Association of Carotid Plaque and Serum Lipoprotein-Associated Phospholipase A2 (LP-PLA2) with Postoperative Delirium in Geriatric Patients Undergoing Hip Replacement: A Prospective Cohort Study.

BACKGROUND The aim of this study was to investigate the relationships among carotid plaque (CP), serum lipoprotein-associated phospholipase (LP-PLA2), and POD in elderly patients. MATERIAL AND METHODS Sixty-two elderly patients undergoing hip replacement with spinal-epidural anesthesia were divided into CP and non-CP groups based on the preoperative presence or absence of carotid atherosclerotic plaques, as assessed by ultrasound. POD was diagnosed by means of the Confusion Assessment Method (CAM). Blood samples were collected (preoperatively, postoperatively, and postoperative day 2) for the assessment of serum LP-PLA2 by enzyme-linked immunosorbent assay. The CP group was further divided into POD and no-POD subgroups based on the occurrence of POD. RESULTS The incidence of POD was higher in the CP group than in the non-CP group (P0.05), it was higher in the CP group than in the non-CP group postoperatively and on postoperative day 2 (P0.05), but was significantly higher in the POD subgroup than in the no-POD subgroup on postoperative day 2 (P<0.05). Furthermore, the LP-PLA2 level on postoperative day 2 was an independent risk factor for POD (odds ratio: 1.03, 95% confidence interval: 1.00-1.07). CONCLUSIONS The preoperative presence of carotid plaque is closely associated with a higher incidence of POD. The potential mechanism may involve the increased expression of LP-PLA2 in the serum, which can lead to plaque destabilization and subsequent inflammatory cascades.

Cholinesterase alterations in delirium after cardiosurgery: a German monocentric prospective study.

OBJECTIVES: Postoperative delirium (POD) is a common complication after elective cardiac surgery. Recent evidence indicates that a disruption in the normal activity of the cholinergic system may be associated with delirium. DESIGN: Prospective observational study. SETTING: Single-centre at a European academic hospital. PRIMARY AND SECONDARY OUTCOME MEASURES: In our study the enzyme activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined preoperatively as well as on the first and second postoperative day. The confusion assessment method for the intensive care unit was used to screen patients for the presence of POD. RESULTS: A total of 114 patients were included in the study. POD was associated with a decrease in BChE activity on postoperative day 1 (p=0.03). In addition, patients who developed POD, had significantly lower preoperative AChE activity than patients without POD (p<0.01). Multivariate analysis identified a preoperatively decreased AChE activity (OR 3.1; 95% CI 1.14 to 8.46), anticholinergic treatment (OR 5.09; 95% CI 1.51 to 17.23), elevated European System for Cardiac Operative Risk Evaluation (OR 3.68; 95% CI 1.04 to 12.99) and age (OR 3.02; 95% CI 1.06 to 8.62) to be independently associated with the development of POD. CONCLUSIONS: We conclude that a reduction in the acetylcholine hydrolysing enzyme activity in patients undergoing cardiac surgery may correlate with the development of POD.

Acetylcholinesterase Activity Measurement and Clinical Features of Delirium.

AIMS: Cholinergic deficiency is commonly implicated in the pathophysiology of delirium. We aimed to investigate the relationship between directly measured serum acetylcholinesterase (AChE) activity and (1) clinical features of delirium and (2) outcomes among older hospital patients with delirium. METHODS: Hospitalised patients with delirium were recruited, and delirium motor subtype, severity and duration of delirium were measured. Serum AChE activity was measured using a colorimetric assay. RESULTS: The mean AChE activity for the whole sample was 2.46 µmol/µL/min (standard deviation 1.75). Higher AChE activity was associated with increased likelihood of hypoactive delirium rather than the hyperactive or mixed subtype (odds ratio 1.98, 95% confidence interval 1.10-3.59). CONCLUSION: Higher AChE activity was associated with hypoactive delirium but did not predict outcomes. Simple enhancement of cholinergic neurotransmission may not be sufficient to treat delirium.

Involvement of the NADPH Oxidase NOX2-Derived Brain Oxidative Stress in an Unusual Fatal Case of Cocaine-Related Neurotoxicity Associated With Excited Delirium Syndrome.

