Long-Term Self-Reported Cognitive Problems After Delirium in the Intensive Care Unit and the Effect of Systemic Inflammation.

OBJECTIVES: To describe the association between intensive care unit (ICU) delirium and self-reported cognitive problems in 1-year ICU survivors, and investigate whether this association was altered by exposure to systemic inflammation during ICU stay. DESIGN: Prospective cohort study. SETTING: Dutch medical-surgical ICU. PARTICIPANTS: One-year ICU survivors, admitted to the ICU ≥48 hours. MEASUREMENTS: Self-reported cognitive problems were measured with the Cognitive Failures Questionnaire (CFQ). Cumulative exposure to systemic inflammation was based on all daily C-reactive protein (CRP) measurements during ICU stay, expressed as the area under the curve (AUC). Multivariable linear regression was conducted to evaluate the association between delirium and the CFQ. The effect of inflammation on the association between delirium and CFQ was assessed, comparing the effect estimate (B) of delirium and CFQ between models with and without inclusion of the AUC of CRP. RESULTS: Among 567 1-year ICU survivors, the CFQ was completed by 363 subjects. Subjects with multiple days of delirium during ICU stay reported more self-reported cognitive problems (Badj = 5.10, 95% CI 1.01-9.20), whereas a single day delirium was not associated with higher CFQ scores (Badj = -0.72, 95% CI -5.75 to 4.31). Including the AUC of CRP did not change the association between delirium and the CFQ (ratio for a single and multiple days were respectively: 1.00, 95%CI 0.59-1.44 and 0.86, 95% CI 0.47-1.16). CONCLUSION: Multiple days of delirium was associated with long-term self-reported cognitive problems. The cumulative exposure to systemic inflammation did not alter this association, suggesting that delirium in the context of little inflammation is also detrimental.

Long-Term Mental Health Problems After Delirium in the ICU.

OBJECTIVES: To determine whether delirium during ICU stay is associated with long-term mental health problems defined as symptoms of anxiety, depression, and posttraumatic stress disorder. DESIGN: Prospective cohort study. SETTING: Survey study, 1 year after discharge from a medical-surgical ICU in the Netherlands. PATIENTS: One-year ICU survivors of an ICU admission lasting more than 48 hours, without a neurologic disorder or other condition that would impede delirium assessment during ICU stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One year after discharge, ICU survivors received a survey containing the Hospital Anxiety and Depression Scale with a subscale for symptoms of depression and a subscale for symptoms of anxiety, and the Impact of Event Scale 15 item measuring symptoms of posttraumatic stress disorder. Participants were classified as having experienced no delirium (n = 270; 48%), a single day of delirium (n = 86; 15%), or multiple days of delirium (n = 211; 37%) during ICU stay. Log-binomial regression was used to assess the association between delirium and symptoms of anxiety, depression, and posttraumatic stress disorder. The study population consisted of 567 subjects; of whom 246 subjects (43%) reported symptoms of anxiety (Hospital Anxiety and Depression Scale with a subscale for anxiety, ≥ 8), and 254 (45%) symptoms of depression (Hospital Anxiety and Depression Scale with a subscale for depression, ≥ 8). In 220 patients (39%), the Impact of Event Scale 15 item was greater than or equal to 35, indicating a high probability of posttraumatic stress disorder. There was substantial overlap between these mental health problems-63% of the subjects who scored positive for the presence of any three of the mental health problems, scored positive for all three. No association was observed between either a single day or multiple days of delirium and symptoms of anxiety, depression, or posttraumatic stress disorder. CONCLUSIONS: Although symptoms of anxiety, depression, and posttraumatic stress disorder were found to be common 1 year after critical illness, the occurrence of delirium during ICU stay did not increase the risk of these long-term mental health problems.

[Long-term outcomes of ICU treatment]. / Langetermijnuitkomsten van IC-behandeling.

Patients admitted to an intensive care unit (ICU) comprise of a heterogeneous population with substantial differences in admission diagnosis, length of stay and co-morbidity. Therefore, very often the prognosis for each patient differs. In the Netherlands, over 20% of the more than 80,000 patients treated in ICU annually will die within a year of admission. Some of those who survive and are discharged from ICU experience persistent physical, mental and cognitive health problems post-discharge; this is called post-intensive care syndrome (PICS). One year following discharge, circa 50% of patients continue to report physical symptoms, including muscle weakness and walking difficulties. Approximately one in five patients discharged from ICU will develop symptoms akin to post-traumatic stress disorder, and one third will experience depressive symptoms for some time. It remains unclear to what extent the actual ICU admission may potentially contribute to the decline in performance status and quality of life.

