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Preserving Perioperative Brain Health Through a Patient Safety Lens

Riccio, Christina A. MD*; Lu, Amy C. MD; Lin, Della M. MS, MD, FASA§,‡

International Anesthesiology Clinics: Summer 2019 - Volume 57 - Issue 3 - p 96–110
doi: 10.1097/AIA.0000000000000238
Review Articles

*Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, Texas

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California

Armstrong Institute for Patient Safety and Quality, Johns Hopkins University, Baltimore, Maryland

§Department of Surgery, University of Hawaii, Honolulu, Hawaii

The authors declare that they have nothing to disclose.

Address Correspondence to: Della M. Lin, MS, MD, FASA, 1329 LUSITANA, #604, HONOLULU, HI 96813. E-mail:

Preserving perioperative brain function is an emerging concept in patient safety, a crucial public health concern, and, undeniably, a quality of life issue, especially in patients ages 65 years and older.1 Research in this field has sought to better identify the etiologies, risk factors, and pathophysiology of perioperative neurocognitive disorders (NCDs) and to develop methods to protect and prevent cognitive decline in the elderly. Several comprehensive review articles can be found in the literature.2–5 Omitting mention of perioperative NCDs in a themed issue on topics in emerging patient safety would be unwise.

In 2015, the American Society of Anesthesiologists (ASA) recognized brain health as a key patient safety topic, launching the Brain Health Initiative (BHI).6 This initiative aims to engage multidisciplinary teams to optimize cognitive recovery in elderly surgical patients. It recommends preoperative screening for cognitive deficits and shares protective interventions implementable throughout the perioperative course to lessen the impact of surgical stress on cognitive function. It has generated increasing interest within the research community on brain health, initiating studies looking at both the pathophysiology of cognition dysfunction and the practical application of simple screening tools, evidence-based methods, and pharmacologic changes considered to preserve brain health.6

Unfortunately, differences in terminology—particularly between the research and clinical communities—make attempts to compare the literature surrounding brain health more confusing and complex. New nomenclature has been proposed by a working group of international experts representing anesthesiology, neurology, geriatrics, psychiatry, neuropsychology, surgery, and psychology for simplification and unification. They aligned common terminology used in the literature with that used in cognitive classifications for the general population as defined by The American Psychiatric Association’s Diagnostic and Statistical Manual, 5th edition (DSM-V).7 In November 2018, 6 journals (Anesthesiology, Acta Anaesthesiologica Scandinavica, Anesthesia & Analgesia, British Journal of Anaesthesia, Canadian Journal of Anesthesia, and the Journal of Alzheimer’s Disease) co-published an article detailing the work. The proposal recommends that the overarching term used to refer to perioperative cognitive dysfunction be “neurocognitive disorders.” Perioperative NCDs include both cognitive impairments identified in the preoperative (NCD) or the postoperative period [postoperative delirium (acute), delayed neurocognitive recovery (up to 30 d), and postoperative NCD (up to 12 mo)].8 Throughout the rest of this article, we will utilize this new terminology whenever possible.

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Brief Background Summary

Delirium, defined as an acute change in cognition, with a hallmark of inattention, is the most common complication affecting hospitalized patients older than 65 years of age. It affects ∼23% of hospitalized elderly patients, and is even more prevalent in surgical patients.9,10 The DSM-V describes delirium with several key features, including an acute, often fluctuating, disturbance in attention, and a disruption in cognition, such as memory deficits, disorientation, and difficulties with language or perception, not attributed to a preexisting condition or decreased state of arousal. Variable emotional changes can accompany the confusional state. Delirium can present clinically as hypoactive, hyperactive, or mixed behavior. The hypoactive form is characterized by lethargy and reduced psychomotor function, oftentimes unrecognized and misattributed to depressed mood and fatigue, and therefore associated with a poorer prognosis. Hyperactive delirium presents with psychomotor agitation and unstable mood, leading many patients to refuse medical care.7

Cognitive dysfunction contributes significantly to the US economic and health care burden, with estimated hospital costs at 6.9 billion Medicare dollars and upwards of 152 billion dollars for long-term care costs (eg, nursing home placement, home health, and rehabilitation).11–13

