Management of Postoperative Nausea and Vomiting

By Jeremy Benger D.O., and Andrew Herlich D.M.D., M.D.

Introduction
Physiology
Risk Factors
Prevention and Treatment
Conclusion

Introduction

Postoperative nausea and vomiting (PONV) is a common problem that affects approximately 30 percent of patients undergoing surgery, but can be as high as 80 percent in high risk patients.^1,2 PONV is one of the most common reasons for unanticipated admissions after surgery.³ It can be such a horrific experience that patients say that it is worse than postoperative pain.⁴  Some patients are even willing to pay out of pocket to prevent experiencing PONV.⁵  Reported rare, but serious, complications of postoperative vomiting include aspiration, suture disruption, esophageal rupture, subcutaneous emphysema, and pneumothorax.^6,7,8,9  The annual cost of PONV is estimated to be on the order of several hundred million dollars.¹⁰


Physiology

The vomiting center in the reticular formation of the lateral medulla controls nausea and vomiting. It also receives afferent input from the gastrointestinal tract via the vagus nerve, peripheral pain receptors, vestibular system, cerebral cortex, and chemoreceptor trigger zone (CTZ). Of the many neurotransmitters linked to nausea and vomiting, some important ones include acetylcholine, histamine, dopamine, and 5-hydroxytryptamine (5-HT). A reflex involving efferent neural pathways from the vomiting center to autonomic and motor nerves ultimately results in vomiting.¹¹



Risk Factors

PONV is multifactorial with certain factors that help predict those patients with increased risk. Risk factors can be classified as patient related, anesthesia related, or surgery related. Patient related risk factors include young females, nonsmokers, history of PONV or motion sickness, history of migraine, preoperative anxiety, and lower ASA physical status classification. Anesthesia related risk factors include use of volatile anesthetics, nitrous oxide, increased neostigmine doses (>2.5mg), intraoperative and postoperative opioids, increased duration of anesthesia, hypovolemia, and general anesthesia. Surgery related risk factors are type of surgery (intraabdominal, laparoscopic, orthopedic, major gynecologic, ENT, thyroid, breast and plastic surgery, neurosurgery, adenotonsillectomy, strabismus surgery) and increased duration of surgery. Obesity, lack of supplemental oxygen, and phase of menstrual cycle were once thought to be risk factors for PONV, but have since been discounted. Possibly the strongest risk factor for PONV is being a young, postpubertal female. ¹²



Prevention and Treatment

Several pharmacologic agents have been used in the prevention and treatment of PONV. These include anticholinergics, antihistamines, dopamine antagonists (phenothiazines, butyrophenones, prokinetic agents), serotonin (5-HT­­3) receptor antagonists, neurokinin-1(NK-1) antagonists, and corticosteroids. Anticholinergics that cross the blood brain barrier (scopolamine) are thought to exert an antiemetic effect at the muscarinic receptors in the cerebral cortex. However, scopolamine has an onset of two to four hours and can cause sedation. Other side effects are blurry vision, dry mouth, and dizziness. Antihistamines such as diphenhydramine or dimenhydrinate, which are also weak anticholinergics, exert their effect in the vestibular system with high levels of histamine and muscarinic receptors. Common side effects of these drugs include drowsiness, dry mouth, blurred vision, and dizziness. Dopamine antagonists (droperidol, haloperidol, promethazine, prochlorperazine, metoclopramide) block receptors in the CTZ and vomiting center. Droperidol has an FDA black box warning that it may cause QT interval prolongation and arrhythmia (torsades de pointes); consequently its use has fallen out of favor as a first-line agent.

An FDA safety alert has also been issued regarding intravenous haloperidol and reports of cardiac arrhythmias leading to death. Promethazine has an FDA safety alert warning that intravenous administration may result in extravasation and local tissue necrosis. Additionally, dopamine antagonists may also cause sedation, hypotension, and extrapyramidal symptoms (EPS). Should EPS occur, antihistamines can be used for treatment. Serotonin receptor antagonists (ondansetron, dolasetron, tropisetron, granisetron) work at the CTZ and the vagal afferents of gastrointestinal system. Side effects are fewer with this class of antiemetic. Headache is the most common side effect. Other less common side effects include elevated liver enzymes and constipation.

Neurokinin-1 antagonists (aprepitant) block central and peripheral NK-1 receptors. NK-1 antagonists are a relatively new class of drugs and a more expensive treatment option. Side effects are few with this class of medication as well, but fatigue, headache, dizziness, or elevated liver enzymes may occur. The mechanism the antiemetic effects of corticosteroids (dexamethasone) are unclear, but may be the result of increased endorphin release.^13,21

Ephedrine 0.5mg/kg IM has also shown to be an effective antiemetic, possibly by increasing sympathetic tone to combat increased vagal tone associated with PONV.¹⁴  Propofol 10-20mg IV every 5-10 minutes or an infusion of 10µg/kg/min can be effective as well. Its antiemetic properties are thought to be the result of lowering serotonin in the area postrema by its interaction with GABA receptors.15  Benzodiazepines, especially midazolam, have  been reported to decrease the incidence of PONV in some studies. Proposed mechanisms include reduced anxiety and decreased dopamine and serotonin levels by interaction with GABA receptors.^15,16  See the table below for drug doses, routes, and receptors effected.

