Sheila Wilhelm
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Identify several causes of nausea and vomiting.
2. Describe the pathophysiologic mechanisms of nausea and vomiting.
3. Identify the three stages of nausea and vomiting.
4. Distinguish between simple and complex nausea and vomiting.
5. Create goals for treating nausea and vomiting.
6. Recommend a treatment regimen for a patient with nausea and vomiting associated with cancer chemotherapy, surgery, pregnancy, or motion sickness.
7. Outline a monitoring plan to evaluate the treatment outcomes for nausea and vomiting.
KEY CONCEPTS
Nausea and vomiting are symptoms that can be due to a number of different causes.
To treat nausea and vomiting most effectively, it is important to first identify the underlying cause of the symptoms.
Nonpharmacologic approaches to treating nausea and vomiting include dietary, physical, and psychological changes.
For prevention of acute chemotherapy-induced nausea and vomiting (CINV) for patients receiving moderately or highly emetogenic chemotherapy, a combination of antiemetics with different mechanisms of action is recommended.
Droperidol or a 5-hydroxytryptamine (serotonin) type 3 (5-HT3) receptor antagonist should be administered at the end of surgery to patients at high risk for developing postoperative nausea and vomiting (PONV).
Nausea and vomiting affect the majority of pregnant women; the teratogenic potential of the therapy is the primary consideration in drug selection.
Because the vestibular system is replete with muscarinic type cholinergic and histaminic (H1) receptors, anticholinergics and antihistamines are the most commonly used pharmacologic agents to prevent and treat motion sickness.
INTRODUCTION
Nausea and vomiting are due to complex interactions of the GI system, the vestibular system, and various portions of the brain. Nausea and vomiting have a variety of causes that can be simple or complex. Preventing and treating nausea and vomiting require pharmacologic and nonpharmacologic measures tailored to individual patients and situations.
ETIOLOGY AND EPIDEMIOLOGY
Nausea and vomiting are symptoms that can be due to a number of different causes. Various disorders of the GI, cardiac, neurologic, and endocrine systems can lead to nausea and vomiting (Table 20–1).1–4 Cancer chemotherapy agents are rated according to their emetogenic potential, and anti-emetic therapy is prescribed based on these ratings. Due to potentially severe nausea and vomiting, some patients are unable to complete their chemotherapy treatment regimen. Radiation therapy can induce nausea and vomiting, especially when it is used to treat abdominal malignancies.5
Oral contraceptives, hormone therapy, oral hypoglycemic agents, anticonvulsants, and opioids are other common therapies that can cause nausea and vomiting.1,6 Some medications, such as digoxin and theophylline, cause nausea and vomiting in a dose-related fashion. Nausea and vomiting may indicate higher-than-desired drug concentrations. Ethanol and other toxins also cause nausea and vomiting.
Table 20–1 Causes of Nausea and Vomiting
Postoperative nausea and vomiting (PONV) occurs in 30% of surgical patients overall and in up to 70% of high-risk patients.7–9 This can be due to severing or disturbing the vagus nerve leading to gastric motility abnormalities. Additional risk factors for PONV include female gender, history of motion sickness or PONV, nonsmoking status, and use of opioids in the postoperative period.9–11 The choice of anesthetic agents and the duration of surgery may also contribute to PONV.7,9,11
Pregnancy-associated nausea and vomiting is common, affecting 70% to 85% of pregnant women, especially early in pregnancy.12 Approximately one-half of pregnant women experience nausea and vomiting of pregnancy (NVP), one-quarter experience nausea alone, and one-quarter are not affected.12 In 0.5% to 2% of pregnancies, this can lead to hyperemesis gravidarum, a potentially life-threatening condition of prolonged nausea, vomiting, and consequently, malnutrition.12
PATHOPHYSIOLOGY
Nausea and vomiting consist of three stages: (a) nausea; (b) retching; and (c) vomiting. Nausea is the subjective feeling of a need to vomit.1,6 It is often accompanied by autonomic symptoms such as pallor, tachycardia, diaphoresis, and salivation. Retching, which follows nausea, consists of diaphragm, abdominal wall, and chest wall contractions and spasmodic breathing against a closed glottis.1 Retching can occur without vomiting, but this stage produces the pressure gradient needed for vomiting, although no gastric contents are expelled. Vomiting, or emesis, is a reflexive, rapid, and forceful oral expulsion of upper GI contents due to powerful and sustained contractions in the abdominal and thoracic musculature.1 Vomiting, like nausea, can be accompanied by autonomic symptoms.
