The Impact of Non-Pharmacological Interventions on Delirium in Neurological Intensive Care Unit Patients: A Single-Center Interrupted Time Series Trial.

Background: Delirium is a pathobiological brain process that is frequently observed in Intensive Care Unit (ICU) patients, and is associated with longer hospitalization as well as long-term cognitive impairment. In neurological ICU patients, delirium may be more treatment-resistant due to the initial brain injury. This study examined the effects of a multicomponent non-pharmacological nursing intervention program on delirium in neurological ICU patients. Methods: A single-center interrupted time series trial was conducted in adult neurological ICU patients at high risk for developing delirium who were non-delirious at admission. A multicomponent nursing intervention program focusing on modifiable risk factors for delirium, including the optimalization of vision, hearing, orientation and cognition, sleep and mobilization, was implemented as the standard of care, and its effects were studied. The primary outcome was the number of delirium-free and coma-free days alive at 28 days after ICU admission. The secondary outcomes included delirium incidence and duration, ICU and hospital length-of-stay and duration of mechanical ventilation. Results: Of 289 eligible patients admitted to the ICU, 130 patients were included, with a mean age of 68 ± 11 years, a mean APACHE-IV score of 79 ± 25 and a median predicted delirium risk (E-PRE-DELIRIC) score of 42 [IQR 38-50]). Of these, 73 were included in the intervention period and 57 in the control period. The median delirium- and coma-free days alive were 15 days [IQR 0-26] in the intervention group and 10 days [IQR 0-24] in the control group (level change -0.48 days, 95% confidence interval (95%CI) -7 to 6 days, p = 0.87; slope change -0.95 days, 95%CI -2.41 to 0.52 days, p = 0.18). Conclusions: In neurological ICU patients, our multicomponent non-pharmacological nursing intervention program did not change the number of delirium-free and coma-free days alive after 28 days.

The Impact of Nursing Delirium Preventive Interventions in the ICU: A Multicenter Cluster-randomized Controlled Clinical Trial.

Rationale: Delirium is common in critically ill patients and is associated with deleterious outcomes. Nonpharmacological interventions are recommended in current delirium guidelines, but their effects have not been unequivocally established. Objectives: To determine the effects of a multicomponent nursing intervention program on delirium in the ICU. Methods: A stepped-wedge cluster-randomized controlled trial was conducted in ICUs of 10 centers. Adult critically ill surgical, medical, or trauma patients at high risk of developing delirium were included. A multicomponent nursing intervention program focusing on modifiable risk factors was implemented as standard of care. The primary outcome was the number of delirium-free and coma-free days alive in 28 days after ICU admission. Measurements and Main Results: A total of 1,749 patients were included. Time spent on interventions per 8-hour shift was median (interquartile range) 38 (14-116) minutes in the intervention period and median 32 (13-73) minutes in the control period (P = 0.44). Patients in the intervention period had a median of 23 (4-27) delirium-free and coma-free days alive compared with a median of 23 (5-27) days for patients in the control group (mean difference, -1.21 days; 95% confidence interval, -2.84 to 0.42 d; P = 0.15). In addition, the number of delirium days was similar: median 2 (1-4) days (ratio of medians, 0.90; 95% confidence interval, 0.75 to 1.09; P = 0.27). Conclusions: In this large randomized controlled trial in adult ICU patients, a limited increase in the use of nursing interventions was achieved, and no change in the number of delirium-free and coma-free days alive in 28 days could be determined. Clinical trial registered with www.clinicaltrials.gov (NCT03002701).

High Early Fluid Input After Aneurysmal Subarachnoid Hemorrhage: Combined Report of Association With Delayed Cerebral Ischemia and Feasibility of Cardiac Output-Guided Fluid Restriction.

BACKGROUND: Guidelines on the management of aneurysmal subarachnoid hemorrhage (aSAH) recommend euvolemia, whereas hypervolemia may cause harm. We investigated whether high early fluid input is associated with delayed cerebral ischemia (DCI), and if fluid input can be safely decreased using transpulmonary thermodilution (TPT). METHODS: We retrospectively included aSAH patients treated at an academic intensive care unit (2007-2011; cohort 1) or managed with TPT (2011-2013; cohort 2). Local guidelines recommended fluid input of 3 L daily. More fluids were administered when daily fluid balance fell below +500 mL. In cohort 2, fluid input in high-risk patients was guided by cardiac output measured by TPT per a strict protocol. Associations of fluid input and balance with DCI were analyzed with multivariable logistic regression (cohort 1), and changes in hemodynamic indices after institution of TPT assessed with linear mixed models (cohort 2). RESULTS: Cumulative fluid input 0 to 72 hours after admission was associated with DCI in cohort 1 (n=223; odds ratio [OR] 1.19/L; 95% confidence interval 1.07-1.32), whereas cumulative fluid balance was not. In cohort 2 (23 patients), using TPT fluid input could be decreased from 6.0 ± 1.0 L before to 3.4 ± 0.3 L; P = .012), while preload parameters and consciousness remained stable. CONCLUSION: High early fluid input was associated with DCI. Invasive hemodynamic monitoring was feasible to reduce fluid input while maintaining preload. These results indicate that fluid loading beyond a normal preload occurs, may increase DCI risk, and can be minimized with TPT.

