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Optimal Intraoperative Technique to Prevent Postoperative Delirium
INTRODUCTION
Delirium after surgery is an increasing concern for older adults, caregivers, and health care providers. Approximately 37% of all surgical procedures are performed on patients over the age of 65 years in Western countries. In the United States, this represented over 19 million patients in 2010. Postoperative delirium (POD) is a common adverse cognitive event, occurring in up to 65% of older patients after anesthesia and surgery. Delirium, characterized by inattention, confusion, and altered mental state, is not only disturbing for patients and families during the acute episode but also can have significant long-term consequences, including an association with long-term cognitive and functional impairment and mortality. Patients who experience POD have an increased risk for reduced cognitive performance for weeks to months after surgery. Although there are some differing results in studies, many have shown patients who experience delirium either to fail to fully recover baseline cognitive function or to have an increased incidence of dementia. In a study of patients undergoing elective surgery, functional recovery was incomplete in patients who experience delirium for up to 18 months postoperatively. A meta-analysis showed incident POD was associated with an unadjusted fourfold increased risk for mortality (odds ratio [OR] = 4.12; 95% confidence interval [CI], 3.29’ Äì 5.17; I2 = 24.9%). In addition, delirium significantly increases health care costs with totals of more than $164 billion in US expenditures annually for patients with delirium. The total 1-year cost of care for a patient who experienced delirium is estimated to be 2.5 times the cost of a similar patient without delirium. Finally, POD after elective surgery in the United States was found to increase the annual cost of health care by $19,000 per patient with delirium for a total increase in cost of $3.2 billion.
OPTIONS
Screening for High-Risk Patients
The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Guidelines for Optimal Perioperative Care of the Geriatric Patient and American Geriatric Society (AGS) Best Practices Guidelines both recommend for patients older than 65 to assess cognitive performance. Recently an International Perioperative Neurotoxicity Working Group sponsored by the American Society of Anesthesiologists (ASA) Brain Health Initiative also suggested preoperative cognitive screening of all older surgical patients in their Best Practices paper. ,
Medications
Intraoperative medications can have an influence on the patient’s risk for developing POD. Medications to avoid that either increase the risk for delirium or have been associated with an increased incidence of delirium include medications on the Beers Criteria list developed by the AGS ( Table 44.1 ). Common medications pertinent to the anesthesiologist include benzodiazepines, anticholinergics, barbiturates, corticosteroids, meperidine, and antipsychotics. The search for medications administered intraoperatively to prevent delirium has been an active but disappointing area of research. Dexmedetomidine holds promise, but there have been numerous negative studies. The evidence for investigated medications is presented in the following section.
TABLE 44.1
American Geriatrics Society Beers Criteria for Potentially Inappropriate Medication Use in Older Adults a
| Organ System, Therapeutic Category, Drug(s) | Rationale | Recommendation | Quality of Evidence | Strength of Recommendation |
|---|---|---|---|---|
| Anticholinergics b | ||||
| First-generation antihistamines Brompheniramine Carbinoxamine Chlorpheniramine Clemastine Cyproheptadine Dexbrompheniramine Dexchlorpheniramine Dimenhydrinate Diphenhydramine (oral) Doxylamine Hydroxyzine Meclizine Promethazine Pyrilamine Triprolidine |
Highly anticholinergic; clearance reduced with advanced age, and tolerance develops when used as hypnotic; risk for confusion, dry mouth, constipation, and other anticholinergic effects or toxicity Use of diphenhydramine in situations such as acute treatment of severe allergic reaction may be appropriate |
Avoid | Moderate | Strong |
| Antiparkinsonian agents Benztropine (oral) Trihexyphenidyl |
Not recommended for prevention or treatment of extrapyramidal symptoms with antipsychotics; more effective agents available for treatment of Parkinson disease | Avoid | Moderate | Strong |
| Antispasmodics Atropine (excludes ophthalmic) Belladonna alkaloids Clidinium-chlordiazepoxide Dicyclomine Homatropine (excludes ophthalmic) Hyoscyamine Methscopolamine Propantheline Scopolamine |
Highly anticholinergic, uncertain effectiveness | Avoid | Moderate | Strong |
| Antithrombotics | ||||