Regurgitation, unlike vomiting, is a passive process without involvement of the abdominal wall and diaphragm wherein gastric or esophageal contents move into the mouth.1 In patients with gastroesophageal reflux disease (GERD), one hallmark symptom is acid regurgitation.
Various areas in the brain and the GI tract are stimulated when the body is exposed to noxious stimuli (e.g., toxins), GI irritants (e.g., infectious agents), or chemotherapy. These areas include the chemoreceptor trigger zone(CTZ) in the area postrema of the fourth ventricle of the brain, the vestibular system, visceral afferents from the GI tract, and the cerebral cortex.2,3,6 These in turn stimulate regions of the reticular areas of the medulla within the brain stem. This area is the central vomiting center, the area of the brain stem that coordinates the impulses sent to the salivation center, respiratory center, and the pharyngeal, GI, and abdominal muscles that lead to vomiting (Fig. 20–1).13
The CTZ, located outside the blood-brain barrier, is exposed to cerebrospinal fluid and blood.2,3 Therefore, it is easily stimulated by uremia, acidosis, and the circulation of toxins such as chemotherapeutic agents. The CTZ has many 5-hydroxytryptamine (serotonin) type 3 (5-HT3), neurokinin-1 (NK1), and dopamine (D2) receptors.2,14 Visceral vagal nerve fibers are rich in 5-HT3 receptors. They respond to GI distention, mucosal irritation, and infection.
Motion sickness is caused by stimulation of the vestibular system.15 This area contains many histaminic (H1) and muscarinic cholinergic receptors. The higher brain (i.e., cerebral cortex) is affected by sensory input such as sights, smells, or emotions that can lead to vomiting. This area is involved in anticipatory nausea and vomiting associated with chemotherapy.
Nausea and vomiting can be classified as either simple or complex.4 Simple nausea and vomiting occurs occasionally and is either self-limiting or relieved by minimal therapy. It does not have detrimental effects on hydration status, electrolyte balance, or weight because it is short-lived. Alternatively, complex nausea and vomiting requires more aggressive therapy because electrolyte imbalances, dehydration, and weight loss may occur. Unlike simple nausea and vomiting, complex nausea and vomiting can be caused by exposure to noxious agents.
CLINICAL PRESENTATION AND DIAGNOSIS
TREATMENT
Desired Outcomes
The primary goal of treatment is to relieve the symptoms of nausea and vomiting, which should increase the patient’s quality of life. Drug therapy for nausea and vomiting should be safe, effective, and economical.
General Approach to Treatment
To treat nausea and vomiting most effectively, it is important to first identify the underlying cause of the symptoms. Treating the cause (if possible) will in turn eliminate the nausea and vomiting.
Profuse or prolonged vomiting can lead to complications of dehydration and metabolic abnormalities. Patients must have adequate hydration and electrolyte replacement orally (if tolerated) or IV to prevent and correct these problems. Some pharmacologic treatments work locally in the GI tract (e.g., antacids and prokinetic agents), whereas others work in the CNS (e.g., antihistamines and anticholinergics).1
Nonpharmacologic Therapy
A variety of effective pharmacologic treatments exist for nausea and vomiting, but they all have unwanted adverse treatment effects. For this reason, nonpharmacologic treatment options may be considered in selected patients.
Nonpharmacologic options are desirable for treating NVP due to concern for teratogenic effects with drug therapies. When treating PONV, the nonpharmacologic approach is appealing to minimize additive CNS depression with antiemetics and anesthetic agents. Nonpharmacologic approaches to treating nausea and vomiting include dietary, physical, and psychological changes.
