Nausea and Vomiting
Virginia P. Arcangelo
Veronica F. Wilbur
Nausea and vomiting are common complaints in humans. The severity of the event can range from a slight discomfort or queasiness to uncontrollable, forceful vomiting. Despite this range of symptoms, all are perceived to be uncomfortable and troublesome and should be treated in a proper and timely manner. Patients may refer to this experience by many different names: upchuck, urp, queasy, throw up, and puke, to name a few. There are many different causes of nausea and vomiting, such as motion sickness, pregnancy, and medications. Likewise, many treatment options can be used to manage this complication. People of all ages experience emesis, although the etiology may be related to age-specific factors. Drugs are most frequently used for the treatment of nausea and vomiting, but alterations of nondrug factors may decrease the severity of emesis. This chapter reviews the pathophysiology and pharmacotherapy of specific types of nausea and vomiting.
CAUSES
There are multiple causes for nausea and vomiting; however, some of the most common are from the ingestion or administration of substances or drugs, gastrointestinal (GI) disorders, neurologic processes, and metabolic disorders. The presence of noxious stimuli is frequently a cause of nausea and vomiting. Supratherapeutic digoxin (Lanoxin) and theophylline (Theo-Dur or Slo-Phyllin) are known to produce emesis. Nausea and vomiting occur more frequently with high-dose chemotherapy than with moderate doses of the same drugs. Erythromycin and some penicillin derivatives are acknowledged for inducing uncomfortable GI complications. Emesis can also result from excessive ethanol intake. It is well known that other sensory experiences, such as pungent odors or gruesome sights, can induce nausea and vomiting. Box 28.1 presents specific etiologies for nausea and vomiting.
Patient-specific factors that increase susceptibility to nausea and vomiting include age, previous nausea and vomiting experiences, and sex. Most of the research identifying these characteristics was done in patients receiving chemotherapy. Poor control of nausea and vomiting with previous surgeries or chemotherapy predisposes a patient to subsequent episodes of emesis, also referred to as anticipatory nausea and vomiting. This form of emesis is often difficult to treat with standard antiemetics drug therapy.
Patients who receive previously received chemotherapy have been noted to experience emesis compared to those who are chemotherapy naive. Additionally, younger female patients are noted to have a greater risk of emesis (Hesketh, 2008). Surprisingly, patients who have higher chronic ethanol intake exceeding 100 g/d (roughly 5 beers or mixed drinks per day) are associated with better emesis control and decreased incidence of vomiting. A history of motion sickness may increase the risks of nausea and vomiting in another situation, such as with chemotherapy or surgery. Children in general experience nausea and vomiting more frequently than do adults. Obesity and anxiety have also been associated with heightened emesis incidence (Hesketh, 2008).
The prevalence of nausea and vomiting may complicate 20% to 70% of surgical procedures (Gan, 2008). Prevalence is also increased by the use of certain inhalation agents (nitrous oxide, in particular) and by concomitant use of opiate medications; the use of propofol as an intravenous anesthetic agent lowers the risk of postoperative nausea and vomiting (PONV). PONV is more likely to occur after general than regional anesthesia, and its prevalence increases in parallel with the duration of surgery and anesthesia. PONV is especially common
after gynecologic and middle ear surgery and also occurs more commonly with abdominal and orthopedic surgery than with laparoscopic or other extra-abdominal operations. PONV is also more likely in those with a history of PONV or motion sickness.
after gynecologic and middle ear surgery and also occurs more commonly with abdominal and orthopedic surgery than with laparoscopic or other extra-abdominal operations. PONV is also more likely in those with a history of PONV or motion sickness.
BOX 28.1
Etiologies of Nausea and Vomiting
Etiologies of Nausea and Vomiting
Therapy-induced causes | ||
Chemotherapy Radiation therapy Opiates Anticonvulsants Ipecac Antibiotics Digitalis or digoxin toxicity Theophylline Nonsteroidal anti-inflammatory drugs Hormonal therapies | ||
Drug withdrawal | ||
Opiates Benzodiazepines | ||
Metabolic disorders | ||
Addison disease Water intoxication Volume depletion Diabetic ketoacidosis Hypercalcemia Renal dysfunction-uremia | ||
Gastrointestinal mechanisms | ||
Mechanical gastric outlet obstruction | ||
Peptic ulcer disease Gastric carcinoma Pancreatic disease | ||
Motility disorders | ||
Gastroparesis Drug-induced gastric stasis Irritable bowel syndrome Postgastric surgery Idiopathic gastric stasis | ||
Intra-abdominal emergencies | ||
Acute pancreatitis Acute pyelonephritis Acute cholecystitis Acute cholangitis Acute viral hepatitis Intestinal obstruction | ||
Acute gastroenteritis | ||
Viral gastroenteritis Salmonellosis Shigellosis Staphylococcal gastroenteritis (enterotoxins) | ||
Cardiovascular disease | ||
Acute myocardial infarction Congestive heart failure Shock and circulatory collapse | ||
Neurologic processes | ||
Cerebellar hemorrhage Increased intracranial pressure | ||
Hematoma Subdural effusion Tumor (benign or malignant) Hydrocephalus Reye syndrome | ||
Headache | ||
Migraine Severe hypertension | ||
Head trauma Vestibular disorders | ||
Psychogenic causes | ||
Anorexia nervosa Anticipatory | ||
Miscellaneous causes | ||
Pregnancy Noxious odors Ingestion of an irritant Operative procedures Septicemia Nicotine | ||
PATHOPHYSIOLOGY
The pathophysiology of nausea and vomiting is complex (Figure 28.1) and involves the modulation of medullary sites and neurotransmitters. Many sensory centers accept noxious stimuli from the body, including the chemoreceptor trigger zone (CTZ), visceral afferent nerves, cerebral cortex, limbic system, vestibular system, and midbrain intracranial pressure receptors.