| Dipyridamole, oral short acting (does not apply to the extended-release combination with aspirin) | May cause orthostatic hypotension; more effective alternatives available; IV form acceptable for use in cardiac stress testing | Avoid | Moderate | Strong |
| Anti-infective | ||||
| Nitrofurantoin | Potential for pulmonary toxicity, hepatoxicity, and peripheral neuropathy, especially with long-term use; safer alternatives available | Avoid in individuals with creatinine clearance <30 mL/min or for long-term suppression | Low | Strong |
| Cardiovascular | ||||
| Peripheral alpha-1 blockers for treatment of hypertension Doxazosin Prazosin Terazosin |
High risk for orthostatic hypotension and associated harms, especially in older adults; not recommended as routine treatment for hypertension; alternative agents have superior risk/benefit profile | Avoid use as an antihypertensive | Moderate | Strong |
| Central alpha-agonists Clonidine for first-line treatment of hypertension Other CNS alpha-agonists Guanabenz Guanfacine Methyldopa Reserpine (>0.1 mg/day) |
High risk for adverse CNS effects; may cause bradycardia and orthostatic hypotension; not recommended as routine treatment for hypertension | Avoid other CNS alpha-agonists as listed | Low | Strong |
| Disopyramide | May induce heart failure in older adults because of potent negative inotropic action; strongly anticholinergic; other antiarrhythmic drugs preferred | Avoid | Low | Strong |
| Dronedarone | Worse outcomes have been reported in patients taking dronedarone who have permanent atrial fibrillation or severe or recently decompensated heart failure | Avoid in individuals with permanent atrial fibrillation or severe or recently decompensated heart failure | High | Strong |
| Digoxin for first-line treatment of atrial fibrillation or heart failure | Use in atrial fibrillation: Should not be used as a first-line agent in atrial fibrillation because there are safer and more effective alternatives for rate control supported by high-quality evidence Use in heart failure: Evidence for benefits and harms of digoxin is conflicting and of lower quality; most but not all evidence concerns use in HFrEF. There is strong evidence for other agents as first-line therapy to reduce hospitalizations and mortality in adults with HFrEF. In heart failure, higher dosages are not associated with additional benefit and may increase risk for toxicity. Decreased renal clearance of digoxin may lead to increased risk for toxic effects; further dose reduction may be necessary in those with stage 4 or 5 chronic kidney disease. |
Avoid this rate control agent as first-line therapy for atrial fibrillation Avoid as first-line therapy for heart failure If used for atrial fibrillation or heart failure, avoid dosages >0.125 mg/day |
Atrial fibrillation: low Heart failure: low Dosage >0.125 mg/day: moderate |
Atrial fibrillation: strong Heart failure: strong Dosage >0.125 mg/day: strong |
| Nifedipine, immediate release | Potential for hypotension; risk for precipitating myocardial ischemia | Avoid | High | Strong |
| Amiodarone | Effective for maintaining sinus rhythm but has greater toxicities than other antiarrhythmics used in atrial fibrillation; may be reasonable first-line therapy in patients with concomitant heart failure or substantial left ventricular hypertrophy if rhythm control is preferred over rate control | Avoid as first-line therapy for atrial fibrillation unless patient has heart failure or substantial left ventricular hypertrophy | High | Strong |
| Central nervous system | ||||
| Antidepressants, alone or in combination Amitriptyline Amoxapine Clomipramine Desipramine Doxepin >6 mg/day Imipramine Nortriptyline Paroxetine Protriptyline Trimipramine |
Highly anticholinergic, sedating, and can cause orthostatic hypotension; safety profile of low-dose doxepin (≤ mg/day) comparable with that of placebo | Avoid | High | Strong |
| Antipsychotics, first (conventional) and second (atypical) generation | Increased risk for cerebrovascular accident (stroke) and greater rate of cognitive decline and mortality in persons with dementia Avoid antipsychotics for behavioral problems of dementia or delirium unless nonpharmacologic options (e.g., behavioral interventions) have failed or are not possible and the older adult is threatening substantial harm to self or others |
Avoid except in schizophrenia or bipolar disorder, or for short-term use as an antiemetic during chemotherapy | Moderate | Strong |
| Barbiturates Amobarbital Butabarbital Butalbital Mephobarbital Penobarbital Phenobarbital Secobarbital |
High rate of physical dependence, tolerance to sleep benefits, greater risk for overdose at low dosages | Avoid | High | Strong |
