The effect of depth of anesthesia monitoring on postoperative delirium: A narrative review

Postoperative cognitive dysfunction in clinical practice

Dexmedetomidine plays a pivotal role in mitigating postoperative delirium and cognitive dysfunction while enhancing the overall quality of life among surgical patients. Nevertheless, the influence of dexmedetomidine on such complications in various anaesthesia techniques remains inadequately explored. As such, in the present study, a meta-analysis was conducted to comprehensively evaluate its effects on postoperative delirium and cognitive dysfunction. A number of databases were searched for randomised controlled trials comparing intravenous dexmedetomidine to other interventions in preventing postoperative delirium and cognitive dysfunction in non-cardiac and non-neurosurgical patients. These databases included PubMed, Embase, and Cochrane Library. Statistical analysis and graphing were performed using Review Manager, STATA, the second version of the Cochrane risk-of-bias tool for randomised controlled trials, and GRADE profiler. This meta-analysis comprised a total of 24 randomised controlled trials, including 20 trials assessing postoperative delirium and 6 trials assessing postoperative cognitive dysfunction. Across these 24 studies, a statistically significant positive association was observed between intravenous administration of dexmedetomidine and a reduced incidence of postoperative delirium (RR: 0.55; 95% CI 0.47 to 0.64,p < 0.00001, I2 = 2%) and postoperative cognitive dysfunction (RR: 0.60; 95% CI 0.38 to 0.96,p = 0.03, I2 = 60%). Subgroup analysis did not reveal a significant difference in the incidence of postoperative delirium between the general anaesthesia and non-general anaesthesia groups, but a significant difference was observed in the incidence of postoperative cognitive dysfunction. Nonetheless, when the data were pooled, it was evident that the utilisation of dexmedetomidine was associated with an increased incidence of hypotension (RR: 1.42; 95% CI 1.08 to 1.86,p = 0.01, I2 = 0%) and bradycardia (RR: 1.66; 95% CI 1.23 to 2.26,p = 0.001, I2 = 0%) compared with other interventions. However, there was no significantly higher occurrence of hypertension in the DEX groups (RR = 1.35, 95% CI 0.81-2.24, p = 0.25,I2 = 0%). Compared with other interventions, intravenous dexmedetomidine infusion during non-cardiac and non-neurosurgical procedures may significantly reduce the risk of postoperative delirium and cognitive dysfunction. The results of subgroup analysis reveal a consistent preventive effect on postoperative delirium in both general and non-general anaesthesia groups. Meanwhile, continuous infusion during general anaesthesia was more effective in reducing the risk of cognitive dysfunction. Despite such findings, hypotension and bradycardia were more frequent in patients who received dexmedetomidine during surgery.

