Background Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium. Methods This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5. Results Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs. 123 of 683 [18%], P < 0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size ( P = 0.078 for moderation). Conclusions A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect. Editor’s Perspective What We Already Know about This Topic Postoperative delirium is common in older surgical patients Intraoperative electroencephalogram suppression has been associated with postoperative delirium Patients with preoperative cognitive impairment have an increased risk of developing postoperative delirium What This Article Tells Us That Is New The indirect effect of intraoperative electroencephalogram suppression on the development of postoperative delirium among patients with preexisting cognitive impairment is probably small but nonzero Approximately 28 cognitively impaired patients would need to be kept out of electroencephalogram suppression to avoid 1 case of postoperative delirium

Background Mechanisms of postoperative delirium remain poorly understood, limiting development of effective treatments. We tested the hypothesis that intraoperative oxidative damage is associated with delirium and neuronal injury and that disruption of the blood–brain barrier modifies these associations. Methods In a prespecified cohort study of 400 cardiac surgery patients enrolled in a clinical trial of atorvastatin to reduce kidney injury and delirium, we measured plasma concentrations of F 2 -isoprostanes and isofurans using gas chromatography-mass spectrometry to quantify oxidative damage, ubiquitin carboxyl-terminal hydrolase isozyme L1 to quantify neuronal injury, and S100 calcium-binding protein B using enzyme-linked immunosorbent assays to quantify blood–brain barrier disruption before, during, and after surgery. We performed the Confusion Assessment Method for the Intensive Care Unit twice daily to diagnose delirium. We measured the independent associations between intraoperative F 2 -isoprostanes and isofurans and delirium (primary outcome) and postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (secondary outcome), and we assessed if S100 calcium-binding protein B modified these associations. Results Delirium occurred in 109 of 400 (27.3%) patients for a median (10th, 90th percentile) of 1.0 (0.5, 3.0) days. In the total cohort, plasma ubiquitin carboxyl-terminal hydrolase isozyme L1 concentration was 6.3 ng/ml (2.7, 14.9) at baseline and 12.4 ng/ml (7.9, 31.2) on postoperative day 1. F 2 -isoprostanes and isofurans increased throughout surgery, and the log-transformed sum of intraoperative F 2 -isoprostanes and isofurans was independently associated with increased odds of postoperative delirium (odds ratio, 3.70 [95% CI, 1.41 to 9.70]; P = 0.008) and with increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 (ratio of geometric means, 1.42 [1.11 to 1.81]; P = 0.005). The association between increased intraoperative F 2 -isoprostanes and isofurans and increased postoperative ubiquitin carboxyl-terminal hydrolase isozyme L1 was amplified in patients with elevated S100 calcium-binding protein B ( P = 0.049). Conclusions Intraoperative oxidative damage was associated with increased postoperative delirium and neuronal injury, and the association between oxidative damage and neuronal injury was stronger among patients with increased blood–brain barrier disruption. Editor’s Perspective What We Already Know about This Topic Postoperative delirium occurs in approximately 25% of cardiac surgery patients. Hyperoxic cerebral perfusion during cardiac surgery has been associated with increased postoperative delirium, and oxidative damage may mediate this association. What This Article Tells Us That Is New In a cohort of 400 cardiac surgery patients, intraoperative plasma concentrations of F 2 -isoprostanes and isofurans (markers of oxidative damage) were independently associated with both increased postoperative delirium and increased plasma concentrations of ubiquitin carboxyl-terminal hydrolase isozyme L1, a marker of neuronal injury. The association between increased systemic markers of oxidative damage and increased neuronal injury was stronger in patients with elevated plasma S100 calcium-binding protein B, a marker of blood–brain barrier disruption. This suggests that blood–brain barrier disruption may increase susceptibility to neuronal injury associated with systemic oxidative stress.

Editor’s Perspective What We Already Know about This Topic Postoperative delirium and postoperative cognitive dysfunction both occur in a substantial number of older surgical patients Postoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, although their relationship is unclear What This Article Tells Us That Is New Postoperative delirium increased the risk of postoperative cognitive dysfunction at 1 month postoperatively but there was no association between postoperative delirium and cognitive dysfunction at 2 and 6 months after major noncardiac surgery Postoperative delirium and longer-term postoperative cognitive dysfunction may be different disorders Background Postoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up. Methods This study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method–based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months. Results One hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small ( r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07–1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72–1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71–2.09). Conclusions Delirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.

