Articles

Nausea and Vomiting

Introduction

Nausea and vomiting are common complaints seen in a variety of settings. The cause may be associated with something as innocuous as spinning too fast on an amusement park ride. It also may be a therapy induced adverse reaction, or a symptom in a much more serious and complicated clinical presentation. Nausea and vomiting may occur independently, but generally they are closely allied and are presumed to be mediated by the same neural pathway, and therefore will be discussed together. Nausea denotes the imminent desire to vomit, usually referred to the throat or epigastrium. Vomiting (or emesis) refers to the forceful oral expulsion of gastric contents. Retching denotes the labored rhythmic contraction of respiratory and abdominal musculature that frequently precedes or accompanies vomiting. (1)

Nausea usually precedes vomiting and is associated with diminished functional activity of the stomach (e.g., hypoperistalsis, hyposecretion, and hypotonicity), and altered activity of the small intestine. Other distressing occurrences include parasympathetic autonomic activities such as increased diaphoresis, hypersalivation, skin pallor, and defecation. Sometimes hypotension and bradycardia (vasovagal syndrome) may be present.

The act of vomiting requires the coordinated contractions of the abdominal muscles, pylorus and antrum, a raised gastric cardia, diminished lower esophageal sphincter pressure, and esophageal dilatation. (2) The stomach itself plays a relatively passive role in emesis, with the major force being provided by the abdominal musculature. Two functionally distinct medullary centers are actually responsible for the act of vomiting. Those centers are the chemoreceptor trigger zone, located in the area postrema of the floor of the fourth ventricle, and the vomiting center, located in the dorsal portion of the lateral reticular formation.

The vomiting center is located in close proximity to other medullary centers, which regulate respiration, vasomotor, and other autonomic functions that may play a role in vomiting. It is the vomiting center that actually controls and integrates the act of vomiting. It receives afferent stimuli from the gastrointestinal tract and other parts of the body, from higher brainstem and cortical centers, especially the labyrinthine apparatus, and from the chemoreceptor trigger zone. (3) When excited, afferent impulses are integrated by the vomiting center, resulting in efferent impulses to the salivation center, respiratory center, and the pharyngeal, GI, and abdominal muscles, leading to vomiting. (4)

The chemoreceptor trigger zone by itself cannot mediate the act of vomiting. However, impulses are sent from this area to the vomiting center, which initiates emesis. The chemoreceptor trigger zone is usually associated with chemically induced vomiting, and can be activated by a number of different drugs, as well as other stimuli such as bacterial toxins, radiation, and metabolic abnormalities that occur with uremia and hypoxia. Similarly, the vomiting associated with pregnancy is probably initiated through the chemoreceptor trigger zone. Vomiting should be distinguished from regurgitation, which refers to the expulsion of food in the absence of nausea, and without the abdominal diaphragmatic muscular contractions associated with vomiting. Regurgitation may occur, for example, as a result of pressure differences caused from an incompetent lower esophageal sphincter, seen in gastroesophageal reflux disease, or from pyloric spasm or obstruction seen in peptic ulcer disease.

Nausea and vomiting are associated with many organic and functional disorders. Many acute abdominal emergencies such as acute appendicitis, acute cholecystitis, intestinal obstruction, or peritonitis may be associated with nausea and vomiting, as well as other disorders of the alimentary tract. Viral, bacterial, and parasitic infections of the GI tract are typically associated with severe nausea and vomiting. As many as 70 percent of patients with inferior myocardial infarction, or diabetic ketoacidosis may experience nausea and vomiting.

One of the most common etiologies of vomiting in children is viral gastroenteritis caused by rotavirus. Vomiting in infants may be associated with something as simple as overfeeding, too rapid feeding, inadequate burping, or lying down too soon after feeding. Vomiting in a newborn on the first day of life may suggest upper digestive tract obstruction or increase in intracranial pressure.

Anticipatory nausea and vomiting may be elicited either by specific stimuli associated with the administration of noxious, often cytotoxic, agents or by the anxiety associated with these treatments. Many patients demonstrate both types. The most often accepted theory for this pattern of conditioning is that by repeated pairing of chemotherapy and its after effects, previously neutral stimuli such as odors, sounds, and settings acquire the ability to elicit nausea and vomiting. (5) , (6)

An understanding of nausea and vomiting in relation to eating patterns may be of help diagnostically. For example, vomiting that occurs often in the morning may be associated with early pregnancy or uremia. Vomiting immediately after or during eating may suggest psychogenic vomiting or pyloric spasm in peptic ulcer disease. Vomiting that occurs four to six hours or longer after meals and involves the eliminating of large quantities of undigested food is indicative of gastric retention. This may be a symptom of pyloric obstruction or gastroparesis, and certain esophageal disorders such as achalasia, or Zenker’s diverticulum. Vomiting that is projectile or without antecedent nausea suggests the possibility of a central nervous system lesion. (7)

