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Delirium in advanced cancer patients.

Delirium in advanced cancer is often poorly identified and inappropriately managed. It is one of the most common causes for admission to clinical institutions and is the most frequently cited psychiatric disorder in terminal cancer. Diagnosis of delirium is defined as a disturbance of consciousness and attention with a change in cognition and/or perception. In addition, it develops suddenly and follows a fluctuating course and it is related to other causes, such as cancer, metabolic disorders or the effects of drugs. Delirium occurs in 26% to 44% of cancer patients admitted to hospital or hospice. Of all advanced cancer patients, over 80% eventually experience delirium in their final days. In advanced cancer, delirium is a multifactorial syndrome where opioids factor in almost 60% of episodes. Delirium in such patients, excluding terminal delirium, may be reversible in 50% of cases. Providing adequate end-of-life care for a patient with delirium is the main challenge. The family needs advice and it is important to create a relaxing environment for the patient. The primary therapeutic approach is to identify the reversible causes of delirium. Some therapeutic strategies have been shown to be effective: reduction or withdrawal of the psychoactive medication, opioid rotation, and hydration. Haloperidol is the most frequently used drug, and new neuroleptics such as risperidone or olanzapine are being tested with good results. Methylphenidate has been used for hypoactive delirium.

Antineoplastic Agents↗

Can olanzapine cause delirium in the elderly?

OBJECTIVE: To report a case of delirium probably caused by the atypical antipsychotic olanzapine in a 74-year-old man with dementia. CASE SUMMARY: A 74-year-old white man with a diagnosis of severe dementia of mixed etiology with behavioral disturbances was admitted to an urban teaching hospital for increasing agitation in the context of worsening dementia. Olanzapine 2.5 mg each evening was started for agitation, and the dose was titrated to 5 mg each evening with additional emergent doses. Memantine, an N-methyl-D-aspartate antagonist, was increased from the admission dose of 10 mg/day to 15 mg/day. The patient developed symptoms of delirium on hospital day 4. Neuroleptic malignant syndrome and other causes of delirium were ruled out. Discontinuation of olanzapine resulted in resolution of the delirium. DISCUSSION: Antipsychotic medications are commonly used to treat symptoms of delirium. Atypical antipsychotics are better tolerated in the elderly because of their fewer adverse reactions compared with other antipsychotics. Olanzapine has been successfully used in the treatment of delirium. However, there have been case reports of delirium associated with olanzapine, probably related to its intrinsic anticholinergic effect. Application of the Naranjo probability scale indicated a probable relationship between the onset of delirium and the use of olanzapine in this patient. As of December 1, 2005, this was the second such report of a case in the elderly. CONCLUSIONS: Although olanzapine is useful in the treatment of delirium, elderly patients treated with this drug can develop delirium and hence should be closely monitored.

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Serotonin and amino acids: partners in delirium pathophysiology?

Delirium may be the result of dysfunction of multiple interacting neurotransmitter systems. Changes in the levels of various amino acids being precursors of cerebral neurotransmitters may affect their function and, thus, contribute to the development of delirium. Serotonin is one of the neurotransmitters that may play an important role in medical and surgical delirium. Normal serotonin synthesis and release in the human brain is, among others, dependent on the availability of its precursor tryptophan (Trp) from blood. The essential amino acid Trp competes with the other large neutral amino acids (LNAA) tyrosine, phenylalanine, valine, leucine, and isoleucine for transport across the blood-brain barrier. This competition determines its uptake into the brain, represented by the ratio of the plasma level of Trp to the sum of the other LNAA. The plasma ratio of Trp/LNAA, plasma level of Trp, and serotonin in plasma and platelets have been used as indirect peripheral measures for central serotonergic functioning. Both increased and decreased serotonergic activity have been associated with delirium. Serotonin agonists can induce psychosis, both elevated Trp availability and increased cerebral serotonin have been associated with hepatic encephalopathy, and excess serotonergic brain activity has been related to the development of the serotonin syndrome of which delirium is a main symptom. On the other hand, alcohol withdrawal delirium, delirium in levodopa-treated Parkinson patients, and postoperative delirium have been related to reduce cerebral Trp availability from plasma suggesting diminished serotonergic function. Rick factors for delirium such as severe illness, surgery, and trauma can induce immune activation and a physical stress response comprising increased activity of the limbic-hypothalamic-pituitary-adrenocortical axis, the occurrence of a low T3 syndrome, and, possibly, changes in the permeability of the blood-brain barrier. There are indications that these changes have their effect on plasma amino acid concentrations, e.g., Trp, and multiple cerebral neurotransmitters, including serotonin. This stress response may be different depending on the stage of illness being acute or chronic. It will require further study to determine the complex influence of the stress response and immune activation on plasma amino acids, neurotransmitter function and the development of delirium, especially in the more vulnerable older patients.

