Benzodiazepines and postoperative delirium: should we be as cautious as we are?

A recent systematic review and meta-analysis by Wang and colleagues in the British Journal of Anaesthesia calls into question the concept that perioperative benzodiazepine administration is associated with development of postoperative delirium in older individuals after anaesthesia and surgery. This editorial focuses on potential bias within the systematic review and addresses major concerns surrounding benzodiazepine use in the older perioperative population.

Volatile versus intravenous anaesthesia and perioperative neurocognitive disorders: anything to see here?

There is a potential differential effect of sevoflurane compared with propofol on postoperative delirium and other perioperative neurocognitive disorders. More generally, there are perhaps differences between volatile and intravenous anaesthetic agents in their possible impact on perioperative neurocognitive disorders. Strengths and limitations of a recent study in this journal and its contribution to our understanding of the impact of anaesthetic technique on perioperative neurocognitive disorders are discussed.

Examining Subjective Psychological Experiences of Postoperative Delirium in Older Cardiac Surgery Patients.

BACKGROUND: Postoperative delirium (POD) is an acute syndrome including inattention and impaired cognition that affects approximately 42% of older cardiac surgical patients. POD is linked to adverse outcomes including morbidity, mortality, and further cognitive decline. Less is known about the subjective psychological experience of POD and its ongoing impact on well-being. METHODS: We performed a qualitative analysis of the long-term psychological sequelae of older adults who experience POD after cardiac surgery. We sampled 30 patients aged 60 years and older who experienced at least 2 episodes of POD during a prior hospital admission. We administered semistructured interviews with participants via telephone 3 to 5 years postoperatively. Interviews were transcribed and thematically analyzed. Data were interpreted in accordance with the naturalist paradigm. RESULTS: Three overarching themes emerged in our qualitative analysis. The first reflected the multifaceted presentation of POD, including distortion of time and reality; feelings of isolation; and a loss of self, identity, and control. The second theme reflected the psychological challenges associated with functional decline after surgery. Common examples of functional decline included cognitive difficulties, excessive fatigue, and a perceived loss of independence. The final theme captured the emotional sequelae of acute illness, which included low mood, reduced motivation, and social comparisons. CONCLUSIONS: Our findings emphasize the multidimensional experience of POD and long-term effects on psychological wellbeing. Our research highlights the beneficial role multidisciplinary clinicians play in managing POD including strategies that may be embedded into clinical practice and helps anesthesiologists understand why patients who have experienced POD in the past may present with specific concerns should they require subsequent surgery.

Methodology of measuring postoperative cognitive dysfunction: a systematic review.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is an adverse outcome that impacts patients' quality of life. Its diagnosis relies on formal cognitive testing performed before and after surgery. The substantial heterogeneity in methodology limits comparability and meta-analysis of studies. This systematic review critically appraises the methodology of studies on POCD published since the 1995 Consensus Statement and aims to provide guidance to future authors by providing recommendations that may improve comparability between future studies. METHODS: This systematic review of literature published between 1995 and 2019 included studies that used baseline cognitive testing and a structured cognitive test battery, and had a minimal follow-up of 1 month. For cohorts with multiple publications, data from the primary publication were supplemented with available data from later follow-up studies. RESULTS: A total of 274 unique studies were included in the analysis. In the included studies, 259 different cognitive tests were used. Studies varied considerably in timing of assessment, follow-up duration, definition of POCD, and use of control groups. Of the 274 included studies, 70 reported POCD as a dichotomous outcome at 1 to <3 months, with a pooled incidence of 2998/10 335 patients (29.0%). CONCLUSIONS: We found an overwhelming heterogeneity in methodology used to study POCD since the publication of the 1995 Consensus Statement. Future authors could improve study quality and comparability through optimal timing of assessment, the use of commonly used cognitive tests including the Consensus Statement 'core battery', application of appropriate cut-offs and diagnostic rules, and detailed reporting of the methods used. PROSPERO REGISTRY NUMBER: CRD42016039293.

Anaesthetic depth and delirium after major surgery: a randomised clinical trial.