MORE than 50 yr ago, clinicians reported changes in mental function after anesthesia and surgery in the elderly. As these phenomena have been elucidated in subsequent years, they have been categorized into the distinct syndromes of delirium and postoperative cognitive dysfunction (POCD). These phenomena seem to be increasing in prevalence, concomitant with the increase in the number of elderly patients undergoing surgery. In this brief clinical review, we describe the presentation of, course of, risk factors for, and when applicable, management of these syndromes. Delirium and cognitive function after cardiac and neurosurgical procedures are distinct subjects beyond the scope of this review.Delirium was well described in the writings of Hippocrates 2,500 yr ago. The key diagnostic features, as described in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders are (1) that it is a change in mental status, characterized by a prominent disturbance of attention and reduced clarity of awareness of the environment; and (2) that it has an acute onset, developing within hours to days, and tends to fluctuate during the course of the day. The inability to focus, sustain, and shift attention is accompanied by other cognitive symptoms (e.g ., disorientation, episodic memory dysfunction) and/or perceptual disturbances (misinterpretations, illusions, or hallucinations). Associated features include disturbances of the sleep–wake cycle and activity level, as well as affective disturbance (mood lability, anger, sadness, euphoria) and thought disorder (disorganized thinking, delusions). The symptoms of delirium are numerous, vary from patient to patient, vary within patients over time, and are shared by a variety of other disorders such as dementia, anxiety, depression, and psychosis, all of which contribute to difficulties in diagnosis.The heterogeneous presentation of delirium has led to the identification of hyperactive, hypoactive, and mixed subtypes.1,2The hyperactive form of delirium tends to be clinically obvious. The hypoactive form, however, is often unrecognized, misdiagnosed, mistaken for depression or dementia, or simply attributed to old age, because patients may seem quiet and subdued in their disorientation. Furthermore, the relation between delirium and dementia is complex, and the syndromes may overlap.1,2Delirium can be caused by, or associated with, a wide variety of conditions,1,2and the current Diagnostic and Statistical Manual of Mental Disorders system differentiates subtypes based on the presumed etiology. These are delirium due to a general medical condition , substance-induced delirium (due to medication use or toxin exposure), substance intoxication delirium (due to intoxication), substance withdrawal delirium , delirium due to multiple etiologies , and delirium not otherwise specified (for cases in which there is insufficient evidence to establish a specific etiology).Delirium in the postoperative period can be divided into emergence delirium and postoperative delirium (PD), based on the time of onset (fig. 1). Emergence delirium is seen during or immediately after emergence from general anesthesia and usually resolves within minutes or hours. It occurs in all age groups, with some predominance in children. It seems to be directly correlated with the administration of general anesthesia, because it occurs during the emergence process, mimics stage II (excitation) of ether anesthesia as described by Guedel, and usually resolves without sequelae. Emergence delirium fits the Diagnostic and Statistical Manual of Mental Disorders , fourth edition, diagnostic criteria for a substance-induced delirium . The reader is referred to a more complete review of this subject.3After surgery, another type of delirium occurs that is not clearly related to emergence from anesthesia. Elderly patients commonly emerge from anesthesia smoothly and demonstrate coherence in the postanesthesia care unit. After a lucid interval, some patients develop a syndrome referred to as interval delirium or postoperative delirium .1,4Postoperative delirium tends to first be observed between postoperative days 1 and 3, and usually resolves within hours to days, although symptoms may persist for weeks to months. Postoperative delirium is more likely to result in complete recovery than other forms of delirium.5The term intensive care unit (ICU) delirium describes delirium that occurs in the intensive care unit, primarily in those patients requiring mechanical ventilation; it was previously referred to as ICU psychosis . ICU delirium makes no distinction between medical and surgical patients, so many cases of ICU delirium could also be classified as postoperative delirium.6There are a number of structured instruments available that can be used by a variety of personnel to diagnosis and assess delirium. Three validated methods include the Confusion Assessment Method,7the Delirium Rating Scale Revised-98,1and the Delirium Symptom Interview.1The confusion assessment method has been used for most postoperative delirium research and has been modified and validated for use in critical care patients receiving mechanical ventilation.8The reported incidence of PD is 5–15% in older adults after general anesthesia.9The reported incidence in patients undergoing surgery for hip fracture is higher, ranging from 16% to 62%, with an average rate of 35% across 12 studies of 1,823 patients.10Delirium is indeed the most common complication after hip fracture, but this patient population also has a high incidence of delirium before surgery.In elderly patients hospitalized for reasons other than surgery, the risk of developing delirium while hospitalized is predicted by an interaction between vulnerability factors present at the time of hospitalization and noxious injuries, or precipitating factors that occur during hospitalization.2Among the predisposing risk factors identified are vision impairment, severe illness, cognitive impairment, and serum urea nitrogen:creatinine ratio of 18 or greater. The precipitating factors identified are use of physical restraints, malnutrition, more than three medications added 24–48 h before the onset of delirium, use of a urinary bladder catheter, and iatrogenic events, including fluid and electrolyte abnormalities and infections.2Studies in surgical patients have identified age 70 yr or older, history of delirium, history of alcohol abuse, and preoperative use of narcotic analgesics as preoperative predisposing risk factors for PD.11Preoperative depression also seems to be a risk factor for postoperative delirium.12Perioperative risk factors include greater intraoperative blood loss, more postoperative transfusions, postoperative hematocrit less than 30%, and severe postoperative pain.13There are contradictory reports on the role of perioperative hypotension and hypoxemia in the development of PD. The role that postoperative pain plays in the development of PD is not attributable to method of analgesia, type of opioid analgesia, or cumulative opioid dose.14Drug effects are considered an important cause of delirium. In medical patients, the most important drug classes associated with delirium are the sedative–hypnotics, narcotics, and anticholinergics,1all of which are routinely used in perioperative care. The role of benzodiazepines is controversial.1Lorazepam has been specifically associated with the development of delirium in the ICU.15There is extensive literature investigating the proposition that regional anesthesia would be associated with less delirium than general anesthesia; however, the majority of these studies show no difference.16,17The underlying pathophysiology of delirium in general, and PD specifically, remains elusive. Delirium is the behavioral manifestation of diffuse cortical dysfunction and is associated with diffuse slowing of background activity in the electroencephalogram (except in cases of alcohol withdrawal, in which there is an increase in fast wave activity).1It is also associated with disturbances in a wide variety of neurotransmitter systems, and disruption of cholinergic transmission seems to be especially important.2Toxicity from anticholinergic agents mimics the electroencephalographic and behavioral aspects of delirium and is reversed by physostigmine. Serum anticholinergic activity is associated with delirium in postoperative patients.18Other potential mediators include melatonin, norepinephrine, and lymphokines.1,2Postoperative delirium is associated with increased morbidity (including risk of injury), mortality, duration of hospital stay, nursing home placement, and technical (nonphysician), consultant, and nursing costs.19In a recent study, duration of hospital stay for surgical patients was 6.0 days for those who developed delirium and 4.6 for those who did not.19The average additional in-hospital cost per surgical patient with PD was $2,947, which equates to more than $2 billion additional healthcare dollars per year in the United States.It is possible to prevent PD in some patients using safe and effective interventions for systematic detection and management of predisposing factors.1The most widely studied intervention program to prevent delirium in elderly medical patients is the Hospital Elder Life Program.20Interventions are targeted towards six risk factors for delirium: cognitive impairment, sleep deprivation, immobility, visual impairment, hearing impairment, and dehydration. Some of the specific interventions include frequent presentation of orienting information (such as prominent display of the date, time, schedule, and names of hospital personnel), cognitive stimulation activities, physical exercise, use of visual aids and adaptations, use of auditory amplifying devices, nonpharmacologic methods to promote sleep (such as drinking warm milk before bed, relaxing music, back massage, noise-reduction strategies), and feeding and fluid assistance. Other protocols have focused on coordinated geriatric services, geriatric–psychiatric consultations, and patient and family education. A series of randomized and nonrandomized trials indicate that a substantial absolute risk reduction (in the range of 13–19%) can be achieved.1,2A trial of proactive geriatric consultation in hip fracture patients reduced delirium by more than one third and reduced cases of severe delirium by more than one half.21Treatment of agitation poses a special problem. Agitation puts the patient, visiting family, and staff at risk for physical injury and interferes with administration of normal postoperative care, but current treatment options are less than optimal. Attempts should be made to avoid the use of physical restraints, which may worsen delirium and agitation. Pharmacologic therapy is used specifically to decrease agitation.22Haloperidol, a typical antipsychotic dopaminergic antagonist, is administered to adults at a dose of 0.5–1 mg intravenously every 10–15 min until the agitated behavior is controlled.