Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness

BACKGROUND: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS: In 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. RESULTS: Written 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. CONCLUSIONS: The 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 .)

Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids - More common than expected?

Background: Hypothalamic pituitary adrenal axis suppression (HPAS) when treating asthmatic children with inhaled corticosteroids (ICS) is thought to be rare. Objective: To determine the prevalence of HPAS in asthmatic children treated with ICS and nasal steroids (NS). Methods: Twenty-six asthmatic children were recruited. Clinical features of HPAS, height, weight, height and weight velocity, steroid dose, adherence, symptom control and lung functions were documented. Metyrapone test was performed if the serum cortisol was >83 nmol/L (>3 μg/dL). Results: No child had a serum cortisol <83 nmol/L (<3 μg/dL). Prevalence of HPAS was 35 (CI=17%-56%). Daily NS dose/m 2 and cumulative NS dose/m2 were significantly (p=0.03) inversely correlated with the post-metyrapone ACTH (r=-0.42 for both). Current ICS dose was not associated with the post-metyrapone ACTH (r=0). There was a weak correlation with the daily ICS dose/m2(r=-0.12) and cumulative ICS dose/m2 (r=-0.26). Conclusions: A third of asthmatic children on ICS and NS develop HPAS. Contributing factors are the use of NS, body size and cumulative dose of ICS. © 2011 by Walter de Gruyter Berlin Boston.Articl

Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids: Is the early-morning serum adrenocorticotropic hormone (ACTH) a useful screening test?

Background: Hypothalamic-pituitary-adrenal axis suppression (HPAS) in asthmatic children treated with inhaled corticosteroids (ICS), with or without nasal steroids (NS), may be more common than previously thought. Only dynamic testing will identify children at risk of adrenal crisis. It is impractical to test all asthmatic children for HPAS with a gold standard adrenal function test, i.e. the metyrapone or insulin tolerance test. Objective: To determine which clinical or biochemical parameter is the most useful screening test for HPAS in asthmatic children. Methods: Twenty-six asthmatic children, 5-18yr old, on ICS±NS, not treated with oral or topical steroids in the preceding year were recruited. Height, weight, height velocity, weight velocity and a change in systolic blood pressure from the recumbent to the standing position (ΔSBP) were recorded. Early-morning urine for urinary free cortisol (UFC) and urinary cortisol metabolites (UCM) was collected. UFC was analysed by both a chemiluminescent assay and gas chromatography/mass spectrometry (GC-MS). Morning serum cortisol and adrenocorticotropic hormone (ACTH) levels were measured. The overnight metyrapone test was performed if the fasting morning serum cortisol was >83nmol/l. HPAS was diagnosed if the ACTH failed to rise >100pg/ml after metyrapone. Spearman correlation coefficients ® were calculated between the post-metyrapone ACTH and each variable. A receiver-operating characteristics (ROC) curve was drawn for the most promising test, and the diagnostic performance was calculated. Results: All clinical and biochemical parameters investigated were weakly and non-significantly correlated with the post-metyrapone ACTH, except for the morning serum ACTH (r=0.68; p<0.001). The best discrimination between those who have and those who do not have HPAS is a morning serum ACTH level of 11.7pg/ml. This corresponds to a sensitivity of 0.89 (0.57-0.98), a specificity of 0.77 (0.53-0.90), a positive predictive value of 0.67 (0.39-0.87), a negative predictive value of 0.93 (0.69-0.99), an accuracy of 0.81 (0.61-0.94), a positive likelihood ratio of 3.78 (1.68-9.49) and a negative likelihood ratio of 0.15 (0.03-0.60). Conclusions: The morning serum ACTH level was found to be the most useful screening test to detect HPAS in this sample of children receiving ICS±NS. A larger study should be undertaken to refine the diagnostic precision of the morning serum ACTH level. © 2011 John Wiley & Sons A/S.Articl

Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids: Is the early-morning serum adrenocorticotropic hormone (ACTH) a useful screening test?

Background: Hypothalamic-pituitary-adrenal axis suppression (HPAS) in asthmatic children treated with inhaled corticosteroids (ICS), with or without nasal steroids (NS), may be more common than previously thought. Only dynamic testing will identify children at risk of adrenal crisis. It is impractical to test all asthmatic children for HPAS with a gold standard adrenal function test, i.e. the metyrapone or insulin tolerance test. Objective: To determine which clinical or biochemical parameter is the most useful screening test for HPAS in asthmatic children. Methods: Twenty-six asthmatic children, 5-18yr old, on ICS±NS, not treated with oral or topical steroids in the preceding year were recruited. Height, weight, height velocity, weight velocity and a change in systolic blood pressure from the recumbent to the standing position (ΔSBP) were recorded. Early-morning urine for urinary free cortisol (UFC) and urinary cortisol metabolites (UCM) was collected. UFC was analysed by both a chemiluminescent assay and gas chromatography/mass spectrometry (GC-MS). Morning serum cortisol and adrenocorticotropic hormone (ACTH) levels were measured. The overnight metyrapone test was performed if the fasting morning serum cortisol was >83nmol/l. HPAS was diagnosed if the ACTH failed to rise >100pg/ml after metyrapone. Spearman correlation coefficients ® were calculated between the post-metyrapone ACTH and each variable. A receiver-operating characteristics (ROC) curve was drawn for the most promising test, and the diagnostic performance was calculated. Results: All clinical and biochemical parameters investigated were weakly and non-significantly correlated with the post-metyrapone ACTH, except for the morning serum ACTH (r=0.68; p<0.001). The best discrimination between those who have and those who do not have HPAS is a morning serum ACTH level of 11.7pg/ml. This corresponds to a sensitivity of 0.89 (0.57-0.98), a specificity of 0.77 (0.53-0.90), a positive predictive value of 0.67 (0.39-0.87), a negative predictive value of 0.93 (0.69-0.99), an accuracy of 0.81 (0.61-0.94), a positive likelihood ratio of 3.78 (1.68-9.49) and a negative likelihood ratio of 0.15 (0.03-0.60). Conclusions: The morning serum ACTH level was found to be the most useful screening test to detect HPAS in this sample of children receiving ICS±NS. A larger study should be undertaken to refine the diagnostic precision of the morning serum ACTH level. © 2011 John Wiley & Sons A/S.Articl

Glass compositions suitable for PFR wastes Annual Progress Report 1986-87

5.25Available from British Library Document Supply Centre- DSC:9091.9F(AERE-G--4618) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Glass compositions suitable for PFR wastes Annual Progress Report 1985-86

Available from British Library Document Supply Centre- DSC:9091.9F(AERE-G--4393) / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo