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Early Postoperative Actigraphy Poorly Predicts Hypoactive Delirium.

ABSTRACT: STUDY OBJECTIVES:Delirium is a postoperative complication accompanied by disturbances in attention, cognition, arousal, and psychomotor activity. Wrist actigraphy has been advocated to study inactivity and inferred sleep patterns during delirium. We hypothesized that altered patterns of motor activity or immobility, reflective of disordered sleep and wakefulness patterns, would serve as predictive markers of hypoactive postoperative delirium. METHODS:Eighty-four elderly surgical patients were classified into three groups based on the timing of hypoactive delirium following surgery: intact with no delirium throughout postoperative days (POD) 0-5 (n = 51), delirium during POD 0-1 (n = 24), and delirium during POD 2-5 (n = 13). Delirium was detected on daily Confusion Assessment Method evaluations and chart review. Actigraphy measures were calculated from accelerometry signals acquired on the first postoperative day (POD 0, 16:00-23:00) and night (POD 0, 23:00-POD 1, 06:00). RESULTS:Actigraphy metrics showed substantial interpatient variability. Among the three patient groups, only those without delirium showed greater movement during the day compared to night and also fewer minutes of night immobility (P = .03 and P = .02, Wilcoxon rank-sum tests). These patients were poorly discriminated from those with delirium during either POD 0-1 or POD 2-5, using differences in day and night activity (C-statistic, 95% confidence interval [CI]: 0.66 [0.53-0.79] and C-statistic, 95% CI: 0.71 [0.55-0.87], respectively). Inclusion of low-frequency signals improved performance of immobility measures without affecting those based on activity. Cognitively intact patients during POD 0-5 were distinguished from those with delirium during POD 0-1, based on differences in the number of day and night immobile minutes (C-statistic 0.65, 95% CI: [0.53-0.78]). Actigraphy metrics with the strongest association to delirium incidence were not reliably correlated with an increased risk during POD 0-5, when accounting for patient age, sex, intensive care unit admission, and Charlson Comorbidity Index (adjusted odds ratio of 1.7, 95% CI: [1.0-3.0], P = .09, likelihood ratio test). CONCLUSIONS:Early postoperative wrist actigraphy metrics that serve as markers of sleep and wakefulness offer limited capacity as sole predictors or markers of hypoactive delirium. CLINICAL TRIAL REGISTRATION:Registry: ClinicalTrials.gov; Title: Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) Study; Identifier: NCT02241655; URL: https://clinicaltrials.gov/ct2/show/NCT02241655.

SUBMITTER: Maybrier HR

PROVIDER: S-EPMC6329546 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Early Postoperative Actigraphy Poorly Predicts Hypoactive Delirium.

Maybrier Hannah R HR King C Rya CR Crawford Amanda E AE Mickle Angela M AM Emmert Daniel A DA Wildes Troy S TS Avidan Michael S MS Palanca Ben Julian A BJA

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine 20190115 1

<h4>Study objectives</h4>Delirium is a postoperative complication accompanied by disturbances in attention, cognition, arousal, and psychomotor activity. Wrist actigraphy has been advocated to study inactivity and inferred sleep patterns during delirium. We hypothesized that altered patterns of motor activity or immobility, reflective of disordered sleep and wakefulness patterns, would serve as predictive markers of hypoactive postoperative delirium.<h4>Methods</h4>Eighty-four elderly surgical p ...[more]

PMID: 30621829

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Project description:Postoperative delirium is a common complication associated with increased morbidity and mortality, longer hospital stays, and greater health care expenditures. Intraoperative electroencephalogram (EEG) slowing has been associated previously with postoperative delirium, but the relationship between intraoperative EEG suppression and postoperative delirium has not been investigated.In this observational cohort study, 727 adult patients who received general anesthesia with planned intensive care unit admission were included. Duration of intraoperative EEG suppression was recorded from a frontal EEG channel (FP1 to F7). Delirium was assessed twice daily on postoperative days 1 through 5 with the Confusion Assessment Method for the intensive care unit. Thirty days after surgery, quality of life, functional independence, and cognitive ability were measured using the Veterans RAND 12-item survey, the Barthel index, and the PROMIS Applied Cognition-Abilities-Short Form 4a survey.Postoperative delirium was observed in 162 (26%) of 619 patients assessed. When we compared patients with no EEG suppression with those divided into quartiles based on duration of EEG suppression, patients with more suppression were more likely to experience delirium (?(4) = 25, P < 0.0001). This effect remained significant after we adjusted for potential confounders (odds ratio for log(EEG suppression) 1.22 [99% confidence interval, 1.06-1.40, P = 0.0002] per 1-minute increase in suppression). EEG suppression may have been associated with reduced functional independence (Spearman partial correlation coefficient -0.15, P = 0.02) but not with changes in quality of life or cognitive ability. Predictors of EEG suppression included greater end-tidal volatile anesthetic concentration and lower intraoperative opioid dose.EEG suppression is an independent risk factor for postoperative delirium. Future studies should investigate whether anesthesia titration to minimize EEG suppression decreases the incidence of postoperative delirium. This is a substudy of the Systematic Assessment and Targeted Improvement of Services Following Yearlong Surgical Outcomes Surveys (SATISFY-SOS) surgical outcomes registry (NCT02032030).

