Research Needs for Inpatient Management of Severe Alcohol Withdrawal Syndrome: An Official American Thoracic Society Research Statement.

Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0-T4 continuum to advance the care of hospitalized patients who experience SAWS. Methods: Clinicians and researchers with unique and complementary expertise in basic, clinical, and implementation research related to unhealthy alcohol consumption and alcohol withdrawal were invited to participate in a workshop at the American Thoracic Society 2019 International Conference. The committee was subdivided into four groups on the basis of interest and expertise: T0-T1 (basic science research with translation to humans), T2 (research translating to patients), T3 (research translating to clinical practice), and T4 (research translating to communities). A medical librarian conducted a pragmatic literature search to facilitate this work, and committee members reviewed and supplemented the resulting evidence, identifying key knowledge gaps. Results: The committee identified several investigative opportunities to advance the care of patients with SAWS in each domain of the translational science spectrum. Major themes included 1) the need to investigate non-γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice. Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.

Clinical Profile and Length of Hospital Stay in a Sample of Psychogeriatric Patients Referred to Consultation Liaison Psychiatric Unit.

Background and objectives: There has been a recent increase in older patients admitted to general hospitals. A significant percentage of hospitalized older patients are ≥75 years old, which differ from the patients aged 65 to 74 years old in terms of functional status at patient discharge. This study aims to compare sociodemographic, clinical features, and factors associated with length of hospital stay in youngest-old and oldest-old populations of inpatients referred to the consultation liaison psychiatry unit. Material and methods: This is an observational, cross-sectional, retrospective, and comparative study. We obtained data from a sample of 1017 patients (≥65 years) admitted to a general hospital and referred from different services (medicine, surgery, etc.) to the consultation liaison psychiatry unit. The sample was divided into two groups of patients: youngest-old (65-74 years) and oldest-old (≥75 years). Psychiatric evaluations were performed while the patients were on wards at the hospital. Psychopharmacs were started as needed. A comparative analysis was carried out and predictive factors related to length of hospital stay were calculated. Results: The reference rate to consultation liaison psychiatry unit was 1.45% of the total older patients hospitalized. Our study demonstrates differences between the groups of older people: the oldest-old group were mainly female (p < 0.001), had more previous psychiatric diagnoses (p < 0.001), physical disabilities (p = 0.02), and neurocognitive disorders (p < 0.001), they used more antipsychotics (p < 0.001), and more frequently had a discharge disposition to a nursing home (p = 0.036). The presence of physical disability (beta = 0.07, p < 0.001) and logtime to referral to consultation liaison psychiatry unit (beta = 0.58, p < 0.001) were associated with increased length of hospital stay. Conclusions: Youngest-old and oldest-old people should be considered as two different types of patients when we consider clinical features. The time to referral to consultation liaison psychiatry unit seems to be a relevant factor associated with length of hospital stay.

A Study of the Psychometric Properties of the "Stanford Proxy Test for Delirium" (S-PTD): A New Screening Tool for the Detection of Delirium.

BACKGROUND: Delirium is a prevalent neuropsychiatric disorder associated with increased morbidity and mortality. Half the cases remain misdiagnosed. OBJECTIVE: Assess the effectiveness of the Stanford Proxy Test for Delirium (S-PTD) in detecting delirium in an inpatient setting. METHODS: This is a comparison study. Daily assessment with S-PTD, by the patient's nurse, and a neuropsychiatric assessment by a psychiatrist. Assessments were blinded. Inclusion criteria included 18 years or older. Exclusion criteria included patient's or surrogate's unwillingness to participate, inability to consent if a surrogate was not available, and inability to communicate in English or Spanish. A total of 309 patients were approached: 27 declined participation, 4 were excluded, and 278 subjects were followed up throughout their hospital stay. In the end, 78 were excluded for lack of neuropsychiatric assessment, S-PTD, or both. One was excluded for lack of demographic data. The sensitivity and specificity of the S-PTD in detecting delirium when compared with a neuropsychiatric assessment. RESULTS: Participants were on average 60.8 years old and 54.3% were male. Patients who developed delirium were, on average, older (15.12 y, confidence interval: 8.94-21.32). A total of 199 patients were analyzed; 43 patients (21.6%) met criteria for delirium. S-PTD detected 67 days with delirium (16.5%) of 405 hospital days, while neuropsychiatric evaluation identified 83 (20.5%). S-PTD had a sensitivity of 80.72% and a specificity of 90.37%. CONCLUSION: S-PTD is an effective, comprehensive, and simple screening tool for delirium, which is robust despite fluctuating symptoms and lack of cooperation. The use of S-PTD may enhance early diagnosis of delirium.

