[Friday] Classic high-scoring literature reading · Postoperative delirium and postoperative cognitive dysfunction

By Danny & Cat & MiaoPostoperative Delirium and Postoperative Cognitive DysfunctionPostoperative Delirium and Postoperative Cognitive DysfunctionAbstractAbstract Postoperative Delirium (POD) and Postoperative Cognitive Dysfunction (POCD) Are Associated with Morbidity, Mortality, and Resources Postoperative phenomena associated with increased utilization
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This review carefully examines many studies to better characterize POD/POCD, with a particular focus on the etiology, associated risk factors, prevention, and management of the disease
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Despite their clinical importance, evidence-based protocols for the prevention and treatment of POD and POCD are lacking
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To ensure improved safety and cost-effective management of POD/POCD, future research should focus on screening protocols to identify high-risk patients, in addition to developing standardized treatment regimens for high-risk patients
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Keywords Introduction Postoperative delirium Postoperative cognitive dysfunction Postoperative cognitive dysfunction Anesthesia recovery Anesthesia recovery Anesthetic complications Anesthesia complications Perioperative complications Cognitive impairment Cognitive impairment Postoperative Delirium Postoperative delirium diagnosis and statistics Delirium is well described in the fifth edition of the handbook [2]
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Its main feature is a sharp change in mental status from the patient's baseline
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There is usually an acute onset and a fluctuating clinical course
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Patients often exhibit decreased concentration, but this may be observed as the patient is easily distracted or has difficulty keeping up with conversations
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Patients often exhibit disorganized thinking
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Language can be confusing, incoherent, or illogical
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Patients may exhibit behavior ranging from hypoactivity to hyperactivity or mixed psychomotor disorder
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Memory impairment is often present
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Emerging delirium should not be confused with true postoperative delirium because POD is not limited to the time a patient emerges from anesthesia
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In fact, most POD patients show wakefulness after onset, and POD only occurs on postoperative day 1-3 [1]
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There are several methods for diagnosing POD at present
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The most commonly used method in research is the Confusion Assessment Method (CAM) [3]
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There is also a CAM tool for intensive care units (CAM-ICU), and a short CAM that contains only items 1-4 of the original CAM
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The Delirium Rating Scale Revised is a 16-item clinician-rating scale with 13 severity items and 3 diagnostic items
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It is a comprehensive tool, especially suitable for monitoring patients over a specific period of time [4]
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More detailed is the Delirium Symptom Interview, a structured interview with 107 items, 63 of which are interview questions and the remaining observations [5]
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The NEECHAM Confusion Scale is a screening scale that nurses can use to assess patient behavior while providing routine care to patients
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The scale takes 10 minutes to complete
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It has high inter-rater reliability, good validity and high sensitivity (95%) and specificity [6]
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Emergence Delirium Delirium Delirium that occurs when a patient emerges from general anesthesia is called emergent delirium (ED)
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ED, also known as emergence agitation, is related to the time period during which a patient emerges from general anesthesia, usually subsides within 1 hour of emergence from anesthesia (in relation to anesthetics, it may persist for several days)
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Although it is more common in the pediatric population, people of all ages can exhibit the condition
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Incidence has also increased in the elderly population compared to younger adults
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Patients often exhibit agitation, confusion, and violent behavior
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Risk factors for developing delirium include the patient's age, with increased risk in patients under the age of 40 and over the age of 64 [7]
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There are conflicting reports about the effect of anesthetics on ED morbidity
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Some studies have linked benzodiazepines to the development of ED, while other studies have suggested a protective effect of benzodiazepines [8-10]
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In some studies, ketamine has been associated with an increased risk of ED [11]
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Inhalation anesthetics may play a role in the development of ED, with sevoflurane and desflurane most relevant compared to drugs with higher blood solubility (and therefore slower emergence from general anesthesia)
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It has been hypothesized that a relatively rapid emergence from general anesthesia using a new generation of volatile anesthetics increases susceptibility to ED [10-12]
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Certain surgical procedures show higher rates of ED, with breast and abdominal procedures showing the highest risk
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Patients with a known history of post-traumatic stress disorder (PTSD) are at increased risk of developing ED after general anesthesia [13]
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Usually, delirium usually resolves with no sequelae, as long as the patient is protected from harming himself
