1.03 p = 0.077). A prior history of depression was associated with higher BDI-II scores at 3 and 12 months (3 months OR 2.15, 95% CI, 1.42-3.24 p = <0.001; 12 months OR 1.89, 95% CI, 1.24-2.87 p = 0.003). We did not observe an association between preadmission history of depression and cognitive performance at either 3 or 12 months (3 months beta coefficient -0.04, 95% CI, -2.70-2.62 p = 0.97; 12 months 1.5, 95% CI, -1.26-4.26 p = 0.28). CONCLUSION: Patients with a depression history prior to ICU stay exhibit a greater severity of depressive symptoms in the year after hospitalization.

Community pharmacists' perspectives on assessing kidney function and medication dosing for patients with advanced chronic kidney disease: A qualitative study using the theoretical domains framework.

Background: The kidneys are responsible for the elimination of many drugs. Chronic kidney disease (CKD) is common, and medications may require adjustment to avoid adverse outcomes. Despite the availability of kidney drug dosing resources, people with CKD are at risk of inappropriate drug prescribing. Community pharmacists are in the ideal position to mitigate harm from inappropriate prescribing in this population. Methods: In this qualitative study, community pharmacists were interviewed on their perspective on kidney function assessment and dose adjustment in people with advanced CKD (estimated glomerular filtration rate <30 mL/min/1.73 m2). The theoretical domains framework for targeting behavioural change was used to inform the interview guide and analysis. Purposeful sampling was employed until data saturation. Semistructured virtual interviews were audio-recorded, transcribed verbatim and uploaded into NVIVO 12 Pro to facilitate thematic analysis. Deductive and inductive iterative coding approaches were employed to determine categories and themes. Results: Twelve pharmacists were interviewed, with a mean age of 42 years and 16 years of experience. Four themes comprising 10 categories were identified to influence kidney function assessment and dosing, including resources (information access, technology, references), environment (pharmacy infrastructure, practice setting), reflection (triggers, experience and training, collaboration) and leadership and governance (pharmacist role, advocacy). Feedback on an optimal CKD tool was collected, and enabling themes (categories) for implementation included knowledge and skills (education, training) and reflection (role, support, integration). Conclusions: Findings will inform the interventions needed to improve implementation of kidney assessment and dosing of high-risk medications in people with kidney impairment into community pharmacy practice. Can Pharm J (Ott) 2023;156:xx-xx.

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.

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.

Prospective Validation of the Preschool Confusion Assessment Method for the ICU to Screen for Delirium in Infants Less Than 6 Months Old.

OBJECTIVES: ICU delirium is a predictor of greater morbidity and higher mortality in the pediatric population. The diagnostic obstacles and validity of delirium monitoring among neonates and young infants have yet to be fully delineated. We sought to validate the Preschool Confusion Assessment Method for the ICU in neonates and young infants and determine delirium prevalence in this young population. DESIGN: Prospective cohort study to validate the Preschool Confusion Assessment Method for the ICU for the assessment of ICU delirium in neonates and young infants compared with the reference standard, Child and Adolescent Psychiatry. SETTING: Tertiary medical center PICU, including medical, surgical, and cardiac patients. PARTICIPANTS: Infants less than 6 months old admitted to the PICU regardless of admission diagnosis. MEASUREMENTS AND MAIN RESULTS: We enrolled 49 patients with a median age of 1.8 months (interquartile range, 0.7-4.1 mo), 82% requiring mechanical ventilation. Enrolled patients were assessed for delirium in blinded-fashion by the research team using the Preschool Confusion Assessment Method for the ICU and independently assessed by the psychiatry reference rater using Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A total of 189 paired assessments were completed, and the Preschool Confusion Assessment Method for the ICU performed with a sensitivity of 95% (95% CI, 89-100%), specificity of 81% (68-90%), "negative and positive predictive values" of 97% (94-100%) and 69% (55-79%), respectively, compared with the reference rater. Delirium prevalence was 47%, with higher rates of 61% observed among neonates (< 1 mo old) and 39% among infants 1-6 months old. CONCLUSIONS: The Preschool Confusion Assessment Method for the ICU is a valid screening tool for delirium monitoring in infants less than 6 months old. Delirium screening was feasible in this population despite evolving neurocognition and arousal architecture. ICU delirium was prevalent among infants. The consequence of acute brain dysfunction during crucial neurocognitive development remains unclear. Future studies are necessary to determine the long-term impact of ICU delirium and strategies to reduce associated harm in critically ill infants.

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.

Improving Communication in Outpatient Consultations in People With Cirrhosis: The Development of a Question Prompt List (QPL).

BACKGROUND AND AIMS: Liver health professionals have difficulty discussing liver cirrhosis and its prognosis with patients and families. Question Prompt Lists (QPLs), which are evidence-based lists of "recommended questions," may improve communication but need to be designed specifically for the target population. This study aimed to develop and pilot a QPL for patients with cirrhosis. METHODS: A mixed-methods design in 3 phases. In phase 1 (item generation), potential questions for inclusion in the QPL were identified from 3 sources-a scoping literature review; an online survey; and interviews with patients, family members, and health professionals. In phase 2 (QPL construction), a multidisciplinary expert panel finalized the selection of questions and the format of the QPL. In phase 3 (pilot study), the QPL was assessed for acceptability and feasibility in a hepatology outpatient clinic population. RESULTS: From 258 topics initially identified, 30 questions were included in the first draft of the QPL. After review by a multidisciplinary expert panel including patients, the QPL was reduced to 22 questions. In the pilot study, 133/215 eligible patients consented to participate, although only 67/133 used the QPL in their clinic appointment. Among those who used the QPL, all questions were asked at least once. The most commonly asked question related to life expectancy. Most participants expressed support for the content of the QPL. CONCLUSIONS: A QPL, suitable for use in patients with liver cirrhosis attending hepatology outpatient clinics, has been developed and piloted. The QPL seems to be feasible to use and acceptable to patients and clinicians. Further work is needed to evaluate its effectiveness and to determine optimum delivery in clinical practice.