Here, we investigated the possible role of the Nicotinamide Adenine Dinucleotide Phosphate oxidase NOX2-derived brain oxidative stress in a fatal case of cocaine-related neurotoxicity, associated to excited delirium syndrome. We detected a strong NOX2 immunoreactivity, mainly in cortical GABAergic neurons and astrocytes, with a minor presence in microglia, glutamatergic and dopaminergic neurons as well as a significant immunostaining for other markers of oxidative stress (8OhDG, HSP70, HSP90, and NF-κB) and apoptotic phenomena. These results support a crucial role of NOX2-derived brain oxidative stress in cocaine-induced brain dysfunctions and neurotoxicity.

The Impact of Plasma Cholinergic Enzyme Activity and Other Risk Factors for the Development of Delirium in Patients Receiving Palliative Care.

CONTEXT: Delirium is an important complication in palliative care patients. One of the potential risk factors for cognitive disorders is deterioration in cholinergic neurotransmission. Anticholinergic medications are known to be important owing to the association of their metabolites with significant morbidity, which is often the result of cumulative effects of medications (anticholinergic burden). Additionally, cholinergic enzymes are possible candidates reflecting the cholinergic situation in patients. However, the role of cholinesterases (CHE) for delirium in palliative care patients is unknown. OBJECTIVES: Following local Ethics Board approval and written informed consent, we recruited a cohort of patients who had been admitted to the Heidelberg University Palliative Care Unit related to CHE and other factors at risk for delirium. METHODS: Delirium was assessed using the Nursing Delirium Screening Scale once daily in all cancer patients (N = 100) during their stay on the palliative care unit. In a subgroup of 69 probes, blood samples were analyzed for acetyl- and butyrylcholinesterase activity spectrophotometrically. Furthermore, patients' medications were recorded. Logistic regression analysis was used to evaluate potential predictors of delirium. RESULTS: Delirium was identified in 29% of patients. Karnofsky Performance Status Scale score was significantly lower (P = 0.021) and mortality higher (P = 0.018) in patients with delirium. Plasma CHE activity was not associated with delirium. However, a significant effect of anticholinergic medication on plasma CHE activity was detected; so far midazolam (P = 0.01) seems to play an important role in that process. CONCLUSION: Special care might be necessary with anticholinergic medication to minimize risk for delirium in palliative cancer patients.

Incidence of cholinesterase inhibitor therapy initiation among hospitalized patients.

BACKGROUND: Initiation of cholinesterase inhibitor (ChEI) therapy for delirium during hospitalization is ineffective and may be associated with increased morbidity and mortality. OBJECTIVE: To describe the incidence of initiating ChEI therapy during hospitalization. DESIGN: A retrospective cross-sectional study. SETTING: A tertiary-care academic medical center. PATIENTS: Inpatient admissions from September 2010 through March 2011 with ChEI administration. INTERVENTION: None. MEASUREMENTS: Incidence of ChEI exposure, initiation of ChEI therapy, initiation of antipsychotics and benzodiazepines, infection, in-hospital mortality, and hospital length of stay. RESULTS: The incidence of adult admissions with ChEI exposure and ChEI initiation was 23.2 (95% confidence interval: 21.2-25.4) and 2 (95% confidence interval 1.5-2.8) per 1000 admissions, respectively. Of 476 admissions receiving ChEI, 9% (n = 42) initiated therapy during the hospital stay and 91% (n = 434) continued on previously started therapy. Patients initiated on ChEI therapy frequently had infection (20 of 42) and were commonly initiated on antipsychotics (14 of 42) and benzodiazepines (13 of 42). Patients were hospitalized for a median of 2 days (interquartile range, 1-4) before initiation of ChEI and were exposed to therapy for a median of 3 days (interquartile range, 2-6). Of the 41 patients discharged from the hospital, 90% (n = 37) had orders to continue the ChEI postdischarge. CONCLUSIONS: Despite a lack of evidence to support the practice, 9% of patients who received ChEI therapy were initiated during the inpatient setting. These patients were not routinely screened for delirium and frequently received treatments associated with delirium.

Polymorphisms in the catechol-o-methyltransferase gene and delirium in the elderly.