Project description:ObjectivesDelirium, a heterogenous syndrome, is associated with worse long-term cognition after critical illness. We sought to determine if duration of motoric subtypes of delirium are associated with worse cognition.DesignSecondary analysis of prospective multicenter cohort study.SettingAcademic, community, and Veteran Affairs hospitals.PatientsFive-hundred eighty-two survivors of respiratory failure or shock.InterventionsWe assessed delirium and level of consciousness using the Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale daily during hospitalization. We defined a day with hypoactive delirium as a day with positive Confusion Assessment Method-ICU and corresponding Richmond Agitation Sedation Scale score less than or equal to 0 and a day with hyperactive delirium as a day with positive Confusion Assessment Method-ICU and corresponding Richmond Agitation Sedation Scale score greater than 0. At 3 and 12 months, we assessed global cognition with the Repeatable Battery for the Assessment of Neurologic Status and executive function with the Trail Making Test Part B. We used multivariable regression to examine the associations between days of hypoactive and hyperactive delirium with cognition outcomes. We allowed for interaction between days of hypoactive and hyperactive delirium and adjusted for baseline and in-hospital covariates.Measurements and resultsHypoactive delirium was more common and persistent than hyperactive delirium (71% vs 17%; median 3 vs 1 d). Longer duration of hypoactive delirium was associated with worse global cognition at 3 (-5.13 [-8.75 to -1.51]; p = 0.03) but not 12 (-5.76 [-9.99 to -1.53]; p = 0.08) months and with worse executive functioning at 3 (-3.61 [-7.48 to 0.26]; p = 0.03) and 12 (-6.22 [-10.12 to -2.33]; p = 0.004) months; these associations were not modified by hyperactive delirium. Hyperactive delirium was not associated with global cognition or executive function in this cohort.ConclusionsLonger duration of hypoactive delirium was independently associated with worse long-term cognition. Assessing motoric subtypes of delirium in the ICU might aid in prognosis and intervention allocation. Future studies should consider delineating motoric subtypes of delirium.

Project description:Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with development of postoperative delirium in older surgical patients. We employed a nested case–control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort and the associations between preoperative protein levels and postoperative delirium were assessed using t-test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium (t-test p<0.05). Due to the limited sample size these proteins did not remain significant by multiple hypothesis testing using the Benjamini-Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40/48 case-control samples correctly, principal components analysis separated 43/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80-0.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identifies 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.

Project description:BACKGROUND:Postoperative delirium is a common complication associated with increased morbidity and mortality. A recently-reported association between intraoperative electroencephalogram suppression and postoperative delirium might be mediated in some patients by a heightened sensitivity to volatile anaesthetics. METHODS:This retrospective cohort study included 618 elective surgery patients with planned intensive care unit admission, who also received intraoperative electroencephalogram monitoring and had delirium assessments documented in the medical record. Sensitivity to volatile anaesthetics was assessed using a mixed effects model predicting the likelihood of electroencephalogram suppression at each time point based on the current end-tidal anaesthetic concentration. Patients with a random intercept above the population median (electroencephalogram suppression at lower anaesthetic concentrations) were classified as having heightened sensitivity to volatile anaesthetics. Delirium was defined as a positive Confusion Assessment Method for the Intensive Care Unit assessment anytime in the first five postoperative days. RESULTS:Postoperative delirium was observed in 162 of 618 patients (26%). Patients who experienced electroencephalogram suppression at lower volatile anaesthetic concentrations had a higher incidence of postoperative delirium [109/309 (35%)] than other patients [53/309 (17%)] [unadjusted odds ratio 2.63; 95% confidence interval (CI), 1.81-3.84, P<0.001]. This association remained significant after adjusting for patient characteristics, surgical variables, and duration of electroencephalogram suppression (adjusted odds ratio 2.13; 95% CI 1.24-3.65, P=0.006). CONCLUSIONS:These data support the hypothesis that patients with electroencephalogram suppression at lower volatile anaesthetic concentrations have an increased incidence of postoperative delirium. Such patients appear to exhibit a phenotype of anaesthetic sensitivity, which might predispose them to adverse cognitive outcomes.

Project description:To determine whether the use of flumazenil reverses hypoactive delirium and increases delirium-free days in critically ill patients who were exposed to benzodiazepine therapy during the ICU admission.DesignThis was a single-center, double-blinded, randomized placebo-controlled pilot study.SettingAdult ICUs at a large academic medical center in the United States.PatientsAdult, critically ill patients with benzodiazepine exposure and hypoactive delirium based on the Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale assessments were considered for enrollment.InterventionsPatients received a test dose of flumazenil starting at 0.1 mg intravenously and titrated up every 5 minutes by 0.1 mg increments up to a maximum total dose of 2 mg. Patients who demonstrated a Richmond Agitation Sedation Scale score increase of greater than 1 point were considered responders and randomized to flumazenil (0.05-0.3 mg/hr) or placebo infusion for up to 72 hours. Confusion Assessment Method-ICU scores were assessed twice daily for resolution of delirium.Measurements and main resultsThe trial was stopped early based on the observed size effect and power analysis. Twenty-two of the 25 patients responded to the flumazenil test dose (88%). The median number of delirium-free days alive without coma within 14 days of enrollment was similar between the two infusion groups (12.7 vs 9.2; p = 0.19). There was no difference in the probability of delirium resolution within the first 14 days with 90% versus 70% in the flumazenil and placebo groups, respectively (p = 0.2). There was no statistical difference (odds ratio, 0.17; 95% CI, 0.022-1.23; p = 0.079) in delirium- and coma-free days at the end of the study drug infusion. There was no difference between groups in ICU length of stay (7.8 ± 4.8 vs 7 ± 8; p = 0.74). No serious adverse events occurred.ConclusionsThis study found that flumazenil test dose and infusion present a potential option for hypoactive delirium associated with benzodiazepine exposure; however, the possible benefit is unknown. Larger studies are warranted to further evaluate these findings.

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Early Postoperative Actigraphy Poorly Predicts Hypoactive Delirium.

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Early Postoperative Actigraphy Poorly Predicts Hypoactive Delirium.

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