Functional connectivity and network analysis during hypoactive delirium and recovery from anesthesia.

OBJECTIVE: To gain insight in the underlying mechanism of reduced levels of consciousness due to hypoactive delirium versus recovery from anesthesia, we studied functional connectivity and network topology using electroencephalography (EEG). METHODS: EEG recordings were performed in age and sex-matched patients with hypoactive delirium (n=18), patients recovering from anesthesia (n=20), and non-delirious control patients (n=20), all after cardiac surgery. Functional and directed connectivity were studied with phase lag index and directed phase transfer entropy. Network topology was characterized using the minimum spanning tree (MST). A random forest classifier was calculated based on all measures to obtain discriminative ability between the three groups. RESULTS: Non-delirious control subjects showed a back-to-front information flow, which was lost during hypoactive delirium (p=0.01) and recovery from anesthesia (p<0.01). The recovery from anesthesia group had more integrated network in the delta band compared to non-delirious controls. In contrast, hypoactive delirium showed a less integrated network in the alpha band. High accuracy for discrimination between hypoactive delirious patients and controls (86%) and recovery from anesthesia and controls (95%) were found. Accuracy for discrimination between hypoactive delirium and recovery from anesthesia was 73%. CONCLUSION: Loss of functional and directed connectivity were observed in both hypoactive delirium and recovery from anesthesia, which might be related to the reduced level of consciousness in both states. These states could be distinguished in topology, which was a less integrated network during hypoactive delirium. SIGNIFICANCE: Functional and directed connectivity are similarly disturbed during a reduced level of consciousness due to hypoactive delirium and sedatives, however topology was differently affected.

Use of physical restraints in Dutch intensive care units: a prospective multicenter study.

BACKGROUND: Increasing evidence indicates that harmful effects are associated with the use of physical restraint. OBJECTIVES: To characterize the use of physical restraint in intensive care units. Prevalence, adherence to protocols, and correlates of the use of physical restraint were determined. For comparisons between ICUs, adjustments were made for differences in patients' characteristics. METHODS: A prospective, cross-sectional, observational multicenter study with a representative sample (n = 25) of all Dutch intensive care units, ranging from local hospitals to academic centers. Each unit was visited twice, and all 379 patients admitted during these visits were included and were examined for use of physical restraint. RESULTS: Physical restraint was used in 23% of all patients (range, 0%-56% for different units). Of all 346 nurses interviewed, 31% reported using a protocol when applying physical restraint. When corrections were made for clustering within units, the risk for use of physical restraint was increased in patients with delirium or coma, in patients who could not communicate verbally, and in patients receiving psychoactive or sedative medications. Sex, severity of illness, and nurse to patient ratio were not independently related to use of physical restraint. In 11 units (44%), use of physical restraint was more frequent than expected on the basis of patients' characteristics, although this finding was not significant. CONCLUSIONS: Physical restraint is frequently used in Dutch intensive care units. The differences in frequency between units suggest that opportunities exist to limit the use of physical restraint.

Benzodiazepine-associated delirium in critically ill adults.

PURPOSE: The association between benzodiazepine use and delirium risk in the ICU remains unclear. Prior investigations have failed to account for disease severity prior to delirium onset, competing events that may preclude delirium detection, other important delirium risk factors, and an adequate number of patients receiving continuous midazolam. The aim of this study was to address these limitations and evaluate the association between benzodiazepine exposure and ICU delirium occurrence. METHODS: In a cohort of consecutive critically ill adults, daily mental status was classified as either awake without delirium, delirium, or coma. In a first-order Markov model, multinomial logistic regression analysis was used, which considered five possible outcomes the next day (i.e., awake without delirium, delirium, coma, ICU discharge, and death) and 16 delirium-related covariables, to quantify the association between benzodiazepine use and delirium occurrence the following day. RESULTS: Among 1112 patients, 9867 daily transitions occurred. Benzodiazepine administration in an awake patient without delirium was associated with increased risk of delirium the next day [OR 1.04 (per 5 mg of midazolam equivalent administered) 95 % CI 1.02-1.05). When the method of benzodiazepine administration was incorporated in the model, the odds of transitioning to delirium was higher with benzodiazepines given continuously (OR 1.04, 95 % CI 1.03-1.06) compared to benzodiazepines given intermittently (OR 0.97, 95 % CI 0.88-1.05). CONCLUSIONS: After addressing potential methodological limitations of prior studies, we confirm that benzodiazepine administration increases the risk for delirium in critically ill adults but this association seems to be limited to continuous infusion use only.

Myotonic discharges discriminate chloride from sodium muscle channelopathies.

Non-dystrophic myotonic syndromes represent a heterogeneous group of clinically quite similar diseases sharing the feature of myotonia. These syndromes can be separated into chloride and sodium channelopathies, with gene-defects in chloride or sodium channel proteins of the sarcolemmal membrane. Myotonia has its basis in an electrical instability of the sarcolemmal membrane. In the present study we examine the discriminative power of the resulting myotonic discharges for these disorders. Needle electromyography was performed by an electromyographer blinded for genetic diagnosis in 66 non-dystrophic myotonia patients (32 chloride and 34 sodium channelopathy). Five muscles in each patient were examined. Individual trains of myotonic discharges were extracted and analyzed with respect to firing characteristics. Myotonic discharge characteristics in the rectus femoris muscle almost perfectly discriminated chloride from sodium channelopathy patients. The first interdischarge interval as a single variable was longer than 30 ms in all but one of the chloride channelopathy patients and shorter than 30 ms in all of the sodium channelopathy patients. This resulted in a detection rate of over 95%. Myotonic discharges of a single muscle can be used to better guide toward a molecular diagnosis in non-dystrophic myotonic syndromes.

Delirium detection using EEG: what and how to measure.

BACKGROUND: Despite its frequency and impact, delirium is poorly recognized in postoperative and critically ill patients. EEG is highly sensitive to delirium but, as currently used, it is not diagnostic. To develop an EEG-based tool for delirium detection with a limited number of electrodes, we determined the optimal electrode derivation and EEG characteristic to discriminate delirium from nondelirium. METHODS: Standard EEGs were recorded in 28 patients with delirium and 28 age- and sex-matched patients who had undergone cardiothoracic surgery and were not delirious, as classified by experts using Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria. The first minute of artifact-free EEG data with eyes closed as well as with eyes open was selected. For each derivation, six EEG parameters were evaluated. Using Mann-Whitney U tests, all combinations of derivations and parameters were compared between patients with delirium and those without. Corresponding P values, corrected for multiple testing, were ranked. RESULTS: The largest difference between patients with and without delirium and highest area under the receiver operating curve (0.99; 95% CI, 0.97-1.00) was found during the eyes-closed periods of the EEG, using electrode derivation F8-Pz (frontal-parietal) and relative δ power (median [interquartile range (IQR)] for delirium, 0.59 [IQR, 0.47-0.71] and for nondelirium, 0.20 [IQR, 0.17-0.26]; P = .0000000000018). With a cutoff value of 0.37, it resulted in a sensitivity of 100% (95% CI, 100%-100%) and specificity of 96% (95% CI, 88%-100%). CONCLUSIONS: In a homogenous population of nonsedated patients who had undergone cardiothoracic surgery, we observed that relative δ power from an eyes-closed EEG recording with only two electrodes in a frontal-parietal derivation can distinguish among patients who have delirium and those who do not.

Heart rate variability in intensive care unit patients with delirium.

Sympathovagal balance, assessed with heart rate variability (HRV), may be altered in intensive care unit (ICU) delirium. HRV was measured in the frequency domain [low frequencies (LF)=0.04-0.15 Hz and high frequencies (HF)=0.15-0.40 Hz] with HF in normalized units (HFnu) to evaluate parasympathetic tone and LF:HF ratio for sympathovagal balance. The authors assessed 726 ICU patients and excluded patients with conditions affecting HRV. No difference could be found between patients with (N=13) and without (N=12) delirium by comparing the mean (±standard deviation) of the HFnu (75±7 versus 68±23) and the LF:HF ratio (-0.7±1.0 versus -0.1±1.1). This study suggests that autonomic function is not altered in ICU delirium.

The attributable mortality of delirium in critically ill patients: prospective cohort study.