Systemic Corticosteroids and Transition to Delirium in Critically Ill Patients.

OBJECTIVE: Corticosteroids are frequently used in critically ill patients. We investigated whether systemic corticosteroid use increases the probability of transitioning to delirium in a large population of mixed medical-surgical ICU patients. DESIGN: Prospective cohort study. SETTING: A 32-bed medical-surgical ICU at an academic medical center. PATIENTS: Critically ill adults (n = 1,112), admitted to the ICU for more than 24 hours without a condition that could hamper delirium assessment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Systemic corticosteroid exposure was measured daily and converted to prednisone equivalents (milligrams). Daily mental status was classified as coma, delirium, or an awake without delirium state. Transitions between states were analyzed using a first-order Markov multinomial logistic regression model with 11 different covariables, with the transition from an awake without delirium state to delirium as a primary interest. Among the 1,112 patients, corticosteroids were administered on 35% (3,483/9,867) of the ICU days at a median dose of 50 mg (interquartile range, 25-75 mg) prednisone equivalent. Administration of a corticosteroid, and any increase in the dose of the corticosteroid given on exposure days, was not significantly associated with the transition to delirium (adjusted odds ratio, 1.08; 95% CI, 0.89-1.32 and adjusted odds ratio, 1.00; 95% CI, 0.99-1.01, per 10 mg increase in prednisone equivalent). CONCLUSIONS: In a large population of mixed medical-surgical ICU patients, systemic corticosteroid use was not associated with an increased probability of transitioning to delirium.

Anticholinergic Medication Use and Transition to Delirium in Critically Ill Patients: A Prospective Cohort Study.

OBJECTIVE: Although cholinergic deficiency is presumed to increase delirium risk and use of medication with anticholinergic properties in the ICU is frequent, the relationship between anticholinergic medication use and delirium in this setting remains unclear. We investigated whether exposure to medication with anticholinergic properties increases the probability of transitioning to delirium in critically ill adults and whether this relationship is affected by age or the presence of acute systemic inflammation. DESIGN: Prospective cohort study. SETTING: A 32-bed medical-surgical ICU at an academic medical center. PATIENTS: Critically ill adults admitted to the ICU for more than 24 hours without an acute neurological disorder or another condition that would hamper delirium assessment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily anticholinergic burden was calculated for each patient based on the sum of the Anticholinergic Drug Scale score for each medication administered. Daily mental status was classified as "coma," "delirium," or an "awake without delirium" state. The primary outcome, the daily transition from an "awake without delirium" state to "delirium," was analyzed using a first-order Markov model that adjusted for eight covariables. A total of 1,112 patients were evaluated over 9,867 ICU days. The daily median summed Anticholinergic Drug Scale score was 2 (interquartile range, 1-3). The transition from being in an "awake without delirium" state to "delirium" occurred on 562 of ICU days (6%). After correcting for confounding, a one-unit increase in the Anticholinergic Drug Scale score resulted in a nonsignificant increase in the probability of delirium occurring the next day (odds ratio, 1.05; 95% CI, 0.99-1.10). Neither age nor the presence of acute systemic inflammation modified this relationship. CONCLUSIONS: Exposure to medication with anticholinergic properties, as defined by the Anticholinergic Drug Scale, does not increase the probability of delirium onset in patients who are awake and not delirious in the ICU.

Long-term outcome of delirium during intensive care unit stay in survivors of critical illness: a prospective cohort study.