Associated symptoms may also provide diagnostic clues. For example, if nausea and vomiting are associated with tinnitus and vertigo, Meniere’s disease should be considered. Relief of abdominal pain with vomiting is often due to peptic ulcer. Characteristics of the vomitus itself may hold clues to diagnosing a patient’s illness. If there are large amounts of hydrochloric acid present, gastric outlet obstruction due to ulcer or hypersecretory condition such as Zollinger-Ellison might be considered. Absence of free hydrochloric acid is more compatible with gastric malignancy. A putrid odor may be the result of bacterial action, or peritonitis, among other things.

Clearly it is impossible to detail all the clinical situations in which nausea and vomiting may be a pertinent finding. It should become evident, however, that because of the variable etiologies, management may vary from simple to quite complex.

Statistic

Support Care Cancer; 6(3):244-7. 1998.

    Anticipatory nausea (AN) appears to occur in approximately 29% of patients receiving chemotherapy, or about 1:3, while anticipatory vomiting (AV) appears to occur in 11% of patients, or about 1:10.

Signs and Symptoms

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Not available

Three stages of emesis

    Nausea including diaphoresis, pallor, hypersalivation Retching Vomiting

Treatment Options

Conventional

The overall goal of therapy is to prevent or eliminate nausea and vomiting; however, treatment approaches vary greatly depending on the associated medical condition. For simple nausea and vomiting, the patient may choose to do nothing or to select from available over-the-counter medications.

If symptoms worsen or are prolonged, patients may benefit from prescription antiemetic drugs. These agents represent a variety of pharmacologic and chemical classes as well as dosage regimens and routes of administration. With so many treatment possibilities available, factors that enable the clinician to discriminate among various choices must be recognized. These factors include: the suspected etiology of the symptoms; the frequency, duration, and severity of the episodes; the ability of the patient to use oral, rectal, injectable, or transdermal topical medications; and the success of previous antiemetic medications. (8)

Products available for self-medication include antacids; histamine 2 antagonists such as cimetidine, famotidine, and ranitidine; antihistimine-anticholinergic agents such as meclizine, cyclizine, dimenhydrinate, and diphenhydramine; and phosphorylated carbohydrate solutions. Agents requiring a prescription are some of the antihistamine-anticholinergic drugs and the phenothiazines. Both nonprescription and prescription drugs are usually effective in small, infrequently administered doses.

For more complicated cases of nausea and vomiting, a combination of more than one antiemetic drug may be required. Each drug is prescribed in small to moderate dosages, achieving control through different pharmacologic mechanisms. Effective combinations may include two or more of the following medications: benzquinamide, prochlorperazine, promethazine, dimenhydrinate, droperidol, thiethylperazine, trimethobenzamide, chlorpromazine, or hydroxyzine.

Antiemetic regimens for patients receiving cancer chemotherapy should include medication prior to chemotherapy, and one or more doses during and/or after chemotherapy. Drugs commonly used in this setting include prochlorperazine alone or in combination with lorazepam; granisetron, ondancetron, or dolasetron alone or one of the three in combination with dexamethasone or methylprednisolone.

The therapeutic endpoint should be absence of or an acceptable reduction in nausea and vomiting. Evaluation for adverse reactions to antiemetics should include monitoring for sedation and extrapyramidal effects.

Nutritional Supplementation


Vitamin B6

Several studies have reported that pyridoxine can reduce nausea and vomiting associated with morning sickness in the early stages of pregnancy. In one randomized, double-blind placebo-controlled study, 31 women took 25 mg of vitamin B6 orally every 8 hours for 72 hours, while an additional 28 pregnant women received a placebo. In women with severe nausea, those taking vitamin B6 experienced significantly better improvement in nausea scores compared to the women taking the placebo. However, there were no significant differences between treatment and placebo groups in cases of mild to moderate nausea. Women taking vitamin B6 also had a much greater improvement in vomiting after 3 days of therapy in comparison to the placebo group. (9)

In another trial, which was double-blind, 342 pregnant women took 30 mg of vitamin B6/day orally for 5 days or a placebo. The results revealed that women taking vitamin B6 had a significant decrease in their nausea scores compared to the placebo women and they also had a greater reduction in the mean number of vomiting episodes. Although these outcomes did not reach statistical significance, these results suggest that vitamin B6 may help to reduce the severity of nausea in the first few months of pregnancy. (10)