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Postoperative Cognitive Dysfunction Postoperative Cognitive Impairment The potential relationship between POD and POCD has been the subject of much debate over the past few years
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Although POD and POCD are highly related phenomena, they represent two distinct clinical groups on the continuum of cognitive impairment after anesthesia and surgery
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POCD can occur after POD, and its incidence appears to depend on the duration of POD
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However, surgery-related cognitive decline may also manifest in the absence of clearly identifiable POD; thus, POCD may also develop in patients who have not experienced POD
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In contrast to POD, POCD is characterized by a long-term deterioration in postoperative mental capacity
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Definition and diagnosis are more difficult, and the diagnosis of POCD requires complex baseline neuropsychological testing before and after surgery [14, 15]
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In addition, there are currently no universally accepted diagnostic criteria for POCD, and they are not included in the latest editions of the International Classification of Diseases (ICD-11) and the Diagnostic and Statistical Manual of Mental Disorders
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The manifestations of POCD are often subtle, and the range of cognitive abilities that may be affected is varied
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Most psychometric tests analyzing cognitive function focus on memory and intellectual tasks that measure abilities related to learning, verbal fluency, perception, attention, executive function, and abstract thinking
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Cases of postoperative cognitive impairment were identified by performing preoperative neurophysiological tests that test the ability to learn, memory, language, perception, attention, executive function, and abstract thinking
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Unfortunately, to date, no standardized methods have been used in clinical practice or research to identify POCD and assess its prevalence
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Therefore, determining the presence and incidence of POCD is somewhat difficult
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In any case, despite being similar to POD, POCD is a separate part
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Its temporal relationship to surgical events has not been fully elucidated
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The risk factors for both were very similar, and the temporal relationships that occurred in the postoperative period following the initial brief period of wakefulness were also very similar
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The incidence of POD ranges from 5% to 15%, and some high-risk groups, such as hip fracture patients, average as high as 35% [16]
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The incidence of POCD is more difficult to describe, given the definition of POCD used and the various tests available to establish a diagnosis and their statistical evaluation
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In some studies, the incidence of POCD in patients over 60 years of age at discharge was as high as 40%, and about 10% of patients had postoperative POCD that persisted for at least 3 months [15]
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Nonetheless, POCD has emerged in young, adult, and elderly populations
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Similar to POD, POCD is more common in the elderly population and has a longer course of disease in this population
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POCD is usually transient, but in a small percentage of patients (about 1%) it can persist for several years
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Whether these persistent POCD cases reflect permanent POCD remains controversial [17-19]
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Risk Factors The causes of delirium caused by risk factors are multifactorial
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Risk factors include advanced age, history of dementia or previous peroxidase disease, history of hearing loss or visual impairment, and history of cognitive impairment
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Metabolic and physiological disturbances are also relevant
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Hypoxemia, hypercapnia, and hypoglycemia are potentially life-threatening causes of delirium and should be recognized and treated promptly
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POCD has long been considered a potential complication of cardiac surgery
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The reasons for the increased prevalence of cardiac surgery may be multifactorial and related to surgery, anesthesia, and patient factors
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POCD was previously considered a complication of cardiopulmonary bypass (CPB) with a physiological disorder [20–22]
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However, randomized controlled trials have shown that POCD rates are similar whether cardiac surgery is performed on cardiopulmonary bypass or on a beating heart ("off-pump") [23]
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Inflammatory markers were also similar in patients randomized to "in-pump" and "out-pump" cardiac surgery [24]
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Furthermore, there appears to be no advantage of using pulsatile flow compared to non-pulsatile flow in the prevention of peroxidase/POCD disease when using cardiopulmonary bypass [25]
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The stress of open heart surgery places a severe systemic inflammatory burden on the body
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This inflammatory response results in an up-regulation of thresholds for macrophages, neutrophils, cytokines, and free radical production
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This inflammatory process disrupts the blood-brain barrier and increases the susceptibility of the brain to ischemic injury
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This acute brain inflammatory process may be an exacerbation of the chronic inflammatory state caused by the atherosclerotic process and aging
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This acute brain inflammatory state, which may lead to neuronal dysfunction and neuronal loss, is the most likely mechanism to explain the high incidence of peroxidase/POCD in this population [26]