BACKGROUND: Postoperative delirium is a serious complication of surgery associated with prolonged hospitalisation, long-term cognitive decline, and mortality. This study aimed to determine whether targeting bispectral index (BIS) readings of 50 (light anaesthesia) was associated with a lower incidence of POD than targeting BIS readings of 35 (deep anaesthesia). METHODS: This multicentre randomised clinical trial of 655 at-risk patients undergoing major surgery from eight centres in three countries assessed delirium for 5 days postoperatively using the 3 min confusion assessment method (3D-CAM) or CAM-ICU, and cognitive screening using the Mini-Mental State Examination at baseline and discharge and the Abbreviated Mental Test score (AMTS) at 30 days and 1 yr. Patients were assigned to light or deep anaesthesia. The primary outcome was the presence of postoperative delirium on any of the first 5 postoperative days. Secondary outcomes included mortality at 1 yr, cognitive decline at discharge, cognitive impairment at 30 days and 1 yr, unplanned ICU admission, length of stay, and time in electroencephalographic burst suppression. RESULTS: The incidence of postoperative delirium in the BIS 50 group was 19% and in the BIS 35 group was 28% (odds ratio 0.58 [95% confidence interval: 0.38-0.88]; P=0.010). At 1 yr, those in the BIS 50 group demonstrated significantly better cognitive function than those in the BIS 35 group (9% with AMTS ≤6 vs 20%; P<0.001). CONCLUSIONS: Among patients undergoing major surgery, targeting light anaesthesia reduced the risk of postoperative delirium and cognitive impairment at 1 yr. CLINICAL TRIAL REGISTRATION: ACTRN12612000632897.

Postoperative Cognitive Dysfunction and Noncardiac Surgery.

Postoperative cognitive dysfunction (POCD) is an objectively measured decline in cognition postoperatively compared with preoperative function. POCD has been considered in the anesthetic and surgical literature in isolation of cognitive decline which is common in the elderly within the community and where it is labeled as mild cognitive impairment, neurocognitive disorder, or dementia. This narrative review seeks to place POCD in the broad context of cognitive decline in the general population. Cognitive change after anesthesia and surgery was described over 100 years ago, initially as delirium and dementia. The term POCD was applied in the 1980s to refer to cognitive decline assessed purely on the basis of a change in neuropsychological test results, but the construct has been the subject of great heterogeneity. The cause of POCD remains unknown. Increasing age, baseline cognitive impairment, and fewer years of education are consistently associated with POCD.In geriatric medicine, cognitive disorders defined and classified as mild cognitive impairment, neurocognitive disorder, and dementia have definitive clinical features. To identify the clinical impact of cognitive impairment associated with the perioperative period, POCD has recently been redefined in terms of these geriatric medicine constructs so that the short-, medium-, and long-term clinical and functional impact can be elucidated. As the aging population present in ever increasing numbers for surgery, many individuals with overt or subclinical dementia require anesthesia. Anesthesiologists must be equipped to understand and manage these patients.

Prevalence of Dementia 7.5 Years after Coronary Artery Bypass Graft Surgery.

BACKGROUND: Although postoperative cognitive dysfunction (POCD) is well described after coronary artery bypass graft (CABG) surgery, a major concern has been that a progressive decline in cognition will ultimately lead to dementia. Since dementia interferes with the ability to carry out daily functions, the impact has far greater ramifications than cognitive decline defined purely by a decreased ability to perform on a battery of neurocognitive tests. The authors hypothesized that early cognitive impairment measured as baseline cognitive impairment is associated with an increased risk of long-term dementia. METHODS: The authors conducted a prospective longitudinal study on 326 patients aged 55 yr and older at the time of undergoing CABG surgery. Dementia was classified by expert opinion on review of performance on the Clinical Dementia Rating Scale and several other assessment tasks. Patients were also assessed for POCD at 3 and 12 months and at 7.5 yr using a battery of neuropsychologic tests and classified using the reliable change index. Associations were assessed using univariable analysis. RESULTS: At 7.5 yr after CABG surgery, the prevalence of dementia was 36 of 117 patients (30.8%; 95% CI, 23 to 40). POCD was detected in 62 of 189 patients (32.8%; 95% CI, 26 to 40). Due to incomplete assessments, the majority (113 patients), but not all, were assessed for both dementia and POCD. Fourteen of 32 (44%) patients with dementia were also classified as having POCD. Preexisting cognitive impairment and peripheral vascular disease were both associated with dementia 7.5 yr after CABG surgery. POCD at both 3 (odds ratio, 3.06; 95% CI, 1.39 to 9.30) and 12 months (odds ratio, 4.74; 95% CI, 1.63 to 13.77) was associated with an increased risk of mortality by 7.5 yr. CONCLUSIONS: The prevalence of dementia at 7.5 yr after CABG surgery is greatly increased compared to population prevalence. Impaired cognition before surgery or the presence of cardiovascular disease may contribute to the high prevalence.

