Inadequately Treated Post-Discharge Adverse Events After Ambulatory Surgery: Nausea, Pain, and Pruritus

In a multicenter study of over 2,000 U.S. adults, the overall incidence of post-discharge nausea and vomiting (PDNV) was 37.1% (Anesthesiology 2012;117:475-86). Table 1 lists the incidence of nausea and vomiting in various postoperative periods (Anesthesiology 2012;117:475-86). Of note, the incidence of PDNV is higher than nausea and vomiting in the postanesthesia care unit (PACU), particularly for severe nausea and vomiting (Anesthesiology 2012;117:475-86). Children under 3 years of age rarely suffer from nausea and vomiting.

The five independent risk factors for PDNV are listed in Table 2 (Anesthesiology 2012;117:475-86). In the presence of zero to five of these risk factors, the incidence of PDNV was 10%, 20%, 30%, 50%, 60%, or 80%, respectively (Anesthesiology 2012;117:475-86). Nausea in the PACU triples the risk of PDNV (Anesthesiology 2012;117:475-86).

In the PACU, the independent risk factors for nausea and vomiting were female gender, age less than 50 years, history of PONV, higher doses of intraoperative and postoperative opioids, increasing duration of surgery over one hour, and laparoscopic surgery (Anesthesiology 2012;117:475-86). Occurrence of pain increases the incidence of nausea and vomiting (Clin J Pain 2015;31:845-51). Inhalational anesthetics increase the risk of nausea and vomiting. However, there is no difference in the incidence of PONV between inhalation anesthesia and total intravenous anesthesia with propofol if antiemetic prophylaxis is used (Curr Opin Anaesthesiol 2021;34:695-702).

Commonly used antiemetics act as antagonists on receptors in the area postrema and on free nerve endings of the vagus nerve. Three classes of drugs, serotonin antagonists acting on 5-hydroxytryptamine-3 receptors (e.g., ondansetron, granisetron, palonosetron, and tropisetron), corticosteroids (e.g., dexamethasone), and dopamine antagonists acting on D2 receptors (e.g., droperidol and haloperidol), have a relative risk reduction of about 25% for each class (Anesth Analg 2020;131:411-48). When used in combination, the effect of each of the three classes is additive. All patients should receive at least two antiemetics for prophylaxis, whereas patients at a high risk of PONV should receive at least three antiemetics (Curr Opin Anaesthesiol 2021;34:695-702; Anesth Analg 2020;131:411-48).

Intraoperative ondansetron does not reduce the risk of PDNV as its plasma half-life is about three hours. Intraoperative ondansetron I.V. 4 mg, followed by enteral ondansetron 8 mg before discharge and again 12 hours after discharge, reduces PDNV (Anesth Analg 2002;94:1199-200). For patients who have received intraoperative ondansetron without relief in the PACU, promethazine is more effective than a repeat dose of ondansetron (Anesth Analg 2007;104:548-51). Promethazine 6.25 mg I.V. was as effective as higher doses (Anesth Analg 2007;104:548-51).

Dexamethasone has a slow onset and a duration of action of 36-54 hours. Palonosetron in a dose of 0.075 mg has a binding affinity 100 times that of ondansetron, a 40-hour half-life, and a duration of action of up to 72 hours (Curr Opin Anaesthesiol 2021;34:695-702; Anesth Analg 2020;131:411-48; Cochrane Database Syst Rev 2020;10:CD012859). Unlike ondansetron, it does not prolong QT interval. Enteral aprepitant, a neurokinin antagonist that acts on NK1 receptors, when given preoperatively is effective in reducing the incidence of vomiting up to 48 hours (Curr Opin Anaesthesiol 2021;34:695-702; Anesth Analg 2020;131:411-48; Cochrane Database Syst Rev 2020;10:CD012859).

Transdermal scopolamine has a slow onset and is released over 72 hours. It is a centrally acting anticholinergic. A meta-analysis demonstrated that the 1 mg dose reduced nausea and vomiting during the first 24 hours after the start of anesthesia (Clin Ther 2010;32:1987-2002). The only significant side effect was increased visual disturbances at 24-48 hours after surgery (Clin Ther 2010;32:1987-2002). Other previously reported adverse events, including sedation, confusion, central cholinergic syndrome, and dry mouth, were not found to be significant. Although scopolamine patch may be applied the evening prior to surgery, preoperative application is suitable.

Pain control improves patient satisfaction, mobilization, and reduces complications (J Pain 2016;17:131-57; Best Pract Res Clin Anaesthesiol 2019;33:259-67; Anesthesiology 2021;134:645-59; Anaesth Crit Care Pain Med 2019;38:405-11; Anesthesiology 2022;136:115-26).

Because of their abuse potential, the U.S. Drug Enforcement Administration has made them controlled substances and placed them in the following schedules (asamonitor.pub/3uu3cIG). If effective, an analgesic from the higher schedule is preferred.

Schedule II: Most of the opioids are in this schedule because they have a high potential for abuse, which may lead to severe psychological or physical dependence. Included are combinations with less than 15 mg of hydrocodone (e.g., Vicodin), oxycodone with or without acetaminophen, hydromorphone, meperidine, and fentanyl.