Dietary approaches are the cornerstone of treatment for NVP.16 They are included in treatment guidelines even though there is little evidence to support their effectiveness.12 Recommendations include eating frequent, small meals; avoiding spicy or fatty foods; eating high-protein snacks; and eating bland or dry foods the first thing in the morning.12,16,17 In addition to dietary changes, there is some evidence that women taking a multivitamin at the time of conception are less likely to seek medical attention for NVP.12
FIGURE 20–1. Physiologic pathways that result in nausea and vomiting. (5-HT3, serotonin type 3 receptor; D2, dopamine type 2 receptor; H1 histamine type 1 receptor, NK1, neurokinin-1.) (From Ref. 13.)
Clinical Presentation and Diagnosis of Nausea and Vomiting
Symptoms
• Patients with nausea often complain of autonomic symptoms such as diaphoresis, general disinterest in surroundings, pallor, faintness, and salivation.
Signs
• With complex and prolonged nausea and vomiting, patients may show signs of malnourishment, weight loss, and dehydration (dry mucous membranes, skin tenting, tachycardia, and lack of axillary sweat).
Laboratory Tests
• Dehydration, electrolyte imbalances, and acid-base disturbances may be evident in complex and prolonged nausea and vomiting.
• Dehydration is suggested by elevated blood urea nitrogen (BUN) and serum creatinine (SCr) concentrations, especially with a BUN to SCr ratio of 20:1 or greater (using traditional units of measurement).
• Calculated fractional excretion of sodium (FeNa) less than 1% in patients with compromised baseline renal function and less than 0.2% in patients with normal baseline renal function indicates dehydration and reduced renal perfusion.
• Low serum chloride and elevated serum bicarbonate levels indicate metabolic alkalosis.
• Arterial blood gases with a normal or elevated pH indicates metabolic alkalosis that may or may not be compensated.
• Hypokalemia may occur from Gl potassium losses and intracellular potassium shifts to compensate for alkalosis.
Acupressure and acupuncture have been investigated based on the theory that certain points on the body control specific bodily functions.16 The P6 (Neiguan) point on the inside of the wrist has been used historically by acupuncturists to treat nausea and vomiting. While this approach seems safe and cost effective, efficacy data in the treatment of NVP are conflicting. The majority of studies showed a benefit to this approach, but the studies had methodological flaws.12,18 P6 acupressure and electroacupoint stimulation have also been investigated as preventative tools for PONV and motion sickness.19–21
Hypnosis maybe effective for severe NVP.22 Psychotherapy is another noninvasive treatment approach that is safe during pregnancy or in situations in which adverse treatment effects and drug interactions are a concern. One small study suggested that patients with hyperemesis gravidarum may benefit from the combination of psychotherapy and antiemetics.
Pharmacologic Therapy
Table 20–2 contains the names, usual dosages, and common adverse effects of the pharmacologic treatments for nausea and vomiting.1,4,5,9
Anticholinergics (Scopolamine)
The anticholinergic agent scopolamine blocks muscarinic receptors in the vestibular system, thereby halting signaling to the CNS. It is effective for preventing and treating motion sickness and perhaps for preventing PONV as well.23,24 Scopolamine is available as an adhesive transdermal patch (Transderm Scop) that is effective for up to 72 hours after application. This may be beneficial for patients unable to tolerate oral medications or those requiring continuous prevention of motion sickness (e.g., passengers on cruise ships). Scopolamine is associated with adverse anticholinergic effects such as sedation, visual disturbances, dry mouth, and dizziness.
Antihistamines
Antihistamines are commonly used to prevent and treat nausea and vomiting due to motion sickness, vertigo, or migraine headache.1,15,25 Their efficacy is presumably due to the high concentration of Hl and muscarinic cholinergic receptors within the vestibular system. Similarly to scopolamine, antihistamines such as diphenhydramine and meclizine cause undesired effects including drowsiness and blurred vision. Cetirizine and fexofenadine, two second-generation antihistamines without CNS depressant properties, were found to be ineffective for treating motion sickness, perhaps because they lack CNS effects.25
Some antihistamines such as diphenhydramine, dimen-hydrinate, and meclizine are available without a prescription, making self-treatment convenient for patients. Antihistamines are available in a variety of dosage forms, including oral capsules, tablets, and liquids. Liquid formulations are convenient for children or adults who are unable to swallow solid dosage forms.