Delirium may be the only early sign of deteriorating health,4 making early diagnosis and intervention desirable and necessary. Yet, the rate of undiagnosed delirium has been estimated to be as high as 61%.14 In addition, patients who develop delirium are at elevated risk for long-term cognitive and functional decline, traditionally referred to as postoperative cognitive dysfunction (POCD).4

POCD is defined by an objective decline in postoperative cognition compared with the patient’s baseline preoperative state.15 Therefore, unlike delirium, POCD cannot be officially diagnosed unless a patient has undergone neuropsychological testing before and after surgery, which typically does not occur outside a research setting.3 Berger et al3 suggest conceptualizing POCD as a syndrome rather than a distinct entity with specific etiology, describing it as a lack of cognitive resilience to surgical stressors. POCD has often been considered a subset of delirium with associated long-term negative effects on cognition that may persist for days, weeks, months, or even years.16–18 Unlike the emergence delirium anesthesiologists often see, POCD disproportionately affects the elderly and is often exaggerated in patients with baseline cognitive deficits.8,19

The Successful Aging after Elective Surgery (SAGES) trial is an ongoing study following 566 elderly patients 70 years and older without a preoperative diagnosis of dementia for 8 years after discharge. Importantly, it reports that after surgery, 24% of patients developed POCD and POCD was associated with a significant increase in length of stay, rehospitalization within 30 days, and discharge to an institution. Patients with postoperative complications in addition to POCD had the worst outcomes.13,20 At 3 years, patients with the highest delirium severity experienced the greatest rate of cognitive decline, exceeding the rate observed for patients with dementia. These results suggest that delirium should be considered a postoperative complication, that a dose-response relationship between delirium severity and long-term cognitive decline exists, and that acute postoperative delirium may have very long-term harmful consequences.21 These findings, along with the understanding that the majority of postoperative delirium events go unrecognized, and may be preventable in up to 40% of cases,6 makes this a public health crisis.

POCD has been linked to preexisting cognitive impairment, older age, and lower education, supporting the notion that patients with less cognitive reserve are at a higher risk of developing POCD.16,22 The SAGES work shows that patients with POCD have lower preoperative cognitive performance, greater impairment 1 month after surgery, and greater long-term cognitive decline compared with patients without POCD.17 Mild cognitive impairment (MCI) and dementia are known risk factors for POCD. Interestingly, patients without a preoperative diagnosis of cognitive impairment who experience POCD are more likely to be diagnosed later with MCI or dementia.18,23 Yet, studies have also reported a similar incidence of cognitive dysfunction compared with nonsurgical elderly patients at 12 months, suggesting that POCD may be temporary.22,24,25 Still, older patients have more risk factors for neurovascular disease and greater damage to cerebral white matter3,26 and thus less reserve, rendering them vulnerable to perioperative stressors.

Surgery and anesthesia have also been associated with POCD, although a causal relationship has not been shown. Like delirium, POCD can be linked to postoperative infection, inflammatory mediators, hypotension, and hypoxemia.16,22 Some have hypothesized that POCD is related to vision or hearing impairment, electrolyte or neurotransmitter imbalance, substance abuse, dehydration, or medications, specifically centrally acting anesthetic drugs and those used to treat postoperative pain.8 Studies suggest that increasing length and type of surgery and duration of anesthesia are related to POCD development.16 Early work in this field targeted cardiac surgery in patients undergoing cardiopulmonary bypass, with a higher incidence of POCD immediately after cardiac surgery compared with noncardiac surgery. However, at 3 months, the incidence of POCD appears to be independent of the type of surgery and anesthetic performed.15 Exposure to anesthesia and surgery may, in fact, only be associated with a small decline in cognition, although still significant for patients with baseline cognitive deficits.27 The Strategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients (STRIDE) study by Sieber et al28 found that moderate sedation compared with deep sedation is associated with 50% less POCD in elderly patients. Less sedation did not reduce the overall incidence of delirium, but did result in a significant reduction in delirium in patients with low baseline comorbidity indices.28 Avoidance of general anesthesia by using regional anesthesia techniques did not decrease the risk of POCD if sedative drugs were used concurrently.8,29 Studies examining titration of anesthesia using various brain monitors [eg, cerebral oximetry30 and processed electroencephalogram (EEG) monitoring30,31] are promising, but lack sufficient evidence to recommend their routine use intraoperatively. The role of anesthesia and surgery in the development of POCD has yet to be clarified. However, it has been theorized that they may synergistically enhance the neuropathologic changes in Alzheimer disease, leading to a more rapid rate of deterioration.32