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Postoperative delirium.

Delirium is a global impairment of upper brain functions caused by an organic substrate. It is frequently observed in the postoperative period, particularly in elderly people. Vascular and orthopedic surgery and long-duration surgery are associated with a higher incidence of postoperative delirium. When it occurs, postoperative delirium makes patient management much more difficult, increases costs, and, above all, causes severe discomfort to the patient. Delirium is also associated with higher postoperative mortality and morbidity, and with delayed functional recovery, but it is still unclear whether worse prognosis is directly caused by delirium or results from the neurological damage of which delirium is simply a symptom. Drug therapy should be part of a complex approach to prevent and treat this complication. Neuroleptics like haloperidol and droperidol, and benzodiazepines are usually employed in order to control symptoms like agitation, restlessness, and altered perceptions. Atypical neuroleptics, like risperidone, have not yet been studied in postoperative delirium, although some case reports in which they were successfully used have been published. Physiostigmine is effective in delirium caused by anticholinergic syndrome; vitamins may be useful in alcoholics; melatonin use has been suggested in order to prevent and treat delirium by normalizing sleep-wake cycle alterations. Environmental interventions are often costless and may be very useful to prevent and treat postoperative delirium in patients at risk.

Anti-Anxiety Agents↗

Prevention of delirium in hospitalized older patients: risk factors and targeted intervention strategies.

Delirium is a common, costly, and potentially devastating condition for hospitalized older patients. Delirium is a multifactorial syndrome, involving the inter-relationship between patient vulnerability, or predisposing factors at admission, and noxious insults or precipitating factors during hospitalization. Through a series of studies, we first identified significant predisposing factors for delirium, including vision impairment, severe illness, cognitive impairment, and dehydration. Subsequently, significant precipitating factors were identified, including physical restraint use, malnutrition, adding more than three drugs, bladder catheter use, and any iatrogenic event. Through targeting preventive strategies towards six identified risk factors in a controlled clinical trial, we were successful in the primary prevention of delirium. In 852 subjects, the incidence of delirium was significantly reduced in the intervention group compared with usual care (9.9% vs 15.0%, matched odds ratio: 0.60; 95% confidence interval: 0.39-0.92). The total number of days and episodes of delirium were also significantly reduced in the intervention group. Based on this work, evidence-based recommendations for delirium prevention are proposed. While not all cases of delirium will be preventable with this approach, unifying medical and epidemiological approaches to delirium represents a key advance essential to reducing the high morbidity and mortality associated with delirium in the older population.

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Consequences of not recognizing delirium superimposed on dementia in hospitalized elderly individuals.

OBJECTIVE: The purpose of this study was to describe the recognition and management of delirium in hospitalized patients with and without dementia. DESIGN: A descriptive, exploratory design was used with a convenience sample of 20 hospitalized older patients who were observed indepth using qualitative interviews and observations of 13 family members and 11 staff members. SETTING: This research was conducted on the medical-surgical units of a 550-bed, nonprofit, state-supported teaching hospital in the southeastern United States. The facility provides primary and tertiary care with five intensive care units and eight medical-surgical units. PARTICIPANTS: This study did not exclude individuals with dementia or pre-existing delirium. Subjects were not excluded on the basis of race or gender. Twenty patients in the sample underwent observation and mental and functional status testing. Thirteen family members and 11 staff members were interviewed and observed. MEASUREMENTS: In Phase 1 of the study, patients had daily mental status testing performed by the investigator. In Phase 2, family members and staff members were interviewed about the confusion event. For each patient, demographics and information regarding their health status and current diagnosis and treatment were obtained. The Mini-Mental State Examination (MMSE) and the Confusion Assessment Method were completed on each subject within 36 hours of being admitted to the hospital. The Cornell Depression Scale and Katz Activities of Daily Living scale were completed within 48 hours of admission. RESULTS: The prevalence of delirium in this study was 60%. The incidence, or new onset of delirium, was 30%. The presence of delirium was associated with new onset incontinence, lower baseline MMSE scores, depression, weight loss, and comorbidity. Of the eight individuals with delirium superimposed on dementia, 63% (n = 5) were re-admitted to the hospital within 30 days, compared to none of the individuals with delirium in the absence of dementia. Delirium superimposed on dementia also was less likely to be recognized by nurses and physicians. CONCLUSIONS: Delirium in individuals with dementia should be assessed and treated routinely because the failure to recognize delirium superimposed on dementia promptly has significant negative personal, social and financial consequences.

