CAUSES AND SYMPTOMS

Nausea is defined as a subjectively unpleasant sensation associated with awareness of the urge to vomit. It is usually felt in the back of the throat and epigastrium and is accompanied by the loss of gastric tone, duodenal contractions, and reflux of the intestinal contents into the stomach. Retching is defined as labored, spasmodic, rhythmic contractions of the respiratory muscles (including the diaphragm, chest wall, and abdominal wall muscles) without the expulsion of gastric contents. Vomiting, or emesis, is the forceful expulsion of gastric contents from the mouth and is brought about by the powerful sustained contraction of the abdominal muscles, the descent of the diaphragm, and the opening of the gastric cardia (the cardiac orifice of the stomach).

Nausea and vomiting are important defense mechanisms against the ingestion of toxins. The act of emesis involves a sequence of events that can be divided into three phases: preejection, ejection, and postejection. The preejection phase includes the symptoms of nausea, along with salivation, swallowing, pallor, and tachycardia (an abnormally fast heartbeat). The ejection phase comprises retching and vomiting. Retching is characterized by rhythmic, synchronous, inspiratory movements of the diaphragm, abdominal, and external intercostal muscles, while the mouth and the glottis are kept closed. As the antral (cavity) portion of the stomach contracts, the proximal (nearest the center) portion relaxes and the gastric contents oscillate between the stomach and the esophagus. During retching, the hiatal portion of the diaphragm does not relax, and intra-abdominal pressure increases are associated with a decrease in intrathoracic pressure.

In contrast, relaxation of the hiatal portion of the diaphragm (near the esophagus) permits a transfer of intra-abdominal pressure to the thorax during the act of vomiting. Contraction of the muscles of the anterior abdominal wall, relaxation of the esophageal sphincter, an increase in intrathoracic and intragastric pressure, reverse peristalsis (movement of the contents of the alimentary canal), and an open glottis and mouth result in the expulsion of gastric contents. The postejection phase consists of autonomic and visceral responses that return the body to a quiescent phase, with or without residual nausea.

The complex act of vomiting, involving coordination of the respiratory, gastrointestinal, and abdominal musculature, is controlled by what researchers label the emetic center. This center in the brain stem has access to the motor pathways responsible for the visceral and somatic output involved in vomiting, and stimuli from several areas within the central nervous system can affect this center. These include afferent (inward-directed) nerves from the pharynx and gastrointestinal tract, as well as afferents from the higher cortical centers (including the visual center) and the chemoreceptor trigger zone (CTZ) in the area postrema (a highly vascularized area of the brain stem). The CTZ can be activated by chemical stimuli received through the blood or the cerebrospinal fluid. Direct electrical stimulation of the CTZ, however, does not result in emesis.

Clinical assessment of nausea and vomiting usually focuses on the occurrence of vomiting, that is, the frequency and number of episodes. Nausea, however, is a subjective phenomenon unobservable by another. Few data collection instruments that measure separately the patient’s experience of nausea and vomiting and his or her symptom distress have been reported in the literature. In fact, the Rhodes Index of Nausea and Vomiting (INV) Form 2 is the only available tool that measures the individual components of nausea, vomiting, and retching. This index measures the patient’s perception of the duration, frequency, and distress from nausea. The frequency, amount, and distress from vomiting; and the frequency, amount, and distress from retching (dry heaves). The INV score provides a measurement of the total symptom experience of the patient.

While the causes of nausea and vomiting are numerous-they include gastrointestinal diseases, infections, intracranial disease, toxins, radiation sickness, psychological trauma, migraines, and circulatory syncope-three of the most common causes are motion sickness (air, sea, land, or space), pregnancy, and anesthesia administered during operative procedures.

The sequence of symptoms and signs that constitute motion sickness is fairly characteristic. Premonitory symptoms often include yawning or sighing, lethargy, somnolence, and a loss of enthusiasm and concern for the task at hand. Increasing malaise is directed toward the epigastrium, a sensation best described as “stomach awareness,” which progresses to nausea. Diversion of the blood flow from the skin toward the muscles results in pallor. A feeling of warmth and a desire for cool air is often accompanied by sweating. Frontal headache and a sensation of disorientation, dizziness, or light-headedness may also occur. As symptoms progress, vomiting occurs early in the sequence of symptoms for some; in others, malaise is severe and prolonged and vomiting is delayed. After vomiting, there is often a temporary improvement in well-being; however, with continued provocative motion, symptoms build again and vomiting recurs. The symptoms may last for minutes, hours, or even days.