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Hypothermia is frequently used during CPB because it may be an important modality for neuroprotection, but it may also contribute to POD/POCD in cardiac surgery [27]
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Hypothermia reduces cerebral metabolic rate, attenuates neuroinflammatory responses to CPB, and reduces production of free reactive species and release of excitatory neurotransmitters (which may play a role in neuronal death)
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However, rapid rewarming prior to the onset of CPB may disrupt brain autoregulatory mechanisms and lead to cerebral edema [28]
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The resulting cerebral edema may lead to increased intracranial pressure, impaired brain metabolism, and increased risk of POD/POCD
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Metabolic syndrome is characterized by a range of conditions (hypertension, hyperglycemia, hyperlipidemia, excess body fat) that increase the risk of heart disease and atherosclerosis, and is a pro-inflammatory state that increases POD/ Risk of POCD [29, 30]
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This hyperinflammatory state predisposes older patients to cognitive decline at baseline and an increased risk of POD/POCD [31]
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This chronic inflammatory state, combined with an acute exacerbation of inflammation, may be a mechanism for the increased incidence of POD/POCD after cardiac surgery
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This sharp rise in inflammation can lead to neuronal loss and dysfunction
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Hyperglycemia is an important modifiable risk factor for postoperative delirium
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Hyperglycemia has long been implicated as a cause of a pro-inflammatory state, thus suggesting a possible mechanism for its association with delirium
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In patients undergoing open heart surgery, intraoperative hyperglycemia (>200 mg/dL) was associated with POCD [32]
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Interestingly, strict glycemic control (intraoperative blood glucose between 80 and 100 mg/dL) may be detrimental for a number of reasons, one of which is a possible increased risk of POD compared to traditional intraoperative glycemic control [ 33]
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Hypoxia, whether arising acutely from perioperative hypoxia or secondary to anemia, appears to be an important risk factor for the development of delirium
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However, insomnia may also occur with chronic impaired oxygenation
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Patients with obstructive sleep apnea are at increased risk of developing POD/POCD, although the mechanism by which this occurs is unclear [34]
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Obstructive sleep apnea is a disorder of oxygenation during sleep, most commonly caused by excess pharyngeal tissue leading to sleep obstruction, hypoxia, and hypercapnia, resulting in frequent awakenings and impaired rest
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This impaired oxygenation may be an important cause of delirium in these patients
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Consistent with this hypothesis, there is an increased risk of POCD in patients with cerebral oxygen desaturation (normospheric oxygen saturation) after cardiac surgery [35]
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In older patients, acute illness or exacerbation of chronic illness may lead to delirium [36, 37]
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The risk of POD delirium in this population is as high as 10%, but may be higher depending on the surgical procedure and patient population
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The surgery with the highest risk is hip surgery, with an incidence of about 35%, which may reflect the frailty and overall decline represented by hip fracture patients
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Increased morbidity associated with cardiac, thoracic, vascular, and emergency surgery has also been reported
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In the elderly population, even relatively minor procedures, such as cataract extraction, are associated with POD, thus reflecting the particular susceptibility of this population
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Both hyponatremia and azotemia are considered to be contributing factors to or aggravating delirium [36]
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Infections, especially urinary and respiratory tract infections, are well-documented causes of delirium in surgical and medical patients
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Elevated preoperative leukocyte counts have been found to be a risk factor for postoperative peroxidase development, which may reflect the risk of even latent infection or inflammation during the development of delirium [38]
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Advanced age has been clearly shown to be an important risk factor for the development of postoperative delirium as well as delirium during acute illness
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Poor preoperative functional status and a higher American Society of Anesthesiologists rating have been shown to be independent risk factors for postoperative delirium [39]
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Lower preoperative albumin and higher preoperative bilirubin were associated with POD, thus raising the possibility that nutritional strategies or improvement in liver function may help prevent or treat POD
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Life>
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Smoking history has been shown to increase the risk of POCD
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In a study of patients undergoing abdominal aortic aneurysm surgery, the risk of developing POD was associated with an increased pack/year history [40]
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The underlying mechanisms by which smoking increases the risk of delirium are microvascular damage and increased atherosclerosis in the cerebrovascular system
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Furthermore, nicotine withdrawal may have similar biochemical similarities to delirium [41]
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Nicotine withdrawal is thought to be a relative deficiency of acetylcholine in the central nervous system