| Benzodiazepines Short- and intermediate-acting: Alprazolam Estazolam Lorazepam Oxazepam Temazepam Triazolam Long-acting: Chlordiazepoxide (alone or in combination with amitriptyline or clidinium) Clonazepam Clorazepate Diazepam Flurazepam Quazepam |
Older adults have increased sensitivity to benzodiazepines and decreased metabolism of long-acting agents; in general, all benzodiazepines increase the risk for cognitive impairment, delirium, falls, fractures, and motor vehicle crashes in older adults May be appropriate for seizure disorders, rapid eye movement sleep behavior disorder, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, and periprocedural anesthesia |
Avoid | Moderate | Strong |
| Meprobamate | High rate of physical dependence; sedating | Avoid | Moderate | Strong |
| Nonbenzodiazepine, benzodiazepine receptor agonist hypnotics (i.e., “Z-drugs”) Eszopiclone Zaleplon Zolpidem |
Nonbenzodiazepine, benzodiazepine receptor agonist hypnotics (i.e., Z drugs) have adverse events similar to those of benzodiazepines in older adults (e.g., delirium, falls, fractures); increased emergency room visits/ hospitalizations; motor vehicle crashes; and minimal improvement in sleep latency and duration | Avoid | Moderate | Strong |
| Ergoloid mesylates (dehydrogenated ergot alkaloids) Isoxsuprine |
Lack of efficacy | Avoid | High | Strong |
| Endocrine | ||||
| Androgens Methyltestosterone Testosterone |
Potential for cardiac problems; contraindicated in men with prostate cancer | Avoid unless indicated for confirmed hypogonadism with clinical symptoms | Moderate | Weak |
| Desiccated thyroid | Concerns about cardiac effects; safer alternatives available | Avoid | Low | Strong |
| Estrogens with or without progestins | Evidence of carcinogenic potential (breast and endometrium); lack of cardioprotective effect and cognitive protection in older women Evidence indicates that vaginal estrogens for the treatment of vaginal dryness are safe and effective; women with a history of breast cancer who do not respond to nonhormonal therapies are advised to discuss the risks and benefits of low-dose vaginal estrogen (dosages of estradiol <25 µg twice weekly) with their health care provider |
Avoid systemic estrogen (e.g., oral and topical patch) Vaginal cream or vaginal tablets: acceptable to use low-dose intravaginal estrogen for management of dyspareunia, recurrent lower urinary tract infections, and other vaginal symptoms |
Oral and patch: high Vaginal cream or vaginal tablets: moderate |
Oral and patch: strong Topical vaginal cream or tablets: weak |
| Growth hormone | Impact on body composition is small and associated with edema, arthralgia, carpal tunnel syndrome, gynecomastia, and impaired fasting glucose | Avoid, expect for patients rigorously diagnosed by evidence-based criteria with growth hormone deficiency because of an established etiology | High | Strong |
| Insulin, sliding scale (insulin regimens containing only short- or rapid-acting insulin dosed according to current blood glucose levels without concurrent use of basal or long-acting insulin) | Higher risk for hypoglycemia without improvement in hyperglycemia management regardless of care setting. Avoid insulin regimens that include only short- or rapid-acting insulin dosed according to current blood glucose levels without concurrent use of basal or long-acting insulin. This recommendation does not apply to regimens that contain basal insulin or long-acting insulin. | Avoid | Moderate | Strong |
| Megestrol | Minimal effect on weight; increases risk for thrombotic events and possibly death in older adults | Avoid | Moderate | Strong |
| Sulfonylureas, long-acting Chlorpropamide Glimepiride Glyburide (also known as glibenclamide) |
Chlorpropamide: Prolonged half-life in older adults; can cause prolonged hypoglycemia; causes SIADH Glimepiride and glyburide: Higher risk for severe prolonged hypoglycemia in older adults | Avoid | High | Strong |
| Gastrointestinal | ||||
| Metoclopramide | Can cause extrapyramidal effects, including tardive dyskinesia; risk may be greater in frail older adults and with prolonged exposure | Avoid, unless for gastroparesis with duration of use not to exceed 12 weeks except in rare cases | Moderate | Strong |
| Mineral oil, given orally | Potential for aspiration and adverse effects; safer alternatives available | Avoid | Moderate | Strong |
| Proton-pump inhibitors | Risk for Clostridium difficile infection and bone loss and fractures | Avoid scheduled use for >8 weeks unless for high-risk patients (e.g., oral corticosteroids and chronic NSAID use), erosive esophagitis, Barrett esophagitis, pathologic hypersecretory condition, or demonstrated need for maintenance treatment (e.g., because of failure of drug discontinuation trial or H2-receptor antagonists) | High | Strong |
| Pain medications | ||||