The Psychosocial Assessment of Transplant Candidates: Inter-Rater Reliability and Predictive Value of the Italian Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT).

BACKGROUND: The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a comprehensive instrument developed to accurately assess the main pretransplant psychosocial risk factors that may impact transplant outcomes. OBJECTIVE: As neither established assessment procedures nor standardized tools designed to perform pretransplant psychosocial evaluation are currently available in Italy, the present study was designed to develop and preliminarily validate the Italian version of the SIPAT. METHODS: First, our team developed the Italian version of the SIPAT, following standard forward-back translation procedures. Then, the Italian version of the SIPAT was retrospectively and blindly applied to 118 randomly selected transplant cases (40 heart, 40 lung, and 38 liver) by 2 independent examiners. Information about the patients' final transplant listing recommendation (i.e., listing vs. deferral) was independently collected from the respective transplant teams. RESULTS: The inter-rater reliability of the Italian version of the SIPAT scores was substantial (Cohen's kappa = 0.77; P < 0.001). Moreover, the predictive value of the SIPAT ratings on the final transplant listing recommendation (i.e., listing vs. deferral) for each examiner was significant (both P < 0.05). CONCLUSION: Current findings suggest that SIPAT is a promising and reliable instrument in its Italian version. Given these excellent psychometric characteristics, the use of the SIPAT as part of the pretransplant psychosocial evaluation in Italian medical settings is highly encouraged.

Translation, adaptation, and reliability of the Stanford Integrated Psychosocial Assessment for Transplantation in the Spanish population.

BACKGROUND: Psychosocial risk factors influence the course of transplantation. Psychosocial evaluation is an important part of pre-transplantation evaluation processes, yet there are no standardized instruments in Spanish. OBJECTIVE: To translate, adapt, and test the reliability of the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) in organ and cell transplantation patients in the Spanish context. METHOD: A Spanish version was developed and adapted using WHO's guidelines. The first 30 candidates' SIPAT interviews were recorded and scored by four independent examiners to test the inter-rater reliability. The internal consistency of the SIPAT items was calculated with a sample of 150 heart, liver, and allogeneic haematopoietic stem cell transplant candidates. Evaluations were conducted by SIPAT-trained and transplantation-experienced clinical psychologists and psychiatrists. RESULTS: Stanford Integrated Psychosocial Assessment for Transplantation achieved excellent intra-class correlation reliability coefficients between investigators (ICC = 0.93 for the general score and from 0.77 to 0.94 for domain scores). Good internal consistency was found with Cronbach's alpha of 0.84 (from 0.69-0.71 for domains). DISCUSSION: This study presents the translated and adapted version of SIPAT. It has been found to have strong inter-rater reliability and good internal consistency. Further research is needed to confirm reliability (eg, test-retest) and establish its validity (eg, concurrent, predictive).

Refining Delirium: A Transtheoretical Model of Delirium Disorder with Preliminary Neurophysiologic Subtypes.

