Hypoactive Delirium Research Articles

Effect of Flumazenil on Hypoactive Delirium in the ICU: A Double-Blind, Placebo-Controlled Pilot Study.

This was a single-center, double-blinded, randomized placebo-controlled pilot study. Adult ICUs at a large academic medical center in the United States. Adult, critically ill patients with benzodiazepine exposure and hypoactive delirium based on the Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale assessments were considered for enrollment. Patients received a test dose of flumazenil starting at 0.1 mg intravenously and titrated up every 5 minutes by 0.1 mg increments up to a maximum total dose of 2 mg. Patients who demonstrated a Richmond Agitation Sedation Scale score increase of greater than 1 point were considered responders and randomized to flumazenil (0.05-0.3 mg/hr) or placebo infusion for up to 72 hours. Confusion Assessment Method-ICU scores were assessed twice daily for resolution of delirium. The trial was stopped early based on the observed size effect and power analysis. Twenty-two of the 25 patients responded to the flumazenil test dose (88%). The median number of delirium-free days alive without coma within 14 days of enrollment was similar between the two infusion groups (12.7 vs 9.2; p = 0.19). There was no difference in the probability of delirium resolution within the first 14 days with 90% versus 70% in the flumazenil and placebo groups, respectively (p = 0.2). There was no statistical difference (odds ratio, 0.17; 95% CI, 0.022-1.23; p = 0.079) in delirium- and coma-free days at the end of the study drug infusion. There was no difference between groups in ICU length of stay (7.8 ± 4.8 vs 7 ± 8; p = 0.74). No serious adverse events occurred. This study found that flumazenil test dose and infusion present a potential option for hypoactive delirium associated with benzodiazepine exposure; however, the possible benefit is unknown. Larger studies are warranted to further evaluate these findings.

Postoperative delirium: the findings from a multidisciplinary survey.

Delirium is a common postoperative neurocognitive complication in the older population and can lead to significant morbidity and mortality, as well as cognitive and functional impairment. Hypoactive delirium is characterised by drowsiness and inactivity, and expert opinions suggest that it is more likely to be missed and can lead to more complications. Current guidelines and literature evidence both support the use of non-pharmacological management of delirium. To investigate the recognition of hyperactive and hypoactive delirium by the surgical multidisciplinary team, and to investigate staff understanding regarding the management and prognosis of postoperative delirium. We conducted a single-centre, multidisciplinary survey on the diagnosis, management and complication of postoperative delirium. We found that hypoactive delirium is significantly less likely to be identified. In contrast, acute psychosis is likely to be misdiagnosed as delirium. Only a small proportion of the respondents had knowledge of the supportive management options for delirium; and the medical complications and higher mortality risk associated with postoperative delirium. The finding of the survey demonstrates a need for delirium education. Surveys such as this may be conducted in other centres to identify areas of focus on staff delirium education.

Health Care Professionals' Reports of Cancer Pain Cues Among Older People With Delirium: A Qualitative-Quantitative Content Analysis

ContextHealth care professionals (HCPs) currently judge pain presence and intensity in patients with delirium despite the lack of a valid, standardized assessment protocol. However, little is known about how they make these judgments. This information is essential to develop a valid and reliable assessment tool. ObjectivesTo identify pain cues that HCPs report to judge pain in patients with delirium and to examine whether the pain cues differed based on patient cognitive status and delirium subtype. MethodsMixed qualitative-quantitative design. Doctors and nurses were recruited. All participants provided written informed consent, and before the recorded interview, demographic information was collected; then participants were asked to describe their practices and beliefs regarding pain assessment and management with older patients who are cognitively intact and patients with delirium. Interviews were transcribed verbatim and coded for pain cues. Coded data were imported into SPSS software (IBM SPSS Statistics Version 24; IBM Corporation, Armonk, NY) to conduct bivariate analyses. ResultsThe pain cue self-report was stated more often for intact than for delirium patients (χ2 [1; N = 106] = 22.56; P < 0.001). HCPs stated yelling (χ2 [2; N = 159] = 11.14; P = 0.004), when describing pain in hyperactive than in hypoactive and mixed delirium patients; and significantly more HCPs stated grimace (χ2 [2; N = 159] = 6.88; P = 0.03), when describing pain in hypoactive than hyperactive and mixed patients. ConclusionThis study outlines how HCPs conduct pain assessment in patients who are delirious and, also, identifies pain behavior profiles for the subtypes of delirium.