Modulation of Nausea and Vomiting
These stimuli are transmitted to the emetic complex (EC), a loose group of organized neurons throughout the medulla, which coordinates the sensory inputs and the act of vomiting. The EC is the key component in the modulation of nausea and vomiting. Located in the lateral reticular formation
of the medulla, it receives afferent impulses from the aforementioned sensory centers. On activation of the EC, efferent impulses are sent to the nucleus tractus solitarius, an intertwined neural network that innervates the salivary, vasomotor, and respiratory centers and cranial nerves VIII and X. Efferent impulses are also sent to the stomach, abdominal muscles, diaphragm, and associated sphincters to execute the involuntary act of vomiting. Much like the sensory centers that stimulate it, the vomiting center is rich in dopamine, histamine, serotonin, and acetylcholine receptors and can also be affected by binding to opiate and benzodiazepine receptors. An intact EC is essential for coordination of the vomiting act or the emetic reflex.
of the medulla, it receives afferent impulses from the aforementioned sensory centers. On activation of the EC, efferent impulses are sent to the nucleus tractus solitarius, an intertwined neural network that innervates the salivary, vasomotor, and respiratory centers and cranial nerves VIII and X. Efferent impulses are also sent to the stomach, abdominal muscles, diaphragm, and associated sphincters to execute the involuntary act of vomiting. Much like the sensory centers that stimulate it, the vomiting center is rich in dopamine, histamine, serotonin, and acetylcholine receptors and can also be affected by binding to opiate and benzodiazepine receptors. An intact EC is essential for coordination of the vomiting act or the emetic reflex.
 FIGURE 28.1 Pathophysiology of nausea and vomiting. (Reprinted from Koda-Kimble, M. A., & Young, L. Y. (2012). Nausea and vomiting. In M. A. Koda-Kimble, L. Y. Young, & B. J. Guglielmo (Eds.), Applied therapeutics: The clinical use of drugs (10th ed.). Philadelphia, PA: Lippincott Williams & Wilkins, with permission.) |
Stimulatory Centers
The CTZ is one of the most important chemosensory organs responsible for the detection of noxious stimuli. It is uniquely located in the area postrema in the floor of the fourth ventricle of the (medulla) brain and is exposed to both blood and cerebrospinal fluid (CSF). Thus, toxins in both the blood and CSF can stimulate a response by the CTZ. These toxins may be drugs (chemotherapy, opiates, and digoxin), poisons, or substances found naturally in the body (excess calcium, hormones). The CTZ is rich in neurotransmitter receptors for dopamine, serotonin, histamine, and acetylcholine. Neurokinin 1 (NK) receptors found in the cerebral cortex/thalamus/limbic system also feed in the EC. An antiemetic effect is elicited when these receptors are blocked.
Gastrointestinal Tract
The GI tract and pharynx are sites of origin for the stimulation of nausea and vomiting. Visceral afferent nerves, also referred to as splanchnic nerves, from the pharynx and GI tract transmit impulses from local neuroreceptors along the vagus nerve to the vomiting center. The GI tract is rich in local dopamine, histamine, and serotonin receptors. The visceral afferent nerves are also responsible for transmitting stimuli from other peripheral sites such as the heart, lungs, and testes; hence, the vomiting response may occur when a person has been punched in the abdomen or kicked in the groin. Abdominal surgery is another example in which visceral afferent nerves are involved in nausea and vomiting.