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Long-term exposure to nicotine can lead to upregulation and desensitization of acetylcholine receptors [42]
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During nicotine withdrawal, the vacant state of these receptors is thought to be a key mechanism of withdrawal symptoms
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Nicotine withdrawal and POD share some similar characteristics, such as restlessness, irritability, and confusion
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Nicotine replacements in the form of transdermal patches may have therapeutic benefits in preventing POD in patients who are unable to quit smoking before surgery
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Alcohol abuse has been identified as another risk factor for postoperative delirium and postoperative cognitive impairment
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Long-term alcoholism can lead to atrophy of the frontal lobe, as well as a decrease in the metabolism of the frontal cortex [43, 44]
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These chronic changes can lead to impaired executive function, impaired memory and, in severe cases, dementia not related to alcoholism
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Compared with non-alcoholics, alcoholics exhibited greater neurocognitive impairment preoperatively and higher levels of neurocognitive impairment compared with non-alcoholics [45, 46]
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However, abstinence for up to 5 weeks was not protective in chronic alcoholics, suggesting that neurocognitive impairment may be chronic, not easily reversible, or even permanent [47] Pathophysiology Pathophysiology Causes of POD and POCD It's not clear
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Several mechanisms have been hypothesized
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General anesthetics in aged rats have been shown to negatively affect spatial memory for up to 2 weeks after exposure [48]
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In addition, laboratory studies have shown that beta-amyloid oligomerization is enhanced after inhalation of volatile anesthetics [49]
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Therefore, it is easy to speculate that the mechanisms of POD and POCD are mainly related to the effects of anesthetics on the CNS
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Interestingly, when local anesthesia was used instead of general anesthesia for surgery, it was not shown to be protective [50, 51]
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However, major surgery appears to be an important culprit in the development of POD/POCD, while outpatient surgery is less risky [52]
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This suggests that the main cause of POD/POCD may be related to the increased inflammatory activity associated with major surgery [53]
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Delirium and cognitive impairment support a role for inflammation in the development of delirium, elevated C-reactive protein is associated with the development of delirium, and low levels of CRP predict resolution of delirium [54, 55]
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This suggests that the underlying mechanisms of delirium involve leukocyte migration into the central nervous system and disruption of the blood-brain barrier [56]
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Another potential risk factor for delirium is increased blood loss associated with surgery
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Postoperative delirium was found to be associated with increased intraoperative blood loss, increased postoperative blood transfusion, and postoperative hematocrit below 30% [57]
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Blood transfusion is a well-documented trigger and amplifier of systemic inflammation and a cause of increased oxidative damage [58]
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Conversely, lower hemoglobin levels were also associated with an increased risk of POD/POCD [59]
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Currently, there is no clear clinical recommendation for the relationship between perioperative anemia management and POD/POCD
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However, it is increasingly clear that increased bleeding risk and procedures requiring blood transfusions may significantly increase the risk of POD/POCD, especially in the elderly population or in patients with other risk factors for POD/POCD
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Prevention and Treatment In view of the prevalence of POD/POCD and the increase in morbidity and mortality, recent research has focused on the prevention and treatment of POD
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Anti-inflammatory pharmacology shows promise for the prevention and treatment of POD
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Hydroxymethylglutaryl-CoA reductase inhibitors (statins) have been shown to be neuroprotective in animal and human studies [60]
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These neuroprotective effects may originate from the immunomodulatory, anti-inflammatory and antithrombotic properties of statins [61]
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In a prospective observational study, preoperative statin administration was found to reduce POD in patients undergoing cardiopulmonary bypass surgery [62]
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Interestingly, another retrospective study found an increased association between preoperative statin use and increased POD in elderly patients undergoing elective surgery [63]
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Clearly, more research is needed to determine the role of statins in POD development
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Treatment of POD should begin with identification of the underlying medical conditions that may contribute to the cause, optimization of the environment and pain control, and drug therapy in refractory cases
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Medication should be considered in cases where POD puts the patient or caregiver at risk of physical harm or where POD interferes with routine postoperative care
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Haloperidol, a typical antipsychotic drug, remains one of the mainstays of delirium as a dopamine receptor type 2 (D2) antagonist regardless of etiology
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Recent studies suggest that prophylactic use of haloperidol may be beneficial in preventing postoperative delirium [64]
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When used in therapy, a dose of 0.