∥Intramuscular dosing is less desirable but can be employed using 2–10 mg, waiting 60–90 min between doses. By careful dosing, practitioners should limit the degree of haloperidol's sedative side effect, because this drug has an extended half-life in the elderly (up to 72 h) and deep sedation can last for several days. It is important for the clinician to recognize that haloperidol can be useful in the immediate management of agitation but does not alter the duration of delirium. Newer antipsychotic medications, such as ziprasidone and olanzapine, are administered intramuscularly and are reportedly effective in the management of acute agitation but have not been tested in patients with either medical or surgical comorbidities.22Although most typical antipsychotics increase the corrected QT interval and may predispose to arrhythmias, haloperidol has a relatively lower propensity to do so. Cases of sudden death are rare and have not been clearly related to haloperidol.22Although it is reasonable to assume that benzodiazepines would be an effective treatment for agitation in the context of PD, anecdotal experience has shown that these medications may have a paradoxical effect in elderly patients and may worsen agitation.22If alcohol withdrawal is suspected to be the underlying cause of delirium, however, benzodiazepines are the treatment of choice.The term postoperative cognitive dysfunction (POCD) describes a deterioration of cognition that is temporally associated with surgery. As opposed to delirium, in which pathognomonic behavior must be detected, detecting, assessing the severity of, and characterizing POCD depends on valid assessments of preoperative and postoperative cognitive function. The neuropsychological examination measures the information processing abilities of the brain through a battery of tests (assessing attention, perception, verbal abilities, learning and memory, and abstract thinking) that are sensitive to the effects of brain injury and disease.23The wide variability in normal human cognitive capacities associated with aging and a possible incidence of preexisting mild cognitive impairment in the elderly make baseline (i.e ., preoperative) measures a critical component of these evaluations. In the absence of baseline data, it is impossible to associate low postoperative test scores to surgical, anesthetic, or illness variables with certainty. Subjective self-reported cognitive symptoms do not substitute for objective cognitive testing, because a poor relation between the two types of data has been demonstrated repeatedly.24There are a number of methodologic inconsistencies among studies that make the limited literature on POCD difficult to interpret. These include the selection of test instruments, timing of postoperative testing, inclusion and exclusion criteria, the inherent variability of cognitive testing, and most fundamentally, the operational definition of POCD.Mental status screening instruments such as the Mini-Mental State Examination are useful for detecting frank dementia but lack the sensitivity and specificity required to detect milder or more selective forms of cognitive impairment.23High-functioning patients who have experienced a mild decline in cognitive function and patients with "focal," as opposed to "diffuse," cognitive dysfunction may achieve high Mini-Mental State Examination scores. Cognition is not a unitary process, but rather is the result of activity in multiple complex, distributed, and interacting neuronal circuits that underlie specific information processing functions. There is no single measure of cognitive status; therefore, comprehensive neuropsychological assessment requires that a battery of tests assessing a variety of cognitive domains must be used. There are, however, a wide variety of tests available, which differ in their test–retest reliability, sensitivity, specificity, and the degree to which they are subject to practice effects.Another methodologic inconsistency among the studies is the timing of postoperative cognitive testing. In general, studies measuring cognitive function shortly after surgery find a much higher incidence of POCD than studies measuring cognitive function weeks to months after surgery. Longitudinal studies have the problem of attrition, which does not occur randomly but is influenced by the postoperative health status, functional status, and possibly the cognitive status of the patient. Patients who develop POCD may be more likely to drop out of the study, thus underestimating the true incidence of POCD.It is also important to consider the subject inclusion and exclusion criteria when interpreting study findings. Recently, the term mild cognitive impairment has come to represent a transitional zone in the spectrum of cognitive function from normal aging to progressive dementing conditions, such as Alzheimer and cerebrovascular diseases. Unfortunately, patients with preoperative mild cognitive impairment have not been differentiated in studies of POCD. Therefore, there is no information available concerning the impact of surgery and anesthesia on this subset of patients that may be at greatest risk for POCD. There is no evidence that anesthesia and surgery increase the incidence of Alzheimer disease.One of the greatest problems facing the investigation of postoperative cognitive function is the absence of a consensus regarding the operational definition of POCD. Variations in the methods that different groups have used to define deterioration in cognitive function in part underlie the difficulty in comparing studies. Furthermore, few studies use control groups and take practice effects into account.25The percent change method involves converting the preoperative to postoperative difference score into a percent of baseline score, i.e ., (postoperative score − preoperative score)/preoperative score. This method generates continuous data, which can then be averaged across patients for group comparisons. The use of group mean analyses, however, is discouraged, because a subset of subjects experiencing significant deterioration may be masked when other subjects exhibit improved performance over time. The SD method involves identifying patients who experience a postoperative decline of some criterion number of SD units (Z scores). The International Study of Postoperative Cognitive Dysfunction (ISPOCD) studies (see below) required a 2-SD decline to qualify as POCD. Limitations of the SD method include the following: (1) in patients with low baseline scores, it may not be possible to decline by more than 1 SD (i.e ., floor effect); and (2) the absolute magnitude of change in raw test scores required to meet the criterion differs between studies, because they are derived from the preoperative test scores of the baseline sample. A third strategy involves identifying patients who experience a specific percentage (e.g ., 20%) decline from baseline of at least a specific percentage (e.g ., 20%) of the tests administered. A limitation of this technique is that patients with lower preoperative test scores require a smaller decline in raw score to meet the 20% criterion. It should be noted that the methodology used by ISPOCD is a subset of the general assessment technique referred to as a reliable change index . Lewis has recently explored a number of issues related to the use of this technique.26In 1998, Möller et al .27presented the first of a series of multicenter studies from the ISPOCD that primarily included European centers. Information from the ISPOCD studies is available at the ISPOCD Web site.#The ISPOCD1 study tested the hypothesis that insufficient oxygen delivery to the brain, as assessed by the presence of hypotension and/or hypoxemia, is a causative factor for POCD. The study included 1,218 patients, aged 60 yr or older, who underwent major abdominal, noncardiac thoracic, or orthopedic surgery during general anesthesia. Patients were tested preoperatively and at 1 week and 3 months postoperatively. Test results were compared with a total of 321 controls recruited from the United Kingdom, 11 centers in and centers in Patients were classified as experiencing cognitive dysfunction when two scores in tests by or the average score greater than 1 week of patients experienced a decline in cognitive compared with of control 3 months of patients experienced a decline to preoperative of compared with of number of subsequent studies have described cognitive impairment within the first days after surgery and et al a rate of POCD of at months after surgery, although in the absence of a control the is to A study that patients at 1 and yr that the rate of POCD to which was not it seems that elderly patients deterioration shortly after surgery and anesthesia at 2–10 with such that the incidence at 3 at at 1 to from control subjects by 1 important are that (1) the of patients to drop out of such studies, the may the true incidence of and (2) the clinical course of an patient be clearly from this in that there is inconsistency between the In the ISPOCD studies, less than of the who were classified at POCD at 3 months decline at 1 week (i.e ., POCD at 1 week did not POCD at 3 a of the data from the ISPOCD studies, et al . to the impact of test–retest variability on the of that variability in cognitive results could after surgery would be as frequent as This that cognitive decline at 1 week but that there was no significant change at 3 months. study be required to impairment is an important clinical in cognitive is an important factor that to the low between that should be in studies of all of the studies to have that age is a risk factor for POCD. of patients aged yr undergoing major surgery a but significant decline in cognitive function at 1 week that was no at 3 months the ISPOCD that POCD is primarily a problem of elderly surgery seems to be the for POCD. A study comparing patients undergoing general anesthesia and surgery with at least a single hospital stay with patients who underwent general anesthesia for surgery that surgery was not associated with significant major surgery, postoperative cognitive dysfunction at 1 week was associated with increased age, increased duration of anesthesia, of postoperative and age was a significant risk factor for POCD at 3 postoperative pain has also been associated with postoperative cognitive function. In a study of patients aged who underwent surgery, greater pain on postoperative 1 was associated with performance on some neuropsychological degree of preoperative pain was not related to preoperative cognitive test date, the of POCD remains in neurotransmitter and system have all been but the has been general anesthesia. anesthesia is a with multiple medications, many of which are to cause delirium. The method of the potential of general anesthesia to POCD has been randomized trials of general regional anesthesia. studies that of anesthesia is not an important factor in the development of is in greater such different as regional and general anesthesia have impact on postoperative cognitive function in clinical studies, there are studies that general agents have effects on and of this to the clinical syndromes described require significant additional and are potential etiologies of POCD for which potential (e.g ., that were in the first ISPOCD study the role of hypotension and hypoxemia as potential was by continuous and blood was by the perioperative high of hypoxemia and condition was associated with POCD. may additional into this problem. research is to the role of in the of of the is associated with the development of Alzheimer but has not been to be an important of POCD in general for either a to POCD or a of POCD is but all such In studies of cardiac surgery patients, but not may be useful as a of research including that for different aspects of (in cardiac and require substantial additional research to establish clinical is that general anesthesia, which specifically the brain, as compared with regional anesthesia, which primarily the or would be associated with different of POCD. in a series of relatively studies that patients undergoing general anesthesia, but not anesthesia, were at greater risk for et al an randomized study of POCD that used neuropsychological This study compared the effect of general anesthesia on the incidence of POCD in patients undergoing total assessment was days preoperatively and 1 week and months postoperatively. mean scores for of the measures were compared between the two anesthesia groups, but no significant were observed postoperatively. In the of patients clinically important for test by were of patients a decline in cognitive function months after surgery, but no significant were between the anesthesia As this was a there was no control group for Recently, et al a comprehensive review of studies that the of anesthesia and that it does not the incidence of the of PD and it is important to consider that there may be an between Postoperative delirium may be a of POCD or an Patients who developed delirium in the ISPOCD1 study were not the patients who developed POCD. In ICU patients, delirium does seem to be of term cognitive majority of studies to have focused on either PD or POCD. In the studies that for PD and POCD should on this system dysfunction after anesthesia and surgery is primarily a problem of the elderly. The of an aging population and in anesthesia and surgery has led to in the number of elderly patients undergoing surgery. It is therefore, that postoperative dysfunction an common delirium is an diagnostic that requires research to as well as to effective and treatment There are available that seem to postoperative delirium. of these may be difficult limited however, assessment of patients for delirium has a of care in some European and should be with the and management of to PD, the that to define the presence or absence of POCD are The are not regarding the of cognitive that are associated with do they regarding the degree of dysfunction that is clinically illness requiring hospitalization may be associated with cognitive the that cognitive decline occurs as a of illness rather than it related to surgery and/or anesthesia. There are patients who significant after surgery and anesthesia. study, of clinical with mild cognitive impairment be for practitioners to the of cognitive dysfunction after noncardiac dysfunction is a health problem of study to the risk and and underlying should the current status of postoperative delirium and cognitive dysfunction and to prevent and delirium as studies to postoperative function.

