Owing to advancements in various anesthetic techniques, such as regional anesthesia, and the development of rapid-acting anesthetic agents, the number and scope of ambulatory anesthesia have been steadily increasing [1]. Some advantages of ambulatory surgery include minimizing the hospitalization period and avoiding unnecessary medical expenses. However, thorough preparation and contingency plans are necessary to enable same-day postoperative discharge, which can burden healthcare providers [2]. Therefore, adequately anticipating and addressing potential complications is essential.

Anesthesia has been associated with cognitive changes for over a century [3]. However, it has only recently been intensively investigated through animal experiments and clinical research with objective testing. Many studies have suggested that anesthesia may have harmful consequences on cognitive function [4–8].

One important postoperative neurocognitive disorder (PoNCD) is postoperative delirium (POD). POD is an acute neuropsychiatric disorder that can occur starting on the first postoperative day and is characterized by impaired perception, attention, and cognitive function [9,10]. Although mostly transient and reversible, this condition can be a risk factor for developing dementia [11] and is associated with postoperative cognitive dysfunction (POCD), another potential concern for surgical patients. Even when symptoms are not immediately evident, a consistent decline in cognitive function has been observed in the short-term (7 days) and medium-term (1–3 months) following anesthesia and surgery [12].

POCD is distinct from POD [13]. While POD is relatively well-defined, conceptualizing POCD remains challenging, even though the term has been defined according to the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5), and the neurocognitive testing methods used are heterogeneous. Patients with POCD experience cognitive decline compared to preoperative levels, which manifests as dysfunctions in memory, mental ability, language, and/or other cerebral functions [14,15]. These conditions not only compromise recovery from surgery and quality of life after surgery, but also potentially contribute to an elevated patient mortality rate [16,17].

Considering that characteristics of POD and POCD progression can occur even after ambulatory surgery and recognizing the subsequent rapid decline in the continuity of patient care post-discharge, these conditions are likely underdiagnosed. Therefore, we conducted a narrative review of the overall patterns of disease occurrence and preventive and treatment methods. This study aimed to gain a better understanding of these conditions, particularly in ambulatory surgery. 

After several meetings that began in 2014, the Working Group on Perioperative Cognitive Nomenclature, comprising experts from various disciplines, reached a consensus with the following recommendation: perioperative neurocognitive disorders (NCDs) be used as the comprehensive term for any impairment in cognitive function identified in the preoperative or postoperative period, including cognitive impairment diagnosed before surgery (described as NCDs), any form of acute event (POD), and cognitive decline diagnosed up to 30 days (delayed neurocognitive recovery) or 12 months (PoNCD) after the procedure [12]. Although these definitions are recommended, we were unable to follow the diagnostic and testing methods used by the Working Group for the terms POD and POCD as most of the included studies used different definitions and diagnostic methods. In this review, the term POCD is used to describe cognitive dysfunction from the late period of delayed neurocognitive recovery to the entire postoperative period in which NCDs can occur.

Recent studies have reported that frailty in older patients increases the incidence of postoperative complications [18–21]. In addition, studies have reported that frailty status is a better predictor of patient mortality and complications, and prolonged hospital length of stay than chronological age [20]. Frailty is a term that describes a patient’s diminished ability to cope with physiologically stressful events, such as surgery. Frailty can be defined in several ways. Although no clear consensus exists, the Fried criteria, which assess unintentional weight loss, weakness or poor grip strength, self-reported exhaustion, low physical activity, and slow walking speed, have been widely used [22,23]. Brown et al. [22] reported a frailty prevalence of 30.9% in a cohort of patients (>55 years old) scheduled to undergo cardiac surgery in 2016. In addition, a 2001 study conducted by Fried et al. [23] reported that the overall prevalence of frailty in a community-dwelling population was 6.9%, and the prevalence was proportional to age and higher in women.

Preoperative frailty is an important risk factor for POD. In a prospective observational pilot study of 55 patients undergoing coronary artery bypass graft surgery, Brown et al. [22] reported that patients with preoperative frailty had a significantly higher incidence of POD than those without preoperative frailty (47.1% vs. 2.6%; P < 0.001). A prospective cohort study of 167 patients aged ≥ 65 years undergoing noncardiac surgery reported that patients determined to be frail or pre-frail were associated with increased odds of POD compared to healthy patients (odds ratio: 2.7, 97.5% CI [1.0, 7.3]) [24]. These results suggest that the degree of frailty in elderly patients undergoing surgery should be assessed in advance.