The development of delirium indicates neurophysiologic disruption and predicts unfavorable outcomes. This relationship between delirium and its outcomes has inspired a generation of studies aimed at identifying, predicting, and preventing both delirium and its associated sequelae. Despite this, evidence on delirium prevention and management remains limited. No medication is approved for the prevention or treatment of delirium or for its associated psychiatric symptoms. This unmet need for effective delirium treatment calls for a refined approach. First, we explain why a one-size-fits-all approach based on a unitary biological model of delirium has contributed to variance in delirium studies and prevents further advance in the field. Next, in parallel with the shift from dementia to "major neurocognitive disorder," we propose a transtheoretical model of "delirium disorder" composed of interactive elements-precipitant, neurophysiology, delirium phenotype, and associated psychiatric symptoms. We explore how these relate both to the biopsychosocial factors that promote healthy cognition ("procognitive factors") and to consequent neuropathologic sequelae. Finally, we outline a preliminary delirium typology of specific neurophysiologic disturbances. Our model of delirium disorder offers several avenues for novel insights and clinical advance: it univocally differentiates delirium disorder from the phenotype of delirium, highlights delirium neurophysiology as a treatment target, separates the core features of delirium from associated psychiatric symptoms, suggests how procognitive factors influence the core elements of delirium disorder, and makes intuitive predictions about how delirium disorder leads to neuropathologic sequelae and cognitive impairment. Ultimately, this model opens several avenues for modern neuroscience to unravel this disease of antiquity.

Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure.

BACKGROUND: Delirium is the most common neuropsychiatric syndrome encountered by clinicians dealing with older adults and the medically ill and is best characterized by 5 core domains: cognitive deficits, attentional deficits, circadian rhythm dysregulation, emotional dysregulation, and alteration in psychomotor functioning. DESIGN: An extensive literature review and consolidation of published data into a novel interpretation of known pathophysiological causes of delirium. RESULTS: Available data suggest that numerous pathological factors may serve as precipitants for delirium, each having differential effects depending on patient-specific patient physiological characteristics (substrate). On the basis of an extensive literature search, a newly proposed theory, the systems integration failure hypothesis, was developed to bring together the most salient previously described theories, by describing the various contributions from each into a complex web of pathways-highlighting areas of intersection and commonalities and explaining how the variable contribution of these may lead to the development of various cognitive and behavioral dysfunctions characteristic of delirium. The specific cognitive and behavioral manifestations of the specific delirium picture result from a combination of neurotransmitter function and availability, variability in integration and processing of sensory information, motor responses to both external and internal cues, and the degree of breakdown in neuronal network connectivity, hence the term acute brain failure. CONCLUSIONS: The systems integration failure hypothesis attempts to explain how the various proposed delirium pathophysiologic theories interact with each other, causing various clinically observed delirium phenotypes. A better understanding of the underlying pathophysiology of delirium may eventually assist in designing better prevention and management approaches.

Delirium after lung transplantation: Association with recipient characteristics, hospital resource utilization, and mortality.

BACKGROUND: Delirium is associated with increased morbidity and mortality. The factors associated with post-lung transplant delirium and its impact on outcomes are under characterized. METHODS: The medical records of 163 consecutive adult lung transplant recipients were reviewed for delirium within 5 days (early-onset) and 30 hospital days (ever-onset) post-transplantation. A multivariable logistic regression model assessed factors associated with delirium. Multivariable negative binomial regression and Cox proportional hazards models assessed the association of delirium with ventilator duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, and one-year mortality. RESULTS: Thirty-six percent of patients developed early-onset, and 44% developed ever-onset delirium. Obesity (OR 6.35, 95% CI 1.61-24.98) and bolused benzodiazepines within the first postoperative day (OR 2.28, 95% CI 1.07-4.89) were associated with early-onset delirium. Early-onset delirium was associated with longer adjusted mechanical ventilation duration (P=.001), ICU LOS (P<.001), and hospital LOS (P=.005). Ever-onset delirium was associated with longer ICU (P<.001) and hospital LOS (P<.001). After adjusting for clinical variables, delirium was not significantly associated with one-year mortality (early-onset HR 1.65, 95% CI 0.67-4.03; ever-onset HR 1.70, 95% CI 0.63-4.55). CONCLUSIONS: Delirium is common after lung transplant surgery and associated with increased hospital resources.