The etiology of POCD remains unclear and is likely multifactorial, representing a complex interaction between risk factors and a vulnerable brain. Irrespective of etiology, POCD is associated with an increased risk of mortality and decreased quality of life in elderly patients.22,33,34 Patients with POCD are more likely to die in the years after surgery, more likely to be diagnosed with dementia or MCI, or require institutionalization.35 Patients with delirium superimposed on dementia have a higher 1-year mortality even when adjusted for age and comorbid conditions.19 Duration of POCD is a prognostic factor in 6-month mortality; thus, efforts to decrease the length of these episodes become important as well.9

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Best Practices

Several studies have examined the utility of preoperative testing to screen for patients at high risk for developing perioperative NCDs.36–41 Examples of commonly used screening tools include the Mini-Cog and the AWOL tool.36–41 AWOL refers to age 80 years and older, failure to spell “World” backward, disorientation to place, and higher nurse-rated illness severity.36 The Mini-Cog involves a three-item recall test for memory, and a clock drawing test that evaluates visuospatial representation, recall, and executive function. The Mini-Cog has been shown to be relatively easy to implement, while having high inter-rater reliability.6

The presence of preoperative cognitive impairment remains a strong predictor of cognitive dysfunction across all surgical procedures and may be a starting point for identification of at-risk individuals and implementation of early intervention.37–40,42 Poor performance on preoperative cognitive screening tests in older surgical patients has been shown to predict postoperative complications, such as development of POCD, longer hospital stays, and lower likelihood of being discharged home.28 Although the evidence is in its favor, routine implementation of these tools in a busy preoperative anesthesia and surgery clinic is challenging. Additional assessments, such as frailty, functional dependency, history of falls, and walking speed, have also been correlated with the ability to detect an increased incidence of postoperative complications in older adults.29 Frail patients have a 47% incidence of delirium compared with 2.6% in nonfrail patients, and frailty scales can be used in the preoperative identification of high-risk patients.29 Taking the time to utilize a preoperative screening tool to identify high-risk patients can reduce the incidence of perioperative NCDs.6,37–41 Furthermore, a recent consensus statement published on the perioperative management of NCDs stated: “Baseline cognition should be objectively evaluated with a brief screening tool during preoperative evaluation in all patients over the age of 65 and in any patient with risk factors for preexisting cognitive impairment.”38

During the intraoperative period, a number of interventions have been shown to mitigate the postoperative occurrence of delirium and long-term cognitive dysfunction.37–41 Recent recommendations for intraoperative interventions include avoiding certain classes of medications, titrating anesthetic depth using intraoperative EEG monitoring, monitoring age-adjusted end-tidal MAC fractions, maintaining normothermia, and avoiding intraoperative hypotension.6,37–41 Examples of medications to avoid are listed in Table 1.

Table 1

Table 1

Use of processed EEG (eg, bispectral index) and evoked potentials to titrate anesthetic depth has been supported in the literature which suggests that avoiding burst suppression may be particularly important.31,43,44 A recent Cochrane meta-analysis showed that adjusting anesthetic administration using processed EEG guidance reduced the risk of postoperative delirium in patients 60 years of age and older in noncardiac and non-neurosurgical patient populations.43 Furthermore, the incidence of POCD at 3 months was reduced. However, long-term effects >1 year remained unclear and the meta-analysis did not find a significant difference in all-cause mortality and postoperative length of stay.43 Further investigation in this field of emerging research is clearly warranted before endorsing the routine use of such intraoperative monitoring by anesthesia providers.