Cardiac surgery, the brain, and inflammation.

Cognitive deterioration can reliably be measured after procedures requiring anesthesia and surgery. Cardiac surgery has had the spotlight because of the high reported incidence of postoperative cognitive dysfunction in early studies, but such effects occur after other surgical procedures as well. "Early" postoperative cognitive dysfunction should be considered as a different phenomenon, relating to acute pharmacological, physiological, and stress-related recovery. The focus should be on what is affecting patients at 3 months, 12 months, and 5 years later. Like with many other aspects of perioperative risk, a significant element is the patient's preoperative cognitive status. We now know that up to one-third of overtly "normal" elective cardiac surgical patients enter surgery with some degree of pre-existing cognitive impairment or, when applying psychogeriatric measures, mild cognitive impairment. The latter is a known prodrome or early stage of the amyloid associated Alzheimer's disease dementia. Inflammatory responses during cardiac surgery have been recognized for years, but our understanding of the complexity of systemic inflammatory response has grown significantly with the ability to assay neurohumoral markers such as interleukins. The blood-brain barrier is made vulnerable by both pre-existing disorders (mild cognitive impairment/amyloid; vascular disease) and by the inflammatory response to surgery and cardiopulmonary bypass. Inflammation affecting the brain at this time may set in motion accelerated neurological and hence cognitive decline that, despite an initial recovery and even functional improvement, may proceed to further long-term decline at an accelerated rate in susceptible individuals. Clinical data are emerging from longer-term studies to support this concern, but evidence for effective preventive or therapeutic strategies is limited.

Postoperative neurocognitive disorders: A clinical guide.

For years, postoperative cognitive outcomes have steadily garnered attention, and in the past decade, they have remained at the forefront. This prominence is primarily due to empirical research emphasizing their potential to compromise patient autonomy, reduce quality of life, and extend hospital stays, and increase morbidity and mortality rates, especially impacting elderly patients. The underlying pathophysiological process might be attributed to surgical and anaesthesiological-induced stress, leading to subsequent neuroinflammation, neurotoxicity, burst suppression and the development of hypercoagulopathy. The beneficial impact of multi-faceted strategies designed to mitigate the surgical and perioperative stress response has been suggested. While certain potential risk factors are difficult to modify (e.g., invasiveness of surgery), others - including a more personalized depth of anaesthesia (EEG-guided), suitable analgesia, and haemodynamic stability - fall under the purview of anaesthesiologists. The ESAIC Safe Brain Initiative research group recommends implementing a bundle of non-invasive preventive measures as a standard for achieving more patient-centred care. Implementing multi-faceted preoperative, intraoperative, and postoperative preventive initiatives has demonstrated the potential to decrease the incidence and duration of postoperative delirium. This further validates the importance of a holistic, team-based approach in enhancing patients' clinical and functional outcomes. This review aims to present evidence-based recommendations for preventing, diagnosing, and treating postoperative neurocognitive disorders with the Safe Brain Initiative approach.

A first assessment of the safe brain initiative care bundle for addressing postoperative delirium in the postanesthesia care unit.