Editor’s Perspective What We Already Know about This Topic Delirium is a frequently occurring disorder in intensive care unit patients associated with impaired short-term and long-term outcomes Prophylactic haloperidol neither reduces delirium incidence nor its short-term clinical consequences Many intensive care unit survivors suffer from long-term impairment of physical, cognitive, or mental health status, but there is a gap in knowledge regarding which factors are associated with such a change in quality of life in the post–intensive care unit period What This Article Tells Us That Is New Prophylactic haloperidol does not affect long-term outcome of critically ill patients at high risk for delirium Every additional day of sedation-induced coma is associated with further decline of long-term physical and mental function Background Delirium incidence in intensive care unit patients is high and associated with impaired long-term outcomes. The use of prophylactic haloperidol did not improve short-term outcome among critically ill adults at high risk of delirium. This study evaluated the effects of prophylactic haloperidol use on long-term quality of life in this group of patients and explored which factors are associated with change in quality of life. Methods A preplanned secondary analysis of long-term outcomes of the pRophylactic haloperidol usE for DeliriUm in iCu patients at high risk for dElirium (REDUCE) study was conducted. In this multicenter randomized clinical trial, nondelirious intensive care unit patients were assigned to prophylactic haloperidol (1 or 2 mg) or placebo (0.9% sodium chloride). In all groups, patients finally received study medication for median duration of 3 days [interquartile range, 2 to 6] until onset of delirium or until intensive care unit discharge. Long-term outcomes were assessed using the Short Form-12 questionnaire at intensive care unit admission (baseline) and after 1 and 6 months. Quality of life was summarized in the physical component summary and mental component summary scores. Differences between the haloperidol and placebo group and factors associated with changes in quality of life were analyzed. Results Of 1,789 study patients, 1,245 intensive care unit patients were approached, of which 887 (71%) responded. Long-term quality of life did not differ between the haloperidol and placebo group (physical component summary mean score of 39 ± 11 and 39 ± 11, respectively, and P = 0.350; and mental component summary score of 50 ± 10 and 51 ± 10, respectively, and P = 0.678). Age, medical and trauma admission, quality of life score at baseline, risk for delirium (PRE-DELIRIC) score, and the number of sedation-induced coma days were significantly associated with a decline in long-term quality of life. Conclusions Prophylactic haloperidol use does not affect long-term quality of life in critically ill patients at high risk for delirium. Several factors, including the modifiable factor number of sedation-induced coma days, are associated with decline in long-term outcomes.

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions. Two major classification guidelines (Diagnostic and Statistical Manual for Mental Disorders, fifth edition [DSM-5] and National Institute for Aging and the Alzheimer Association [NIA-AA]) are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that ‘perioperative neurocognitive disorders’ be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder ); any form of acute event ( postoperative delirium ) and cognitive decline diagnosed up to 30 days after the procedure ( delayed neurocognitive recovery ) and up to 12 months ( postoperative neurocognitive disorder ).

For half a century, it has been known that some patients experience neurocognitive dysfunction after cardiac surgery; however, defining its incidence, course, and causes remains challenging and controversial. Various terms have been used to describe neurocognitive dysfunction at different times after cardiac surgery, ranging from “postoperative delirium” to “postoperative cognitive dysfunction or decline.” Delirium is a clinical diagnosis included in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Postoperative cognitive dysfunction is not included in the DSM-5 and has been heterogeneously defined, though a recent international nomenclature effort has proposed standardized definitions for it. Here, the authors discuss pathophysiologic mechanisms that may underlie these complications, review the literature on methods to prevent them, and discuss novel approaches to understand their etiology that may lead to novel treatment strategies. Future studies should measure both delirium and postoperative cognitive dysfunction to help clarify the relationship between these important postoperative complications.

