AGS Guideline for Postoperative Delirium in Older Adults

Pharmacologic Treatments/Interventions Used Perioperatively to Prevent Postoperative Delirium in Older Surgical Patients

VI. Anesthesia Depth

Recommendation. The anesthesia practitioner may use processed electroencephalographic (EEG) monitors of anesthetic depth during intravenous sedation or general anesthesia of older patients to reduce postoperative delirium (strength of recommendation: insufficient evidence; quality of evidence: low).

Evidence for Recommendation. There is insufficient evidence to determine the net benefits or risks in the relationship of depth of anesthesia and the development of postoperative delirium. Depth of anesthesia is measured by specialized processed EEG monitors. In one small, randomized controlled trial in hip fracture patients, deeper levels of adjunctive intravenous sedation with propofol (not general anesthesia) were associated with increased rates of postoperative delirium. This finding is consistent with nonrandomized, retrospective observations. In two (nonrandomized) trials in which the anesthesiologist was able to see the Bispectral Index Monitor, patients receiving general anesthesia had lower rates of postoperative delirium. To date, there is equipoise regarding the long-term cognitive effects of intraoperative depth of anesthesia.
Potential Harms of Recommendation. The safety of conducting "light anesthesia" in patients who require general anesthesia has not been demonstrated. Lighter anesthesia may lead to several adverse events, including intraoperative recall or movement, sympathetic stimulation and adverse hemodynamic changes, particularly in older patients or in those with vascular disease. Use of processed EEG monitors may increase cost and cause the anesthesia practitioner to overfocus on a single clinical parameter.

VII. Regional Anesthesia

Recommendation. A healthcare professional trained in regional anesthetic injection may consider providing regional anesthetic at the time of surgery and postoperatively to improve pain control and prevent delirium in older adults (strength of recommendation: weak; quality of evidence: low).

Evidence for Recommendation. Two low-quality clinical studies with high risk of bias, one of hip fracture patients and the other of patients undergoing total knee replacement found that regional anesthesia was beneficial in reducing the incidence of postoperative delirium. Findings cannot be readily generalized, however, since both studies included only patients undergoing lower extremity orthopedic operations.
Potential Harms of Recommendation. Complications of regional anesthesia, such as nerve injury, hematoma, intravascular injection, neurotoxicity, and cardiac toxicity are uncommon.

VIII. Analgesia

Recommendation. Healthcare professionals should optimize postoperative pain control, preferably with nonopioid pain medications, to minimize pain in older adults to prevent delirium (strength of recommendation: strong; quality of evidence: low).

Evidence for Recommendation. Adequate postoperative analgesia is associated with decreased delirium. Two studies of postoperative pain in noncardiac surgery in older adults found that increased levels of pain were independently associated with a greater risk of postoperative delirium. Additional research has found an association between undertreated pain and the occurrence of delirium. The evidence for prescribing nonopioid alternatives to manage postoperative pain to reduce delirium is less compelling than the evidence that adequate pain control reduces delirium. Two studies, one of prophylactic gabapentin in spine surgery and the other using gabapentin, paracetamol (acetaminophen), and celecoxib in a fast-track surgery model reported reduced incidence of delirium with nonopioid pain management.
Potential Harms of Recommendation. Opioid analgesics carry risks of constipation, nausea, vomiting, respiratory depression, sedation, impaired judgment, altered psychomotor function, rash, pruritis, and anaphylactic allergic reactions. Long-term opioid use can lead to dependence. Opioid dosing needs to be properly monitored, and patients must be managed for potential respiratory depression. Nonopioid medications such as gabapentin, paracetamol or acetaminophen, and nonsteroidal anti-inflammatory agents also have potential harms.

IX. Avoidance of Inappropriate Medications

Recommendation. The prescribing practitioner should avoid medications that induce delirium postoperatively in older adults to prevent delirium (strength of recommendation: strong; quality of evidence: low).

Evidence for Recommendation Relevant medications or medication classes include benzodiazepines, anticholinergics (e.g., cyclobenzaprine, oxybutynin, prochlorperazine, promethazine, tricyclic antidepressants, paroxetine and drugs with high anticholinergic properties), diphenhydramine, hydroxyzine, histamine₂-receptor antagonists (e.g., cimetidine), sedative-hypnotics, and meperidine. Since the studies regarding specific medications provide generally low-level evidence, the current recommendation relied on the 2012 AGS Beers Criteria. Current evidence most strongly associates use of anticholinergic drugs, meperidine and benzodiazepines with increased postoperative delirium. Studies have identified the following medications with increased delirium: diphenhydramine, meperidine, midazolam, and anticholinergic medications. Drugs that contribute to serotonin syndrome can increase delirium risk, as can the use of multiple medications (five or greater).
Potential Harms of Recommendation. Specific conditions may warrant use of these medications. For example, a patient with a history of alcohol abuse or chronic benzodiazepine usage may require treatment with a benzodiazepine to prevent withdrawal complications, or a patient may require treatment with diphenhydramine for a severe allergic or transfusion reaction.

X. Antipsychotics Used Prophylactically to Prevent Delirium

Recommendation. There is insufficient evidence to recommend for or against the use of antipsychotic medications prophylactically in older surgical patients to prevent delirium (strength of recommendation: not applicable; quality of evidence: low).

Evidence for Recommendation. Prophylactic use of antipsychotic medications to prevent delirium in postoperative patients has limited, inconsistent, and contradictory support in the literature. Five studies found decreased incidence of delirium, and three did not. Most studies are of low quality and often have a high risk of bias.
Potential Harms of Recommendation. The potential harms associated with antipsychotic medications are numerous and include, but are not limited to, central nervous system effects (such as somnolence, extrapyramidal effects such as muscle rigidity, tremor, restlessness, swallowing difficulty, decreased seizure threshold, and neuroleptic malignant syndrome), systemic and cardiovascular effects (such as QT prolongation, dysrhythmias, sudden death, hypotension, and tachycardia), pneumonia, urinary retention, postural instability, falls, deep venous thrombosis, anticholinergic effects, syndrome of antidiuretic hormone, and metabolic effects (such as weight gain, insulin resistance, and hypertriglyceridemia). Even short-term treatment is associated with increased mortality. The inadvertent chronic administration of antipsychotics after inpatient initiation during an episode of delirium is an important harm. One review found that 47% of patients continued to receive the drug after discharge from the ICU and 33% as an outpatient after discharge from hospital, without a clear indication.

XI. Cholinesterase Inhibitors

Recommendation. In older adults not currently taking cholinesterase inhibitors, the prescribing practitioner should not newly prescribe cholinesterase inhibitors perioperatively to older adults to prevent or treat delirium (strength of recommendation: strong; quality of evidence: low).

Evidence for Recommendation. Newly prescribing prophylactic cholinesterase inhibitors in the perioperative setting has been found by four randomized controlled trials not to be effective in reducing incidence of postoperative delirium. They may also be associated with more adverse effects, and increased mortality risk. Two other studies found no differences in duration of delirium with cholinesterase inhibitors, and one reported a higher trend toward mortality in critically ill patients.
Potential Harms of Recommendation. Adverse effects of cholinesterase inhibitors include diarrhea, anorexia, dyspepsia, bradycardia, and potential to exacerbate peptic ulcer disease, cardiac conduction disorders, seizures, asthma, and benign prostatic hypertrophy. Withholding cholinesterase inhibitors in patients on chronic treatment may cause worsening symptoms.