BACKGROUND: Postoperative delirium (POD) following surgery is a prevalent and distressing condition associated with adverse patient outcomes and an increased healthcare burden. OBJECTIVES: To assess the effectiveness of the Safe Brain Initiative care bundle (SBI-CB) in reducing POD in the postanesthesia care unit (PACU). DESIGN: A multicenter, quality-improvement initiative with retrospective analysis of collected data. SETTING: The study was conducted in the operating rooms and postanesthesia care units (PACUs) of four hospitals across Denmark and Turkey. PATIENTS: The convenience sample of patients were aged ≥18 years, scheduled for surgery, and could communicate verbally. Age, sex, preoperative delirium, and the American Society for Anesthesiology physical status classification were used in statistical methods to control for potential confounding influences. INTERVENTION: The SBI-CB, 18 delirium-reducing recommendations aligned with international guidelines. The intervention included patient education, staff training, coordination meetings across centers, and a dashboard for the monitoring of outcomes in the PACU. MAIN OUTCOME MEASURES: The primary outcome was the POD trend in the PACU during implementation months, assessed through Nu-DESC screening at up to three time points in the PACU. We also examined the length of hospital stay. RESULTS: Data were collected from 18,697 adult patients across four hospitals. Initial POD incidence in the PACU after the first three months was 16.36% across all sites (n = 1021). POD in the PACU was observed across all age groups, with peak incidence in younger (18-35 years) and older (>75 years) patients. General anesthesia and longer surgical duration (>1 h) were identified as significant risk factors for POD in the PACU. Matched patients who experienced POD in the PACU had longer stays in hospital, with a mean increase from 35 to 69 h (p < 0.001). Implementation of the SBI-CB was associated with a decreased risk of POD in the PACU for each month of SBI-CB implementation (adjusted odds ratio 0.96, 95% confidence interval: [0.94, 0.97], p < 0.001). CONCLUSIONS: The presented pragmatic implementation of a multidisciplinary care bundle, encompassing pre-, intra-, and postoperative measures alongside outcome monitoring, has the potential to significantly reduce the incidence of POD in the PACU. Improved patient outcomes may be achieved for general surgical departments with patient cohorts not typically considered at risk for developing POD. TRIAL REGISTRATION: Clinicaltrials.gov, identifier NCT05765162.

Incidence and Impact of a Single-Unit Red Blood Cell Transfusion: Analysis of The Society of Thoracic Surgeons Database 2010-2019.

BACKGROUND: As the adverse effects of blood transfusions are better understood, recommendations support single-unit red blood cell (RBC) transfusions (SRBCT). However, an isolated SRBCT across the entire index admission suggests even the single unit may be avoidable. We sought to identify the characteristics of cardiac surgery patients receiving an isolated SRBCT and analyze the impact on outcomes. METHODS: The Society of Thoracic Surgeons Adult Cardiac Surgery Database was queried for the period between January 1, 2010, and December 31, 2019. Patients aged >18 years undergoing isolated coronary artery bypass grafting or isolated aortic valve replacement were included. A total of 2,151,430 encounters were analyzed. RESULTS: Of the 847,442 patients (39.3%) receiving any RBC transfusion during their index admission, 206,555 (24.4%) received only 1 unit. Propensity-matching analysis determined SRBCT patients were significantly older (67.26 vs 64.02 years; odds ratio [OR], 1.02; P < .001), female (39.1% vs 17.8%; OR, 1.57; P < .001), non-White (18.2% vs 13.1%; OR, 0.81; P < .001), and had a smaller body surface area (1.94 vs 2.07 m2; OR, 0.20; P < .001). They also had higher mortality (1.4% vs 1.0%, P < .001), stroke (1.7% vs 1.2%, P < .001), prolonged ventilation (6.4% vs 3.4%, P < .001), renal failure (1.8% vs 0.9%, P < .001), and reoperations (1.3% vs. 0.5%, P < .001) than patients who received 0 RBCs. CONCLUSIONS: SRBCT is a common occurrence in adult cardiac surgery. This low-volume transfusion is strongly associated with higher morbidity, even after controlling for preoperative risk factors.

A Real-Time Neurophysiologic Stress Test for the Aging Brain: Novel Perioperative and ICU Applications of EEG in Older Surgical Patients.