BackgroundSeveral studies have investigated the effects of dexamethasone on post-operative cognitive dysfunction (POCD) or post-operative delirium (POD); however, their conclusions have been inconsistent. Thus, we conducted a meta-analysis to determine the effects of dexamethasone on POCD and POD in adults following general anaesthesia.MethodsThe Cochrane Central Register of Controlled Trials (2018, Issue 11 of 12) in the Cochrane Library (searched 17 November 2018), MEDLINE OvidSP (1946 to 16 November 2018) and Embase OvidSP (1974 to 16 November 2018) were searched for randomised controlled trials that evaluated the incidence of POCD and POD following dexamethasone administration in adults (age ≥ 18 years) under general anaesthesia. We used the Grading of Recommendations, Assessment, Development and Evaluations framework to assess the quality of the evidence.ResultsFive studies were included (three studies with 855 participants in the dexamethasone group and 538 participants in the placebo group for the incidence of POCD, and two studies with 410 participants in the dexamethasone group and 420 participants in the placebo group for the incidence of POD). There was no significant difference between the dexamethasone group and the placebo group in terms of the incidence of POCD 30 days after surgery (RR [relative risk] 1.00; 95% CI [confidence interval: 0.51, 1.96], P = 1.00, I2 = 77%) or the incidence of POD (RR 0.96; 95% CI [0.68, 1.35], P = 0.80, I2 = 0%). However, both analyses had some limitations because of limited evidence and clinical heterogeneity, and we considered the quality of the evidence for the post-operative incidence of POCD and POD to be very low.ConclusionsThis meta-analysis revealed that prophylactic dexamethasone did not reduce the incidence of POCD and POD. Trials of alternative preventive strategies for POCD and POD, as well as a better understanding of the pathophysiology of those complex syndromes, are still needed to make progress in this field.Trial registrationrThis study is registered with PROSPERO, 23 October 2018, number CRD42018114552. Available from https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

