CHAPTER 14 Nausea and Vomiting
Nausea, retching, and vomiting may occur separately or together. When they occur together they are often in sequence, as manifestations of the various physiologic events that integrate the emetic reflex. Vomiting is a complex act that requires central neurologic coordination, whereas nausea and retching do not imply activation of the vomiting reflex. When nausea, retching, or vomiting manifest as isolated symptoms, their clinical significance may differ from the stereotypical picture of emesis.1,2
Vomiting is a partially voluntary act of forcefully expelling gastric or intestinal content through the mouth. Vomiting must be differentiated from regurgitation, an effortless reflux of gastric contents into the esophagus that sometimes reaches the mouth but is not usually associated with the forceful ejection typical of vomiting (see Chapter 12).
PATHOPHYSIOLOGY
The mechanism of vomiting has been well characterized in experimental animals and humans (Fig. 14-1).3 Neurologic coordination of the various components of vomiting is provided by the emetic center (or vomiting center) located in the medulla, specifically in the dorsal portion of the lateral reticular formation in the vicinity of the fasciculus solitarius. The afferent neural pathways that carry activating signals to the emetic center arise from many locations in the body. Afferent neural pathways arise from various sites along the digestive tract—the pharynx, stomach, and small intestine. Afferent impulses from these organs are relayed at the solitary nucleus (nucleus tractus solitarius) to the emetic center. Afferent pathways also arise from nondigestive organs such as the heart and testicles. Pathways from the chemoreceptor trigger zone (CTZ) located in the area postrema on the floor of the fourth ventricle activate the emetic center. Despite its central location, the CTZ is outside, at least in part, the blood-brain barrier and serves primarily as a sensitive detection apparatus for circulating endogenous and exogenous molecules that may activate emesis. Finally, pathways arise from other central nervous system structures, including the cortex, brainstem, and vestibular system, via the cerebellum.
Figure 14-1. Schematic of the proposed neural pathways that mediate vomiting. GI, gastrointestinal; 5-HT, 5-hydroxytryptamine.
The circuitry of the emetic reflex involves multiple receptors.4 The following elements are the most relevant to clinical issues:
When activated, the emetic center sets into motion, through neural efferents, the various components of the emetic sequence.11 First, nausea develops as a result of activation of the cerebral cortex; the stomach relaxes concomitantly, and antral and intestinal peristalsis are inhibited. Second, retching occurs as a result of activation of spasmodic contractions of the diaphragm and intercostal muscles combined with closure of the glottis. Third, the act of vomiting occurs when somatic and visceral components are activated simultaneously. The components include brisk contraction of the diaphragm and abdominal muscles, relaxation of the lower esophageal sphincter, and a forceful retrograde peristaltic contraction in the jejunum that pushes enteric content into the stomach and from there toward the mouth.12 Simultaneously, protective reflexes are activated. The soft palate is raised to prevent gastric content from entering the nasopharynx, respiration is inhibited momentarily, and the glottis is closed to prevent pulmonary aspiration, which is a potentially serious complication of vomiting. Other reflex phenomena that may accompany this picture include hypersalivation, cardiac arrhythmias, and passage of gas and stool rectally.
CLINICAL CHARACTERISTICS OF VOMITING
Certain clinical features may be characteristic of specific causes of vomiting. Nausea and vomiting that occur in the morning or with an empty stomach and with emission of mucoid material (swallowed saliva) or gastroenteric secretions are characteristic of vomiting produced by direct activation of the emetic center or CTZ. This type of emesis is most typical of pregnancy, drugs, toxins (e.g., alcohol abuse), or metabolic disorders (diabetes mellitus, uremia). Psychogenic vomiting also may exhibit these characteristics. Clinical tradition holds that excessive nocturnal postnasal drip may be responsible for this type of vomiting, although direct evidence for this association is lacking. Vomiting that occurs outside the immediate postprandial period and that is characterized by evacuation of retained and partially digested food is typical of slowly developing gastric outlet obstruction or gastroparesis.13 Pseudovomitus, in which totally undigested food that has not been exposed to gastric juice is expelled, may occur in long-standing achalasia or with a large Zenker’s diverticulum. Bilious vomiting is commonly seen after multiple vomiting episodes occur in close succession because of retrograde entry of intestinal material into the stomach. It is also characteristic of patients with a surgical enterogastric anastomosis, in whom the gastric contents normally include bile-stained enteric refluxate. Vomitus with a feculent odor suggests intestinal obstruction, ileus associated with peritonitis, or long-standing gastric outlet obstruction. Vomiting that develops abruptly without preceding nausea or retching (projectile vomiting) is characteristic of, but not specific for, direct stimulation of the emetic center, as may occur with intracerebral lesions (tumor, abscess) or increased intracranial pressure.14
CAUSES
In clinical practice, establishing the cause of vomiting promptly is critical, because specific treatment may be feasible. Acute (less than 1 week) and chronic vomiting should be considered separately, because the respective causes generally differ. Patients with chronic vomiting tend to consult a specialist after being symptomatic for some time, whereas patients with severe acute vomiting require immediate medical attention. Causes of nausea and vomiting are listed in Table 14-1.