Activities of Daily Living↗

Severity and course of delirium in medically hospitalized nursing facility residents.

Delirium is a common and serious complication of medical illness in frail elderly patients. The authors report on a series of nursing facility delirium patients followed for 3 months during and after acute medical hospitalization. Delirium was persistent to time of death or hospital discharge in 72%. At 1 and 3 months, 55% and 25%, respectively, showed delirium. Mortality rate was high, with in-hospital and 3-month mortality rates of 18% and 47%, respectively. More severe delirium and failure to improve delirium while in the hospital were both associated with increased mortality. A purely hypoactive delirium vs. a hyperactive or mixed was associated with delirium persistence. Delirium is associated with high mortality and frequent persistence. Additional research is needed to clarify who is at risk for delirium with associated persistence and/or mortality.

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Systematic detection and multidisciplinary care of delirium in older medical inpatients: a randomized trial.

BACKGROUND: Delirium is common and often goes undetected in older patients admitted to medical services. It is associated with poor outcomes. We conducted a randomized clinical trial to determine whether systematic detection and multidisciplinary care of delirium in older patients admitted to a general medical service could reduce time to improvement in cognitive status. METHODS: Consecutive patients aged 65 or more who were newly admitted to 5 general medical units between Mar. 15, 1996, and Jan. 31, 1999, were screened with the Confusion Assessment Method within 24 hours after admission to detect prevalent delirium and rescreened within a week to detect incident cases. Patients with delirium were randomly allocated to receive the intervention or usual care. Subjects in the intervention group were seen by a geriatric specialist consultant and followed in hospital for up to 8 weeks by an intervention nurse who liaised with the consultant, attending physicians, family and the primary care nurses. Subjects in the usual care group received standard hospital services but could consult geriatric specialists as needed. A research assistant, blinded as to treatment allocation, administered within 24 hours after enrolment the MiniMental Status Exam (MMSE), Delirium Index (measuring the severity of the delirium) and Barthel Index (measuring independence of personal care). Improvement was defined as an increase in the MMSE score of 2 or more points, with no decrease below baseline plus 2 points, or no decrease below a baseline MMSE score of 27. A short form of the Informant Questionnaire on Cognitive Decline in the Elderly was completed to identify patients with possible dementia. Subjects were assessed 3 times during the first week and weekly thereafter for up to 8 weeks in hospital or until discharge. Data on clinical severity of illness, length of stay and living arrangements after discharge were also collected. The primary outcome measure was time to improvement in MMSE score. RESULTS: Of the 1925 patients who met the inclusion criteria and were screened, 227 had prevalent or incident delirium and consented to participate (113 in intervention group and 114 in usual care group). There were no clinically significant differences between the intervention and usual care groups except for sex (female 58.4% v. 50.0%) and marital status (married 34.8% v. 41.2%). Overall, 48% of the patients in the intervention group and 45% of those in the usual care group met the predetermined criteria for improvement. The Cox proportional hazards ratio (HR) for a shorter time to improvement with the intervention versus usual care, adjusted for age, sex and marital status, was 1.10 (95% confidence interval [CI] 0.74-1.63). There were no significant differences within 8 weeks after enrolment between the 2 groups in time to and rate of improvement of the Delirium Index, the Barthel Index, length of stay, rate of discharge to the community, living arrangements after discharge or survival. Outcomes between the 2 groups did not differ statistically significantly for patients without dementia (HR 1.54, 95% CI 0.80-2.97), for those who had less co-morbidity (HR 1.36, 95% CI 0.75-2.46) or for those with prevalent delirium (HR 1.15, 95% CI 0.48-2.79). INTERPRETATION: Systematic detection and multidisciplinary care of delirium does not appear to be more beneficial than usual care for older patients admitted to medical services.