Dopamine Antagonists
Stimulation of D2 receptors in the CTZ leads to nausea and vomiting (Fig. 20–1). Phenothiazine antiemetics act primarily via a central antidopaminergic mechanism in the CTZ.1 Common phenothiazines that have long been used for treating nausea and vomiting include promethazine, prochlorperazine, chlorpromazine, and thiethylperazine. They are available as oral solids and liquids, rectal suppositories, and parenteral formulations. This permits effective use of phenothiazines in a variety of settings including treatment of severe motion sickness or vertigo, gastritis or gastroenteritis, NVP, PONV, or chemotherapy-induced nausea and vomiting (CINV).5,7,9,12,26-29
Table 20–2 Antiemetic Agents: Doses for Adults and Children and Adverse Effects
Phenothiazines may cause sedation, orthostatic hypotension, and extrapyramidal symptoms (EPS) such as dyst-onia (involuntary muscle contractions), tardive dyskinesia (irreversible and permanent involuntary movements), and akathisia (motor restlessness or anxiety).1,30,31 Chronic phenothiazine use has been associated with EPS, but single doses have also caused these effects.32
Akathisia is disturbing for patients and can be disruptive to patient care. Giving diphenhydramine with prochlorperazine may reduce the incidence of akathisia, but the combination increases the risk of sedation.33 Slowing the IV infusion rate of prochlorperazine does not decrease akathisia.31,32
Droperidol, abutyrophenone derivative, is another centrally acting antidopaminergic agent effective for preventing PONV and treating opioid-induced nausea and vomiting.1,7 It may also be used for treating CINV for patients who are intolerant to serotonin receptor antagonists and corticosteroids.26
Adverse effects of droperidol include sedation, agitation, and restlessness. In addition, droperidol carries a U.S. FDA black box warning regarding the potential for QT interval prolongation and cardiac arrhythmias that may result in torsades de pointes and sudden cardiac death.34 Droperidol should not be used in patients with a prolonged QT interval or in those who are at risk for developing a prolonged QT interval (e.g., heart failure, electrolyte abnormalities, or concurrently taking other medications that may prolong the QT interval).34 A 12-lead ECG is recommended prior to treatment with droperidol. Haloperidol is another butyrophenone with some antiemetic effects at low doses (0.5-2 mg).9 It has been explored as an alternative to droperidol.35–37
The substituted benzamides metoclopramide and domperidone (not available in the United States) act as D2 antagonists both centrally in the CTZ and peripherally in the GI tract.1,38 They also display cholinergic activity, which increases lower esophageal sphincter tone and promotes gastric motility. Metoclopramide at high doses has antiserotonergic properties as well. Because metoclopramide and domperidone have both antiemetic and prokinetic effects, both are used for a variety of disorders including PONV, CINV, NVP, gastroparesis, GERD, and migraine headaches.1,7,12,26,39,40 Metoclopramide is available in injectable, oral solid, and oral liquid dosage forms, allowing for its use in both hospitalized and ambulatory patients. Other substituted benzamides include trimethobenzamide and benzquinamide.
Metoclopramide crosses the blood-brain barrier and has centrally mediated adverse effects. Young children and the elderly are especially susceptible to these effects, which include somnolence, reduced mental acuity, anxiety, depression, and EPS (akathisia, dystonia, and tardive dyskinesia).41 The overall incidence of adverse effects is estimated to be 10% to 20%.1
Domperidone minimally crosses the blood-brain barrier; it acts in the CTZ that lies outside of the blood-brain barrier. As such, domperidone is less likely to cause the centrally mediated adverse effects seen with metoclopramide and has an estimated overall incidence of 5% to 10%.1,41 However, domperidone has been associated with prolonged QT intervals, cardiac arrhythmias, and sudden death.42 It should not be used for patients with underlying long QT interval or for those on other medications that prolong the QT interval. Both metoclopramide and domperidone can cause hyperprolactinemia, galactorrhea, and gynecomastia.