INTRODUCTION: Delirium is associated with impaired outcome, but it is unclear whether this relationship is limited to in-hospital outcomes and whether this relationship is independent of the severity of underlying conditions. The aim of this study was to investigate the association between delirium in the intensive care unit (ICU) and long-term mortality, self-reported health-related quality of life (HRQoL), and self-reported problems with cognitive functioning in survivors of critical illness, taking severity of illness at baseline and throughout ICU stay into account. METHODS: A prospective cohort study was conducted. We included patients who survived an ICU stay of at least a day; exclusions were neurocritical care patients and patients who sustained deep sedation during the entire ICU stay. Delirium was assessed twice daily with the Confusion Assessment Method for the ICU (CAM-ICU) and additionally, patients who received haloperidol were considered delirious. Twelve months after ICU admission, data on mortality were obtained and HRQoL and cognitive functioning were measured with the European Quality of Life - Six dimensions self-classifier (EQ-6D). Regression analyses were used to assess the associations between delirium and the outcome measures adjusted for gender, type of admission, the Acute Physiology And Chronic Health Evaluation IV (APACHE IV) score, and the cumulative Sequential Organ Failure Assessment (SOFA) score throughout ICU stay. RESULTS: Of 1101 survivors of critical illness, 412 persons (37%) had been delirious during ICU stay, and 198 (18%) died within twelve months. When correcting for confounders, no significant association between delirium and long-term mortality was found (hazard ratio: 1.26; 95% confidence interval (CI) 0.93 to 1.71). In multivariable analysis, delirium was not associated with HRQoL either (regression coefficient: -0.04; 95% CI -0.10 to 0.01). Yet, delirium remained associated with mild and severe problems with cognitive functioning in multivariable analysis (odds ratios: 2.41; 95% CI 1.57 to 3.69 and 3.10; 95% CI 1.10 to 8.74, respectively). CONCLUSIONS: In this group of survivors of critical illness, delirium during ICU stay was not associated with long-term mortality or HRQoL after adjusting for confounding, including severity of illness throughout ICU stay. In contrast, delirium appears to be an independent risk factor for long-term self-reported problems with cognitive functioning.

Cognitive impairment after intensive care unit admission: a systematic review.

PURPOSE: There is increasing evidence that critical illness and treatment in an intensive care unit (ICU) may result in significant long-term morbidity. The purpose of this systematic review was to summarize the current literature on long-term cognitive impairment in ICU survivors. METHODS: PubMed/MEDLINE, CINAHL, Cochrane Library, PsycINFO and Embase were searched from January 1980 until July 2012 for relevant articles evaluating cognitive functioning after ICU admission. Publications with an adult population and a follow-up duration of at least 2 months were eligible for inclusion in the review. Studies in cardiac surgery patients or subjects with brain injury or cardiac arrest prior to ICU admission were excluded. The main outcome measure was cognitive functioning. RESULTS: The search strategy identified 1,128 unique studies, of which 19 met the selection criteria and were included. Only one article compared neuropsychological test performance before and after ICU admission. The 19 studies that were selected reported a wide range of cognitive impairment in 4-62 % of the patients after a follow-up of 2-156 months. CONCLUSION: The results of most studies of the studies reviewed suggest that critical illness and ICU treatment are associated with long-term cognitive impairment. Due to the complexity of defining cognitive impairment, it is difficult to standardize definitions and to reach consensus on how to categorize neurocognitive dysfunction. Therefore, the magnitude of the problem is uncertain.

Risk factors for hypoglycaemia in neurocritical care patients.

PURPOSE: To identify risk factors for hypoglycaemia in neurocritical care patients receiving intensive insulin therapy (IIT). METHODS: We performed a nested case-control study. All first episodes of hypoglycaemia (glucose <80 mg/dL, <4.4 mmol/L) in neurocritical care patients between 1 March 2006 and 31 December 2007 were identified. Patients were treated according to the local IIT protocol, with target blood glucose levels between 4.5 and 6.0 mmol/L (81.0-108.0 mg/dL). The first hypoglycaemic event of every patient (index moment) was used to match to a control patient. Possible risk factors preceding the index moment were scored using hospital records and analysed with conditional logistic regression. RESULTS: Of 786 neurocritical care patients, 449 developed hypoglycaemia (57.1 %). Independent risk factors for hypoglycaemia were lowering nutrition 6 h before the index moment without insulin dose reduction (odds ratio (OR) 5.25, 95 % confidence interval (95 % CI) 1.32-20.88), mechanical ventilation (OR 2.59, 95 % CI 1.56-4.29), lowering the dosage of norepinephrine 3 h before the index moment (OR 2.44, 95 % CI 1.07-5.55), a hyperglycaemic event (>10 mmol/L, >180.0 mg/dL) in the 24 h preceding the index moment (OR 2.40, 95 % CI 1.26-4.58), gastric residual in the 6 h preceding the index moment without insulin dose reduction (OR 1.76, 95 % CI 1.05-2.96) and dosage of insulin at the index moment (OR 0.83, 95 % CI 0.76-0.90). CONCLUSION: Hypoglycaemia occurs in a considerable proportion of neurocritical care patients. We recommend the identification of these risk factors in these patients to avoid the occurrence of hypoglycaemia.