Risk factors and outcomes among delirium subtypes in adult ICUs: A systematic review

PurposeUse systematic review methodology to summarize risk factors and outcomes for each delirium subtype (hypoactive, hyperactive and mixed) in an adult ICU population. Materials and methodsWe searched the MEDLINE, Embase, CINAHL, SCOPUS, Web of Science and PsycINFO databases from database inception until August 13, 2018, with no restrictions. ResultsOf 9635 abstracts, 20 studies were included. Older age was not associated with any delirium subtype in 4/7 (57%) studies. Sex was not associated with any delirium subtype in 4/4 (100%) studies. Mortality was consistently associated with hypoactive delirium in 4/7 (57%) studies. The evidence supporting the association of APACHE-II score, mechanical ventilation, length of stay, duration of delirium and removal of tubes were inconsistent across studies. ConclusionsAlthough included studies reported on many subtype-specific risk factors and outcomes, heterogeneity in reporting and methodological quality limited the generalizability of the results and the evidence for many subtype-specific risk factors or outcomes is inconsistent across studies. Standardized methodology and the creation of a universal template for collecting data in ICU delirium studies are essential moving forward; helping to identify subtype-specific risk factors or outcomes and strengthen the association of potential risk factors or outcomes.

A prospective cohort study on predictors of mortality of delirium in an emergency observational unit.

Delirium is often an underdiagnosed and underestimated neuropsychiatric syndrome, especially in low- and middle-income countries. To document the prevalence and clinical profile of delirium and to detect the baseline parameters associated with in-hospital mortality. A prospective cohort study conducted between January 2016 to December 2016 at an adult medical emergency observational unit of an academic hospital in north India. Confusion Assessment Method for the intensive care unit was used for screening and diagnosis of delirium. Subtypes of delirium and severity were defined with the Richmond agitation-sedation scale and Delirium Rating Scale-Revised-98 (DRS-R-98). Out of 939 screened patients, 312 (33.2%) had delirium, including 73.7% unrecognized cases. The mean age was 49.1 ± 17.3 years (range 17-90), and only 33.3% of the patients were above 60 years. The prevalence of hypoactive, mixed and hyperactive delirium was 39.1, 33.7 and 27.2%, respectively. Usual predisposing factors were alcohol use disorder (57.4%) and hypertension (51.0%), and infections remain the most common precipitating factors (42.0%). In total, 96.1% of patients received midazolam before delirium onset, and physical restraints were used in 73.4%. Mortality was higher in delirium (19.9% vs. 6.4%). The independent predictors of death in delirium were low diastolic blood pressure (P-value = 0.000), Glasgow coma scale score <15 (P = 0.026), high Acute Physiology and Chronic Health Evaluation II score (P = 0.007), high DRS-R-98 severity score (P = 0.000) and hyperactive delirium (P = 0.024). Rapid screening with Confusion Assessment Method for the intensive care unit detected a high prevalence of delirium (even in young patients), and it associated withhigh mortality.

Clinical profile of acute confusional state in elderly patients in a tertiary hospital in western Rajasthan

Context: Acute confusional state can be predisposed by preexisting chronic health conditions and drug/substance abuse or can be precipitated by acute insults such as infections and electrolyte imbalance. It is more common in the elderly population, and adverse outcomes include prolonged hospital stay and increased risk of complication or mortality. Aims: The aim of this study was to find out the clinical profile of confusional state in western Rajasthan. Settings and Design: This was a cross-sectional prospective design. Materials and Methods: The study was conducted on 180 elderly patients presenting with acute confusional state diagnosed according to the Confusion Assessment Method Instrument. After a thorough history, all patients went through a complete physical examination and were monitored systematically every 12 h until discharge or death. Routine blood tests were done in all the patients and imaging done as indicated. Statistical Analysis: SPSS was used for statistical analysis. Results: Predominantly affected group in both the genders was 60–70 years. One hundred and fifty-one patients had a history of comorbid illnesses, 47.78' of the patients had a significant history of substance abuse, and 137 had psychosomatic disorders. Around one-third of the study population was socially isolated. The most common acute insults were metabolic encephalopathy, infection, and dehydration. Hypoactive delirium was found to be most common (72.77'). Almost half of the patients presenting with confusion (49.5') expired. Vasopressor and ventilator support were required in more than half of the patients. Most of the patients had multiple causes for confusion with only 10.5' of the patients having a single cause. Conclusion: Timely diagnosis and appropriate interventions are necessary to reduce hospital stay and further complications associated with it.