Surgical injury increases neuroinflammation and decreases neuronal growth, both of which are strongly associated with the development of POD and POCD [14]. This suggests that neuroinflammation plays an important role in both disorders, although the pathophysiology is not fully understood [25]. The hypothesis that surgical trauma disrupts the blood-brain barrier (BBB), leading to central nervous system (CNS) inflammation and subsequent functional impairment of neuronal activity, resulting in POCD has received increasing attention [13]. Further studies of these mechanisms may increase our understanding of the pathogenesis of POD and POCD and improve prevention and treatment strategies.

Cells injured at the site of surgery release substances known as damage-associated molecular patterns (DAMPs). These DAMPs bind to receptors on the cell membrane of bone marrow-derived monocytes (BMDMs) and activate nuclear factor kappa B (NF-kB), which enters the nucleus and triggers upregulation of inflammatory cytokines, such as interleukin (IL)-1, tumor necrosis factor-α (TNF-α), and IL-6. This further activates NF-kB, which in turn promotes the synthesis of prostaglandins. Prostaglandins alter the permeability of the BBB and allow BMDMs to enter the CNS and activate dormant microglia, which in turn promotes the release of IL-1 and TNF-α from BMDMs. As a result, BMDMs are present in the CNS and continue to secrete pro-inflammatory cytokines, leading to neuroinflammation [13]. Animal studies have reported that modulating the release of substances that act at each of these stages can reduce the risk of POCD. For example, inhibiting NF-kB and pro-inflammatory cytokines [26,27] or depleting BMDMs [28] has been reported to reduce POCD. These findings could lead to the development of treatments for POCD.

Studies on epigenetic mechanisms [14] and the gut-brain axis [29] to better understand the mechanism of neuroinflammation after anesthesia and surgery have also been conducted. In particular, cognitive dysfunction following surgery can persist over a long period, and changes in the epigenetic profile have been suggested as a possible cause. Epigenetics has been implicated in cognitive impairment for many reasons, including exposure to inflammation in the hippocampus due to general anesthesia, hypotension, hypoxia, psychotropic drugs, and surgery. Early studies have suggested that these factors may induce epigenetic dysfunction in the brain because chromatin remodeling is required for the transcription and expression of genes involved in memory, which may be particularly important in older patients [14]. Epigenetic modulators may be promising targets for mitigating the neurotoxic effects of anesthetics on the brain. However, further studies on whether anesthetics cause epigenetic changes are needed.

Preoperative cognitive impairment is an important risk factor for POD and POCD [30,31]. However, existing pre-anesthesia assessment systems do not include cognitive testing as part of routine preoperative patient evaluations [23]. The proportion of elderly patients undergoing ambulatory surgery continues to increase, and the prevalence of cognitive impairment in elderly patients increases with age. In a study of 1,465 patients undergoing ambulatory surgery in 2019, Sherman et al. [32] reported that 6.4% of participants aged 65–75 years, 13.4% of participants aged 76–85 years, and 19.3% of participants aged ≥ 86 years had cognitive impairment. Given that preoperative cognitive impairment is associated with increased postoperative mortality and morbidity and the development of delirium [23] and POCD cannot be diagnosed unless the patient undergoes formal cognitive function testing before and after surgery [33], cognitive screening should be conducted during the pre-anesthesia assessment. Indeed, the American College of Surgeons and the American Geriatrics Society recommend preoperative screening for neurocognitive impairment to establish baseline cognitive levels [15].

Screening tools for preoperative cognitive testing should be adapted to clinical practice and should be highly reproducible. Screening tools include the Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), and Mini-Cog; however, the MoCA and MMSE are complex and require standardized test forms, which limits their feasibility in busy clinical settings [19,34]. The Mini-Cog test, on the other hand, is simple to administer and does not require a standardized template [20,35]. Several studies have explored it as a tool for pre-anesthetic cognitive assessments [23,34,36]. The Mini-Cog test consists of two components: items that assess memory, such as word recall, and a clock drawing test that evaluates cognitive domains such as language, fine motor skills, and executive function [35]. Patients are asked to listen to three unrelated words and immediately recall them. They are then asked to draw an analog clock as required by the evaluator and, after drawing the clock, recall the three words again. The patient receives one point per word the patient can recall, and the clock drawing test is scored as normal or abnormal. If the delayed word recall score is 0 out of 3, or if the score is 1 or 2 and the clock drawing test result is abnormal, the test is scored as positive for a possible diagnosis of dementia. If the delayed word recall score is 3, or if the score is 1 or 2 and the clock drawing test result is normal, the test is negative (indicating the absence of dementia) [34]. The Mini-Cog test is a cognitive stratification test, not a diagnostic test [37]. Providers who identify it in the pre-anesthesia assessment can share this information in the electronic medical record to allow for more individualized care before and after surgery.