What We Already Know about This Topic Cardiac surgery is associated with cognitive decline and postoperative delirium The relationship between postoperative delirium and cognitive decline after cardiac surgery is unclear What This Article Tells Us That Is New The development of postoperative delirium is associated with a greater degree of cognitive decline 1 month after cardiac surgery The development of postoperative delirium is not a predictor of cognitive decline 1 yr after cardiac surgery Background Delirium is common after cardiac surgery and has been associated with morbidity, mortality, and cognitive decline. However, there are conflicting reports on the magnitude, trajectory, and domains of cognitive change that might be affected. The authors hypothesized that patients with delirium would experience greater cognitive decline at 1 month and 1 yr after cardiac surgery compared to those without delirium. Methods Patients who underwent coronary artery bypass and/or valve surgery with cardiopulmonary bypass were eligible for this cohort study. Delirium was assessed with the Confusion Assessment Method. A neuropsychologic battery was administered before surgery, at 1 month, and at 1 yr later. Linear regression was used to examine the association between delirium and change in composite cognitive Z score from baseline to 1 month (primary outcome). Secondary outcomes were domain-specific changes at 1 month and composite and domain-specific changes at 1 yr. Results The incidence of delirium in 142 patients was 53.5%. Patients with delirium had greater decline in composite cognitive Z score at 1 month (greater decline by −0.29; 95% CI, −0.54 to −0.05; P = 0.020) and in the domains of visuoconstruction and processing speed. From baseline to 1 yr, there was no difference between delirious and nondelirious patients with respect to change in composite cognitive Z score, although greater decline in processing speed persisted among the delirious patients. Conclusions Patients who developed delirium had greater decline in a composite measure of cognition and in visuoconstruction and processing speed domains at 1 month. The differences in cognitive change by delirium were not significant at 1 yr, with the exception of processing speed.

Background Postoperative pain and opioid use are associated with postoperative delirium. We designed a single-center, randomized, placebo-controlled, parallel-arm, double-blinded trial to determine whether perioperative administration of gabapentin reduced postoperative delirium after noncardiac surgery. Methods Patients were randomly assigned to receive placebo (N = 347) or gabapentin 900 mg (N = 350) administered preoperatively and for the first 3 postoperative days. The primary outcome was postoperative delirium as measured by the Confusion Assessment Method. Secondary outcomes were postoperative pain, opioid use, and length of hospital stay. Results Data for 697 patients were included, with a mean ± SD age of 72 ± 6 yr. The overall incidence of postoperative delirium in any of the first 3 days was 22.4% (24.0% in the gabapentin and 20.8% in the placebo groups; the difference was 3.20%; 95% CI, 3.22% to 9.72%; P = 0.30). The incidence of delirium did not differ between the two groups when stratified by surgery type, anesthesia type, or preoperative risk status. Gabapentin was shown to be opioid sparing, with lower doses for the intervention group versus the control group. For example, the morphine equivalents for the gabapentin-treated group, median 6.7 mg (25th, 75th quartiles: 1.3, 20.0 mg), versus control group, median 6.7 mg (25th, 75th quartiles: 2.7, 24.8 mg), differed on the first postoperative day ( P = 0.04). Conclusions Although postoperative opioid use was reduced, perioperative administration of gabapentin did not result in a reduction of postoperative delirium or hospital length of stay.

Background Previously, we showed experimentally that saturation of slow-wave activity provides a potentially individualized neurophysiologic endpoint for perception loss during anesthesia. Furthermore, it is clear that induction and emergence from anesthesia are not symmetrically reversible processes. The observed hysteresis is potentially underpinned by a neural inertia mechanism as proposed in animal studies. Methods In an advanced secondary analysis of 393 individual electroencephalographic data sets, we used slow-wave activity dose-response relationships to parameterize slow-wave activity saturation during induction and emergence from surgical anesthesia. We determined whether neural inertia exists in humans by comparing slow-wave activity dose responses on induction and emergence. Results Slow-wave activity saturation occurs for different anesthetics and when opioids and muscle relaxants are used during surgery. There was wide interpatient variability in the hypnotic concentrations required to achieve slow-wave activity saturation. Age negatively correlated with power at slow-wave activity saturation. On emergence, we observed abrupt decreases in slow-wave activity dose responses coincident with recovery of behavioral responsiveness in ~33% individuals. These patients are more likely to have lower power at slow-wave activity saturation, be older, and suffer from short-term confusion on emergence. Conclusions Slow-wave activity saturation during surgical anesthesia implies that large variability in dosing is required to achieve a targeted potential loss of perception in individual patients. A signature for neural inertia in humans is the maintenance of slow-wave activity even in the presence of very-low hypnotic concentrations during emergence from anesthesia.