Differential clinical characteristics, management and outcome of delirium among ward compared with intensive care unit patients.

Delirium is common in hospitalised patients but its epidemiology remains poorly characterised. To test the hypothesis that patient demographics, clinical phenotype, management and outcomes of patient with delirium in hospital ward patients differ from intensive care unit (ICU) patients. Retrospective cohort of patients admitted to an Australian university-affiliated hospital between March 2013 and April 2017 and coded for delirium at discharge using the International Classification of Diseases System, 10th revision, criteria. Among 61 032 hospitalised patients, 2864 (4.7%) were coded for delirium. From these, we studied a random sample of 100 ward patients and 100 ICU patients. Ward patients were older (median age: 84 vs 65 years; P < 0.0001), more likely to have dementia (38% vs 2% for ICU patients; P < 0.0001) and less likely to have had surgery (24% vs 62%; P < 0.0001). Of ward patients, 74% had hypoactive delirium, while 64% of ICU patients had agitated delirium (P < 0.0001). Persistent delirium at hospital discharge was more common among ward patients (66% vs 17%, P < 0.0001). On multivariable analysis, age and dementia predicted persistent delirium, while surgery predicted recovery. Delirium in ward patients is profoundly different from delirium in ICU patients. It has a dominant hypoactive clinical phenotype, is preceded by dementia and is less likely to recover at hospital discharge. Therefore, delirium prevention, detection and goals of care should be adapted to the environment in which it occurs.

Delirium in the PICU

Introduction: Delirium is a well-documented problem in the adult population however, its importance in the paediatric population has evolved recently with the development and validation of reliable paediatric delirium (PD) assessment tools. Definition: The key feature of delirium is an alteration in both cognition and arousal. The American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)1, defines delirium as a noticeable change in the patient's neurocognitive baseline with an acute disturbance in attention, awareness, and cognition, and is thought to be a direct result of another medical condition rather than due to an established/evolving neurocognitive disorder. Epidemiology: The overall prevalence of delirium in PICU ranges from 4% to 29%, with a recent multi-institutional PD study assessing 994 children for delirium in 25 different PICUs reporting a prevalence of 25%.2 Higher rates have been reported in children < 5 years of age.3 A PD prevalence of 49% was found in a paediatric cardiac ICU population. A prevalence rate of 27% was described in a postoperative paediatric population (delirium incidence of 65% within 5 days after surgery).3 Pathophysiology: Many hypotheses have been proposed. The neuroinflammatory hypothesis suggests that systemic inflammation leads to endothelial activation, enhanced cytokine activity, and infiltration of leukocytes and cytokines into the central nervous system (CNS), producing local ischemia and neuronal apoptosis. The neurotransmitter hypothesis suggests that dysregulation of neurotransmitters like acetylcholine, dopamine, and gamma aminobutyric acid leads to the development of delirium. The oxidative stress hypothesis suggests that hypoxia coupled with increased cerebral metabolism, leads to the production of reactive oxygen species that cause global CNS dysfunction.3 Risk factors: Risk factors are divided into predisposing and precipitating factors many of which are modifiable (Table 1).3 Presentation: PD presents in three major subtypes. Hyperactive delirium is characterized by agitation, restlessness, hypervigilance, and combative behaviour, hypoactive delirium is characterized by lethargy, inattention, and decreased responsiveness and mixed type delirium which exhibits aspects of both hyperactive and hypoactive delirium.1 Hypoactive and mixed type delirium are common presentations in children followed by hyperactive variety. Hypoactive delirium can be easily missed without appropriate screening and diagnostic tools for assessment.3 PD screening tools: Various screening tools have been developed to detect PD with their advantages and limitations (Table 2). Treatment: Management of delirium involves a multidisciplinary stepwise approach (Figure 1)3 including the management of the underlying medical illness, minimizing iatrogenic triggers, and optimizing the PICU environment. Pharmacotherapies are indicated if delirium persists and a child's agitated behaviour is distressful or interferes with medical care. Haloperidol, risperidone, and quetiapine have been used safely in children.5 Outcome and prevention: PD is associated with increased length of mechanical ventilation, increased hospital stay, higher resource utilization, increased healthcare costs, and increased mortality. PD is a hospital acquired complication which can be prevented by using analgosedation approach with the goal to optimize pain and minimize sedation, minimizing iatrogenic factors, early mobilization, and involvement of family members in daily care.3 Conclusion: PD is an important underrecognized issue in the PICU which needs to be prevented, detected early using screening tools, and managed using a multidisciplinary team approach.