Alternatively, non-pharmacologic treatment with stimulation of the P6 point on the wrist with acupuncture, acupressure, or transcutaneous nerve stimulation has been shown effective in some studies for prevention of PONV. Ginger has been proposed to have antiemetic properties,  but most studies do not support this.¹⁷ Speculation that slower transport speed from the OR to PACU and avoiding quick changes in patient positioning can help prevent PONV exists as well.¹⁸
 
Managing PONV should start with a determination of a patient’s risk for PONV by using risk score analysis, such as described by Apfel et al.² The prediction of PONV is about 55-80 percent accurate using risk scores.¹²  Risk of PONV with no risk factors is about 10 percent, one risk factor 20 percent, two risk factors 40 percent, three risk factors 60 percent, and four risk factors 80 percent using the simplified risk score system. The most consistent risk factors being female gender, nonsmoker, history of PONV, and postoperative opioid use.¹⁹  It is minimally effective to give prophylactic treatment to a patient at low risk for PONV.

Recent changes in national surgical adverse outcomes prevention may change the clinician’s decision to administer medications for PONV. Patients at moderate to high risk should be treated. Patients at moderate risk should receive two prophylactic interventions.  Patients at high risk should receive multimodal therapy with two or more interventions. If treating with more than one antiemetic, the drugs should be from a different class to take advantage of their different mechanisms of action.²⁰  Generally, combination pharmacologic treatment is more efficacious at preventing PONV than using one antiemetic. When using a multimodal approach, pharmacologic therapy along with other methods to reduce PONV can be used. This may include TIVA, regional anesthesia, minimizing opioids by using NSAIDs such as intravenous ketorolac or acetaminophen, avoiding nitrous oxide, optimizing hydration, preoperative anxiolysis, and/or avoidance of neuromuscular blockade reversal.

Ondansetron, dexamethasone, and droperidol are some of the most studied antiemetics and have similar efficacy to one another in preventing PONV. 5-HT­₃ antagonists should be used for prophylaxis toward the end of surgery. They are more effective for treating vomiting than nausea. Dexamethasone should be given at the beginning of surgery to be most effective. Droperidol, a butyrophenone(dopamine antagonist), is recommended to be given at the end of surgery. Dopamine antagonists are better for treatment of nausea than vomiting. Transdermal scopolamine is an effective adjunct for prevention, but needs to be placed four hours before surgery the end of surgery.²⁰  Metoclopramide, a dopamine antagonist and prokinetic, requires a much larger dose than the standard 10 mg to have an antiemetic effects.

At high doses, however, the risk of side effects may be greater than the potential benefit.²¹ It has not been studied as much as other antiemetics, but it is recommended that IM ephedrine be given at the end of surgery if it is used as a treatment option.  Antihistamines given at the end of surgery may delay recovery due to sedation, but timing for optimal antiemetic effect has not yet been established.²⁰ It is possible to administer the antihistamine class of antiemetics with induction of general anesthesia to minimize the impact on postoperative sedation.  The NK-1 antagonist aprepitant has been shown in some studies to be superior to ondansetron in prevention of postoperative vomiting when given preoperatively, but has not proven to be more efficacious in nausea prevention or to decrease the need for rescue treatment.^22,23  The prodrug, fosaprepitant, is also available for intravenous administration in a 115 mg dose.  It has only been studied in chemotherapy induced nausea and vomiting and it is very expensive.  Consequently, fosaprepitant’s use should be quite limited.

If rescue therapy is needed 5-HT₃ antagonists are typically the treatment of choice since they are relatively fast acting and lack sedative effects. The rescue dose is about 25 percent of the prophylactic dose. If they have already been given for prophylaxis it is recommended to use a drug from a different class. If PONV occurs after triple therapy with drugs from different classes, propofol 20 mg intravenously may be given to patients in the PACU as needed. Drugs used for prophylaxis should not be repeated unless given six hours after the initial dose.²⁴ Dexamethasone and scopolamine should not be repeated.²⁰ Other causes of PONV such as hypotension, hypoxia, hypoglycemia, electrolyte disturbances, high intracranial pressure, gastric bleeding or obstruction, and  surgeries(ENT) where blood drains into the pharynx and is swallowed should also be excluded and if warranted treating the cause is more appropriate than treating the symptom.²⁵

Conclusion

No one therapy or combination of therapies will completely eliminate the incidence of PONV. However, understanding which patients are at risk and administering prophylactic antiemetics, using a multimodal approach, and manipulating controllable risks (eg. volatile anesthetics, nitrous oxide, opioids, hydration) can significantly reduce PONV. As a result, proper treatment can lead to higher patient satisfaction, lower unanticipated hospital admissions, and overall decrease in cost.

Antiemetics, Doses, and Effected Receptors

*Referenced from Miller’s Anesthesia²⁶

References
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