Vitamin K

One study reports that extended nausea and vomiting during pregnancy, also known as hyperemesis gravidarum, can result in malnutrition. One manifestation of this malnutrition could be a deficiency of vitamin K, which affects the body’s blood clotting mechanisms. This study provides the case history of a women at 15 weeks' gestation whose prolonged nausea and vomiting was complicated by an episode of severe nose bleeding. Investigation revealed a blood clotting defect caused by a vitamin K deficiency. This problem was completely resolved after vitamin K supplementation. Vitamin K status should be evaluated in those rare cases when a pregnant woman with prolonged nausea and vomiting presents with a bleeding problem. It is suggested that prophylactic vitamin K supplementation should be considered in women with severe and prolonged vomiting. (11)


Multivitamin

For an occasional incident of nausea and vomiting due to the flu, over indulgence in alcohol or food poisoning, no nutritional recommendation is necessary. However, if an individual is experiencing chronic nausea and vomiting for extended periods of time, nutrient depletions might occur due to vomiting and loss of appetite. Examples of conditions that might cause this type of problem include morning sickness, or nausea and vomiting due to chemotherapy for cancer treatment. In these cases, taking a multivitamin/mineral nutritional supplement might be helpful, if tolerated. Cancer patients may benefit greatly by getting intravenous nutritional support during the time they are undergoing chemotherapy.

A portion of one published study was designed to evaluate pregnant women who reported vomiting and seek a relationship between vitamin supplementation episodes of vomiting. The results revealed that women who did not take nutritional supplementation before 6 weeks’ gestation experienced significantly more episodes of vomiting. (12) These results indicate that vitamin and mineral nutritional supplementation before and during the early stages of pregnancy can help to reduce the incidence of vomiting.

Herbal Supplementation


Ginger

Ginger has been used throughout history as both a culinary herb and a medicinal agent. Ginger has gained attention in the United States because of its effect on motion sickness, nausea, and to aid in digestion. Several studies have been published which support ginger’s antiemetic activity compared to drug or placebo therapy. (13) , (14) , (15) , (16) Ginger may be warranted instead of antihistamines for motion sickness because it does not cause drowsiness. (17) Ginger may also be of value in the treatment of hyperemesis gravidarum, a condition in morning sickness where severe dehydration and electrolyte disturbances may occur through excessive vomiting. (18) A double-blind, controlled clinical study reported that the use of ginger for treatment of nausea in pregnancy was found to decrease the number of events as well as lessening the severity of nausea. (19) Studies have shown that women using ginger in early pregnancy can reduce their symptoms. (20) , (21) The effectiveness of ginger root pre-surgically as an antiemetic agent was comparable with metoclopramide in a double-blind, placebo controlled study. (22) Ginger root preparations may be useful in controlling nausea and vomiting in outpatient surgery. (23) Shogaol is thought to give ginger its antiemetic effect. (24)

Also of interest, ginger was reported to decrease the gastric emptying delays associated with using the chemotherapeutic agent cisplatin when administered concurrently with ginger juice – this was reported more effective than ondansetron. (25) Ginger also reported to decrease nausea associated with 8-MOP therapy. (26)


Chamomile

Chamomile has been used as a medicinal herb for centuries. It is most frequently used as a mild sedative for individuals with minor anxiety or nervousness. (27) It does not induce drowsiness or impair motor activity. Chamomile has also been used to soothe digestive upset and is considered a carminative (anti-gas) agent. (28) Chamomile has been used topically for various conditions such as acne, infections, burns, and wounds. (29) Apigenin has been reported to be a ligand for the central benzodiazepine receptors exerting anxiolytic and slight sedative effects but not being anticonvulsant or myorelaxant. (30)

Homeopathic

Ipecacuanha

Typical Dosage: 6X or 6C, 30X or 30CConstant nausea; Diarrhea; Vomiting does not relieve the nausea; A great deal of saliva in the mouth

Nux vomica

Typical Dosage: 6X or 6C, 30X or 30CConstant nausea; Splitting headache; Vomiting; Nausea during menstrual period

Pulsatilla

Typical Dosage: 6X or 6C, 30X or 30CNausea from pastry, ice cream, and greasy food; Eructation tastes like food eaten

Tabacum

Typical Dosage: 6X or 6C, 30X or 30CSevere nausea; Cold sweat; Violent retching and vomiting with every movement; Better in open air and when eyes are closed

Clinical Lab Assessment

Some of the following laboratory testing can provide information necessary for diagnosis and treatment. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.

Chemistry Profile (Blood)

A multifactorial assessment of chemistry profile values can reveal useful information regarding concurrent disorders and possible nutrient imbalances.