Postoperatively, regular assessment of patients for delirium should be encouraged. Postoperative assessment tools commonly used include the Confusion Assessment Method (CAM), Confusion Intensive Care Delirium Screening Checklist (ICDSC), the 4 AT, Delirium Symptom Interview (DS), and the Nursing Delirium Screening Scale (NuDESC).6,37–42 Best practices to reduce the incidence of delirium have targeted several implementation strategies listed in Table 2. Instituting even a few of the techniques listed will aid in the prevention of perioperative NCDs. Increasing adherence by using bundles such as the ABCDEF bundle (Awakening and Breathing coordination, Choice of drugs, Delirium monitoring and management, Early mobility, and Family engagement) has been correlated directly with reduced delirium and improved hospital survival in a dose-dependent manner.45,46 Thus, there are several points throughout the perioperative experience when brief and simple testing can alert health care providers to early signs of perioperative NCDs. Preoperative identification of these patients, implementation of prevention strategies, and early treatment of symptoms are all critical in reducing the incidence of perioperative NCDs.

Table 2

Table 2

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A Patient Safety Science Lens

It is increasingly clear that the brain endures a cognitive “stress” test when undergoing surgery and anesthesia. Unfortunately, it is also becoming evident that this stress can result in short-term and long-term harm, especially in the elderly. This is an important patient safety issue that has long been neglected. The science of patient safety is about recognizing and defining the risks of harm. It attempts to create systems and interventions to reduce and/or eliminate said harm. Applying the lessons and tools developed from patient safety science will improve the likelihood of successful and sustained risk reduction of perioperative NCDs.

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The Hierarchy of Effectiveness

Not all interventions are created equal. A cornerstone of safety engineering and risk management is to optimally design out foreseeable hazard. If this is not possible, physical guards are put in place to reduce risk. Warning and training individuals is a last resort. The Institute for Safe Medication Practices and John Gosbee, MD, MS Human Factors Engineer (VA National Center for Patient Safety) have integrated the principles of safety and human factors engineering into the concept of a “hierarchy” of interventions and effectiveness. This concept is often part of a root-cause analysis action review and is represented graphically in Figure 1.

Figure 1

Figure 1

The least effective intervention is to simply tell an individual “to be more careful and vigilant.” This may be followed by providing written education and information on the risk. Unfortunately, many action plans stop there. The next step is setting rules and policies for individuals. This shifts the statement “you should do this” to “you must do this.” All these interventions rely heavily on human memory, involve very little system engineering, and are inherently weak.

As we climb the hierarchy ladder, interventions include checklists, standardization of tools/equipment, and computerization. These interventions reduce complexity and variation, increasing reliability. Accountability is shared between technical and person-based interventions, and effectiveness depends on the social-technical interface. High-performing and highly reliable teams can make these tools extremely effective.

At the top of this hierarchy are “forcing functions” and constraints, including changes in architectural design and work areas. In anesthesia, there are several physical design examples of forcing function. Examples include the pin index safety system, the fail-safe valves that protect against a fall in oxygen pressure, and the oxygen-nitrous oxide proportioning systems. The further we move toward the upper right-hand corner of Figure 1, the more reliably effective the intervention. Designing interventions at this height of the hierarchy, however, requires a great deal of time and effort—oftentimes necessitating new mindsets.

Changing the architecture and environmental design is highly effective in reducing risk. At New York University (NYU) Winthrop Hospital, environmental defaults to promote brain health have been instituted. Automatic shades and skylights have been installed on the wards and televisions have an automatic shut-off feature based on time and inactivity. These forcing functions no longer require an individual to visit each and every room to ensure that the television has been turned off. The hospital further optimized sleep hygiene by establishing a protected time period between midnight and 5:00 AM, and have stopped scheduled 2:00 AM and 4:00 AM lab draws. (Maureen McGaffney, RN, Senior VP Clinical Operations, personal oral communication, December 4, 2018).