Penehyclidine Hydrochloride Premedication Is Not Associated with Increased Incidence of Post-Operative Cognitive Dysfunction or Delirium:A Systemic Review and Meta-Analysis.

Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common operative neurocognitive disorders, which places a heavy burden on patients, families and society. Therefore, it is very important to search for preventive drugs. Previous studies have demonstrated that perioperative use of dexmedetomidine resulted in a decrease the incidence of POD and POCD. But the specific effect of dexmedetomidine on elderly patients undergoing hepatic lobectomy and its potential mechanism are not clear. This study aims to evaluate the efficacy of intraoperative use of dexmedetomidine on preventing POD and POCD in elderly patients undergoing hepatic lobectomy and the influence on the balance between proinflammation and anti-inflammation. This trial was designed as a single-center, prospective, randomized, controlled study. One hundred and twenty hospitalized patients from January 2019 to December 2020, aged 60-80 years old with American Society of Anesthesiologists (ASA) II-III and scheduled for hepatic lobectomy, were randomly allocated into 3 groups (n=40) using a random number table: A C group, a Dex1 group, and a Dex2 group. After anesthesia induction, saline in the C group, dexmedetomidine [0.3 μg/(kg·h)] in the Dex1 group, and dexmedetomidine [0.6 μg/(kg·h)] in the Dex2 group were infused until the end of operation. The incidences of hypotension and bradycardia were compared among the 3 groups. Confusion Assessment Method (CAM) for assessing POD and Mini Mental State Examination (MMSE) for evaluating POCD were recorded and venous blood samples were obtained for the determination of neuron specific enolase (NSE), TNF-α, IL-1β, and IL-10 at the different time below: the time before anesthesia (T0), and the first day (T1), the third day (T2), the fifth day (T3), and the seventh day (T4) after operation. Compared with the C group, the incidences of bradycardia in the Dex1 group or the Dex2 group increased (both P<0.05) and there was no difference in hypotension in the Dex1 group or the Dex2 group (both P>0.05). The incidences of POD in the C group, the Dex1 group, and the Dex2 group were 22.5%, 5.0%, and 7.5%, respectively. The incidences of POD in the Dex1 group or the Dex2 group declined significantly as compared to the C group (both P<0.05). However, there is no difference in the incidence of POD between the Dex1 group and the Dex2 group (P>0.05). The incidences of POCD in the C group, the Dex1 group, and the Dex2 group were 30.0%, 12.5%, and 10.0%, respectively. The incidences of POCD in the Dex1 group and the Dex2 group declined significantly as compared to the C group (both P<0.05). And no obvious difference was seen in the incidence of POCD in the Dex1 group and the Dex2 group (P>0.05). Compared with the C group, the level of TNF-α and IL-1β decreased and the level of IL-10 increased at each time points (from T1 to T4) in the Dex1 group and the Dex2 group (all P<0.05). Compared with the Dex1 group, the level of IL-1β at T2 and IL-10 from T1 to T3 elevated in the Dex2 group (all P<0.05). Compared with the T0, the concentrations of NSE in C group at each time points (from T1 to T4) and in the Dex1 group and the Dex2 group from T1 to T3 increased (all P<0.05). Compared with the C group, the level of NSE decreased from T1 to T4 in the Dex1 group and the Dex2 group (all P<0.05). Intraoperative dexmedetomidine infusion can reduce the incidence of POCD and POD in elderly patients undergoing hepatic lobectomy, and the protective mechanism appears to involve the down-regulation of TNF-α and IL-1β and upregulation of IL-10 expression, which lead to rebalance between proinflammation and anti-inflammation.