As of 2022, individuals age 65 and older represent approximately 10% of the global population [1], and older adults make up more than one third of anesthesia and surgical cases in developed countries [2, 3]. With approximately > 234 million major surgical procedures performed annually worldwide [4], this suggests that > 70 million surgeries are performed on older adults across the globe each year. The most common postoperative complications seen in these older surgical patients are perioperative neurocognitive disorders including postoperative delirium, which are associated with an increased risk for mortality [5], greater economic burden [6, 7], and greater risk for developing long-term cognitive decline [8] such as Alzheimer's disease and/or related dementias (ADRD). Thus, anesthesia, surgery, and postoperative hospitalization have been viewed as a biological "stress test" for the aging brain, in which postoperative delirium indicates a failed stress test and consequent risk for later cognitive decline (see Fig. 3). Further, it has been hypothesized that interventions that prevent postoperative delirium might reduce the risk of long-term cognitive decline. Recent advances suggest that rather than waiting for the development of postoperative delirium to indicate whether a patient "passed" or "failed" this stress test, the status of the brain can be monitored in real-time via electroencephalography (EEG) in the perioperative period. Beyond the traditional intraoperative use of EEG monitoring for anesthetic titration, perioperative EEG may be a viable tool for identifying waveforms indicative of reduced brain integrity and potential risk for postoperative delirium and long-term cognitive decline. In principle, research incorporating routine perioperative EEG monitoring may provide insight into neuronal patterns of dysfunction associated with risk of postoperative delirium, long-term cognitive decline, or even specific types of aging-related neurodegenerative disease pathology. This research would accelerate our understanding of which waveforms or neuronal patterns necessitate diagnostic workup and intervention in the perioperative period, which could potentially reduce postoperative delirium and/or dementia risk. Thus, here we present recommendations for the use of perioperative EEG as a "predictor" of delirium and perioperative cognitive decline in older surgical patients.

Mitigation of perioperative neurocognitive disorders: A holistic approach.

William Morton introduced the world to ether anesthesia for use during surgery in the Bullfinch Building of the Massachusetts General Hospital on October 16, 1846. For nearly two centuries, the prevailing wisdom had been that the effects of general anesthetics were rapidly and fully reversible, with no apparent long-term adverse sequelae. Despite occasional concerns of a possible association between surgery and anesthesia with dementia since 1887 (Savage, 1887), our initial belief was robustly punctured following the publication in 1998 of the International Study of Post-Operative Cognitive Dysfunction [ISPOCD 1] study by Moller et al. (1998) in The Lancet, in which they demonstrated in a prospective fashion that there were in fact persistent adverse effects on neurocognitive function up to 3 months following surgery and that these effects were common. Since the publication of that landmark study, significant strides have been made in redefining the terminology describing cognitive dysfunction, identifying those patients most at risk, and establishing the underlying etiology of the condition, particularly with respect to the relative contributions of anesthesia and surgery. In 2018, the International Nomenclature Consensus Working Group proposed new nomenclature to standardize identification of and classify perioperative cognitive changes under the umbrella of perioperative neurocognitive disorders (PND) (Evered et al., 2018a). Since then, the new nomenclature has tried to describe post-surgical cognitive derangements within a unifying framework and has brought to light the need to standardize methodology in clinical studies and motivate such studies with hypotheses of PND pathogenesis. In this narrative review, we highlight the relevant literature regarding recent key developments in PND identification and management throughout the perioperative period. We provide an overview of the new nomenclature and its implications for interpreting risk factors identified by clinical association studies. We then describe current hypotheses for PND development, using data from clinical association studies and neurophysiologic data where appropriate. Finally, we offer broad clinical guidelines for mitigating PND in the perioperative period, highlighting the role of Brain Enhanced Recovery After Surgery (Brain-ERAS) protocols.

Preexisting cognitive impairment and mild cognitive impairment in subjects presenting for total hip joint replacement.