The use of the PSH-AM in patients with diffuse axonal injury and autonomic dysregulation: A cohort study and review.

PURPOSE: 1) To determine the clinical expression and consequences of autonomic dysregulation in patients with diffuse axonal injury (DAI), and 2) to study the use of the "paroxysmal sympathetic hyperactivity assessment measure" (PSH-AM). METHODS: Patients clinically diagnosed with autonomic dysregulation were selected from a cohort involving 116 patients with DAI. We studied the incidence of autonomic features, treatment, and outcome. In addition a systematic review was performed. RESULTS: Autonomic dysregulation was diagnosed in 19 of 116 (16.4%). Lower age (OR 0.95) and higher DAI grade (OR 7.2) were risk factors for autonomic dysregulation. Autonomic dysregulation was associated with an unfavourable outcome (OR 5.6) and a longer ICU and hospital stay. On the PSH-AM 57.9% (n = 11) scored a probable paroxysmal sympathetic hyperactivity (PSH), 36.8% (n = 7) scored possible, and 5.2% (n = 1) scored unlikely. The review yielded 30 articles. The incidence of autonomic dysregulation after TBI varied from 7.7-32.6% (mean 13.5%). TBI patients with autonomic dysregulation had a longer ICU stay and poorer outcome. CONCLUSION: Patients with DAI and autonomic dysregulation had a longer ICU stay and a poorer outcome compared to patients without autonomic dysregulation. The PSH-AM is a potential valuable tool to determine the likelihood of autonomic dysregulation.

Induced Hypertension for Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: Induced hypertension is widely used to treat delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage, but a literature review shows that its presumed effectiveness is based on uncontrolled case-series only. We here report clinical outcome of aneurysmal subarachnoid hemorrhage patients with DCI included in a randomized trial on the effectiveness of induced hypertension. METHODS: Aneurysmal subarachnoid hemorrhage patients with clinical symptoms of DCI were randomized to induced hypertension or no induced hypertension. Risk ratios for poor outcome (modified Rankin Scale score >3) at 3 months, with 95% confidence intervals, were calculated and adjusted for age, clinical condition at admission and at time of DCI, and amount of blood on initial computed tomographic scan with Poisson regression analysis. RESULTS: The trial aiming to include 240 patients was ended, based on lack of effect on cerebral perfusion and slow recruitment, when 21 patients had been randomized to induced hypertension, and 20 patients to no hypertension. With induced hypertension, the adjusted risk ratio for poor outcome was 1.0 (95% confidence interval, 0.6-1.8) and the risk ratio for serious adverse events 2.1 (95% confidence interval, 0.9-5.0). CONCLUSIONS: Before this trial, the effectiveness of induced hypertension for DCI in aneurysmal subarachnoid hemorrhage patients was unknown because current literature consists only of uncontrolled case series. The results from our premature halted trial do not add any evidence to support induced hypertension and show that this treatment can lead to serious adverse events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01613235.

Effects of Induced Hypertension on Cerebral Perfusion in Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: The presumed effectiveness of induced hypertension for treating delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage is based on uncontrolled case-series only. We assessed the effect of induced hypertension on cerebral blood flow (CBF) in aneurysmal subarachnoid hemorrhage patients with delayed cerebral ischemia in a randomized clinical trial. METHODS: Aneurysmal subarachnoid hemorrhage patients were randomized to induced or no induced hypertension (control group) at delayed cerebral ischemia onset. CBF was assessed, blinded for treatment allocation, with computed tomographic perfusion in standardized predefined regions at delayed cerebral ischemia onset and after 24 to 36 hours of study treatment. Mean arterial blood pressure was compared between groups (linear mixed model). The primary outcome measure was the difference in change in overall CBF (Mann-Whitney U test). RESULTS: Mean arterial blood pressure was, on average, 12 mm Hg (95% confidence interval, 8.6-14.5) higher in the hypertension group (n=12) than in the control group (n=13). Change in overall CBF (mL/100g per s) was -8.5 (range, -42 to 30) in the control group and 0.1 (range, -31-43) in the hypertension group (P=0.25). CONCLUSIONS: Change in overall CBF did not differ to a statistically significant extent between the groups. Based on our results, 225 to 250 patients per group are needed to find a statistically significant difference in change in overall CBF between induced hypertension and no hypertension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT0161323.

The influence of APACHE II score on the average noise level in an intensive care unit: an observational study.