The Hospital Elder Life Program (HELP) and Acute Care for Elders (ACE) units are additional examples of high-level change through environmental design. Patients admitted to these units have an interdisciplinary team focused on cognitive impairment, sleep deprivation, immobility, visual and/ or hearing impairment, and dehydration. This comprehensive set of strategies has been shown to reduce the incidence of delirium by 53% and falls by 42%.2 If this redesign were available for all patients identified to be at risk for NCDs, this intervention would be a strong forcing function. Most hospitals, however, have only one or few such designated units and when those units reach capacity, patients are then admitted to traditional units.

Vanderbilt University Medical Center also takes measures to design out harm. They are architecturally developing a “High Risk Preoperative Clinic” to ensure that patients who need delirium, frailty, and other relevant screening tests have adequate time for a complete visit. (Christopher Hughes, MD, personal communication, December 7, 2018).

The University of California, San Francisco (UCSF), has put in place several moderate to moderate/high-level interventions. They created a comprehensive program that starts in the preoperative holding area and extends through the postrecovery period.47 Their intervention includes a separate recovery room electronic order set for patients at risk for perioperative NCDs. This order set lists ondansetron as the first-line treatment for postoperative nausea and vomiting, followed by a low dose of haloperidol. It removes the option of prescribing drugs with significant anticholinergic properties (eg, promethazine) to elderly patients and other medications found in the Beers Criteria list (eg, meperidine, metoclopramide).48 Like UCSF, several hospitals embed first-line drop-down options for analgesics in patients at risk for perioperative NCDs to nudge decision-making. These menus might suggest acetaminophen and low-dose opioids (eg, oxycodone 2.5 mg) as first options, whereas patient-controlled analgesia pumps and benzodiazepines are removed as options.

Preoperative cognitive screening tests and postoperative delirium assessment tools have been implemented by several hospitals and are moderately strong interventions.5 UCSF uses AWOL-S, defined above, in their preoperative holding area. The “S” adds ASA status and procedural risk to their assessment (Anne Donovan, MD, Elizabeth Whitlock, MD, UCSF personal oral communication, December 4, 2018). Through software enhancement, the electronic medical record then stratifies an AWOL-S risk (high or low) with an absolute predicted probability for postoperative delirium. High-risk patients are flagged under “anesthesia alerts,” and a decision-support alert encourages the use of the high-risk delirium order set.

These moderate-level interventions can be strengthened by designing them as defaults or “opt-outs.” Even stronger standardization can occur when collaboration occurs to ensure that the same tools are used organization-wide —instead of different techniques being implemented in the preoperative clinic, perioperative floors, emergency department, and intensive care units. At UCSF, perioperative delirium interventions have been harmonized successfully with their house-wide delirium interventions.47

Recently, Halladay et al49 and Wong et al50 published the use of embedded algorithms and machine learning as tools to screen for delirium risk upon admission. Wong and colleagues’ results suggest that their automated system outperforms current nurse-prediction rules. These augmented intelligence methods may play an important role as part of a comprehensive strategy to screen for high-risk patients.

Educational strategies, CME programs, and a department or hospital policy can raise awareness around perioperative NCDs. By themselves, however, they offer limited sustainable risk reduction. Safety science intervention hierarchy informs us that telling people to “be more vigilant” when caring for elderly patients is the weakest stand-alone intervention, placing undue burden on individuals and human memory over the system.

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The Importance of Teams

There is compelling evidence in patient safety science that high-performing teamwork is important to reducing patient harm.51,52 Perioperative medicine works in multidisciplinary distributed health care teams, separated both geographically and by workflow. Maintaining situational awareness is challenging, the risk for “diffusion of responsibility” increases, and failures in communication become more common. The ASA Closed Claims Project reports that loss of situational awareness is a significant source of patient harm.53 There is evidence that briefings, simulation, and standardized communication tools can enhance reliability and safety.51

The Google Aristotle Project studied high-performing teams.54 Their conclusions were that 5 factors were crucial to the success of teams: psychological safety, dependability, structure and clarity, meaning, and impact. Of these, psychological safety is the most important. It is imperative to ensure a flattened hierarchy, where team members feel safe to speak up, offer suggestions, and provide feedback. Mutual trust develops over time and creates appropriate space for team problem-solving.