Frontal Lobe Epilepsy: A Primer for Psychiatrists and a Systematic Review of Psychiatric Manifestations.

BACKGROUND: Frontal lobe epilepsy (FLE) can masquerade as a primary psychiatric condition, be misdiagnosed in-lieu of a true psychiatric disorder, or may be comorbid with psychiatric illness. OBJECTIVES: To (1) qualitatively review psychiatric manifestations of FLE and (2) to systematically review the cases/case series of psychiatric manifestations of FLE presented in the literature to date. METHODS: A systematic review of the literature was performed following the PRISMA guidelines and using PubMed/Medline, PsychInfo, and Cochrane database of systematic reviews to identify cases and case series of psychiatric manifestations of FLE. RESULTS: A total of 35 separate articles were identified. Further, 17 patients primarily presented with psychosis, 33 with affective symptoms, and 16 with personality changes. Also, 62% of cases were males and 38% were females. Ages ranged from 2-83 years with the average age of 32.7. Prior psychiatric history was reported in 27.3% of cases. Causes of seizure were known in 53%, with the most common causes being dysplasia and tumor. Only 6 cases (<10%) did not have electroencephalographic correlations. Psychiatric manifestations were primarily ictal in 74.3% of the cases. Associated manifestations included motor (63.6%), cognitive (34.8%), and medical (9.0%) findings. Surgery was required in 31.8% of the cases, whereas others were treated with medications alone. All, but 3, patients were seizure free and saw an improvement in symptoms with treatment. CONCLUSIONS: Given the complexity and multifunctionality of the frontal lobes, FLE can present with complex, psychiatric manifestations, with associated motor, cognitive, and medical changes; thus, psychiatrists should keep FLE on the differential diagnosis of complex neuropsychiatric cases.

The Stanford Integrated Psychosocial Assessment for Transplantation: A Prospective Study of Medical and Psychosocial Outcomes.

BACKGROUND: Psychosocial factors may significantly affect post-transplant outcomes. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) was developed as an assessment tool to enhance the pre-transplant psychosocial evaluation. METHODS: We identified heart, lung, liver, or kidney transplant recipients assessed with the SIPAT pre-transplantation and transplanted between June 1, 2008, and July 31, 2011, at our institution. We analyzed prospectively accumulated psychosocial and medical outcomes at 1 year of follow-up. RESULTS: 217 patients were identified and included in the analysis. The primary outcomes of organ failure and mortality occurred in 12 and 21 patients, respectively, and were not significantly associated with the pre-transplant SIPAT scores. On the other hand, SIPAT scores were significantly correlated with the probability of poor medical and psychosocial outcomes (secondary outcomes). In fact, higher SIPAT scores predicted higher rates of rejection episodes (Spearman ρ = 0.15, 95% 95% confidence interval [CI] = 0.02-0.28, p = .023), medical hospitalizations (ρ = 0.29, 95% CI = 0.16-0.41, p < .001), infection rates (p = .020), psychiatric decompensation (p = .005), and support system failure (area under the curve = 0.70, 95% CI = 0.60-0.79, p < .001). The relationship with nonadherence suggested a trend, but no statistical significance was observed (area under the curve = 0.60, 95% CI = 0.50-0.71, p = .058). CONCLUSIONS: Study outcomes suggest that SIPAT is a promising pre-transplantation assessment tool that helps identify candidate's areas of psychosocial vulnerability and whose scores are associated with both psychosocial and medical outcomes after transplantation.

Adjunctive Valproic Acid in Management-Refractory Hyperactive Delirium: A Case Series and Rationale.

Patients with delirium may fail to respond to standard therapies. Sixteen patients with management-refractory hyperactive delirium responded to adjunctive valproic acid, with complete resolution of hyperactive delirium in 13 cases. A rationale for using valproic acid in such circumstances is discussed.

