Diabetes and Glucose Dysregulation and Transition to Delirium in ICU Patients.

OBJECTIVES: To investigate whether diabetes and glucose dysregulation (hyperglycemia and/or hypoglycemia) are associated with ICU delirium. DESIGN: Prospective cohort study. SETTING: Thirty-two-bed mixed intensive care in a tertiary care center. PATIENTS: Critically ill patients admitted to the ICU with transitions of mental status from awake and nondelirious to delirious or remaining awake and nondelirious on the next day. Patients admitted because of a neurologic illness were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study population consisted of 2,745 patients with 1,720 transitions from awake and nondelirious to delirious and 11,421 nontransitions remaining awake and nondelirious. Generalized mixed effects models with logit link function were performed to study the association between diabetes mellitus, glucose dysregulation, and delirium, adjusting for potential confounders. Diabetes was not associated with delirium (odds ratio adjusted, 0.93; 95% CI, 0.73-1.18). In all patients, the occurrence of hyperglycemia (odds ratio adjusted, 1.35; 95% CI, 1.15-1.59) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.65; 95% CI, 1.12-2.28) compared with normoglycemia were associated with transition to delirium. Hypoglycemia was not associated with transition to delirium (odds ratio adjusted, 1.86; 95% CI, 0.73-3.71). In patients without diabetes, the occurrence of hyperglycemia (odds ratio adjusted, 1.41; 95% CI, 1.16-1.68) and the occurrence of both hyperglycemia and hypoglycemia on the same day (odds ratio adjusted, 1.87; 95% CI, 1.07-2.89) were associated with transition to delirium. In patients with diabetes, glucose dysregulation was not associated with ICU delirium. CONCLUSIONS: Diabetes mellitus was not associated with the development of ICU delirium. For hypoglycemia, only a nonsignificant odds ratio for ICU delirium could be noted. Hyperglycemia and the occurrence of hyperglycemia and hypoglycemia on the same day were associated with ICU delirium but only in patients without diabetes. Our study supports the institution of measures to prevent glucose dysregulation in nondiabetic ICU patients and contributes to the understanding of the determinants of delirium.

Prophylactic Use of Haloperidol and Changes in Glucose Levels in Hospitalized Older Patients.

BACKGROUND: Treatment with antipsychotic drugs has been associated with glucose dysregulation in older outpatients, especially in the early stage of therapy. The underlying mechanism is, however, unclear. The aim of this study was to investigate changes in glucose levels during haloperidol use compared with the use of placebo among older hospitalized patients. METHODS: This substudy was part of a larger multicenter, randomized, double blind, placebo-controlled clinical trial among hospitalized patients aged 70 years and older who had an increased risk of in-hospital delirium. Patients who were admitted to the Jeroen Bosch Hospital in 's-Hertogenbosch between June 2014 and February 2015 were invited to participate in the study. Participating patients were randomized for treatment and given 1 mg of haloperidol or a placebo twice daily for a maximum of 7 consecutive days (14 doses). Exclusion criteria for this substudy were the use of corticosteroids and changes in diabetes medication. Random blood samples to determine glucose levels were collected before day 1 and on day 6 of the study. Student independent sample t test was used to determine differences in glucose changes between both groups. RESULTS: Twenty-nine patients were included (haloperidol, n = 14; placebo, n = 15). The mean glucose level for placebo users was 139.3 mg/dL (SD, 50.1) on day 1 and 140.8 mg/dL (SD, 45.7) on day 6, and the mean glucose level for haloperidol users was 139.9 mg/dL (SD, 71.0) on day 1 and 150.2 mg/dL (SD, 39.1) on day 6. The difference was not statistically significant (P = 0.685). CONCLUSIONS: Short-term prophylactic use of haloperidol was not associated with changes in glucose levels in older hospitalized patients compared with those given a placebo in this small study.

Risk of Hospitalization for Hypoglycemia in Older Patients with Diabetes Using Antipsychotic Drugs.

OBJECTIVE: Antipsychotics may disrupt metabolic regulation in patients with diabetes mellitus. The risk of hypoglycemia in older users of antipsychotics with diabetes is largely unknown. Therefore, we investigated the association between the use of antipsychotic drugs and hypoglycemia requiring hospital admission in older patients with diabetes. METHODS: In a nested case-control study using community pharmacy records linked to hospital admission data in the Netherlands (1998-2008), a cohort of 68,314 patients at least 65 years with diabetes was studied. Cases were patients from the study cohort with a first hospital admission for hypoglycemia; up to five comparison subjects were selected for each case. Exposure to antipsychotic drugs was the primary determinant of interest. Logistic regression analysis was performed to estimate the strength of the association between antipsychotic drug use and hypoglycemia, taking into account potential confounders. RESULTS: Eight hundred fifteen patients were admitted to hospital for hypoglycemia. Current use of antipsychotic drugs was associated with an increased risk of hypoglycemia compared with non-use (adjusted OR: 2.26; 95% CI: 1.45-3.52; Wald χ(2) = 13.08, df = 1, p ≤0.001), especially in the first 30 days of treatment (adjusted OR: 7.65; 95% CI: 2.50-23.41; Wald χ(2) = 12.72, df = 1, p ≤0.001) and with higher doses (adjusted OR: 8.20; 95% CI: 3.09-21.75; Wald χ(2) = 17.90, df = 1, p ≤0.001). CONCLUSION: Use of antipsychotic drugs by older patients with diabetes mellitus was associated with an increased risk of hospitalization for hypoglycemia. Our findings suggest that glucose levels should be monitored closely after initiation of antipsychotic drugs.