ACUTE VOMITING
In the patient with acute vomiting, the following two questions must be answered immediately:
Acute Intestinal Obstruction
Vomiting may be a presenting feature of intestinal obstruction caused by an incarcerated hernia or stool impaction; the latter entity is seen in older, debilitated, or mentally retarded persons. Distal duodenal and proximal jejunal neoplasms (adenocarcinoma, lymphoma, leiomyosarcoma, carcinoid) may cause gastric outlet or intestinal obstruction that manifests as acute or chronic vomiting. Proximal intestinal obstruction may be particularly difficult to diagnose because the obstructing lesion may be overlooked or unreachable by conventional upper gastrointestinal endoscopy and yet may present without the typical picture of dilated fluid-filled loops of small bowel (air-fluid levels) on plain abdominal films (see Chapter 119).
Gastric Outlet Obstruction
In the past, peptic ulcer disease was a major cause of gastric outlet obstruction (see Chapter 52). Before the 1980s, 12% of patients with a peptic ulcer presented with gastric outlet obstruction, either as a direct consequence of a pyloric channel ulcer with associated edema and pylorospasm or, more commonly, as a result of marked deformity of the entire antroduodenal region in the setting of long-standing ulcer disease. Obstruction caused by a peptic ulcer can occur abruptly with acute vomiting or insidiously, mimicking the clinical picture of gastroparesis (see Chapter 48). As the incidence of peptic ulcer disease has declined sharply and patients are treated early and more effectively in the course of the disease, peptic ulcer disease has become a much less frequent cause of gastric outlet obstruction. Gastric volvulus is a relatively uncommon but important cause of acute vomiting; symptoms may be relapsing as a result of intermittent volvulus formation and spontaneous resolution. Paraesophageal and post-traumatic diaphragmatic hernias also may predispose to acute vomiting as a result of obstruction (see Chapter 24).15
Both acute and chronic pancreatitis, with associated inflammatory masses, necrosis, pseudocysts, or secondary infection, may lead to gastric outlet obstruction at the duodenum or, less commonly, the antrum and pylorus (see Chapters 58 and 59). Similarly, gastric, duodenal, or pancreatic malignancies (adenocarcinoma, lymphoma, cystic pancreatic neoplasms) may cause gastric outlet obstruction, sometimes manifesting as acute vomiting (see Chapters 29–32, 54, 60, and 121).
Intestinal Infarction
A diagnosis of intestinal infarction should be considered in any patient with acute vomiting.16 Intestinal infarction may occur with a paucity of physical signs but requires expeditious management. The diagnosis is more common in patients with vascular disorders and thrombotic diatheses and in older adults (see Chapter 114).
Extraintestinal Causes
Extraintestinal causes of vomiting usually do not present a challenging diagnostic problem because the primary condition is generally clinically apparent. Myocardial infarction may manifest initially as acute vomiting because of afferent connections between the heart and the emetic center. Renal colic and biliary pain similarly may manifest with intense vomiting, although the localization of the pain and other characteristic features usually make these diagnoses evident (see Chapter 65). Ovarian or testicular torsion may manifest initially with intense vomiting.