Valproic Acid for Treatment of Hyperactive or Mixed Delirium: Rationale and Literature Review.

BACKGROUND: Delirium is the most often encountered psychiatric diagnosis in the general hospital, with an incidence of up to 82% in the intensive care unit setting and with significant detrimental effects on patients' morbidity and mortality. Antipsychotics are often considered the first-line pharmacological treatment of delirium, but their use may be limited by lack of efficacy, existing contraindications (e.g., prolonged QTc intervals), or resulting side effects (e.g., akathisia). Valproic acid (VPA) is a potential alternative or adjunct treatment. It has multiple mechanisms of action, including effects on neurotransmitter modulation, neuroinflammation, oxidative stress, and transcription, all of which are implicated in the pathophysiology of delirium. Yet, data on the use of this agent in delirium are limited. OBJECTIVE/METHODS: In this article, we discuss postulated mechanisms of VPA action that provide a theoretical basis for its use in the treatment of hyperactive and mixed type delirium, based on the known and theorized pathophysiology of delirium. We also discuss potential side effects and considerations with use of VPA. CONCLUSIONS: VPA has multiple modulatory effects on neurotransmitter systems, inflammation, oxidative stress, and transcriptional changes implicated in pathophysiology of delirium. When carefully chosen, VPA can be an effective and well-tolerated treatment option for the management of hyperactive and mixed type delirium. Randomized controlled trials are needed to establish tolerability and efficacy of VPA for treatment of delirium.

Prospective Validation Study of the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) in Medically Ill Inpatients: A New Scale for the Prediction of Complicated Alcohol Withdrawal Syndrome.

AIMS: The prevalence of alcohol use disorders (AUDs) among hospitalized medically ill patients exceeds 40%. Most AUD patients experience uncomplicated alcohol withdrawal syndrome (AWS), requiring only supportive medical intervention, while complicated AWS occurs in up to 20% of cases (i.e. seizures, delirium tremens). We aimed to prospectively test and validate the Prediction of Alcohol Withdrawal Severity Scale (PAWSS), a new tool to identify patients at risk for developing complicated AWS, in medically ill hospitalized patients. METHODS: We prospectively considered all subjects hospitalized to selected general medicine and surgery units over a 12-month period. Participants were assessed independently and blindly on a daily basis with PAWSS, Clinical Institute Withdrawal Assessment-Alcohol, Revised (CIWA-Ar) and clinical monitoring throughout their admission to determine the presence and severity of AWS. RESULTS: Four hundred and three patients were enrolled in the study. Patients were grouped by PAWSS score: Group A (PAWSS < 4; considered at low risk for complicated AWS); Group B (PAWSS ≥ 4; considered at high risk for complicated AWS). The results of this study suggest that, using a PAWSS cutoff of 4, the tool's sensitivity for identifying complicated AWS is 93.1% (95%CI[77.2, 99.2%]), specificity is 99.5% (95%CI[98.1, 99.9%]), positive predictive value is 93.1% and negative predictive value is 99.5%; and has excellent inter-rater reliability with Lin's concordance coefficient of 0.963 (95% CI [0.936, 0.979]). CONCLUSION: PAWSS has excellent psychometric characteristics and predictive value among medically ill hospitalized patients, helping clinicians identify those at risk for complicated AWS and allowing for prevention and timely treatment of complicated AWS.

Reliability and Validity of the Spanish Adaptation of the Stanford Proxy Test for Delirium in Two Clinical Spanish-Speaking Communities.