A Challenging Hypoactive Delirium Case with Multiple Etiological Considerations

A Challenging Hypoactive Delirium Case with Multiple Etiological Considerations

Prevalence of delirium in elderly intensive care unit patients of a tertiary care medical college hospital

Background: Delirium is an acute disorder of attention and cognition. It occurs in 20% to 79% of hospitalized older patients. It is also common in ICU patients, occurring in 20% to 50% of non-mechanically ventilated ICU patients and in 60% to 80% of mechanically ventilated ICU patients. Hence delirium is a common, serious, and often fatal condition among older patients. The present study attempts to address the prevalence of Delirium in the Indian elderly population.Methods: A cross sectional study was conducted between January 2019 to June 2019 in a 50 bedded intensive care unit of a tertiary care hospital in Bengaluru, Karnataka. A total of 300 elderly patients aged 60 years and above, satisfying the inclusion criteria was included in the study. Patients were assessed for the presence of delirium within 24 hours of admission using Confusion Assessment Method for Intensive Care Unit (CAM-ICU). Various qualitative variables were expressed in terms of proportions.Results: Prevalence of delirium among elderly, non-ventilated ICU patients was 30% (90 out of 300 patients). Among them, 50 (55.5%) were females and remaining 40 (44.5%) were males. Mean age of the patients was 76 years. About 50 (55.5%) of them belonged to age group of 70-79 years. Most of the delirium patients (44.5%) belonged to hypoactive type of delirium followed by hyperactive (33.3%) and mixed (22.2%) type of delirium.Conclusions: Delirium in elderly ICU patients is significantly prevalent, which is a poor prognostic factor, leading to higher morbidity and mortality. Of the three subtypes- hypoactive delirium is the most common type of delirium among elderly. Yet, it is often overlooked or under-diagnosed. Hence clinicians and/or trained nursing staff managing the patients in the ICUs, should routinely screen the patients for delirium, using brief screening measures, which in turn can improve the patients’ outcome.

The effect of a multidisciplinary care bundle on the incidence of delirium after hip fracture surgery: a quality improvement study.

Delirium is a common complication following hip fracture surgery. We introduced a peri-operative care bundle that standardised management in the emergency department, operating theatre and ward. This incorporated: use of fascia iliaca blocks; rationalisation of analgesia; avoidance of drugs known to trigger delirium; a regular education program for staff; and continuous auditing of compliance. The study was conducted between June 2017 and December 2018. We recruited 150 patients before (control group) and 150 patients after (care bundle group) the introduction of the care bundle. In patients having surgery for a hip fracture, there was a lower incidence of delirium on the third postoperative day in the care bundle group compared with the control group (33 patients (22%) vs. 49 patients (33%)), respectively; p=0.04). Patients in the care bundle group had an adjusted OR of 2.2 (95%CI 1.1-4.4) (p=0.03) for the avoidance of delirium on the third postoperative day. There was no difference between groups for the secondary outcome measures (measured at 30days postoperatively) including: all-cause mortality; composite morbidity; institutionalisation; and walking status. During the study period, compliance with elements of the care bundle improved in the emergency department (49 patients (33%) compared with 85 patients (59%); p<0.001) and anaesthetic department (40 patients (27%) compared with 104 patients (69%); p<0.001), while orthogeriatrics maintained a high level of compliance (140 patients (93%) compared with 143 patients (95%); p=0.45). There was a clinically and statistically significant reduction in the incidence of delirium following hip fracture surgery in patients treated with a multidisciplinary care bundle.