OBJECTIVE: To determine the attributable mortality caused by delirium in critically ill patients. DESIGN: Prospective cohort study. SETTING: 32 mixed bed intensive care unit in the Netherlands, January 2011 to July 2013. PARTICIPANTS: 1112 consecutive adults admitted to an intensive care unit for a minimum of 24 hours. EXPOSURES: Trained observers evaluated delirium daily using a validated protocol. Logistic regression and competing risks survival analyses were used to adjust for baseline variables and a marginal structural model analysis to adjust for confounding by evolution of disease severity before the onset of delirium. MAIN OUTCOME MEASURE: Mortality during admission to an intensive care unit. RESULTS: Among 1112 evaluated patients, 558 (50.2%) developed at least one episode of delirium, with a median duration of 3 days (interquartile range 2-7 days). Crude mortality was 94/558 (17%) in patients with delirium compared with 40/554 (7%) in patients without delirium (P<0.001). Delirium was significantly associated with mortality in the multivariable logistic regression analysis (odds ratio 1.77, 95% confidence interval 1.15 to 2.72) and survival analysis (subdistribution hazard ratio 2.08, 95% confidence interval 1.40 to 3.09). However, the association disappeared after adjustment for time varying confounders in the marginal structural model (subdistribution hazard ratio 1.19, 95% confidence interval 0.75 to 1.89). Using this approach, only 7.2% (95% confidence interval -7.5% to 19.5%) of deaths in the intensive care unit were attributable to delirium, with an absolute mortality excess in patients with delirium of 0.9% (95% confidence interval -0.9% to 2.3%) by day 30. In post hoc analyses, however, delirium that persisted for two days or more remained associated with a 2.0% (95% confidence interval 1.2% to 2.8%) absolute mortality increase. Furthermore, competing risk analysis showed that delirium of any duration was associated with a significantly reduced rate of discharge from the intensive care unit (cause specific hazard ratio 0.65, 95% confidence interval 0.55 to 0.76). CONCLUSIONS: Overall, delirium prolongs admission in the intensive care unit but does not cause death in critically ill patients. Future studies should focus on episodes of persistent delirium and its long term sequelae rather than on acute mortality.Trial registration Clinicaltrials.gov NCT01905033.

Decreased functional connectivity and disturbed directionality of information flow in the electroencephalography of intensive care unit patients with delirium after cardiac surgery.

BACKGROUND: In this article, the authors explore functional connectivity and network topology in electroencephalography recordings of patients with delirium after cardiac surgery, aiming to improve the understanding of the pathophysiology and phenomenology of delirium. The authors hypothesize that disturbances in attention and consciousness in delirium may be related to alterations in functional neural interactions. METHODS: Electroencephalography recordings were obtained in postcardiac surgery patients with delirium (N = 25) and without delirium (N = 24). The authors analyzed unbiased functional connectivity of electroencephalography time series using the phase lag index, directed phase lag index, and functional brain network topology using graph analysis. RESULTS: The mean phase lag index was lower in the α band (8 to 13 Hz) in patients with delirium (median, 0.120; interquartile range, 0.113 to 0.138) than in patients without delirium (median, 0.140; interquartile range, 0.129 to 0.168; P < 0.01). Network topology in delirium patients was characterized by lower normalized weighted shortest path lengths in the α band (t = -2.65; P = 0.01). δ Band-directed phase lag index was lower in anterior regions and higher in central regions in delirium patients than in nondelirium patients (F = 4.53; P = 0.04, and F = 7.65; P < 0.01, respectively). CONCLUSIONS: Loss of α band functional connectivity, decreased path length, and increased δ band connectivity directed to frontal regions characterize the electroencephalography during delirium after cardiac surgery. These findings may explain why information processing is disturbed in delirium.

Delirium detection based on monitoring of blinks and eye movements.