BACKGROUND/AIMS: Catechol-O-methyltransferase, encoded by the COMT gene, is one of the enzymes that degrade dopamine. The aim of this study was to investigate whether polymorphisms in the COMT gene were associated with delirium. METHODS: Patients aged 65 years and older, acutely admitted to the medical department or to the surgical department following hip fracture, were included. rs4680, rs4818, and rs6269 were genotyped. RESULTS: Delirious patients were older, and more frequently had preexisting functional or cognitive impairment (p < 0.001). Polymorphisms in the COMT gene were not associated with the development of delirium. CONCLUSION: Although the COMT gene is a promising candidate gene for delirium in the elderly, functional genetic variations were not associated with delirium.

Altered mental status from olanzapine overdose treated with physostigmine.

BACKGROUND: Olanzapine is commonly prescribed to patients with schizophrenia. One retrospective study demonstrates the efficacy of physostigmine in reversing mental status changes induced by olanzapine. We report two patients with delirium due to confirmed olanzapine overdose treated with physostigmine. One patient's mental status transiently returned to normal. The other patient completely recovered. CASE 1: A 25-year-old man ingested 300 mg of olanzapine. On presentation, he was agitated, delirious, tachycardic, had dry skin and mucous membranes, and dilated pupils (6 mm) minimally reactive to light. Physostigmine, 0.5 mg, was given intravenously (IV) without effect. Additional physostigmine doses of 1.5 mg IV administered 5 minutes later and then 1 mg IV resulted in the patient having a clear sensorium and normal mentation. The patient's mental status continued to remain normal for the duration of his hospital stay. Olanzapine was identified in the urine by high performance liquid chromatography. CASE 2: A 20-year-old female ingested 600 mg of olanzapine. On presentation, she was tachycardic, obtunded, and minimally responsive to painful stimuli, with decreased bowel sounds, dry skin and dry mucous membranes. Physostigmine, 2 mg, was given IV. Shortly thereafter she regained full consciousness and began speaking coherently. She remained in this condition for approximately 30 minutes, and then became obtunded. Her serum olanzapine concentration was 1230 ng/mL. No further doses of physostigmine were administered. On day 3 of admission her mental status returned to normal. CONCLUSION: We report two cases of olanzapine-induced mental status changes treated with physostigmine. The utility of physostigmine as a safe or necessary antidote in the setting of olanzapine overdose remains to be determined.

Enzymes of drug metabolism during delirium.

BACKGROUND: Delirium is common in ill medical patients. Several drugs and polypharmacy are recognised risk factors, yet little is known about drug metabolism in people with delirium. OBJECTIVE: The aim of this study was to investigate the activities of plasma esterases (drug metabolising enzymes) in delirium. DESIGN: This was a prospective study of delirium present at time of hospital admission (community acquired) or developing later (hospital acquired) in patients admitted as a medical emergency and aged 75 years or over. METHODS: Following informed consent or assent cognitive screening was completed on all patients on admission and every 48 hours subsequently. Delirium was diagnosed by Confusion Assessment Method and DSM IV criteria. Blood samples were taken on admission and at onset of delirium if this was later. Four plasma esterase assays were performed spectrophotometrically: acetylcholinesterase, aspirin esterase, benzoylcholinesterase, butyrylcholinesterase. RESULTS: 283 patients (71% of eligible) were recruited, with mean age 82.4 years and 59% female. 27% had community acquired delirium, 10% developed hospital acquired delirium, 63% never developed delirium. On admission the mean activities of all four esterase assays were statistically significantly lower in delirious than non delirious patients. There were no significant differences on admission in any plasma esterase activity between patients with hospital and community acquired delirium. In-hospital mortality was associated with low plasma esterase activities on admission. CONCLUSION: Plasma esterase activities are suppressed during delirium. These data reinforce the need for extreme caution with drugs in this vulnerable population.

A long-term follow-up study of cerebrospinal fluid acetylcholinesterase in delirium.

Cerebrospinal fluid acetylcholinesterase (CSF AChE) was determined for elderly delirious patients during the acute stage and after a 1- and 4-year follow-up periods, and the AChE levels were compared with age-equivalent controls. The AChE levels measured during the index admission correlated with the length of life after delirium, suggesting that cholinergic dysfunction may have prognostic significance in delirious patients. Although the CSF AChE concentrations measured during the index admission were in the same range as in controls, we observed a declining trend in patients with various structural brain diseases during the follow-up period. The decreasing levels may reflect the progression of the underlying dementia in these patients.