Clinical management of delirium: The response depends on the subtypes. An observational cohort study in 602 patients.

The hypoactive, hyperactive, and mixed subtypes of delirium differently impact patient management and prognosis, yet the evidence remains sparse. Therefore, we examined the outcome of varying management strategies in the subtypes of delirium. In this observational cohort study, 602 patients were managed for delirium over 20 days with the following strategies: supportive care alone or in combination with psychotropics, single, dual, or triple+ psychotropic regimens. Cox regression models were calculated for time to remission and benefit rates (BRs) of management strategies. Generally, the mixed subtype of delirium caused more severe and persistent delirium, and the hypoactive subtype was more persistent than the hyperactive subtype. The subtypes of delirium were similarly predictive for mortality (P = 0.697) and transfer to inpatient psychiatric care (P = 0.320). In the mixed subtype, overall, psychotropic drugs were administered more often (P = 0.016), and particularly triple+ regimens were administered more commonly compared to hypoactive delirium (P = 0.007). Patients on supportive care benefited most, whereas those on triple+ regimens did worst in terms of remission in all groups of hypoactive, hyperactive, and mixed subtypes (BR: 4.59, CI 2.01-10.48; BR: 4.59, CI 1.76-31.66; BR: 3.36, CI 1.73-6.52; all P < 0.05). The mixed subtype was more persistent to management than the hypoactive and hyperactive subtypes. Delirium management remains controversial and, generally, supportive care benefited patients most. Psychopharmacological management for delirium requires careful choosing of and limiting the number of psychotropics.

Benzodiazepines and/or neuroleptics for the treatment of delirium in palliative care?-a critical appraisal of recent randomized controlled trials.

Delirium is a frequent condition in patients in a palliative care situation and most often associated with substantial burden or even danger for the persons concerned as well as caregivers and health-care-professionals. Despite the lack of randomized-controlled-trials (RCTs) benzodiazepines and neuroleptic agents are used extensively in palliative care for the pharmacological management of delirium. A focused review for RCTs assessing pharmacotherapy with benzodiazepines and neuroleptics for the treatment of delirium in patients treated in a palliative care or hospice setting published in 2017 was performed in PubMed. A narrative summary of the findings of the RCTs and practical recommendation are presented. Of 42 publications, two RCTs could be included. One trial assessed the use of lorazepam (in addition to haloperidol) in case of agitation, the other placebo or risperidone or haloperidol in delirious palliative care patients. Neither risperidone nor haloperidol were superior compared to placebo, but were associated with higher mortality and morbidity. Lorazepam (along with haloperidol) reduced agitation in patients with delirium compared to placebo (along with haloperidol), but was unable to reduce the severity and incidence of delirium. It is of importance to note that psychopharmacotherapy with antipsychotics is mainly indicated for the hyperactive form of delirium and psychotic symptoms (e.g., delusions or hallucinations) in the hyper- and hypoactive delirium. Severe agitation and aggressivity can be an indication for neuroleptics, when non-pharmacological interventions fail, whereas the use of benzodiazepines has to be limited to critical situations where neuroleptics cannot be applied and cases of delirium due to alcohol withdrawal. Both substances can aggravate, precipitate or mask delirium, result adverse events with substantial distress or unfavorable survival outcomes for the patients. Thus, they should only be used in severely symptomatic patients and the duration of the medication has to be limited in time. When delirium symptoms decay the psychopharmacotherapy has to be tapered. More important than psychopharmacotherapy, the thorough investigation and treatment of potentially reversible causes of delirium (e.g., pharmacotherapy, infection) and the routine identification of patients at risk for delirium along with prophylactic measures are essential. The recently published landmarks RCTs provide moderate evidence to adopt recommendations from other medical specialties (i.e., intensive care, geriatrics) to the field of palliative care.