OBJECTIVE: To investigate whether delirious patients differ from nondelirious patients with regard to blinks and eye movements to explore opportunities for delirium detection. METHODS: Using a single-center, observational study in a tertiary hospital in the Netherlands, we studied 28 delirious elderly and 28 age- and gender-matched (group level) nondelirious elderly, postoperative cardiac surgery patients. Patients were evaluated for delirium by a geriatrician, psychiatrist, or neurologist using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Blinks were automatically extracted from electro-oculograms and eye movements from electroencephalography recordings using independent component analysis. The number and duration of eye movements and blinks were compared between patients with and without delirium, based on the classification of the delirium experts described above. RESULTS: During eyes-open registrations, delirious patients showed, compared with nondelirious patients, a significant decrease in the number of blinks per minute (median: 12 [interquartile range {IQR}: 5-18] versus 18 [IQR: 8-25], respectively; p = 0.02) and number of vertical eye movements per minute (median: 1 [IQR: 0-13] versus 15 [IQR: 2-54], respectively; p = 0.01) as well as an increase in the average duration of blinks (median: 0.5 [IQR: 0.36-0.95] seconds versus 0.34 [IQR: 0.23-0.53] seconds, respectively; p <0.01). During eyes-closed registrations, the average duration of horizontal eye movements was significantly increased in delirious patients compared with patients without delirium (median: 0.41 [IQR: 0.15-0.75] seconds versus 0.08 [IQR: 0.06-0.22] seconds, respectively; p <0.01). CONCLUSION: Spontaneous eye movements and particularly blinks appear to be affected in delirious patients, which holds promise for delirium detection.

Temperature variability during delirium in ICU patients: an observational study.

INTRODUCTION: Delirium is an acute disturbance of consciousness and cognition. It is a common disorder in the intensive care unit (ICU) and associated with impaired long-term outcome. Despite its frequency and impact, delirium is poorly recognized by ICU-physicians and -nurses using delirium screening tools. A completely new approach to detect delirium is to use monitoring of physiological alterations. Temperature variability, a measure for temperature regulation, could be an interesting component to monitor delirium, but whether temperature regulation is different during ICU delirium has not yet been investigated. The aim of this study was to investigate whether ICU delirium is related to temperature variability. Furthermore, we investigated whether ICU delirium is related to absolute body temperature. METHODS: We included patients who experienced both delirium and delirium free days during ICU stay, based on the Confusion Assessment method for the ICU conducted by a research- physician or -nurse, in combination with inspection of medical records. We excluded patients with conditions affecting thermal regulation or therapies affecting body temperature. Daily temperature variability was determined by computing the mean absolute second derivative of the temperature signal. Temperature variability (primary outcome) and absolute body temperature (secondary outcome) were compared between delirium- and non-delirium days with a linear mixed model and adjusted for daily mean Richmond Agitation and Sedation Scale scores and daily maximum Sequential Organ Failure Assessment scores. RESULTS: Temperature variability was increased during delirium-days compared to days without delirium (ß(unadjuste)d=0.007, 95% confidence interval (CI)=0.004 to 0.011, p<0.001). Adjustment for confounders did not alter this result (ß(adjusted)=0.005, 95% CI=0.002 to 0.008, p<0.001). Delirium was not associated with absolute body temperature (ß(unadjusted)=-0.03, 95% CI=-0.17 to 0.10, p=0.61). This did not change after adjusting for confounders (ß(adjusted)=-0.03, 95% CI=-0.17 to 0.10, p=0.63). CONCLUSIONS: Our study suggests that temperature variability is increased during ICU delirium.

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.

What are the opportunities for EEG-based monitoring of delirium in the ICU?

Recognition of delirium in intensive care unit (ICU) patients is poor, despite the use of screening tools. Electroencephalography (EEG) with a limited number of electrodes and automatic processing may be a more sensitive approach for delirium monitoring. The authors conducted a systematic literature search on EEG characteristics that define delirium, finding 14 studies, which were predominantly conducted in elderly patients. The relative power of the theta and alpha frequency band most often (7/14 studies) distinguished delirium from non-delirium subjects. Given the feasibility for continuous EEG monitoring in ICU, EEG delirium monitoring in ICU patients is promising.

Structure and function: planning a new ICU to optimize patient care.

PURPOSE OF REVIEW: To survey the recent medical literature reporting effects of ICU design on patients' and family members' well being, safety and functionality. RECENT FINDINGS: Features of ICU design linked to the needs of patients and their family are single rooms, privacy, quiet surrounding, exposure to daylight, views of nature, prevention of infection, a family area and open visiting hours. Other features such as safety, working procedures, ergonomics and logistics have a direct impact on the patient care and the nursing and medical personnel. SUMMARY: An organization structured on the needs of the patient and their family is mandatory in designing a new ICU. The main aims in the design of a new department should be patient-centered care, safety, functionality, innovation and a future-proof concept.