Corticosteroids
Corticosteroids, especially dexamethasone and methylprednisolone, are used alone or in combination with other antiemetics for preventing and treating PONV, CINV, or radiation-induced nausea and vomiting.5,9,14,43 They are administered either orally or IV. Their efficacy is thought to be due to release of 5-HT, reduction in the permeability of the blood-brain barrier, and reduction of inflammation.44Common adverse effects with short-term use include GI upset, anxiety, insomnia, and hyperglycemia.5 Because their use is generally of short duration, long-term adverse effects (e.g., reduction in bone mineral density, corticosteroid-related diabetes, and cataracts) are not usually seen.
Cannabinoids
Cannabinoids have antiemetic activity when used alone or in combination with other antiemetics.45,46 Dronabinol and nabilone are commercially available oral formulations used for preventing and treating refractory CINV.5,45,46Cannabinoids are thought to exert their antiemetic effect centrally, although the exact mechanism of action is unknown.45,46 Sedation, euphoria, hypotension, ataxia, dizziness, and vision difficulties can occur with cannabinoids.
Benzodiazepines
Benzodiazepines, especially lorazepam, are used to prevent and treat CINV.5,14,43 Lorazepam is thought to prevent input from the cerebral cortex and limbic system from reaching the central vomiting center in the brain stem.13Sedation and amnesia are common side effects. Respiratory depression can occur with high doses or when other central depressants such as alcohol are combined with benzodiazepines.
Serotonin Antagonists
Chemotherapeutic agents cause release of 5-HT from enterochromaffin cells in the intestinal mucosa.44 This increase in 5-HT concentrations leads to stimulation of the visceral vagal nerve fibers and CTZ, thereby triggering nausea and vomiting. Both the CTZ and the vagal visceral nerve fibers are rich in 5-HT3 receptors.2 Selective 5-HT3 receptor antagonists (ondansetron, granisetron, dolasetron, and palonosetron) are available to prevent and treat nausea and vomiting due to stimulation of these receptors, especially for prevention and treatment of CINV and PONV.5,7,9,11,14,43,44,47 These agents are well tolerated; the most common adverse effects are headache, somnolence, diarrhea, and constipation.5
The 5-HT3 antagonist palonosetron is the first of its class to be approved for prevention of both acute and delayed CINV.5 Compared to the other 5-HT3 antagonists, palonosetron has a longer serum half-life (40 hours compared to 4⏻9 hours) and a higher receptor-binding affinity, which may contribute to its efficacy in preventing delayed CINV.48 Despite these pharmacokinetic properties, palonosetron has not been shown to be superior to other 5-HT3antagonists. It is recommended as an alternative and equally effective 5-HT3 antagonist in the most recent (2006) American Society of Clinical Oncology (ASCO) guideline.5
NK1 Receptor Antagonists
Aprepitant is the first NK1 receptor antagonist antiemetic drug.49 NK1 receptors are present in the CTZ and GI tract and are involved in the nausea and vomiting response, especially CINV.5,44 Aprepitant is effective for preventing acute and delayed CINV when used with a 5-HT3 antagonist and a corticosteroid.5,49,50 It is also effective for the prevention of PONV.9,51
Chemotherapy-Induced Nausea and Vomiting
CINV is classified as: (a) acute (occurring within 24 hours after receiving chemotherapy); (b) delayed (occurring more than 24 hours after receiving chemotherapy); or (c) anticipatory (occurring prior to chemotherapy in patients who experienced acute or delayed nausea and vomiting with previous courses).5,43,47 Risk factors for CINV include poor emetic control with prior chemotherapy, female gender, low chronic alcohol intake, and younger age.43,52
Chemotherapeutic agents are classified according to their emetogenic potential (Table 20–3), which aids in predicting CINV.5,14,53 Risk factors that are useful in predicting anticipatory nausea and vomiting include poor prior control of CINV and a history of motion sickness or NVR.5,47