POD is a serious problem that increases the incidence of postoperative complications [38] and represents a decrease in cerebral responses due to one or more pathophysiological stressors [39]. The DSM-5 provides the following revised diagnostic criteria for delirium: 1) an impairment of attention and awareness that occurs over a short period (hours to days), with rapid changes in baseline status and frequent fluctuations in severity throughout the day; 2) additional cognitive impairment (loss of memory and orientation) that cannot be explained by a pre-existing, ongoing neurocognitive disorder and does not result in a severely depressed level of arousal, such as a coma; and 3) the condition does not result from other medical conditions (e.g., substance intoxication or withdrawal) or exposure to toxic substances. POD occurs when the antecedent factors of surgery and anesthesia interact with a patient’s vulnerability to delirium [40]; therefore, assessing the preoperative status of patients scheduled for surgery and individualizing the approach for those at high risk for POD are important for reducing the incidence of delirium and improving patient outcomes [41].

The incidence of POCD is significantly lower in ambulatory surgery than in inpatient surgery [2]. However, because older patients are more likely to have preexisting cognitive impairment [32] and surgery in elderly patients can result in rapid cognitive decline [36,56], prevention and treatment of POCD should not be neglected despite the low incidence. To evaluate for the development of POCD, baseline cognitive function needs to be assessed preoperatively. This can then be compared with the postoperative state. However, no clear consensus regarding the level of cognitive decline that is clinically significant has been reached [33].

Increased mortality, decreased quality of life, and labor market withdrawal associated with POCD have been addressed in several studies [23,33,57]. Steinmetz et al. [38] reported a long-term prognostic study of patients undergoing noncardiac surgery with a median follow-up of 8.5 years. The risk of leaving the labor market prematurely for disability reasons was higher in patients with POCD at 1 week postoperatively (hazard ratio: 2.26, 95% CI [1.24, 4.12], P = 0.01). These patients were found to receive social transfer payments for a more extended time during the observational period (prevalence ratio: 1.45, 95% CI [1.03, 2.04], P = 0.03). This is an example of the impact of POCD on socioeconomic status. Bickel et al. [58] studied the causal relationship between POD and cognitive impairment, functional impairment, and death in 200 patients aged > 60 years who underwent hip surgery. POD occurred in 41 patients, 53.8% of which had cognitive impairment 38 months after discharge, whereas only 4.4% of patients without POD developed cognitive impairment. This suggests that POD adversely affects the preservation of cognitive function and provides important evidence for the need for proactive prevention of POD.

Table 1 summarizes POD and POCD in ambulatory surgery. PoNCDs are significant complications that can adversely affect a patient’s mental and cognitive wellbeing. The stress of surgery and anesthesia on the patient may contribute to the development of the disease, and the presence of POD increases the incidence of POCD. In particular, frailty in elderly patients significantly increases the risk of POD, and neuroinflammation plays a vital role in POCD development. Although the risk of developing POD or POCD is considered low in ambulatory surgery, healthcare professionals should be mindful of these potential adverse effects, mitigate the risks associated with PoNCDs, and improve patient outcomes by implementing appropriate preventive measures and pharmacological management strategies. Evaluating cognitive function during ambulatory surgery as a preventive measure for POD and POCD is also important. The incidence of PoNCDs in the ambulatory surgery patient population may be underestimated, as these patients are often not monitored for these specific conditions after discharge. Further studies are thus needed to overcome these limitations.

Patients and their caregivers communicating any cognitive changes to the healthcare team is essential as early intervention can lead to better outcomes. For severe cases or cases in which symptoms persist or worsen, referral to a neurologist or cognitive specialist is warranted for further evaluation and treatment.