5-1 mg intravenously every 10-15 minutes can help control behavior
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Larger doses may be used in severely agitated and aggressive patients, but may cause adverse side effects, particularly excessive sedation
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QT prolongation is an ongoing problem that can be monitored by electrocardiography [65]
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Extrapyramidal side effects have been reported and may be permanent [66]
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Antipsychotic malignant syndrome, a reported side effect of haloperidol, is characterized by hyperthermia, rigidity, cognitive changes, autonomic instability, and elevated creatinine kinase levels [67]
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In the surgical population, patients with these symptoms may be mistaken for those presenting with malignant hyperthermia
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In patients who are particularly concerned about the side effects of haloperidol, atypical antipsychotics may be considered because of their more favorable safety profile
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Risperidone in particular has shown promise in the treatment of postoperative delirium, in one study preventing POD in cardiac patients receiving CPB [68]
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The relative deficiency of acetylcholine remains the main hypothesis explaining the susceptibility to dementia and cognitive decline in the elderly population [69]
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Therefore, several studies have investigated the role of acetylcholinesterase inhibitors in the prevention and treatment of POD
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The beneficial effect of anticholinesterase inhibitors in dementia treatment suggests a potential role in POD therapy
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The results so far have been mixed, however, a recent study involving transdermal administration of rivastigmine via a patch was able to reduce the incidence of POD in patients with hip fractures [70]
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Meanwhile, another prospective study failed to show the benefit of oral rivastigmine for POD prevention in cardiac surgery patients [71]
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The aging brain may be more sensitive to adverse central nervous system (CNS) reactions to commonly used perioperative drugs
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Almost any drug with central nervous system activity has been implicated in causing delirium
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Antihistamines such as diphenhydramine are commonly given as antiemetics, but these drugs often have significant anticholinergic effects and can cause agitation, confusion, and disorientation [72]
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Even small amounts of anticholinergic drugs, such as atropine and scopolamine, can cause delirium in the elderly population (quaternary glycopyrrolate, which does not cross the blood-brain barrier, is a better choice in this population) [73]
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If anticholinergic-induced delirium is suspected, the cholinesterase inhibitor physostigmine can be used as an antidote
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Effective management of surgical pain is another important variable strategy for POD prevention
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An increase in postoperative pain scores in the first 3 postoperative days increases the likelihood of POD (after controlling for other known preoperative risk factors) [74]
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Incomplete pain control appears to be an important cause of POD
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Opioids remain the mainstay of treatment for postoperative pain
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However, there is insufficient evidence whether opioids themselves increase the risk or severity of POD
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Because the importance of adequate postoperative pain control to prevent POD cannot be underestimated, opioids should be used postoperatively for adequate analgesia
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Methranil is the only opioid that consistently shows an increased association with delirium (possibly secondary to its anticholinergic properties) [75]
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The more commonly used perioperative opioids (hydromorphone, fentanyl, and morphine) do not appear to have any clear advantage in preventing delirium
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Because of the hemodynamic stability of opioids, high-dose opioids are common in cardiothoracic surgery, at least until the "fast track" of cardiac patients
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Low-dose fentanyl (10 μg/kg) compared with high-dose (50 μg/kg) for open-heart surgery did not prevent POCD in this high-risk patient group, but may facilitate early postoperative extubation [ 76]
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The literature on whether benzodiazepines may play a role in the development of POD/POCD in the elderly population is not yet conclusive
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Benzodiazepines have variable pharmacodynamics and pharmacokinetics, and their effects on cognition may be more pronounced in older adults
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But it may seem paradoxical, since these patients exhibit agitation and inhibition