BACKGROUND: Noise levels in hospitals, especially in intensive care units (ICUs) are known to be high, potentially affecting not only the patients' well-being but also their clinical outcomes. In an observational study, we made a long-term measurement of noise levels in an ICU, and investigated the influence of various factors on the noise level, including the acute physiology and chronic health evaluation II (APACHE II) score. METHODS: The average noise level was continuously measured for three months in all (eight) patient rooms in an ICU, while the patient data were also registered, including the APACHE II score. The 24-hour trend of the noise level was obtained for the patients of length-of-stay (LOS) ≥1 day, which was compared to the timeline of the ICU routine events. For the patients with LOS ≥4 days, the average noise levels in the first four days were analyzed, and regression models were established using the stepwise search method based on the Akaike information criterion. RESULTS: Features identified in the 24-hour trends (n = 55) agreed well with the daily routine events in the ICU, where regular check-ups raised the 10-minute average noise level by 2~3 dBA from the surrounding values at night, and the staff shift changes consistently increased the noise level by 3~5 dBA. When analyzed in alignment with the patient's admission (n=22), the daytime acoustic condition improved from Day 1 to 2, but worsened from Day 2 to 4, most likely in relation to the various phases of patient's recovery. Regression analysis showed that the APACHE II score, room location, gender, day of week and the ICU admission type could explain more than 50% of the variance in the daily average noise level, LAeq,24h. Where these factors were argued to have causal relations to LAeq,24h, the APACHE II score was found to be most strongly correlated: LAeq,24h increased by 1.3~1.5 dB when the APACHE II score increased by 10 points. CONCLUSIONS: Patient's initial health condition is one important factor that influences the acoustic environment in an ICU, which needs to be considered in observational and interventional studies where the noise in healthcare environments is the subject of investigation.

Delirium in acute stroke: a predictor of subsequent cognitive impairment? A two-year follow-up study.

OBJECTIVE: Delirium is an independent risk factor for cognitive impairment and development of dementia in medical patients. It has never been thoroughly studied whether this association is also present in the stroke population. Our aim was to evaluate the effects of delirium in the acute phase after stroke on cognitive functioning two years later. METHODS: Two years after stroke, 50 patients (22 with and 28 without delirium in the acute phase) were assessed on two screening instruments for dementia and a neuropsychological test battery. RESULTS: Delirium was an independent predictor for development of dementia as assessed by the Clinical Dementia Rating Scale (odds ratio (OR) 4.7; 95% confidence interval (CI) 1.08 to 20.42) and by the Rotterdam-CAMCOG (OR 7.2, 95% CI 1.88 to 27.89). Cognitive domains most affected in patients with previous delirium were memory, language, visual construction and executive functioning. CONCLUSIONS: Delirium in the acute phase after stroke is an independent predictor for severe cognitive impairment two years after stroke. These findings emphasize the importance of both rapid detection and treatment of delirium after stroke. Furthermore, periodic monitoring and evaluation of cognitive functioning in these vulnerable patients in the years after stroke is strongly recommended.

[Delirium on intensive care frequently missed: clinical impression alone is not enough]. / Delirium op de Intensive Care vaak gemist: klinische blik alleen is niet voldoende.

OBJECTIVE: To compare the sensitivity and specificity of a routine assessment (clinical impression) with a structured assessment which uses a validated assessment scale for the recognition of delirium on the intensive care unit (ICU). DESIGN: Observational study. METHOD: During their admission to the intensive care unit, 103 patients were assessed daily (with a maximum of 40 days) for the presence of delirium using the Confusion assessment method for the intensive care unit (CAM-ICU). Their physicians indicated whether or not they considered the patient delirious. These findings were compared. For all patients daily information was also collected about fixation and complications, such as self-extubation or self-removal of catheters. RESULTS: The patients were assessed for a period of 502 patient-days. CAM-ICU scores were positive (n = 108), negative (n = 235) or non-assessable because the patient was comatosed or deeply sedated (n = 159). The sensitivity of clinical detection by the physicians was 45% in comparison to the CAM-ICU. The specificity was high (97%). CONCLUSION: The diagnosis delirium is frequently missed on the ICU when only based on clinical impression. Routine assessment using a validated assessment scale such as the CAM-ICU might possibly improve this.

A pilot study of rivastigmine in the treatment of delirium after stroke: a safe alternative.

BACKGROUND: Delirium is a common disorder in the early phase of stroke. Given the presumed cholinergic deficiency in delirium, we tested treatment with the acetylcholinesterase inhibitor rivastigmine. METHODS: This pilot study was performed within an epidemiological study. In 527 consecutive stroke patients presence of delirium was assessed during the first week with the confusion assessment method. Severity was scored with the delirium rating scale (DRS). Sixty-two patients developed a delirium in the acute phase of stroke. Only patients with a severe and persistent delirium (defined as a DRS of 12 or more for more than 24 hours) were enrolled in the present study. In total 26 fulfilled these criteria of whom 17 were treated with orally administered rivastigmine with a total dose between 3 and 12 mg a day. Eight patients could not be treated because of dysphagia and one because of early discharge. RESULTS: No major side effects were recorded. In 16 patients there was a considerable decrease in severity of delirium. The mean DRS declined from 14.8 on day one to 8.5 after therapy and 5.6 after tapering. The mean duration of delirium was 6.7 days (range; 2-17). CONCLUSION: Rivastigmine is safe in stroke patients with delirium even after rapid titration. In the majority of patients the delirium improved after treatment. A randomized controlled trial is needed to establish the usefulness of rivastigmine in delirium after stroke. TRIAL REGISTRATION: Nederlands Trial Register NTR1395.