For prevention of acute CINV for patients receiving moderately or highly emetogenic chemotherapy, a combination of antiemetics with different mechanisms of action is recommended (Table 20–4).5,14,43,47 Patients receiving chemotherapeutic agents with low emetogenic potential should receive a corticosteroid as CINV prophylaxis, and those receiving chemotherapy with minimal emetogenic risk do not require prophylaxis. Delayed nausea and vomiting is more difficult to prevent and treat. It occurs most often with cis-platin- and cyclophosphamide-based regimens, especially if delayed nausea and vomiting occurred with previous courses of chemotherapy.5,43 Patients at greatest risk are those who previously had poorly controlled acute CINV.5
Table 20–3 Emetogenicity of Chemotherapeutic Agents
Antiemetics can be administered either IV or orally in this situation, depending on patient characteristics such as ability to take oral medications, dosage form availability, and cost considerations.5 The IV and oral routes are equally effective. When used at equipotent doses, the 5-HT3 antagonists have similar efficacy in preventing acute CINV, despite pharmacokinetic and receptor-binding affinity differences.5,14
Patients undergoing chemotherapy should have antiemetics available to treat breakthrough nausea and vomiting even if prophylactic antiemetics were given.5,43 A variety of antiemetics may be used, including lorazepam, dexamethasone, methylprednisolone, prochlorperazine, promethazine, metoclopramide, and dronabinol. If breakthrough CINV occurs, it may be best treated with an antiemetic with a mechanism of action that differs from the medications already administered. The 5-HT3 antagonists are effective for treating breakthrough nausea and vomiting, but they have not been shown to be superior to more traditional and less expensive antiemetics.
Patient Encounter 1, Part 1
A 28-year-old healthy woman seeks your advice. She is about to leave on a 7-day Caribbean cruise and is concerned about motion sickness. She recently experienced nausea and one episode of vomiting while on a sailboat on Lake Michigan for an afternoon. She is not allergic to any medications. She does not smoke and only occasionally drinks alcohol. She takes an oral contraceptive (ethinyl estradiol and norgestimate) and occasional ibuprofen for headaches.
What nonpharmacologic and pharmacologic options are available for this woman?
How would you instruct her to use the recommended modalities?
What adverse effects would you discuss with her?
The best strategy for preventing anticipatory nausea and vomiting is to prevent acute and delayed CINV by using the most effective antiemetic regimens recommended based on the emetogenic potential of the chemotherapy and patient factors. CINV should be aggressively prevented with the first cycle of therapy rather than waiting to assess patient response to less effective regimens. If anticipatory nausea and vomiting occurs, benzodiazepines and behavioral therapy such as relaxation techniques are the recommended approaches.5,14
Postoperative Nausea and Vomiting
PONV is a common complication of surgery and can lead to delayed discharge and unanticipated hospitalization.7 The overall incidence of PONV for all surgeries and patient populations is 25% to 30%, but PONV can occur in 70% to 80% of high-risk patients.7,9,11 Risk factors for PONV include patient factors (female gender, nonsmoking status, and history of PONV or motion sickness), anesthetic factors (use of volatile anesthetics, nitrous oxide, or intraoperative or postoperative opioids), and surgical factors (duration and type of surgery).7,9–11
The first step in preventing PONV is reducing baseline risk factors when appropriate.7,9 For example, the incidence of PONV may be less with regional anesthesia than general anesthesia, and nonsteroidal anti-inflammatory drugs may cause less PONV than opioid analgesics.
Droperidol or a 5-HT3 receptor antagonist should be administered at the end of surgery to patients at high risk for developing PONV.1,7,8,11,54 Dexamethasone is also effective when given as a single dose prior to induction of anesthesia.7,54 Anticholinergics and antihistamines are also effective for preventing PONV.7
Table 20–4 Recommended Drug Regimens for Prevention of CINV Based on Emetogenic Risk
Patient Encounter 2
A 57-year-old woman is scheduled for an abdominal hysterectomy due to uterine fibroids. She is very anxious about her surgery.