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Some benzodiazepines (eg, diazepam) may be slowly metabolized and have multiple active metabolites
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In elderly patients, metabolites of benzodiazepines, especially those of long-acting drugs such as diazepam, can be detected postoperatively even one week after surgery
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However, the detection of these metabolites does not appear to be related to POCD
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Although the role of benzodiazepines in the development of POCD remains controversial, their role in increasing the risk of POD does appear to be more strongly correlated [77]
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This underscores the need for smaller doses of such drugs to adjust treatment for this age group, or even to avoid their concomitant use in the elderly population
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Long-acting benzodiazepines and increasing doses of benzodiazepines were more strongly associated with POD than short-acting or low-dose exposures [78]
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Benzodiazepines may be necessary in certain patient subgroups (active seizures, prophylaxis of delirium tremens in known alcoholics and benzodiazepine dependents), however, try to limit perioperatively in older patients The use of benzodiazepines may be prudent [75]
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Dexmedetomidine is a highly selective alpha-2 agonist that prevents POD in cardiac and non-cardiac surgery
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In elderly patients with cardiac disease, dexmedetomidine was associated with a lower incidence of POD and a shorter duration and severity of POD compared with propofol [79]
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An interesting study in China comparing low-dose (0.
1 μg/kg/h) intravenous dexmedetomidine infusion with placebo in intubated and non-intubated non-cardiac postoperative patients showed POD The incidence was significantly lower (9% in the dexmedetomidine group versus 23% in the placebo group) [80]
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The dexmedetomidine group also reported better scores on the subjective sleep quality scale
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Given the analgesic, sympathetic, and anxiolytic properties of dexmedetomidine, as well as its properties as a sedative, with minimal harm to respiratory depression, dexmedetomidine may prove particularly beneficial in the perioperative setting
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Postoperative sedation with dexmedetomidine may also reduce the need for postoperative benzodiazepines
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Dexmedetomidine may have important anti-inflammatory effects in the perioperative period
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Postoperative administration of dexmedetomidine reduces important markers of inflammation, such as interleukins (IL-6 and IL-8) and tumor necrosis factor alpha (TNF-α), which are associated with an increased risk of POCD [81, 82]
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Dexmedetomidine reduces the risk of POCD in the elderly population with its anti-inflammatory effect as a possible mechanism
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Ketamine is another important anesthetic that may have anti-inflammatory properties and may prevent POD/POCD
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In a study of cardiac patients undergoing CPB surgery, the use of ketamine as one of the inducers significantly reduced the risk of POD compared to a control group (3% of patients treated with ketamine were diagnosed with POD , while the control group was 31%) [83]
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The group receiving ketamine was also found to have lower levels of C-reactive protein, supporting the theory of a protective mechanism as an anti-inflammatory agent
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Ketamine is also known to inhibit IL-6, a potent inflammatory cytokine [84]
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Adequate research into the identification, prevention, and treatment of POD/POCD is essential for the benefit of surgical patients and society
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Incidence of POD and POCD is likely to become an increasingly common problem as the population over 65 years of age increases it, increases hospital stay and resource utilization, and prolongs recovery time after discharge
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Patients with POD and POCD are at increased risk of death and are at risk for long-term cognitive and physical disease
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Future Research Perspectives Future research may lead us to a clearer approach to optimizing care for these patients, as the mechanisms of POD/POCD become more clear, and specific ways to identify these patients perioperatively might be useful
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Ideally, we could identify patients at highest risk of developing POD/POCD and implement specific strategies to prevent POD/POCD progression
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Specifically, future studies focusing on the detection of certain inflammatory biomarkers are expected to identify patients at increased risk for POD/POCD
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Furthermore, specific modalities acting as anti-inflammatory agents may prove useful in preventing and treating the development of POD and POCD
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THE END