Polypharmacy, comorbidity and frailty: a complex interplay in older patients at the emergency department.

PURPOSE: Older adults at the emergency department (ED) with polypharmacy, comorbidity, and frailty are at risk of adverse health outcomes. We investigated the association of polypharmacy with adverse health outcomes, in relation to comorbidity and frailty. METHODS: This is a prospective cohort study in ED patients ≥ 70 years. Non-polypharmacy was defined as 0-4 medications, polypharmacy 5-9 and excessive polypharmacy ≥ 10. Comorbidity was classified by the Charlson comorbidity index (CCI). Frailty was defined by the Identification of Seniors At Risk-Hospitalized Patients (ISAR-HP) score. The primary outcome was 3-month mortality. Secondary outcomes were readmission to an ED/hospital ward and a self-reported fall < 3 months. The association between polypharmacy, comorbidity and frailty was analyzed by logistic regression. RESULTS: 881 patients were included. 43% had polypharmacy and 18% had excessive polypharmacy. After 3 months, 9% died, 30% were readmitted, and 21% reported a fall. Compared with non-polypharmacy, the odds ratio (OR) for mortality ranged from 2.62 (95% CI 1.39-4.93) in patients with polypharmacy to 3.92 (95% CI 1.95-7.90) in excessive polypharmacy. The OR weakened after adjustment for comorbidity: 1.80 (95% CI 0.92-3.52) and 2.32 (95% CI 1.10-4.90). After adjusting for frailty, the OR weakened to 2.10 (95% CI 1.10-4.00) and OR 2.40 (95% CI 1.15-5.02). No significant association was found for readmission or self-reported fall. CONCLUSIONS: Polypharmacy is common in older patients at the ED. Polypharmacy, and especially excessive polypharmacy, is associated with an increased risk of mortality. The observed association is complex given the confounding effect of comorbidity and frailty.

Glucose variability during delirium in diabetic and non-diabetic intensive care unit patients: A prospective cohort study.

PURPOSE: To determine whether glucose variability is altered during delirium days compared to non-delirious days in critically ill patients with and without diabetes in the intensive care unit (ICU). MATERIALS AND METHODS: Critically ill patients with delirious and non-delirious days during ICU stay were included from a prospective cohort study which was conducted from January 2011- June 2013. Glucose variability was measured each observation day using various definitions (change in mean glucose, standard deviation, mean absolute glucose, daily delta and occurrence of hypo- and hyperglycemia). Mixed-effects models and generalized mixed-effects models with logit link function were performed to study the association between delirium and glucose variability, adjusting for potential confounders. RESULTS: With the exception of the risk of hypoglycemia, delirium was not linked to higher glucose variability using the various definitions of this estimate. For hypoglycemia, we did find an association with delirium in diabetic patients (OR adj.: 2.78; 95% CI: 1.71-6.32, p = 0.005), but not in non-diabetic patients (OR adj.: 1.16; 95% CI: 0.58-2.28, p = 0.689). CONCLUSIONS: Despite the positive association between delirium and hypoglycemia in critically ill patients with diabetes, delirium was not associated with more pronounced glucose variability. Our findings suggest that glucose levels should be monitored more closely in diabetic patients during delirium at the ICU to prevent hypoglycemia.

[Acute agranulocytosis from thiamazole: points for improvement in daily practice]. / Acute agranulocytose bij thiamazolgebruik: verbeterpunten voor de dagelijkse praktijk.

Agranulocytosis is a rare but dreaded side-effect of thiamazole. A 61-year-old woman presented at the emergency department with fever and dyspnoea. Because she had recently started therapy with thiamazole for hyperthyroidism, a case of agranulocytosis was feared. Laboratory findings did indeed reveal an absolute neutrophil count of zero. Broad-spectrum antibiotics were given immediately, granulocyte-colony stimulating factor was started and she was admitted to the ICU for supportive care. Unfortunately, she died a day after admission. In this case report, we wanted to place the focus on the importance of this severe side-effect. We emphasize the value of warning the patient, preferably in writing, about the risk of agranulocytosis. We also draw attention to the fact that every doctor must know about agranulocytosis. In this case, the patient consulted her family doctor because she had a sore throat and fever, but was admitted to the hospital only three days after the onset of the symptoms. We believe the risk of agranulocytosis should be understood by every doctor and that the publication of many cases such as this could help heighten general awareness of possibly fatal side-effects like agranulocytosis.