BACKGROUND: Delirium is the most prevalent neuropsychiatric syndrome experienced by patients admitted to inpatient clinical units, occurring in at least 20% of medically hospitalized patients and up to 85% of those admitted to critical care units. Although current guidelines recommend the implementation of universal prevention strategies, the use of management strategies largely depends on constant surveillance and screening. This allows for the timely diagnosis and correction of its underlying causes and implementation of management strategies. OBJECTIVE: It was to adapt and analyze the Spanish adaptation of the Stanford Proxy Test for Delirium (S-PTDsv) instrument for its use among Spanish-speaking populations. The S-PTD is an instrument consisting of 13 observational items to be completed by a clinician observer, usually the patient's nurse. The completion of the questionnaire takes about 1 minute and does not require the active participation of the person evaluated, which has important clinical advantages compared to other available instruments (e.g., the Confusion Assessment Method). METHODS: The psychometric properties of the S-PTDsv were evaluated in a population of 123 patients using a quantitative, cross-sectional design. All subjects were over 18 years of age and hospitalized in various inpatient medico-surgical and intensive care unit services, either at the Barcelona Clinical Hospital (Barcelona, Spain) or the UC-Christus Health Network Clinical Hospital (Santiago, Chile, S.A.). The ultimate diagnosis of delirium was made by a member of the Psychiatry Consult Service by means of an independent neuropsychiatric evaluation based on the Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, published in 2013, which is the latest version of the diagnostic manual. All study tests were performed by study personnel who were blinded to each other's test results within an hour of each other. RESULTS: In the receiver operator characteristic (ROC) curve analysis, the S-PTDsv demonstrated excellent classification qualities when compared with the DSM-5 as the classification reference standard. Using a cutoff point of ≥3, the S-PTDsv had a sensitivity of 94% and a specificity of 97%. The area under the curve indicator was equal to 0.95, suggesting the S-PTDsv has an excellent overall performance in accurately identifying cases of delirium. Accordingly, the S-PTDsv's positive predictive value = 0.93, and the negative predictive value = 0.97. The internal reliability measured with Cronbach's alpha was 0.96. Confirmatory factor analysis revealed a 1-dimensional structure with high loadings (>0.72), demonstrating that all items similarly contribute to the total diagnostic dimension, suggesting adequate construct validity. This provided evidence of convergent validity. CONCLUSIONS: The performance of the S-PTDsv, as compared to a blinded neuropsychiatric assessment based on DSM-5, indicates that it is an effective instrument for the detection of delirium, in the Spanish-speaking populations. These results are comparable and consistent with previously published studies in the English language version.

Neuropathogenesis of delirium: review of current etiologic theories and common pathways.

Delirium is a neurobehavioral syndrome caused by dysregulation of neuronal activity secondary to systemic disturbances. Over time, a number of theories have been proposed in an attempt to explain the processes leading to the development of delirium. Each proposed theory has focused on a specific mechanism or pathologic process (e.g., dopamine excess or acetylcholine deficiency theories), observational and experiential evidence (e.g., sleep deprivation, aging), or empirical data (e.g., specific pharmacologic agents' association with postoperative delirium, intraoperative hypoxia). This article represents a review of published literature and summarizes the top seven proposed theories and their interrelation. This review includes the "neuroinflammatory," "neuronal aging," "oxidative stress," "neurotransmitter deficiency," "neuroendocrine," "diurnal dysregulation," and "network disconnectivity" hypotheses. Most of these theories are complementary, rather than competing, with many areas of intersection and reciprocal influence. The literature suggests that many factors or mechanisms included in these theories lead to a final common outcome associated with an alteration in neurotransmitter synthesis, function, and/or availability that mediates the complex behavioral and cognitive changes observed in delirium. In general, the most commonly described neurotransmitter changes associated with delirium include deficiencies in acetylcholine and/or melatonin availability; excess in dopamine, norepinephrine, and/or glutamate release; and variable alterations (e.g., either a decreased or increased activity, depending on delirium presentation and cause) in serotonin, histamine, and/or γ-aminobutyric acid. In the end, it is unlikely that any one of these theories is fully capable of explaining the etiology or phenomenologic manifestations of delirium but rather that two or more of these, if not all, act together to lead to the biochemical derangement and, ultimately, to the complex cognitive and behavioral changes characteristic of delirium.