Intraperitoneal or retroperitoneal inflammatory conditions, including acute appendicitis, bowel perforation, acute pancreatitis and, in general, any cause of acute abdominal pain, may be associated with vomiting. On occasion, vomiting may be so intense (and, rarely, the only symptom) as to cause diagnostic confusion (see Chapters 10, 26, 37, and 116).
Toxins and Drugs
Cancer chemotherapy is associated with a high likelihood of nausea and vomiting, although routine administration of antiemetic agents before chemotherapy often prevents nausea and vomiting. Vomiting also can be induced by radiotherapy. Chemotherapeutic agents and combinations of agents vary in their propensity to cause nausea and vomiting (see Table 14-1).17,18
The list of drugs that can induce nausea and vomiting is lengthy (see Table 14-1). Some classes of drugs and individual agents are particularly common culprits in clinical practice, especially aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs; their emetic effect is attenuated partially by coadministration of a proton pump inhibitor; see Chapter 52), cardiovascular drugs (digitalis, antiarrhythmics), antibiotics, levodopa and its derivatives, theophylline, opiates, and azathioprine. Patients on multidrug regimens pose a special challenge in determining which drug (or drugs) is the culprit.
Metabolic Causes
Metabolic causes of vomiting include diabetic ketoacidosis, hyponatremia, and hypercalcemia. Diabetic gastroparesis associated with visceral neuropathy is usually associated with chronic relapsing nausea and vomiting (see later). The clinical onset of diabetic gastroparesis, however, may be abrupt (see Chapter 48). Addison’s disease also may manifest clinically with acute vomiting.
Infectious Causes
Vomiting may be caused by acute gastritis or gastroenteritis caused by a virus or bacterium, including bacterial toxins, such as that produced by Staphylococcus.19 During the early stages of the illness, nausea and vomiting may be the predominant or even exclusive clinical manifestation (see Chapters 51 and 107).
Neurologic Causes
Nausea and vomiting may be the sole or predominant manifestation of neurologic disorders. Meningeal inflammation is another potential cause. Nausea and vomiting may be associated with vertigo in patients with vestibular or cerebellar disorders and motion sickness. Migraine headaches may be accompanied by nausea and vomiting with little or no headache, making the diagnosis difficult. Ictal vomiting is a rare manifestation, most often associated with right temporal lobe epilepsy.20 Intracerebral lesions associated with increased intracranial pressure, interference with intracerebral fluid flow, or direct compression of the emetic center may manifest with nausea and vomiting. Projectile vomiting is a common but not invariable feature of intracerebral lesions.
Postoperative Nausea and Vomiting
Postoperative nausea and vomiting is generally a therapeutic rather than a diagnostic problem. About one third of patients who do not receive antiemetic prophylaxis will experience nausea and vomiting after surgery.21 The risk is highest with abdominal, gynecologic, strabismus, and middle ear surgery, and is three times as common in women as in men. The differential diagnosis includes complications of surgery, such as intestinal perforation, peritonitis, and electrolyte disturbances. Cardiac disease (“silent” myocardial infarction, congestive heart failure) also may manifest as nausea and vomiting in the postoperative period.
CHRONIC OR RELAPSING VOMITING
Partial Intestinal Obstruction
In contrast to acute complete intestinal obstruction, partial intestinal obstruction may be associated with relapsing vomiting over long periods of time. Abdominal pain and distention may accompany the clinical picture but may wax and wane as intestinal flow is intermittently interrupted and spontaneously restored. The clinical presentation of long-standing partial intestinal obstruction and chronic intestinal pseudo-obstruction (an intestinal motor disorder) may be similar. In fact, exclusion of occult partial intestinal obstruction is a prerequisite for the diagnosis of pseudo-obstruction (see Chapters 119 and 120). Stenotic Crohn’s disease, neoplasms of the intestine, and ischemic strictures are the main causes of partial mechanical intestinal obstruction (see Chapters 111, 114, and 121). Chronic adhesions from surgery or pelvic inflammatory disease are also potential causes of intestinal obstruction, although establishing their pathogenic role is sometimes difficult. Advanced intra-abdominal cancer is another important cause of intestinal obstruction.22 In older, debilitated, and mentally retarded individuals, constipation may lead to a picture of intestinal obstruction when the colon becomes impacted with stool and ileal outflow is partially impeded (see Chapter 18).23
Gastrointestinal Motility Disorders
Gastroparesis and chronic intestinal pseudo-obstruction may produce chronic vomiting.13,24 Recurrent vomiting, sometimes with symptom-free periods, is a major component of the clinical picture of gastroparesis. As in partial gastric outlet obstruction, abdominal pain is absent, the stomach may become markedly dilated, and the vomitus may contain partially digested food, but these findings are not constant. Some patients with neuropathic gastroparesis, as is associated with diabetes mellitus, may vomit repeatedly, even with an empty stomach; epigastric pain may occur. Nausea and vomiting may be presenting features of intestinal pseudo-obstruction, but other symptoms and signs associated with small bowel dysmotility, such as abdominal pain and distention, are usually present. The distinction between primary and secondary forms of gastroparesis and chronic intestinal pseudo-obstruction often requires specific diagnostic tests (see later; see also Chapters 48 and 120).