CBC

A CBC may suggest the involvement of secondary infections, inflammation, and/or nutrient deficiencies. The major mineral consideration in deficiency disorders is iron. Mean corpuscular volume (MCV) may not be sufficient to assess iron and or B12 status. Analysis of serum iron, total iron binding capacity, ferritin, and/or organic acids may be indicated. The CBC includes screening for leukopenia (low WBC) and thrombocytopenia (low platelet count).

Electrolytes, Plasma, Serum, or Urine

An imbalance in magnesium, potassium, chloride, or sodium may cause or result from vomiting. These values are monitored especially when medications are being used. Many diuretics deplete potassium. Low serum potassium (with or without alkalosis) is indication for further renal function study.

References

  1. Friedman LS, Isselbacher KJ. Nausea, Vomiting, and Indigestion. In: Fauci AS, Braunwald E, Isselbacher KJ et al. eds. Harrison’s Principles of Internal Medicine 14th ed. New York. McGraw-Hill. 1998:230-232.
  2. Feldman M. Nausea and vomiting. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal Disease. Philadelphia. Saunders. 1983:160-177.
  3. Friedman LS, Isselbacher KJ. Nausea, Vomiting, and Indigestion. In: Fauci AS, Braunwald E, Isselbacher KJ et al. eds. Harrison’s Principles of Internal Medicine 14th ed. New York. McGraw-Hill. 1998:230-232.
  4. Taylor AT. Nausea and Vomiting. In: DiPiro JT et al eds. Pharmacotherapy, A Pathophysiologic Approach, 4th ed. Stanford CT. Appleton & Lange. 1999:586-596.
  5. Redd WH. Control of nausea and vomiting in chemotherapy patients: Four effective behavioral methods. Postgrad Med. 1984;75:105-113.
  6. View Abstract: Eyre HJ, Ward JH. Control of cancer chemotherapy-induced nausea and vomiting. Cancer. 1984;54:2642-2648.
  7. Friedman LS, Isselbacher KJ. Nausea, Vomiting, and Indigestion. In: Fauci AS, Braunwald E, Isselbacher KJ et al. eds. Harrison’s Principles of Internal Medicine 14th ed. New York. McGraw-Hill. 1998:230-232.
  8. Friedman LS, Isselbacher KJ. Nausea, Vomiting, and Indigestion. In: Fauci AS, Braunwald E, Isselbacher KJ et al. eds. Harrison’s Principles of Internal Medicine 14th ed. New York. McGraw-Hill. 1998:230-232.
  9. View Abstract: Sahakian V, et al. Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study. Obstet Gynecol. Jul1991;78(1):33-6.
  10. View Abstract: Vutyavanich T, et al. Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial. Am J Obstet Gynecol. Sep1995;173(3 Pt 1):881-4.
  11. View Abstract: Robinson JN, et al. Coagulopathy secondary to vitamin K deficiency in hyperemesis gravidarum. Obstet Gynecol. Oct1998;92(4 Pt 2):673-5.
  12. View Abstract: Emelianova S, et al. Prevalence and severity of nausea and vomiting of pregnancy and effect of vitamin supplementation. Clin Invest Med. Jun1999;22(3):106-10.
  13. Mowry DB, et al. Motion Sickness, Ginger, and Psychophysics. Lancet. 1982; 1(8273):655-67.
  14. View Abstract: Grontved A, et al. Ginger Root Against Seasickness. A Controlled Trial on the Open Sea. Acta Otolaryngol. 1988;105:45-49.
  15. View Abstract: Qian DS, et al. Pharmacologic Studies of Antimotion Sickness Actions of Ginger. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih. 1992;12(2):95-98.
  16. View Abstract: Stewart JJ, et al. Effects of Ginger on Motion Sickness Susceptibility and Gastric Function. Pharmacology. 1991;42(2):111-20.
  17. View Abstract: Holtmann S, et al. The Anti-motion Sickness Mechanism of Ginger. A Comparative Study with Placebo and Dimenhydrinate. Acta Otolaryngol. 1989;108(3-4):168-74.
  18. View Abstract: Fischer-Rasmussen W, et al. Ginger Treatment of Hyperemesis Gravidarum. Eur J Obstet Gynecol Reprod Biol. 1991;38(1): 19-24.
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  20. View Abstract: Smith C, Crowther C, Willson K, Hotham N, McMillian V. A randomized controlled trial of ginger to treat nausea and vomiting in pregnancy. Obstet Gynecol. Apr2004;103(4):639-45.
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  30. View Abstract: Viola H, et al. Apigenin, A Component of Matricaria Recutita Flowers, Is a Central Benzodiazepine Receptors-ligand With Anxiolytic Effects. Planta Med. Jun1995;61(3):213-16.