An example of a perioperative NCD team enabling situational awareness is the High-Risk Older Adult Quality Surgical Committee at the Denver VA Medical Center. Led by Dr Tom Robinson, chief of surgery, they utilize a hospital “tumor board” as their model. This committee works to improve multidisciplinary teamwork and focuses on screening and preservation of perioperative cognitive function. (Tom Robinson, MD, personal oral communication, September 27, 2018).

Highly successful HELP units are another example of teams successfully reducing perioperative NCD risk.2 (Fred Rubin, MD and Tammy T. Hshieh, MD, personal oral communication, October 9 and November 2, 2018). The teams have clearly defined roles. Volunteers, families, and patients are included as critical members of the team structure. They intentionally flatten traditional hierarchy and nurture mutual trust, maintaining an essential culture of psychological safety.

High-performing teams can make interventions, such as standardized protocols, acronyms, and checklists, even more effective. Poor-performing teams can make the same interventions a safety risk. Checklists that overfocus on compliance create a false sense of security that can inadvertently adversely affect patient safety.55 As hospitals endorse broader comanagement teams to optimize care in the elderly, it is crucial to promote and maintain the 5 tenets of high-functioning groups: psychological safety, dependability, structure and clarity, meaning, and impact. “The whole is greater than the sum of its parts.”

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Patient-centered Care as a Patient Safety Principle

It is important to engage “patients’ active involvement in their own care as a patient safety strategy.”56 We should move from doing things “to” patients and even “for” patients, to doing things “with” patients. “Staying sharp” is the number one health concern for individuals older than 70 years of age. Eighty-three percent of individuals older than 40 years of age feel that it is “very important to maintain and improve brain health.”57

The interdisciplinary HELP and ACE units understand the importance of patient and family partnership in successful implementation of their units to reduce delirium while in hospital. Patients at particularly high risk of cognitive dysfunction can have family members educated and available to facilitate patient orientation to their surroundings during provider handoffs and when patients transition on and off a unit (eg, from postanesthesia care unit to floor).

The “Best Practices for Postoperative Brain Health” consensus statement states that “All patients over age 65 should be informed of the risks of perioperative NCDs including confusion, inattention, and memory problems after having an operation.”38 This discussion should also include the opportunity for shared decision-making on the relative appropriateness of surgery, and provide an opportunity for medication reconciliation and deescalation before surgery [ie, reducing the number of meds, stopping medications found on the Beers criteria preoperatively (eg, diphenhydramine) or other medications that might increase the risk for delirium].

Preserving postoperative brain health is a significant, complex topic. We have provided a brief overview of perioperative NCDs, shared some best practices, and applied safety and human factors engineering principles—a hierarchy of interventions, criteria for high-performing teams, and patient-centered engagement—offering suggestions for perioperative teams to effectively reduce the harm of perioperative NCDs. It is alarming that patients who suffer delirium during their hospitalization have odds risks ranging from 6 to 41 of developing worsening cognitive decline.58 It is imperative that, as a specialty leading patient safety, anesthesiologists continue to study and routinely apply evidence-based methods aimed at reducing and eliminating perioperative NCDs.

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The authors wish to thank the following individuals for their comments, suggestions, and wisdom as they developed this paper: Dr Miles Berger, Dr Daniel Cole, Dr Gregory Crosby, Dr John Gosbee, Dr Christopher Hughes, Dr Sharon Inouye, and Dr Carol Peden. The authors wish to thank the following individuals for their interviews, and gracious willingness to share ongoing work in this field noted here as personal communications: Dr Matthias Braehler, Dr Christopher Hughes, Dr Anne Donovan, Maureen Gaffney, Dr Tammy Hshieh, Dr Tom Robinson, Dr Fred Rubin, and Dr Elizabeth Whitlock. Special thanks are due to Sheila Gokul, MD, for help in the organization of the bibliography.

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