NAUSEA AND VOMITING DURING PREGNANCY
Nausea occurs in more than half of all normal pregnancies and frequently is associated with vomiting.25 These symptoms tend to develop early in pregnancy, peak around 9 weeks of gestation, and rarely continue beyond 22 weeks of gestation. Nausea with vomiting is more common in women with multiple gestations than with a single gestation. The origin of nausea and vomiting during pregnancy remains unclear, although hormonal and psychological influences appear to contribute.26,27 Gastric dysrhythmias have been documented by electrogastrography (see Chapter 48). The symptoms may occur even before a woman realizes that she is pregnant; therefore, a pregnancy test must be obtained in any fertile woman with a complaint of nausea and vomiting.28
Nausea and vomiting tend to occur primarily, although not exclusively, in the morning, before food is ingested. The symptoms may warrant pharmacotherapy to alleviate the discomfort they produce but must be regarded as a normal manifestation of pregnancy.29 The prognosis for mother and child is excellent. Drugs that may be used safely to treat nausea and vomiting during pregnancy, as based on published data, include vitamin B6, ondansetron and related 5-HT3 antagonists,30 metoclopramide, and doxylamine, an antihistamine with antiemetic properties available in some European countries.31 Other antiemetics also may be safe, but specific evidence in support of their use is not available. Ancillary nonpharmacologic measures may be helpful.32,33
Hyperemesis gravidarum refers to unusually severe nausea and vomiting that leads to complications (e.g., dehydration, electrolyte imbalance, malnutrition). Multiparous overweight women are at increased risk.34 The syndrome appears to represent an exaggeration of the common nausea and vomiting of pregnancy, and hormonal and psychological factors also are thought to contribute to the pathogenesis. Hyperthyroidism has been reported in some affected persons. The manifestations generally develop in, and may continue beyond, the first trimester. Fluid and electrolyte replacement therapy may be required, together with antiemetic drugs. Glucocorticoids, erythromycin, and powdered ginger root have been reported to be helpful in patients with hyperemesis gravidarum. Behavioral modification and other psychotherapeutic techniques have been reported to be helpful as well. Occasionally, enteral or parenteral nutrition may need to be prescribed to prevent severe malnutrition.35 Patients with hyperemesis gravidarum, however, do not have an increased risk of toxemia of pregnancy or spontaneous abortion, and the condition does not lead to an increased rate of adverse fetal consequences.36
Severe vomiting may accompany acute fatty liver of pregnancy, a serious but uncommon condition that occurs in the third trimester of pregnancy (in contrast to hyperemesis gravidarum).37 Headache, general malaise, and manifestations of preeclampsia (hypertension, edema, proteinuria) are common accompanying features. Progression to hepatic failure and disseminated intravascular coagulation may occur rapidly. Therefore, measurement of serum liver biochemical test levels is advisable in women in whom severe nausea and vomiting develop late in pregnancy. The detection of elevated serum aminotransferase levels may warrant a liver biopsy, which characteristically discloses microvesicular steatosis. The differential diagnosis of acute fatty liver of pregnancy includes fulminant viral hepatitis and drug-induced hepatitis. If the diagnosis of acute fatty liver is confirmed, the pregnancy should be terminated immediately to prevent maternal and fetal death (see Chapter 38).
