ABSTRACT
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.
Subject(s)
Globus Pallidus , Lithium , Humans , Globus Pallidus/diagnostic imaging , Globus Pallidus/injuries , Lithium/toxicityABSTRACT
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.
ABSTRACT
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.
Subject(s)
Brain Diseases , Mental Disorders , Psychiatry , Humans , Brain , ForecastingABSTRACT
BACKGROUND: The growing number of cases presenting with COVID-19 during the pandemic has led to a significant shortage of hospital beds. Many patients may not require hospitalization and can be clinically observed in home settings. We have identified a set of psychosocial factors that correlate with unsuccessful home isolation (HI), which in turn might negatively affect the transmission control in the community. Therefore, we developed the Chula COVID-19 Psychosocial Home Isolation Evaluation Tool (CCPHIET), a new screening tool for assessing the psychosocial suitability for HI. This study examines the CCPHIET's validity and reliability. METHODS: This cross-sectional descriptive study included COVID-19 patients who were deemed to be medically safe for 14-days of HI. The CCPHIET is comprised of eight clinical domains pertinent to HI behavioral compliance and risk for non-adherence. We explored its statistical validity and reliability and discussed the potential utility of this tool. RESULTS: A total of 65 COVID-19 patients participated in this study. Most patients (58.5%) were deemed to be appropriate candidates for HI according to the CCPHIET. The results of this study demonstrate that the CCPHIET has an acceptable content validity (IOC index > 0.5), moderate internal consistency (Cronbach's alpha = 0.611) and substantial to excellent inter-rater reliability (Intraclass correlation coefficient = 0.944, Cohen's kappa= 0.627). CONCLUSIONS: CCPHIET is an easy-to-use tool for assessing the psychosocial suitability of patients advised for at-home isolation with mild and asymptomatic COVID-19. Its implementation can assist clinicians in identifying and redirecting resources to patients at the highest risk for breaking quarantine and save on unnecessary, costly absolute institutional quarantine for those deemed to be psychosocially fit for full adherence.
ABSTRACT
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.
Subject(s)
Alcoholism/therapy , Biomedical Research , Central Nervous System Depressants/adverse effects , Ethanol/adverse effects , Hospitalization , Substance Withdrawal Syndrome/therapy , Alcoholism/physiopathology , Critical Care/methods , Critical Care/standards , Humans , Needs Assessment , Quality Improvement , Societies, Medical , Substance Withdrawal Syndrome/physiopathology , Translational Research, BiomedicalABSTRACT
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.
Subject(s)
Geriatric Psychiatry , Psychiatry , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Length of Stay , Referral and Consultation , Retrospective StudiesABSTRACT
BACKGROUND: Standardized pretransplant psychosocial assessment is critically needed in Thailand to optimize medical and psychosocial outcomes after transplantation. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a comprehensive and evidence-based tool that has demonstrated excellent reliability and predictive value in many psychosocial transplant studies. We translated the SIPAT into Thai and explored the validity and reliability of the SIPAT-Thai version among Thai transplant recipients. METHODS: We translated the original SIPAT into Thai following the World Health Organization's standard forward-backward translation procedure and then cross-sectionally assessed its validity and reliability in 110 Thai solid organ transplant candidates. The correlation between background data, total, and sectional scoring results of SIPAT-Thai were also analyzed. RESULTS: The SIPAT-Thai demonstrated moderate to good reliability, which was represented by internal consistency with a Cronbach α of .751 and interrater reliability with a κ value at 0.767. The index of item-objective congruence value was 0.94, indicating good the content validity. CONCLUSIONS: The SIPAT-Thai was systematically translated and shown to have acceptable validity and a moderate to good reliability index. The use of the SIPAT-Thai would provide a standardized, evidence-based, and a more systematic pretransplant psychosocial evaluation process for transplant candidates in Thailand.