Schedule III: Opioids in this schedule have a lesser potential for abuse and may cause moderate or low physical dependence but high psychological dependence. These include medications containing up to 90 mg of codeine per unit, often in combination with acetaminophen.

Schedule IV: These substances have an even lower abuse potential. They include some sedatives and tramadol, a synthetic opioid that is often used in combination with acetaminophen. Tramadol/acetaminophen tablets (37.5 mg/325 mg) and codeine/acetaminophen capsules (30 mg/300 mg) are nearly equally effective and are commonly used in the post-discharge period.

MME is also called morphine equivalent dose (MED). It is utilized for comparing the potencies of opioids. MMEs for the commonly prescribed opioids according to the Centers for Disease Control and Prevention (CDC) are listed in Table 3 (asamonitor.pub/3LaefNA). For patients utilizing preoperative opioids or having extensive surgery, doses exceeding ≥50 MME/day should be used with caution, even when used for a limited duration. For doses ≥90 MME/day, a pain medicine specialist should be consulted.

If a risk of serious respiratory depression due to opioid overdose is suspected, naloxone should be made available at home to the patient, family, or caregiver. This can reduce the potential of harm due to opioids (JAMA Netw Open 2020;3:e200117). Naloxone nasal spray is available without a prescription. When initiating naloxone administration, immediate medical attention should be sought. A pain medicine specialist may be consulted when considering a prescription of naloxone.

This program is recommended by the CDC and set up by the states (asamonitor.pub/3IC2Rsh). It is a statewide electronic database that tracks all controlled substance prescriptions. States require that prior to prescribing certain controlled substances, a patient’s prescription history should be checked in the PDMP database. Use of PDMP reduces the amount of opioids prescribed postoperatively (JAMA Health Forum 2021;2:e212924). A pain medicine specialist may be consulted before prescribing an opioid to a patient who also utilizes a sedative/soporific.

Their use is not addicting and mitigates the risk of opioid misuse disorder (J Pain 2016;17:131-57; Best Pract Res Clin Anaesthesiol 2019;33:259-67; Anesthesiology 2021;134:645-59; Anaesth Crit Care Pain Med 2019;38:405-11). Because of substantial variability in analgesic requirement between patients and limited opportunity for observation, it is difficult to optimize the analgesic prescription at the time of discharge. The patient may obtain an NSAID or acetaminophen without prescription and may use it instead of or in combination with the prescribed analgesic (Cochrane Database Syst Rev 2015;2015:CD010794).

An NSAID, or less commonly acetaminophen, by itself may provide adequate analgesia. When a combination of an NSAID with acetaminophen is used, a substantially reduced dose of each is required, also reducing side effects. In some cases NSAIDs provide analgesia comparable to opioids (Cochrane Database Syst Rev 2015;2015:CD010794). In other cases, when an NSAID or acetaminophen is used in combination with an opioid, a substantially reduced dose of each is required, also reducing the side effects (J Pain 2016;17:131-57; Best Pract Res Clin Anaesthesiol 2019;33:259-67; Anesthesiology 2021;134:645-59; Anaesth Crit Care Pain Med 2019;38:405-11; Cochrane Database Syst Rev 2015;2015:CD010794).

The reported adverse side effects of chronic use of NSAIDs include cardiovascular and renal complications, gastrointestinal and wound bleeding, and impaired tissue healing and bone union (Am Surg 2021;87:872-9; J Am Coll Surg 2021;232:765-90). None of these have been demonstrated after brief perioperative utilization. No difference in outcome has been demonstrated between COX-2 selective and non-selective NSAIDs after brief perioperative utilization.

These drugs do not provide clinically useful analgesia, but do increase the risk of sedation, dizziness, and visual disturbances and potentiate opioid-induced respiratory depression (Anesthesiology 2020;133:265-79). Patients receiving them preoperatively may continue them postoperatively.

Postoperative pruritus may be due to preexisting disease or medications, especially opioids. Preexisting diseases causing pruritus include renal, hepatic, neurological, hematological, endocrine, and skin diseases. HIV, cancer, diabetic neuropathy, and helicobacter pylori infection also cause pruritus. The most important mechanism by which opioids cause pruritus is via a nonimmunologic release of histamine from mast cells and by stimulating central and cutaneous receptors (Anesthesiology 2005;103:168-78). Diphenhydramine is beneficial for systemic opioid-induced pruritus. Enteral diphenhydramine is suitable for the post-discharge period.

Pruritus is more common after neuraxial opioids. In that setting it is not due to histamine. H1 blockers (e.g., diphenhydramine) have little effect on centrally induced pruritus. However, sedation due to diphenhydramine may be beneficial.

Rapid administration of vancomycin causes histamine-induced red man syndrome, including pruritus. In patients who are allergic, penicillin causes histamine release from mast cells, causing pruritus, bronchospasm, and hypotension. Other medications that can cause pruritus include hetastarch and rifampin.

Ondansetron, propofol, droperidol, naloxone, naltrexone, nalbuphine, lidocaine, metoclopramide, and alizapride may be useful for prophylaxis and treatment of pruritus. Oral naltrexone 6 mg and 9 mg may be utilized in the post-discharge period but may have an anti-analgesic effect (Eur J Anaesthesiol 2001;18:346-57).