Delirium in patients with dementia and in children: Overlap of symptoms profile and possible role for future diagnosis

BackgroundDelirium in the extremes of the age spectrum may show similarities in presentations, and these similarities may provide information to develop tools for the diagnosis of delirium superimposed on dementia (DSD). We sought to investigate the symptom profile and subtypes of delirium in patients with dementia, and in infants and preschool children. MethodsThis was an exploratory analysis of previous prospective cohort studies that evaluated delirium with the DSM-IV criteria in patients with dementia, and in critically ill infants (< 2 years of age) and preschool children (2–5 years of age), respectively. Delirium subtypes were defined based on the Richmond Agitation-Sedation Scale. ResultsWe included 147 patients, 35 adult patients with delirium DSD, 80 infants, and 32 preschool children with delirium. Hypokinesia and apathy were common among both DSD (72%), infants (74%) and preschool children (75%) with delirium, whereas hallucinations and anxiety were less common in both adults with DSD (26%) and infants (10%) and preschool children (14%). Hypoactive delirium was most common delirium subtype among infants (68%) and preschoolers (76%), whereas RASS = 0 (alert) delirium was the most common among adult patients with DSD (55%). ConclusionsThe study reports similarities in the symptoms profile of delirium in a cohort of patients with dementia and delirium, and in infants and preschool-aged children with delirium. These preliminary findings might be informative to design future studies adapting delirium assessments used in in infants and preschool-aged children to patients with dementia, especially in the moderate to severe stages.

Considering Causes for Hypoactive Delirium

Abstract Delirium is defined as a mental disorder characterized by an abnormal state of cognition and awareness. Delirium is associated with an annual cost of $350 billion between the United States and Europe. Approximately 80% of delirium cases are either not identified or misdiagnosed. Older adults have the highest incidence due to the consequences of aging. Hypoactive delirium or “quite delirium” is the most common delirium subtype experienced by older adults. Hypoactive delirium, is difficult to recognize and has worse outcomes than other subtypes. If detected, symptoms of hypoactive delirium are frequently dismissed as depression or dementia. Therefore, nurses need heightened vigilance in assessment and identification of hypoactive delirium. This article seeks to assist nurses in identifying hypoactive delirium by outlining factors that increase an individual’s potential for developing hypoactive delirium.

Early Postoperative Actigraphy Poorly Predicts Hypoactive Delirium.

Delirium is a postoperative complication accompanied by disturbances in attention, cognition, arousal, and psychomotor activity. Wrist actigraphy has been advocated to study inactivity and inferred sleep patterns during delirium. We hypothesized that altered patterns of motor activity or immobility, reflective of disordered sleep and wakefulness patterns, would serve as predictive markers of hypoactive postoperative delirium. Eighty-four elderly surgical patients were classified into three groups based on the timing of hypoactive delirium following surgery: intact with no delirium throughout postoperative days (POD) 0-5 (n = 51), delirium during POD 0-1 (n = 24), and delirium during POD 2-5 (n = 13). Delirium was detected on daily Confusion Assessment Method evaluations and chart review. Actigraphy measures were calculated from accelerometry signals acquired on the first postoperative day (POD 0, 16:00-23:00) and night (POD 0, 23:00-POD 1, 06:00). Actigraphy metrics showed substantial interpatient variability. Among the three patient groups, only those without delirium showed greater movement during the day compared to night and also fewer minutes of night immobility (P = .03 and P = .02, Wilcoxon rank-sum tests). These patients were poorly discriminated from those with delirium during either POD 0-1 or POD 2-5, using differences in day and night activity (C-statistic, 95% confidence interval [CI]: 0.66 [0.53-0.79] and C-statistic, 95% CI: 0.71 [0.55-0.87], respectively). Inclusion of low-frequency signals improved performance of immobility measures without affecting those based on activity. Cognitively intact patients during POD 0-5 were distinguished from those with delirium during POD 0-1, based on differences in the number of day and night immobile minutes (C-statistic 0.65, 95% CI: [0.53-0.78]). Actigraphy metrics with the strongest association to delirium incidence were not reliably correlated with an increased risk during POD 0-5, when accounting for patient age, sex, intensive care unit admission, and Charlson Comorbidity Index (adjusted odds ratio of 1.7, 95% CI: [1.0-3.0], P = .09, likelihood ratio test). Early postoperative wrist actigraphy metrics that serve as markers of sleep and wakefulness offer limited capacity as sole predictors or markers of hypoactive delirium. Registry: ClinicalTrials.gov; Title: Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) Study; Identifier: NCT02241655; URL: https://clinicaltrials.gov/ct2/show/NCT02241655.