Subject(s)
Organ Transplantation/psychology , Patient Selection , Surveys and Questionnaires/standards , Transplant Recipients/psychology , Adult , Female , Humans , Male , Middle Aged , Preoperative Period , Reproducibility of Results , Thailand , TranslationsSubject(s)
Delirium , Mass Screening , Advance Directives , Delirium/diagnosis , Humans , PsychometricsSubject(s)
Adrenergic alpha-2 Receptor Agonists/therapeutic use , Antipsychotic Agents/therapeutic use , Coronavirus Infections/therapy , Delirium/drug therapy , Hypnotics and Sedatives/adverse effects , Pneumonia, Viral/therapy , Psychomotor Agitation/drug therapy , Sleep Aids, Pharmaceutical/therapeutic use , Aged , Analgesics, Opioid/adverse effects , Azepines/therapeutic use , Betacoronavirus , COVID-19 , Central Nervous System Depressants/therapeutic use , Chlordiazepoxide/adverse effects , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Coronavirus Infections/psychology , Delirium/etiology , Delirium/physiopathology , Delirium/psychology , Dexmedetomidine/adverse effects , Female , Guanfacine/therapeutic use , Haloperidol/therapeutic use , Humans , Hydromorphone/adverse effects , Intensive Care Units , Ketamine/adverse effects , Melatonin/therapeutic use , Midazolam/adverse effects , Oxycodone/adverse effects , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Pneumonia, Viral/psychology , Propofol/adverse effects , Psychomotor Agitation/etiology , Psychomotor Agitation/physiopathology , Psychomotor Agitation/psychology , Respiration, Artificial , SARS-CoV-2 , Sleep Disorders, Circadian Rhythm/drug therapy , Sleep Disorders, Circadian Rhythm/etiology , Sleep Disorders, Circadian Rhythm/physiopathology , Tracheostomy , Triazoles/therapeutic use , Valproic Acid/therapeutic useABSTRACT
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.
Subject(s)
Delirium/diagnosis , Mass Screening , Neuropsychological Tests/statistics & numerical data , Psychometrics/statistics & numerical data , Aged , Delirium/psychology , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Male , Middle Aged , Observer Variation , Patient Admission , Reproducibility of Results , United StatesABSTRACT
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.
Subject(s)
Organ Transplantation/psychology , Personality Assessment/statistics & numerical data , Psychosocial Functioning , Adult , Cross-Cultural Comparison , Female , Heart Transplantation/psychology , Humans , Italy , Liver Transplantation/psychology , Lung Transplantation/psychology , Male , Mass Screening/statistics & numerical data , Observer Variation , Predictive Value of Tests , Psychometrics/statistics & numerical data , Reproducibility of Results , Risk Factors , Treatment OutcomeABSTRACT
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).
Subject(s)
Heart Transplantation/psychology , Hematopoietic Stem Cell Transplantation/psychology , Kidney Transplantation/psychology , Language , Liver Transplantation/psychology , Preoperative Care , Risk Assessment/methods , Adaptation, Psychological , Adolescent , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Patient Selection , Prognosis , Psychological Tests , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: The Stanford Proxy Test for Delirium (S-PTD) is a tool developed to be completed by nurses at the end of their shift. It was designed to use the knowledge acquired during a full shift of nurse-patient interaction. The objective of our study was to validate the S-PTD among a mixed sample of patients in both the intensive care unit (ICU) and non-ICU settings. METHODS: A cross-sectional study was conducted in an ICU and three general medical wards in a tertiary care hospital. Patients were independently and blindly assessed for delirium by (1) the patients' primary nurses using the S-PTD at the end of their shift, and (2) a Consultation liaison psychiatrist who conducted a neuropsychiatric evaluation based on the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). RESULTS: A total 288 patients were included in current analysis. Using the S-PTD, delirium was identified in 72 (25.0%), while an expert neuropsychiatric examination, based on DSM-5 identified delirium in 75 (26.0%) patients. This study demonstrated that the S-PTD has very strong discriminative ability (area under the curve= 0.946, p<0.001). An S-PTD cut-off score ≥3 was associated with an 82.7% sensitivity, an 95.3% specificity, an 86.1% positive predictive value, a 94.0% negative predictive value, and a 92.0% overall diagnostic accuracy. These results were similar in both ICU and general ward patients. CONCLUSION: The S-PTD has excellent sensitivity and specificity in detecting delirium in both ICU and ward patients, even when compared with the gold-standard, a DSM-based neuropsychiatric examination.
Subject(s)
Delirium/diagnosis , Diagnostic and Statistical Manual of Mental Disorders , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Sensitivity and SpecificityABSTRACT
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.
Subject(s)
Delirium/classification , Delirium/physiopathology , Models, Theoretical , Delirium/etiology , Delirium/metabolism , HumansABSTRACT
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.