Central Nervous System
Motion sickness is primarily a central nervous system (CNS) response mediated by the vestibular system. Acetylcholine and histamine receptors have been found in the vestibular center. Blockade of these receptors provides some degree of protection from emesis. The cerebral cortex, the largest portion of the brain, is responsible for the motor coordination of the body, sensory perception, learning, memory, and many other functions. Afferent impulses from specific sites of the cerebral cortex can result in emesis. The cerebellum is responsible for the regulation of balance, equilibrium, and coordination. Disruption of this portion of the brain can lead to temporary or chronic nausea and vomiting. These structures may also play a role in anticipatory emesis.
Limbic System
The limbic system and the midbrain intracranial pressure receptors can stimulate nausea and vomiting, although their mechanisms are not fully understood. In humans, the primary function of the limbic system is associated with the expression of mood, emotions, and feelings, as well as memory recall. Anxiety, fear, and other emotions may play a role at this site in the perception of nausea and vomiting. Head trauma, intracranial bleeding, and mass effect from a benign or malignant tumor can produce increased pressure in the brain. This increased intracranial pressure can cause nausea and vomiting. The optimal treatment in these situations is a reduction in intracranial pressure through surgery or corticosteroids.
DIAGNOSTIC CRITERIA
The three identified phases of emesis are nausea, retching, and vomiting. Nausea is the unpleasant physical sensation of impending retching or vomiting. Nausea often occurs without the other two steps of emesis, although they are all treated with the same pharmacologic agents. Common symptoms accompanying nausea are flushing, pallor, tachycardia, and hypersalivation. Gastric stasis, decreased pyloric tone, mucosal blood flow, and contractions of the duodenum with reflux into the stomach are physiologic responses to nausea. Retching, the second phase of emesis, is the involuntary synchronized labored movement of abdominal and thoracic muscles before vomiting. Vomiting is the coordinated contractions of the abdominal and thoracic muscles to expel the gastric contents. The lower esophageal sphincter contracts, allowing GI retroperistalsis. The actual expulsion of gastric contents differentiates vomiting from retching.
The acuteness of the symptomatology is based on history and physical examination. Several issues need to be addressed such as whether this is an acute emergency, such as mechanical obstruction, perforation, or peritonitis, clinical clues that the problem is likely to be self-limited, such as would be expected with viral gastroenteritis or a potentially offending medication. The goal is to determine whether empiric treatment with an antiemetic, a gastric acid-suppressing, or a prokinetic agent would be beneficial or whether the patient should be admitted to the hospital to correct fluid and electrolyte imbalance.
Acute nausea and vomiting differs considerably from that of chronic nausea and vomiting differing in symptom duration. Acute onset of nausea and vomiting suggests gastroenteritis, pancreatitis, cholecystitis, or a drug-related side effect. When nausea and vomiting are associated with diarrhea, headache, and myalgias, the cause is viral gastroenteritis; in this instance, symptoms should resolve spontaneously within 5 days. A more insidious onset of nausea without vomiting is suspicious of gastroparesis, a medication-related side effect, metabolic disorders, pregnancy, or even gastroesophageal reflux disease. Nausea and vomiting are considered chronic when their duration is longer than 1 month.
Timing and description of the vomiting are important. Vomiting that occurs in the morning before breakfast is typical of that related to pregnancy, uremia, alcohol ingestion, and increased intracranial pressure. Projectile vomiting suggests intracranial disorders, especially those that result in increased intracranial pressure. In this case, vomiting may not be preceded by nausea.
The onset of vomiting caused by gastroparesis or gastric outlet obstruction tends to be delayed, usually by more than 1 hour, after meal ingestion. Vomiting may be suggestive of psychiatric disorders.
Associated symptoms such as abdominal pain, fever, diarrhea, vertigo, or a history of a similar contemporaneous illness among family, friends, or associates are important data to gather.
The physical examination looks at vital signs for signs of dehydration. Jaundice, lymphadenopathy, abdominal masses, and occult blood in the stool may reveal features suggestive of thyrotoxicosis or Addison disease. The abdominal examination should look for distention, visible peristalsis, and abdominal or inguinal hernias. Areas of tenderness are important: tenderness in the midepigastrium suggests an ulcer, and in the right upper quadrant, cholecystitis or biliary tract disease. Auscultation may demonstrate increased bowel sounds in obstruction or absent bowel sounds in ileus.
INITIATING THERAPY
The treatment of nausea, retching, or vomiting in any patient begins with an evaluation and correction of possible causes. Most sources of nausea and vomiting may be reversed or palliated by surgery or medical interventions. Infectious causes should be promptly treated with antibiotics, and metabolic disorders require medical management. Some drug toxicities may be treated with antidotes, such as digoxin toxicity reversed with digoxin immune Fab (Digibind). The following section discusses medications used to treat nausea and vomiting. They should be used with definitive treatments when possible.
Alterations in a patient’s daily activities may aid in managing nausea and vomiting and decrease the resources used to control the problem. Nonpharmacologic management of nausea and vomiting should be tailored to the presumed etiology.
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