| Meperidine | Oral analgesic not effective in dosages commonly used; may have higher risk for neurotoxicity, including delirium, than other opioids; safer alternatives available | Avoid | Moderate | Strong |
| Noncyclooxygenase-selective NSAIDs, oral: Aspirin >325 mg/day Diclofenac Diflunisal Etodolac Fenoprofen Ibuprofen Ketoprofen Meclofenamate Mefenamic acid Meloxicam Nabumetone Naproxen Oxaprozin Piroxicam Sulindac Tolmetin |
Increased risk for gastrointestinal bleeding or peptic ulcer disease in high-risk groups, including those >75 years or taking oral or parenteral corticosteroids, anticoagulants, or antiplatelet agents; use of proton-pump inhibitor or misoprostol reduces but does not eliminate risk. Upper gastrointestinal ulcers, gross bleeding, or perforation caused by NSAIDs occur in approximately 1% of patients treated for 3–6 months and in approximately 2%–4% of patients treated for 1 year; these trends continue with longer duration of use. Also can increase blood pressure and include kidney injury. Risks are dose related | Avoid chronic use, unless other alternatives are not effective and patient can take gastroprotective agent (proton-pump inhibitor or misoprostol) | Moderate | Strong |
| Indomethacin Ketorolac, includes parenteral |
Increased risk for gastrointestinal bleeding/peptic ulcer disease and acute kidney injury in older adults Indomethacin is more likely than other NSAIDs to have adverse CNS effects. Of all the NSAIDs, indomethacin has the most adverse effects | Avoid | Moderate | Strong |
| Skeletal muscle relaxants Carisoprodol Chlorzoxazone Cyclobenzaprine Metaxalone Methocarbamol Orphenadrine |
Most muscle relaxants are poorly tolerated by older adults because some have anticholinergic adverse effects, sedation, increased risk of fractures; effectiveness at dosages tolerated by older adults questionable | Avoid | Moderate | Strong |
| Genitourinary | ||||
| Desmopressin | High risk for hyponatremia; safer alternative treatments | Avoid for treatment of nocturia or nocturnal polyuria | Moderate | Strong |
a The primary target audience is the practicing clinician. The intentions of the criteria include: (1) improving the selection of prescription drugs by clinicians and patients; (2) evaluating patterns of drug use within populations; (3) educating clinicians and patients on proper drug usage; and (4) evaluating health-outcome, quality-of-care, cost, and utilization data.
b See also criterion on highly anticholinergic antidepressants CNS , Central nervous system; HFrEF , heart failure with reduced ejection fraction; IV , intravenous; NSAID , nonsteroidal anti-inflammatory drug; SIADH , syndrome of inappropriate antidiuretic hormone secretion. (From The 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Journal of American Geriatrics April 2019 67(4): 674-694.
Anesthetic Choice
Anesthesiologists often have the choice of type of anesthetic to administer, whether it be regional anesthesia with sedation versus general anesthesia (GA) or volatile versus intravenous (IV) GA. There are ongoing multiple multicenter trials that will influence our knowledge on whether one type of anesthesia may reduce the risk for subsequent delirium. Currently, however, there is equipoise, which prevents recommendation of one type over another to prevent delirium.
Electroencephalography-Guided Anesthetic Depth
Monitoring anesthetic depth is a fundamental aspect of anesthetic care either through end-tidal volatile anesthetic levels, knowledge of pharmacokinetics, responsiveness of a sedated patient or through electroencephalographic (EEG) monitors. Increasing age decreases anesthetic requirements leading anesthesiologists to commonly use age-adjusted anesthetic dosing. This population-based adjustment can, however, still lead to deeper levels of anesthesia in a particular patient. Processed EEG monitors, such as the Bispectral Index monitor (BIS, Medtronic) or Sedline (Masimo), may allow individualization and are currently recommended in a joint statement by the American Society for Enhanced Recovery and Perioperative Quality Initiative to guide anesthetic management. A single BIS value between 0 and 100 is displayed on the Medtronic monitor, with lower numbers meant to signify deeper anesthesia. In general, values less than 60 are associated with acceptable GA and values less than 20 are associated with burst suppression (deep anesthesia). Burst suppression during GA has been associated with an increased incidence of POD. , Older adults are more likely to be found in a state of burst suppression during anesthesia. , Nevertheless, randomized controlled trials (RCTs) have not consistently shown a reduction in POD by targeting a lower depth of anesthesia.
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