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[Summary of the Dutch College of General Practitioners' practice guideline 'Delirium in elderly people'].

The Dutch College of General Practitioners' practice guideline 'Delirium in elderly people' contains a number of key messages. These are: Consider the diagnosis of delirium in the case of changes in consciousness and attention, incoherent thinking or disorientation, if this picture developed over a short period of time (hours to days) and if the symptoms vary over the 24-hour period. Delirium is provoked by one or more somatic disorders; investigation and treatment of these disorders is an essential part of managing delirium. It is often difficult to distinguish delirium from dementia and depression. Although delirium is generally reversible, the prognosis in the elderly is relatively poor. If delirium is accompanied by fear or agitation, haloperidol is the drug of first choice, but in delirium induced by alcohol withdrawal or benzodiazepine withdrawal, a short-acting benzodiazepine such as lorazepam or oxazepam is indicated. Part of the treatment, but also prevention of delirium is focused on inducing factors that can provoke a delirium, such as medication with an anticholinergic effect, polypharmacy, inadequate nutrition, dehydration, sleep deprivation, immobility and sensory handicaps.

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[Guideline 'Delirium'].

The Dutch Association of Psychiatry, together with the Dutch Association of Clinical Geriatrics and with methodological support from the Dutch Institute for Healthcare Improvement (CBO) has developed a guideline for the optimal diagnosis, treatment and prevention of delirium. Delirium is caused by somatic illness or the use of medication, drugs or alcohol. Delirium is common among the somatically ill admitted to a general hospital and is associated with increased morbidity and mortality. Important predisposing factors for delirium are: age > or =70 years, cognitive disturbances, sensory impairments, problems in daily activities, and the use of alcohol and opiates. Precipitating factors that may provoke delirium are: infection, fever, dehydration, serum electrolyte imbalance, polypharmacy, and the use of psychotropic medication, particularly anticholinergic drugs. Detection, diagnosis, and assessment of the severity of delirium are based on clinical examination, case history, observation, mental status examination including tests of cognitive function, and diagnosis of underlying somatic diseases. For daily practice, measurement tools are not necessary, nor are laboratory or imaging tests, such as electroencephalography. Haloperidol is the treatment of first choice for delirium due to somatic illness, except in patients with delirium due to drug use or medication, Parkinson's disease or Lewy body dementia. In cases of concurrent alcohol withdrawal syndrome, delirium may be treated with haloperidol and a benzodiazepine and B-vitamins. Medical and environmental interventions have been shown to reduce the incidence and duration of delirium.

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[A nine-year controlled follow-up study of delirium patients discharged after treatment in a psychogeriatric university department].

INTRODUCTION: Although delirium is a reversible cerebral syndrome, the effect of treatment of the elderly is unsatisfactory, involving prolonged hospitalizations and increased risk of relapse and mortality. The purpose of this study was to evaluate whether hospitalization for delirium (severe delirium) diagnosed by ICD-10 criteria predicts increased morbidity, utilization of health services and mortality. MATERIALS AND METHODS: Delirious inpatients (n = 26) discharged after treatment in an old-age psychiatric university clinic were studied for nine years. In a register-based design, the above-mentioned parameters of the delirium cohort were compared with a group of controls (n = 116). RESULTS: There was a trend to increased mortality in the delirium cohort. Compared with the controls, the delirium cohort had a significantly increased incidence of disorders of vital organs, serious psychiatric disorders, particularly depression, increased use of hospital psychiatry and general practitioner's out-of-hours service, but less use of office-hour services. The incidence of delirium in the cohorts was low. In the delirium cohort, there was no significantly increased use of services or the number of diagnoses in somatic hospitals. CONCLUSION: Increased somatic and psychiatric morbidity and a trend to increased mortality indicate a serious prognosis after severe delirium in the elderly. It is noteworthy that the delirium cohort had increased use of GPs' out-of-hours services but less use of office-hour services.

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Occurrence and impact of suspected delirium in hospitalized elderly patients.