Current Pharmacotherapy Does Not Improve Severity of Hypoactive Delirium in Patients with Advanced Cancer: Pharmacological Audit Study of Safety and Efficacy in Real World (Phase-R).

Pharmacotherapy is generally recommended to treat patients with delirium. We sought to describe the current practice, effectiveness, and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer, and to explore predictors of the deterioration of delirium symptoms after starting pharmacotherapy. We included data of patients with advanced cancer who were diagnosed with hypoactive delirium and received pharmacotherapy for treatment of delirium. This was a pharmacovigilance study characterized by prospective registries and systematic data-recording using internet technology, conducted among 38 palliative care teams and/or units. The severity of delirium and other outcomes were assessed using established measures at days 0 (T0), 3 (T1), and 7 (T2). Available data were obtained from 218 patients. The most frequently used agent was haloperidol (37%). A total of 67 and 42 patients (31% and 19%) had died or discontinued pharmacotherapy by T1 and T2, respectively. Delirium symptoms deteriorated between T0 and T1, but this trend did not reach statistical significance. The most prevalent adverse event was sedation (9%). Delirium severity worsened after starting pharmacotherapy in 121 patients (56%) at T1. In patients whose death was expected within a few days and those with delirium caused by organ failure, symptoms of delirium were significantly more likely to deteriorate after starting pharmacotherapy. Current pharmacotherapy for hypoactive delirium in patients with advanced cancer is not recommended, especially in those whose death is expected within a few days and in those with delirium caused by organ failure. Delirium is common among patients with advanced cancer, and hypoactive delirium is the dominant motor subtype in the palliative care setting. Pharmacotherapy is recommended and regularly used to treat delirium. This article describes the effectiveness and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer. The findings of this study do not support the use of pharmacotherapy for treatment of hypoactive delirium in the palliative care setting. Pharmacotherapy should especially be avoided in patients whose death is expected within a few days and in those with delirium caused by organ failure.

Etiological and Symptomatological Differences Between Hyperactive and Hypoactive Delirium Subtypes

Etiological and Symptomatological Differences Between Hyperactive and Hypoactive Delirium Subtypes

Delirium in medical intensive care units: Incidence, subtypes, risk factors, and outcome.

Background:Delirium is a frequent yet underdiagnosed neuropsychiatric condition encountered in intensive care units (ICUs). Being both a preventable and potentially reversible process associated with significant morbidity and mortality, understanding risk factors that predispose and precipitate delirium in any given patient are critical in ICUs.Aims and Objectives:The aim of this study is to evaluate the incidence, motor subtypes, risk factors, and clinical outcome of delirium in the medical ICU.Materials and Methods:We used a prospective study design on a cohort of consecutive medical ICU admissions of a tertiary care teaching hospital. The Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale were used to diagnose and motor subtype delirium, respectively, along with a checklist to assess risk factors.Results:Of the 280 ICU admissions, 88 (31.4%) developed delirium. Hypoactive delirium was the most common motor subtype (55.7%). The detection rate of delirium was 12.5% (lowest for hypoactive delirium at 2.04%). Age, gender, and years of education did not significantly predict delirium (all P > 0.05). Tobacco use, chronic liver disease, and past episodes of delirium significantly predisposed, while mechanical ventilation, hypoxia, fever, raised levels of bilirubin and creatinine, and benzodiazepine administration significantly precipitated ICU delirium. Delirium was significantly associated with longer ICU stay (t = 4.23, P = 0.000) and 1-month postdischarge mortality (χ2 = 6.867, P = 0.009).Conclusion:Detection of delirium is challenging, especially in ICU patients on mechanical ventilation and hypoactive delirium. Screening and monitoring for predisposing and precipitating risk factors can greatly improve the odds of detection and intervention as ICU delirium is associated with significant morbidity and mortality.

Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness

BackgroundThere are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU).MethodsIn a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation.ResultsWritten informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms.ConclusionsThe use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522.)