BACKGROUND: The prevalence of preexisting cognitive impairment (PreCI) is documented before cardiac surgery, but there is less information before noncardiac surgery. In addition, the prevalence of mild cognitive impairment, defined by different cognitive criteria and subjective complaints, and which may progress to Alzheimer disease, is unknown in these subjects. Because anesthesia and surgery have been implicated in Alzheimer disease pathology, we prospectively measured PreCI and mild cognitive impairment in subjects scheduled for total hip joint replacement surgery in an observational study. METHODS: One hundred fifty-two subjects 60 y of age and older who were scheduled for total hip joint replacement surgery underwent assessment, including neuropsychologic testing, 1 week before surgery. Test results were compared with published norms. PreCI was defined as impairment in two or more of seven cognitive tests, for which impairment in an individual test was defined as ≥ 2 SD below norms for that test. Amnestic mild cognitive impairment (aMCI) was defined as impairment ≥1.5 SD below norms for results of the immediate and/or delayed Auditory Verbal Learning Test plus a subjective complaint. RESULTS: Subjects performed worse compared with normative data on five of seven neuropsychologic tests. Thirty (20% [95% CI, 13-26%]) subjects were classified as having PreCI. Thirty-four (22% [95% CI, 16-29%]) were classified as having aMCI. Ten (7%) subjects were classified as having both PreCI and aMCI, representing 33% of the 30 subjects with PreCI. CONCLUSIONS: The prevalence of aMCI in subjects scheduled for total hip joint replacement surgery is similar to that in the general community. PreCI and aMCI tend to identify different subjects. Because aMCI is known to progress to Alzheimer disease, future studies that track cognition before and after anesthesia and surgery should document the presence or absence of aMCI so that the rate of conversion to Alzheimer disease after anesthesia and surgery can be compared with the rate in the nonsurgical population.

Reducing Perioperative Neurocognitive Disorders (PND) Through Depth of Anesthesia Monitoring: A Critical Review.

General anesthesia has been administered for over 150 years, and in that time, has become progressively safer. Improvements in outcomes have been driven by multiple advances, including the use of non-invasive monitors to assess cardiovascular and respiratory status. More recent advances have included the development and use of monitors to measure neurologic status by means of "processed" electroencephalography (pEEG), wherein the frontal EEG signal is analyzed by proprietary algorithms to produce a dimensionless number (scaled from 0 to 100), wherein low values are associated with deepening levels of sedation that progresses to loss of consciousness. Such monitors have been shown to enable anesthetic titration so as to expedite emergence and early recovery, and their use is advocated for the prevention of intraoperative awareness in the setting of administration of total intravenous anesthesia and neuromuscular blockade. Whether their use can minimize, or prevent, longer term adverse events is a matter of debate. In this narrative review of the most recent literature, we provide an assessment on the use of pEEG monitors in the prevention of a notable, and important, postoperative adverse outcome - delirium - in elderly patients. As we will discuss, the existing data do not support its routine use for the prevention of postoperative delirium in this, or any other, patient population.

Impaired cognitive performance on MoCA testing at discharge in elderly patients following day endoscopy and its relationship to preoperative mild cognitive impairment.

In patients admitted to hospital, preoperative mild cognitive impairment predicts postoperative complications. The effect of mild cognitive impairment on discharge readiness among the day stay surgery population is unknown. Our aims were to determine the incidence of impaired cognitive performance at discharge after day stay endoscopy and whether pre-existing mild cognitive impairment was associated with its development. A single-centre cohort study of elective day stay endoscopy patients was undertaken. Over a three-month period, data were collected from 69 patients aged 65 years and over. Patients were cognitively assessed on admission and discharge using the Montreal cognitive assessment tool and the three-minute diagnostic confusion assessment method. At baseline, patients who scored 1.5 or more standard deviations below age-adjusted levels on the Montreal cognitive assessment tool in conjunction with a subjective memory complaint were classified as having mild cognitive impairment. At discharge, patients were classified as having impaired cognitive performance if there was a reduction in the Montreal cognitive assessment tool score by at least two points. We also assessed delirium and subsyndromal delirium at discharge using the three-minute diagnostic confusion assessment method. We identified mild cognitive impairment in 23 patients (33.3%) on admission, and impaired performance on the Montreal cognitive assessment tool test at discharge in 35 (50.7%) patients. There was no association between mild cognitive impairment on admission and impaired cognitive performance at discharge (50.0% versus 51.1%, P = 0.94). This study demonstrates that evidence of impaired cognitive performance on the Montreal cognitive assessment tool testing is present after day stay endoscopy in over 50% of elderly patients, but this is not associated with preoperative cognitive status.