The records of 95 consecutive people older than 65 years and admitted to a community hospital were retrospectively reviewed to determine the prevalence of undiagnosed delirium in hospitalized elderly patients. Chart review focused on identification of patients with documented diagnosed delirium according to Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R) criteria and patients with unrecognized delirium. Unrecognized delirium was considered present when information contained in a patient's chart met some or all criteria for delirium as described in DSM-III-R, but the physician's progress notes failed to indicate delirium as a diagnosed clinical entity. The prevalence of diagnosed delirium was 2%. Thirty-six percent of the patients were suspected of having unrecognized delirium. The mean length of hospital stay and the rate of mortality were significantly higher for patients with suspected delirium than for non-delirious patients. The findings of this study suggest that unrecognized delirium in the hospitalized elderly may occur frequently and is associated with an increased length of hospital stay and increased mortality.

Age Distribution↗

[A study of post-operative delirium in elderly patients].

We investigated the post-operative delirium in elderly patients of over 65 years of age. This investigation consisted of two studies, a prospective study and a retrospective study. In the prospective study, we evaluated the incidence of post-operative delirium and the incidence of post-operative delirium was estimated pre-operatively using State-Trait Anxiety Inventory (STAI) and Mini Mental State Examination (MMSE) in 24 patients scheduled for elective surgery under general anesthesia in the period from Nov. 1995 to Oct. 1996. In the retrospective study, we selected patients with post-operative delirium from 1600 patients who had undergone scheduled and emergency operation under general anesthesia in the same period as in the prospective study and analyzed the incidence of post-operative delirium and background of these patients. Twenty four patients in the prospective study were excluded from the retrospective study. In the prospective study, although post-operative delirium was observed in 2 cases (8.3%), no specific changes were observed in anxiety state and the ability of recognition. In the retrospective study, post-operative delirium was observed in 22 cases (1.37%). In these patients, several factors such as blood transfusion, emergency operation, dehydration, thrombosis of the superior mesenteric artery, history of ischemic heart disease, brain infarction and atrial fibrillation were thought to be major risk factors triggering post-operative delirium. In this study we could not conclude that STAI or MMSE are useful to estimate the incidence of post-operative delirium preoperatively. However, our result suggests that we should be careful about the incidence of post-operative delirium in elderly patients with pre-operative risk factors as mentioned above.

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Donepezil improves symptoms of delirium in dementia: implications for future research.

Delirium is a common complication of dementia and may produce considerable morbidity. In addition to psychotic symptoms such as hallucinations and delusions, delirium may produce considerable agitation, which may be refractory to conventional medications such as antipsychotics and benzodiazepines. The main approach to delirium is to treat any underlying medical problem that could cause the delirium. However, delirium is not always reversible, and there is no specific treatment for persistent delirium. The authors present a case of delirium complicating a preexisting dementia that resolved rapidly following initiation of the cholinesterase inhibitor donepezil, suggesting that cholinergic dysfunction may have played a role in the etiology of this patient's delirium. Future research needs to be directed at the issue of cholinergic activity in delirium through monitoring of serum anticholinergic activity and its response to procholinergic therapy.

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The role of adherence on the effectiveness of nonpharmacologic interventions: evidence from the delirium prevention trial.

BACKGROUND: The impact of adherence on outcome for a nonpharmacologic intervention strategy has not been previously examined. OBJECTIVE: To examine the impact of level of adherence on effectiveness of the intervention strategy in a large clinical trial of nonpharmacologic interventions to prevent delirium. METHODS: The subjects included 422 consecutive patients 70 years or older admitted to the medicine service at a university hospital. The intervention protocols were targeted toward 6 delirium risk factors. The primary outcome was new-onset delirium during hospitalization. RESULTS: During 9882 patient-days, complete adherence rates for individual intervention protocols ranged from 10% for the sleep protocol to 86% for the orientation protocol. The rate of complete adherence with all protocols was 57%, and combined partial and complete adherence was 87%. Higher levels of adherence resulted in lower delirium rates, with a significant graded effect, for orientation, mobility, and therapeutic activities protocols, and for the composite adherence measure. After controlling for potential confounding variables, such as illness severity, comorbidity, baseline delirium risk, and functional status, adherence continued to demonstrate a consistently strong and significant protective effect against delirium (adjusted odds ratio, 0.69; 95% confidence interval, 0.56-0.87). Patients in the highest adherence group demonstrated an 89% reduction in delirium risk compared with patients in the lowest group. CONCLUSIONS: Adherence played an important independent role in the effectiveness of a nonpharmacologic multicomponent intervention strategy. Higher levels of adherence resulted in reduced rates of delirium in a directly graded fashion, with extremely low levels of delirium in the highest adherence group. Thus, adherence must be ensured in nonpharmacologic interventions to optimize effectiveness.