PMH: Uterine fibroids; hypertension for 6 years; hypercholesterolemia for 6 years
FH: Father died of lung cancer; mother is still alive with a history of hypertension and cerebrovascular accident
SH: Works as a high school teacher; drinks one glass of wine with dinner three times per week; does not use tobacco
Meds: Hydrochlorothiazide 25 mg orally once daily; lisinopril 20 mg orally once daily; simvastatin 40 mg orally once daily at bedtime; aspirin 81 mg orally once daily; acetaminophen as needed for headache or body aches
Labs: Within normal limits
ECG: Normal sinus rhythm
Anesthesia for the surgery will be thiopental 4.5 mg/kg, atracurium 0.5 mg/kg, and fentanyl 0.05 mg followed by tracheal intubation, 70% nitrous oxide, and 0.5% to 2% isoflurane in oxygen.
What risk factors for PONVdoes this patient have?
Identify your treatment goals for this patient.
What nonpharmacologic and pharmacologic measures can be taken to prevent PONV?
Discuss any contraindications or adverse effects associated with your recommended treatments.
Aprepitant, an NK1 receptor antagonist, prevents PONV; however, it does not appear to be more effective than other available agents and is costly.9 Conversely, metoclopramide, ginger, and cannabinoids have been shown to be of limited utility for PONV and are not recommended.9
Combinations of antiemetics are the recommended method of preventing PONV for high-risk patients.9 Droperidol plus a 5-HT3 antagonist or dexamethasone plus a 5-HT3 antagonist are effective combinations.9 Three-drug combinations such as dexamethasone, droperidol, and a 5-HT3 antagonist have not been formally studied but may be a reasonable approach.54
If PONV occurs despite appropriate prophylaxis, it should be treated with an antiemetic from a pharmacologic class not already administered.9,11 If no prophylaxis was used, a low-dose 5-HT3 antagonist should be used.9,11
Nausea and Vomiting of Pregnancy
Nausea and vomiting affect the majority of pregnant women; the teratogenic potential of the therapy is the primary consideration in drug selection.12 Risks and benefits of any therapy must be weighed by the health care professional and the patient.
Nonpharmacologic therapy such as dietary, physical, and behavioral approaches should be considered first.12,16 Pyridoxine (vitamin B6) 10 to 25 mg three to four times daily alone or in combination with an antihistamine such as doxylamine is often used for NVR.12,16–18 This combination was previously marketed as Bendectin or Debendox but was withdrawn due to concerns over possible teratogenic effects, although the literature did not support this claim.17,18 Pyridoxine is well tolerated, but doxylamine and other antihistamines commonly cause drowsiness. For more severe NVP, promethazine, metoclopramide, and trimethobenzamide may be effective and have not been associated with teratogenic effects.12,16 Ondansetron, which is pregnancy category B, has been used to treat severe NVP. Animal data do not indicate a safety concern in pregnancy, but safety and efficacy data in humans for NVP are sparse.
In rare instances (0.5–2% of pregnancies), NVP progresses to hyperemesis gravidarum.12 Treatment may require the use of enteral or parenteral nutrition if weight loss is present. A corticosteroid such as methylprednisolone may be considered. Methylprednisolone is associated with oral clefts in the fetus when used during the first trimester. Therefore, corticosteroids should be reserved as a last resort and should be avoided during the first 10 weeks of gestation.12,16,17
Motion Sickness and Vestibular Disturbances
Nausea and vomiting can be caused by disturbances of the vestibular system in the inner ear.15,55 Vestibular disturbances can result from infection, traumatic injury, neoplasm, and motion. Patients may experience dizziness and vertigo in addition to nausea and vomiting. If a patient is susceptible to motion sickness, some general preventive measures include minimizing exposure to movement, restricting visual activity, ensuring adequate ventilation, reducing the magnitude of movement, and taking part in distracting activities.15
Because the vestibular system is replete with muscarinic type cholinergic and histaminic (H1 receptors, anticholinergics and antihistamines are the most commonly used pharmacologic agents to prevent and treat motion sickness. Oral medications should be taken prior to motion exposure to allow time for adequate absorption. Once nausea and vomiting due to motion sickness occur, oral medication absorption may be unreliable, making the therapies ineffective. Scopolamine, the anticholinergic medication used for motion sickness, is available as a transdermal patch delivery system, which may be helpful for patients who cannot tolerate oral medications or who require treatment for a prolonged period.23 Drowsiness and reduced mental acuity are the most bothersome side effects of antihistamines and anticholinergics. Visual disturbances, dry mouth, and urinary retention can also occur.