An Interdisciplinary Reappraisal of Delirium and Proposed Subtypes.

An interdisciplinary plenary session entitled "Rethinking and Rehashing Delirium" was held during the 2021 Annual Meeting of the Academy of Consultation-Liaison Psychiatry to facilitate dialog on the prevalent approach to delirium. Panel members included a psychiatrist, neurointensivist, and critical care specialist, and attendee comments were solicited with the goal of developing a statement. Discussion was focused on a reappraisal of delirium and, in particular, its disparate terminology and history in relation to acute encephalopathy. The authors endorse a recent joint position statement that describes acute encephalopathy as a rapidly evolving (<4 weeks) pathobiological brain process that presents as subsyndromal delirium, delirium, or coma and suggest the following points of refinement: (1) to suggest that "delirium disorder" describe the diagnostic construct including its syndrome, precipitant(s), and unique pathophysiology; (2) to restrict the term "delirium" to describing the clinical syndrome encountered at the bedside; (3) to clarify that the disfavored term "altered mental status" may occasionally be an appropriate preliminary designation where the diagnosis cannot yet be specified further; and (4) to provide rationale for rejecting the terms acute brain injury, failure, or dysfunction. The final common pathway of delirium appears to involve higher-level brain network dysfunction, but there are many insults that can disrupt functional connectivity. We propose that future delirium classification systems should seek to characterize the unique pathophysiological disturbances ("endotypes") that underlie delirium and delirium's individual neuropsychiatric symptoms. We provide provisional means of classification in hopes that novel subtypes might lead to specific intervention to improve patient experience and outcomes. This paper concludes by considering future directions for the field. Key areas of opportunity include interdisciplinary initiatives to harmonize efforts across specialties and settings, enhance underrepresented groups in research, integration of delirium and encephalopathy in coding, development of relevant quality and safety measures, and exploration of opportunities for translational science.

A Retrospective Analysis of Guanfacine for the Pharmacological Management of Delirium.

Background Delirium is a syndrome of acute brain failure that represents a change from an individual's baseline cognitive functioning characterized by deficits in attention and multiple aspects of cognition that fluctuate in severity over time. The symptomatic management of delirium's behavioral manifestations remains difficult. The alpha-2 agonists, dexmedetomidine and clonidine, are efficacious, but their potential cardiovascular adverse effects limit their utilization. Guanfacine is an oral alpha-2 agonist with a lower potential for such adverse outcomes; however, its use in delirium has not been studied. Methods A retrospective descriptive analysis of guanfacine for managing hyperactive or mixed delirium at Tampa General Hospital from January 2020 to October 2020 was conducted. The primary outcome was the time reduction in acute sedative administration. Secondary outcomes included renewed participation in physical therapy or occupational therapy (PT/OT), decreased opioid use, and an incidence of cardiovascular adverse effects. Results One hundred forty-nine patients were identified as having received guanfacine for managing delirium during the study period. All experienced a reduction in acute sedative use after the initiation of guanfacine. In 93 patients receiving PT/OT and no longer participating due to behavioral agitation, 74% had a documented renewal of services within four days. Of 112 patients on opioids, 70% experienced a 25% reduction in opioid administration within four days. No patients experienced consecutive episodes of hypotension that required a change in their clinical care. Two patients experienced a single episode of consecutive bradycardia that led to the discontinuation of guanfacine.  Conclusions Based on our retrospective study, guanfacine is a well-tolerated medication for the management of delirium. Even in medically and critically ill patients, cardiovascular adverse events were rare with guanfacine. Patients treated with guanfacine experienced decreased acute sedative use for behavioral agitation. Additionally, patients treated with guanfacine received fewer opioids and were better able to participate in PT/OT. Future studies with prospective, randomized, placebo-controlled designs are warranted to evaluate this promising intervention for delirium further.