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Clinical subtypes of delirium and their relevance for daily clinical practice: a systematic review.

BACKGROUND: Delirium is a disorder that besides four essential features consists of different combinations of symptoms. We reviewed the clinical classification of clusters of symptoms in two or three delirium subtypes. The possible implications of this subtype classification may be several. The investigation and exploration of clinical subtypes of delirium may provide information concerning the etiology, the pathogenesis, and the prognosis of delirium, but also may have therapeutic consequences. METHODS: We searched several database for English-language articles. Selected articles were cross-checked for other relevant publications. DATA SYNTHESIS AND CONCLUSION: We conducted a systematic review and retrieved ten clinical studies. The studies described in this review show different results, partly due to methodological problems and possibly by lack of a standard classification for delirium subtypes. According to the present literature a useful and reproducible method to classify (patterns of) symptoms in delirium subtypes seems to be the general rating of and division in to psychomotor subtypes. The Memorial Delirium Assessment Scale (MDAS) and the Dublin Delirium Assessment Scale (DAS) appear to be reliable methods, together with the new version of the Delirium Rating Scale (DRS-R-98).

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Risk factors for delirium tremens development.

OBJECTIVE: To identify clinical characteristics associated with inpatient development of delirium tremens so that future treatment efforts can focus on patients most likely to benefit from aggressive therapy. DESIGN: Retrospective cohort study among patients discharged with diagnoses related to alcohol abuse. SETTING: University-affiliated inner-city hospital. PATIENTS/PARTICIPANTS: Two hundred consecutive patients discharged between June 1991 and August 1992 who underwent evaluation and treatment for alcohol withdrawal or detoxification. MEASUREMENTS AND MAIN RESULTS: Mean age was 41.9 years, 85% were male, 57% were white and 84% were unmarried. Forty-eight (24%) of the patients developed delirium tremens during hospitalization. Bivariate analysis indicated that those who developed delirium tremens were more likely to be African-American, unemployed, and homeless, and were more likely to have gone more days since their last drink, and to have concurrent acute medical illness, high admission blood urea nitrogen level and respiratory rate, and low admission albumin level and systolic blood pressure. In multiple logistic regression analyses, patients who developed delirium tremens were more likely to have gone more days since their last drink (odds ratio [OR] 1.3; 95% confidence interval [CI] 1.09, 1.61) and to have concurrent acute medical illness (OR 5.1; 95% CI 2.07, 12.55). These risk factors were combined for assessment of their ability to predict the occurrence of delirium tremens. If no factors were present, 9% developed delirium tremens; if one factor was present, 25% developed delirium tremens; and if two factors were present, 54% developed delirium tremens. CONCLUSIONS: Inpatient development of delirium tremens was common among patients treated for alcohol detoxification or withdrawal and correlated with several readily available clinical variables.

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[Delirium increases morbidity and length of stay after vascular surgery operations. Results of a prospective study].

OBJECTIVE: We intended to analyze the influence of postoperative delirium on postoperative morbidity and length of hospital stay. PATIENTS AND METHOD: 153 patients undergoing elective arterial surgery were studied prospectively. Patients were examined postoperatively by a psychiatrist daily from days 1 to 7. Delirium was diagnosed according to standardised criteria (Diagnostic and Statistical Manual of Mental Disorders). The severity of delirium was quantified using the Delirium Rating Scale. We compared patients without delirium to those who developed postoperative delirium using univariate statistical analysis (t-test, chi (2) test, and Fisher's test). RESULTS: Sixty patients (39.2%) developed postoperative delirium. They removed catheters significantly more frequently than patients without delirium and had more catheter-related infections. Their length of stay in intensive care units was higher, as was their total postoperative length of stay in hospital. CONCLUSIONS: Patients who developed postoperative delirium have significantly more complications and increased postoperative length of stay in hospital and intensive care units.

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