There have been significant advancements in depth of anesthesia (DoA) technology. The Anesthesia Patient Safety Foundation recently published recommendations to use a DoA monitor in specific patient populations receiving general anesthesia. However, the universal use of DoA monitoring is not yet accepted. This review explores the current state of DoA monitors and their potential impact on patient safety. We reviewed the current evidence for using a DoA monitor and its potential role in preventing awareness and preserving brain health by decreasing the incidence of postoperative delirium and postoperative cognitive dysfunction or decline (POCD). We also explored the evidence for use of DoA monitors in improving postoperative clinical indicators such as organ dysfunction, mortality and length of stay. We discuss the use of DoA monitoring in the pediatric population, as well as highlight the current limitations of DoA monitoring and the path forward. There is evidence that DoA monitoring may decrease the incidence of awareness, postoperative delirium, POCD and improve several postoperative outcomes. In children, DoA monitoring may decrease the incidence of awareness and emergence delirium, but long-term effects are unknown. While there are key limitations to DoA monitoring technology, we argue that DoA monitoring shows great promise in improving patient safety in most, if not all anesthetic populations.

Memory and awareness during anaesthesia

Anesthesia objectives have evolved into combining hypnosis, amnesia, analgesia, paralysis, and suppression of the sympathetic autonomic nervous system. Technological improvements have led to new monitoring strategies, aimed at translating a qualitative physiological state into quantitative metrics, but the optimal strategies for depth of anesthesia (DoA) and analgesia monitoring continue to stimulate debate. Historically, DoA monitoring used patient's movement as a surrogate of awareness. Pharmacokinetic models and metrics, including minimum alveolar concentration for inhaled anesthetics and target-controlled infusion models for intravenous anesthesia, provided further insights to clinicians, but electroencephalography and its derivatives (processed EEG; pEEG) offer the potential for personalization of anesthesia care. Current studies appear to affirm that pEEG monitoring decreases the quantity of anesthetics administered, diminishes postanesthesia care unit duration, and may reduce the occurrence of postoperative delirium (notwithstanding the difficulties of defining this condition). Major trials are underway to further elucidate the impact on postoperative cognitive dysfunction. In this manuscript, we discuss the Bispectral (BIS) index, Narcotrend monitor, Patient State Index, entropy-based monitoring, and Neurosense monitor, as well as middle latency evoked auditory potential, before exploring how these technologies could evolve in the upcoming years. In contrast to developments in pEEG monitors, nociception monitors remain by comparison underdeveloped and underutilized. Just as with anesthetic agents, excessive analgesia can lead to harmful side effects, whereas inadequate analgesia is associated with increased stress response, poorer hemodynamic conditions and coagulation, metabolic, and immune system dysregulation. Broadly, 3 distinct monitoring strategies have emerged: motor reflex, central nervous system, and autonomic nervous system monitoring. Generally, nociceptive monitors outperform basic clinical vital sign monitoring in reducing perioperative opioid use. This manuscript describes pupillometry, surgical pleth index, analgesia nociception index, and nociception level index, and suggest how future developments could impact their use. The final section of this review explores the profound implications of future monitoring technologies on anesthesiology practice and envisages 3 transformative scenarios: helping in creation of an optimal analgesic drug, the advent of bidirectional neuron-microelectronic interfaces, and the synergistic combination of hypnosis and virtual reality.

BackgroundIntraoperative awareness is the second most common complication of surgeries, and it negatively affects patients and healthcare professionals. Based on the limited previous studies, there is a wide variation in the incidence of intraoperative awareness and in the practices and attitudes toward depth of anesthesia (DoA) monitoring among healthcare systems and anesthesiologists. This study aimed to evaluate the Jordanian anesthesiologists’ practice and attitudes toward DoA monitoring and estimate the event rate of intraoperative awareness among the participating anesthesiologists.MethodsA descriptive cross-sectional survey of Jordanian anesthesiologists working in public, private, and university hospitals was utilized using a questionnaire developed based on previous studies. Practice and attitude in using DoA monitors were evaluated. Anesthesiologists were asked to best estimate the number of anesthesia procedures and frequency of intraoperative awareness events in the year before. Percentages and 95% Confidence Intervals (95%CI) were reported and compared between groups using chi-square tests.ResultsA total of 107 anesthesiologists responded and completed the survey. About one-third of the respondents (34.6%; 95% CI 26.1–44.2) had never used a DoA monitor and only 6.5% (95% CI 3.1–13.2) reported using it as a “daily practice”. The use of a DoA monitor was associated with experience and type of health sector. However, 81.3% (95% CI 66.5–83.5) believed that currently available DoA monitors are effective for DoA monitoring and only 4.7% (95%CI 1.9–10.8) reported it as being “invalid”. Most respondents reported that the main purpose of using a DoA monitor was to prevent awareness (86.0%; 95%CI 77.9–91.4), guide the delivery of anesthetics (63.6%; 95%CI 53.9–72.2), and reduce recovery time (57%; 95%CI 47.4–66.1). The event rate of intraoperative awareness was estimated at 0.4% among participating anesthesiologists. Most Jordanian hospitals lacked policy intending to prevent intraoperative awareness.ConclusionsMost anesthesiologists believed in the role of DoA monitors in preventing intraoperative awareness, however, their attitudes and knowledge are inadequate, and few use DoA monitors in routine practices. In Jordan, large efforts are needed to regulate the use of DoA monitoring and reduce the incidence of intraoperative awareness.