Background Delirium is an acute and reversible geriatric syndrome that represents a decompensation of cerebral function. Delirium is associated with adverse postoperative outcomes, but controversy exists regarding whether delirium is an independent predictor of mortality. Thus, we assessed the association between incident postoperative delirium and mortality in adult noncardiac surgery patients. Methods A systematic search was conducted using Cochrane, MEDLINE/PubMed, Cumulative Index to Nursing and Allied Health Literature, and Embase. Screening and data extraction were conducted by two independent reviewers. Pooled-effect estimates calculated with a random-effects model were expressed as odds ratios with 95% CIs. Risk of bias was assessed using the Cochrane Risk of Bias Tool for Non-Randomized Studies. Results A total of 34 of 4,968 screened citations met inclusion criteria. Risk of bias ranged from moderate to critical. Pooled analysis of unadjusted event rates (5,545 patients) suggested that delirium was associated with a four-fold increase in the odds of death (odds ratio = 4.12 [95% CI, 3.29 to 5.17]; I 2 = 24.9%). A formal pooled analysis of adjusted outcomes was not possible due to heterogeneity of effect measures reported. However, in studies that controlled for prespecified confounders, none found a statistically significant association between incident postoperative delirium and mortality (two studies in hip fractures; n = 729) after an average follow-up of 21 months. Overall, as study risk of bias decreased, the association between delirium and mortality decreased. Conclusions Few high-quality studies are available to estimate the impact of incident postoperative delirium on mortality. Studies that controlled for prespecified confounders did not demonstrate significant independent associations of delirium with mortality.

Background Inflammation after cardiopulmonary bypass may contribute to postoperative delirium and cognitive dysfunction. The authors evaluated the effect of high-dose methylprednisolone to suppress inflammation on the incidence of delirium and postoperative quality of recovery after cardiac surgery. Methods Five hundred fifty-five adults from three hospitals enrolled in the randomized, double-blind Steroids in Cardiac Surgery trial were randomly allocated to placebo or 250 mg methylprednisolone at induction and 250 mg methylprednisolone before cardiopulmonary bypass. Each completed the Postoperative Quality of Recovery Scale before surgery and on days 1, 2, and 3 and 1 and 6 months after surgery and the Confusion Assessment Method scale for delirium on days 1, 2, and 3. Recovery was defined as returning to preoperative values or improvement at each time point. Results Four hundred eighty-two participants for recovery and 498 participants for delirium were available for analysis. The quality of recovery improved over time but without differences between groups in the primary endpoint of overall recovery (odds ratio range over individual time points for methylprednisolone, 0.39 to 1.45; 95% CI, 0.08–2.04 to 0.40–5.27; P = 0.943) or individual recovery domains (all P > 0.05). The incidence of delirium was 10% (control) versus 8% (methylprednisolone; P = 0.357), with no differences in delirium subdomains (all P > 0.05). In participants with normal (51%) and low baseline cognition (49%), there were no significant differences favoring methylprednisolone in any domain (all P > 0.05). Recovery was worse in patients with postoperative delirium in the cognitive ( P = 0.004) and physiologic ( P < 0.001) domains. Conclusions High-dose intraoperative methylprednisolone neither reduces delirium nor improves the quality of recovery in high-risk cardiac surgical patients.