Patient Encounter 1, Part 2
Four months later, the patient returns to your practice. She is 8 weeks pregnant and complains of nausea and occasional vomiting. She is only taking prenatal vitamins. She does not smoke or drink alcohol. She was told at her last prenatal visit that she was appropriately gaining weight. She asks for your advice about preventing and treating nausea and vomiting.
What general considerations about treating NVP will you discuss with this patient?
What nonpharmacologic and pharmacologic treatment options are available for her?
Patient Care and Monitoring
1. Identify the underlying cause of the nausea and vomiting and eliminate it if possible. Counsel the patient to avoid known triggers.
2. Assess the patient to determine whether the nausea and vomiting is simple or complex and whether patient-directed therapy is appropriate.
3. Obtain a thorough patient history including the prescription, nonprescription, and herbal medications being used. Identify any substances that may be causing or worsening nausea and vomiting. Determine which treatments for nausea and vomiting have been used in the past and their degree of efficacy.
4. Develop a treatment plan with the patient and other health care professionals if appropriate. Choose therapeutic options based on the underlying cause of nausea and vomiting, duration and severity of symptoms, comorbid conditions, medication allergies, presence of contraindications, risk of drug-drug interactions, and treatment adverse-effect profiles.
5. Use the oral route of administration if the patient has mild nausea with minimal or no vomiting. Seek an alternative route (e.g., transdermal, rectal suppository, or parenteral) if the patient is unable to retain oral medications due to vomiting.
6. Educate the patient about nonpharmacologic measures such as stimulus avoidance, dietary changes, acupressure or acupuncture, and psychotherapy.
7. To assess efficacy, ask the patient whether he or she is still experiencing nausea or vomiting while using the therapy. Assess whether treatment failure is due to inappropriate medication use or the need for additional or different treatments and proceed accordingly.
8. Assess adverse effects by asking the patient what he or she has experienced. Also, patient observation or examination is useful for diagnosing adverse effects such as EPS.
9. Provide patient education regarding causes of nausea and vomiting, avoidance of triggers, potential complications, therapeutic options, medication adverse effects, and when to seek medical attention.
OUTCOME EVALUATION
• The symptoms of simple nausea and vomiting are self-limited or can be relieved with minimal treatment. Monitor patients for adequate oral intake and alleviation of nausea and vomiting.
• Patients with complex nausea and vomiting may have malnourishment, dehydration, and electrolyte abnormalities.
• Monitor patients for adequate oral intake. If the patient has weight loss, assess whether enteral or parenteral nutrition is needed.
• Assess for dry mucous membranes, skin tenting, tachycardia, and lack of axillary sweat to determine if dehydration is present.
• Obtain blood urea nitrogen (BUN), serum creatinine (SCr), calculated fractional excretion of sodium (FeNa), serum electrolytes, and arterial blood gases.
• Ask patients to rate the severity of nausea.
• Monitor the number and volume of vomiting episodes.
• Ask patients about adverse effects to the antiemetics used. Use this information to assess efficacy and tailor the patient’s antiemetic regimen.
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
REFERENCES
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2. Kearney DJ. Approach to the patient with gastrointestinal disorders. In: Friedman SL, McQuaid KR, Grendell JH, eds. Current Diagnosis and Treatment in Gastroenterology, 2nd ed. New York: McGraw-Hill, 2003:1-33.
3. Proctor DD. Approach to the patient with gastrointestinal disease. In: Goldman L, Ausiello D, Arend W, et al., eds. Cecil Medicine: Expert Consult (Cecil Textbook of Medicine), 23rd ed. Philadelphia: WB Saunders, 2007.
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