Regional nerve blocks (NBs) mitigate the occurrence of postoperative cognitive dysfunction (POCD) and postoperative delirium (POD) in adult patients undergoing thoracic surgery. This study aimed to determine the exact effect of NBs on POCD and POD. Electronic databases, including PubMed, EMBASE, CINAHL, Scopus, and Web of Science, were searched for studies. The primary outcome was the incidence of POD or POCD. The secondary outcome was pain scores assessed 24 and 48 h postoperatively. We calculated the log odds ratio (LOR) and standardized mean difference (SMD) with 95% confidence intervals (CIs). The LOR was converted to an odds ratio (OR). In the analysis of 1010 patients from seven randomized controlled trials, POD and POCD rates were 14.1% and 16.7%, respectively, in the NB group, and higher, at 27.3% and 35.2%, in the control group. NBs reduced the incidence of POD (OR, 0.44; 95%CI 0.30 to 0.64; p < 0.001; I2 = 0.00%) and POCD (OR, 0.43; 95%CI 0.24 to 0.76; p < 0.001; I2 = 0.00%). NBs reduced pain scores at 24 h (SMD, -2.60; 95%CI -3.90 to -1.30, p < 0.001; I2 = 97.68%) and 48 h (SMD, -1.80; 95%CI -3.18 to -0.41, p = 0.01; I2 = 98.14%) postoperatively. NBs mitigated the occurrence of POD and POCD in adult patients after thoracic surgery.

BackgroundThere is no consensus on whether intraoperative hypotension is associated with postoperative cognitive impairment. Hence, we performed a meta-analysis to evaluate the correlation of intraoperative hypotension and the incidence of postoperative delirium (POD) or postoperative cognitive dysfunction (POCD).MethodsWe searched PubMed, Embase, and Cochrane Library databases to find randomized controlled trials (RCTs) in which reported the relationship between intraoperative hypotension and POD or POCD. The retrieval time is up to January 2020, without language restrictions. Quality assessment of the eligible studies was conducted by two researchers independently with the Cochrane evaluation system.ResultsWe analyzed five eligible RCTs. Based on the relative mean arterial pressure (MAP), participants were divided into low-target and high-target groups. For the incidence of POD, there were two studies with 99 participants in the low-target group and 94 participants in the high-target pressure group. For the incidence of POCD, there were four studies involved 360 participants in the low-target group and 341 participants in the high-target group, with a study assessed both POD and POCD. No significant difference between the low-target and the high-target group was observed in the incidence of POD (RR = 3.30, 95% CI 0.80 to 13.54, P = 0.10), or POCD (RR = 1.26, 95% CI 0.76 to 2.08, P = 0.37). Furthermore, it also demonstrates that intraoperative hypotension prolonged the length of ICU stay, but did not increased the mortality, the length of hospital stay, and mechanical ventilation (MV) time.ConclusionsThere is no significant correlation between intraoperative hypotension and the incidence of POD or POCD.

Post-operative cognitive complications such as delirium have been consistently associated with poor short and long term outcomes, and the role of anesthesia, particularly the role of general versus regional anesthesia, remains unclear. The objective of this systematic review with meta-analysis was to compare the influence of general, regional, or a combination of anesthesia on the development of Post-Operative Cognitive Dysfunction (POCD) and Post-Operative Delirium (POD). Standard bibliographic databases were searched and complimented by hand searching of original and review article references. Included studies were randomized controlled trials comparing general to regional (spinal, epidural, or intravenous block) or a combination of these in a cohort who were pre-operatively cognitively normal and had an average age exceeding fifty. Where POD was the principle outcome, studies must have employed the DSM or ICD criteria. Where POCD was the principal outcome, this was defined as any objective cognitive impairment. Twenty one studies were considered suitable for inclusion. There was no effect of anesthesia type on the odds ratio of developing POD (0.88, 0.51-1.51 with 95% confidence) however general anesthesia was marginally non-significantly associated with POCD (odds ratio of 1.34, 0.93-1.95 with 95% confidence). There was no evidence of publication bias. In conclusion, it appears that general anesthesia, compared to others, may increase the risk of developing POCD; however this has not been shown for POD. Possible reasons for this finding have been explored. This data would advocate for the use of regional anesthesia wherever possible especially in people otherwise vulnerable to developing cognitive symptoms.

Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are frequent complications in elderly patients undergoing cardiac and noncardiac surgery.1 They have been associated with delayed recovery, decreased quality of life, persistent neurocognitive disorders and increased morbidity and mortality within the first year of surgery. The concern that anaesthetic and sedative agents may be implicated in the pathogenesis of POD has prompted multiple studies. Regional anaesthesia, avoiding the use of sedative–hypnotic anaesthetics, rather than general anaesthesia, has thus long been held up as one strategy to prevent postoperative cognitive dysfunction. However, two recent large, randomised studies (the REGAIN and RAGA trials) comparing regional and general anaesthesia in elderly patients undergoing hip fracture surgery reported no significant difference between groups in the percentage of patients with POCD.2,3 In their accompanying editorial, Avidan et al.4 concluded that surgery with general anaesthesia was not implicated in persistent neurocognitive disorders at a population level. Even so, there might still be individuals or patient subgroups with specific vulnerabilities to POD5 including some older surgical patients with mild cognitive impairment (MCI), characterised by subclinical or unnoticed cognitive decline often missed by most of the tests, and where POD and early POCD can reflect a cognitive trajectory towards a clinically apparent cognitive decline.5 Important risk factors for postoperative neurocognitive disorders include pre-operative general and cognitive health, and medical comorbidities.5 Prevention of POD and POCD should, therefore, focus on improvement of pre-operative fitness, optimisation of pre-operative comorbidities and mitigating physiological and biochemical disturbances secondary to surgical stress and inflammatory reactions to avert organ dysfunction and peri-operative stroke.5 Measures to reach these goals should be part of good clinical practice in all patients but they have only been scantily tested specifically to prevent POCD. Neuroinflammation secondary to surgery is also considered a major contributor to the development of POCD,6 and ageing, atherosclerosis and neurodegenerative diseases may lead to an increased systemic and cerebral inflammatory response to surgery. Also, postoperative complications, such as infection, pulmonary complications and hypoxaemia may aggravate the postoperative inflammatory reaction. Several drugs with anti-inflammatory properties (steroids, NSAIDs, intravenous lidocaine, ketamine and dexmedetomidine) have been used to mitigate postoperative systemic inflammation and subsequent neuro-inflammation but without definitive conclusions.1,6 Enhanced recovery after surgery (ERAS) programmes, as those recommended by the ERAS Society (www.erassociety.org) and GRACE (www.grace-asso.fr), form a multidisciplinary, multimodal approach designed to control surgical stress response including inflammatory reaction in order to hasten postoperative recovery and decrease postoperative complications.7,8 Their efficiency has been widely demonstrated in all surgical specialties. Interestingly, several studies using ERAS programmes for colorectal surgery 9,10 and orthopaedic surgery 11,12 reported a significant reduction in the incidence of POD and POCD. These observations are unsurprising as these programmes combine several measures recommended by the European Society of Anaesthesiology and Intensive Care to prevent POD in elderly patients13 by shortening pre-operative fasting, avoidance of premedication, multimodal opioid-sparing analgesia, avoidance of unnecessary indwelling catheters, early mobilisation, early nutrition and discharge to home environment. All these measures are likely to facilitate return to normal circadian rhythm, hasten the recovery of patients’ usual behaviour in hospital and after discharge and improve patient orientation.13 Recommending ERAS programmes to prevent POD, therefore, appears justified especially as elderly patients, at a higher risk of POD and POCD, benefit much from these programmes.14 Likewise, the POSE-study highlights the importance of a comprehensive peri-interventional and patient-centred management for older patients.15 Disappointingly, the literature abounds with examples of large RCTs with short-term interventions for POD/POCD but without information or incorporation of enhanced recovery programmes.1,2,16,17 In summary, future studies on the prevention of POD should, therefore, focus less on hypothetical short-term interventions unless fully implemented ERAS programmes have been instituted, based on the pathophysiological background 7,8 and positive preliminary observations.9–12

The relationship between Alzheimer's disease biomarkers and postoperative complications, such as postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), remains a subject of ongoing debate. This meta-analysis aimed to determine whether there is an association between perioperative Alzheimer's disease biomarkers and postoperative complications. We conducted a meta-analysis of observational clinical studies that explored the correlation between Alzheimer's disease biomarkers and POD or POCD in patients who have undergone surgery, following PRISMA guidelines. The protocol was previously published (INPLASY: INPLASY202350001). A comprehensive search was conducted across PubMed, Embase, Web of Science, and Cochrane databases until March 2023. Surgical patients aged at least 18 years, studies focusing on POD or POCD, research involving Alzheimer's disease biomarkers, including Aβ or tau in blood or cerebrospinal fluid (CSF), and availability of the full text. Our meta-analysis included 15 studies: six focusing on POD and nine on POCD. The findings revealed a negative correlation between preoperative CSF β-amyloid 42 (Aβ42) levels and the onset of POD [mean difference -86.1, 95% confidence interval (CI), -114.15 to -58.05, I2 : 47%]; this association was strongly supported by trial sequential analysis (TSA). A similar negative correlation was discerned between preoperative CSF Aβ42 levels and the incidence of POCD (-165.01, 95% CI, -261.48 to -68.53, I2 : 95%). The TSA also provided robust evidence for this finding; however, the evidence remains insufficient to confirm a relationship between other Alzheimer's disease biomarkers [β-amyloid 40 (Aβ40), total tau (T-tau), phosphorylated tau (P-tau), and Aβ42/T-tau ratio] and POD or POCD. The study results indicate a negative correlation between preoperative CSF Aβ42 levels and the occurrence of both POD and POCD. Future investigations are warranted to identify the predictive cutoff value of preoperative CSF Aβ42 for POD and POCD.