Background Postoperative delirium (POD) is a serious complication after cardiac surgery. Use of dexmedetomidine to prevent delirium is controversial. The authors hypothesized that dexmedetomidine sedation after cardiac surgery would reduce the incidence of POD. Methods After institutional ethics review board approval, and informed consent, a single-blinded, prospective, randomized controlled trial was conducted in patients 60 yr or older undergoing cardiac surgery. Patients with a history of serious mental illness, delirium, and severe dementia were excluded. Upon admission to intensive care unit (ICU), patients received either dexmedetomidine (0.4 μg/kg bolus followed by 0.2 to 0.7 μg kg −1 h −1 infusion) or propofol (25 to 50 μg kg −1 min −1 infusion) according to a computer-generated randomization code in blocks of four. Assessment of delirium was performed with confusion assessment method for ICU or confusion assessment method after discharge from ICU at 12-h intervals during the 5 postoperative days. Primary outcome was the incidence of POD. Results POD was present in 16 of 91 (17.5%) and 29 of 92 (31.5%) patients in dexmedetomidine and propofol groups, respectively (odds ratio, 0.46; 95% CI, 0.23 to 0.92; P = 0.028). Median onset of POD was on postoperative day 2 (1 to 4 days) versus 1 (1 to 4 days), P = 0.027, and duration of POD 2 days (1 to 4 days) versus 3 days (1 to 5 days), P = 0.04, in dexmedetomidine and propofol groups, respectively. Conclusions When compared with propofol, dexmedetomidine sedation reduced incidence, delayed onset, and shortened duration of POD in elderly patients after cardiac surgery. The absolute risk reduction for POD was 14%, with a number needed to treat of 7.1. Abstract When compared with propofol, dexmedetomidine sedation reduced incidence, delayed onset, and shortened duration of postoperative delirium in elderly patients after cardiac surgery.

Background: Postoperative delirium is common in patients recovering from cardiac surgery. Tight glucose control has been shown to reduce mortality and morbidity. Therefore, the authors sought to determine the effect of tight intraoperative glucose control using a hyperinsulinemic–normoglycemic clamp approach on postoperative delirium in patients undergoing cardiac surgery. Methods: The authors enrolled 198 adult patients having cardiac surgery in this randomized, double-blind, single-center trial. Patients were randomly assigned to either tight intraoperative glucose control with a hyperinsulinemic–normoglycemic clamp (target blood glucose, 80 to 110 mg/dl) or standard therapy (conventional insulin administration with blood glucose target, <150 mg/dl). Delirium was assessed using a comprehensive delirium battery. The authors considered patients to have experienced postoperative delirium when Confusion Assessment Method testing was positive at any assessment. A positive Confusion Assessment Method was defined by the presence of features 1 (acute onset and fluctuating course) and 2 (inattention) and either 3 (disorganized thinking) or 4 (altered consciousness). Results: Patients randomized to tight glucose control were more likely to be diagnosed as being delirious than those assigned to routine glucose control (26 of 93 vs. 15 of 105; relative risk, 1.89; 95% CI, 1.06 to 3.37; P = 0.03), after adjusting for preoperative usage of calcium channel blocker and American Society of Anesthesiologist physical status. Delirium severity, among patients with delirium, was comparable with each glucose management strategy. Conclusion: Intraoperative hyperinsulinemic–normoglycemia augments the risk of delirium after cardiac surgery, but not its severity. Abstract Intraoperative hyperinsulinemic–normoglycemia augments the risk of delirium after cardiac surgery, but not its severity.

Background: This study aimed to characterize the electroencephalogram in children who emerged with emergence delirium (ED) compared with children without ED using methods that involved the assessment of cortical functional connectivity. Methods: Children aged 5 to 15 yr had multichannel electroencephalographic recordings during induction and emergence from anesthesia during minor surgical procedures. Of these, five children displayed ED after sevoflurane anesthesia. Measures of cortical functional connectivity previously used to evaluate anesthetic action in adults were compared between ED and age-, sex-, and anesthetic-matched non-ED children during emergence from anesthesia. Results: At the termination of sevoflurane anesthesia, the electroencephalogram in both ED and control patients showed delta frequency slowing and frontally dominant alpha activity, followed by a prolonged state with low-voltage, fast frequency activity (referred to as an indeterminate state ). In children with ED, arousal with delirious behavior and a variety of electroencephalogram patterns occurred during the indeterminate state, before the appearance of normal wake or sleep patterns. The electroencephalogram in children without ED progressed from the indeterminate state to classifiable sleep or drowsy states, before peaceful awakening. Statistically significant differences in frontal lobe functional connectivity were identified between children with ED and non-ED. Conclusions: ED is associated with arousal from an indeterminate state before the onset of sleep-like electroencephalogram patterns. Increased frontal lobe cortical functional connectivity observed in ED, immediately after the termination of sevoflurane anesthesia, will have important implications for the development of methods to predict ED, the design of preventative strategies, and efforts to better understand its pathophysiology.

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.