TREATMENT AND THERAPY

Since the generation of sensory conflict underlies all motion environments that give rise to motion sickness, practical measures that reduce conflict are likely to reduce motion sickness incidence. Motion sickness can be minimized if the subject has the widest possible view of a visual reference in which the earth is stable. Passengers aboard ships are less likely to be seasick if they remain on deck at midship, where vertical motion is minimized, and view the horizon. In a car or bus, individuals should be in a position to see the road directly ahead, since the movement of this visual scene will correlate with the changes in the direction of the vehicle. While head movements in a rotating environment are known to precipitate motion sickness, there is no clear experimental evidence that they elicit nausea in mild linear oscillation. Thus, some nonpharmacologic remedies for motion sickness are restricting head movements, lying in a supine position, or closing the eyes. In addition, the use of acupressure wrist bands has proven effective in combating motion sickness.

Pharmacologically, the drug hyoscine hydrobromide (also called hyoscine or scopolamine) emerged as a valuable prophylactic drug following extensive research during World War II into the problems of motion sickness in troops transported in aircraft, ships, and landing craft. It remains one of the most effective drugs for short-duration exposures to provocative motion. Doses in excess of 0.6 milligram, however, are very likely to lead to drowsiness, and there is much experimental evidence that hyoscine impairs short-term memory. Hyoscine can be absorbed transdermally, and in order to extend the duration of action, a controlled-release patch was developed to deliver 1.2 milligrams on application and 0.01 milligram hourly thereafter. There is substantial evidence of its sustained effectiveness, but, perhaps as a result of variable absorption rates, there is an increased risk of blurred vision after more than twenty-four hours of use.

Amphetamines, ephedrine, and a number of antihistamines (such as dimenhydrinate) have been found to be clinically useful in motion sickness. Following oral administration, these drugs are generally slower than hyoscine in reaching their peak efficacy, but they have a longer duration of action.

For most susceptible subjects whose exposure to motion sickness-inducing stimuli is infrequent, prophylactic drugs offer the only useful treatment. When exposure to provocative stimuli is more frequent, as for example in professional aircraft pilots, spontaneous adaption occurs during training and an initially high incidence of motion sickness decreases with time.

In medical conditions in which the cause is relatively unknown, it is usual to find a wide variety of suggested therapies; nausea and vomiting during pregnancy and hyperemesis gravidarum (the serious, persistent form of vomiting in pregnancy) are no exception. Prior to 1968, treatments numbered approximately thirty. In subsequent years, however, suggested therapy has been mainly drugs of the antiemetic variety. Yet since the thalidomide tragedy (in which severe deformities occurred in the children of women who took this drug), there has been a reluctance to use drugs of any kind during early pregnancy. Probably the only value of drug therapy is at the stage of morning sickness, when antiemetics or mild sedatives may counter the feeling of nausea and prevent women from experiencing excessive vomiting and entering the vicious cycle of dehydration, starvation, and electrolyte imbalance. Once the patient has reached the stage of hyperemesis gravidarum, much more basic therapy is required, and the regimen calls for correction of dehydration, carbohydrate deficiency, and ionic deficiencies. This program is best managed by intravenous therapy, with or without the addition of vitamin supplements and sedative agents.

Nonpharmacologic self-care actions for morning sickness fall into the three broad categories of manipulating diet, adjusting behavior, and seeking emotional support. Some of the most effective self-care actions are getting rest, eating several small meals rather than three large ones, avoiding bad smells, avoiding greasy or fried foods, avoiding cooking, and receiving extra attention and support.

In terms of postoperative nausea and vomiting caused by anesthesia, it has been found that routine antiemetic prophylaxis of patients undergoing elective surgical procedures is not indicated, since fewer than 30 percent of patients experience postoperative nausea and vomiting. Of those who develop these symptoms, many have transient nausea or only one or two bouts of emesis and do not require antiemetic therapy. In addition, commonly used antiemetic drugs can produce significant side effects, such as sedation. Nevertheless, antiemetic prophylaxis may be justified in those patients who are at greater risk for developing postoperative nausea and/or vomiting. Such therapy is often given to patients with a history of motion sickness or to those undergoing gynecologic procedures, inner-ear procedures, oral surgery (in which the jaws are occluded by wires, causing a high risk of breathing in vomitus), and operations on the ear or eye and plastic surgery operations (in order to avoid disruption of delicate surgical work).

Many different antiemetic drugs are available for the treatment of postoperative nausea and vomiting. Researchers have found it difficult to interpret the results of antiemetic drug studies because the severity of postoperative vomiting and the response to therapeutic agents can be influenced by many variables in addition to the antiemetic drug being studied. Even with the use of the same drugs in a homogeneous population undergoing the same procedure, the severity of emesis varies from individual to individual.

Because antiemetic drugs have differing sites of action, better results can be obtained by using a multidrug approach. If a combination of drugs with a similar site of action is used, however, the incidence of side effects may be increased. There are few data regarding combination antiemetic prophylaxis or therapy for postoperative nausea and emesis. Drug combinations have been avoided in postsurgical patients because of concerns about additive central nervous system toxicity. An exception is the combination of low-dose droperidol and metoclopramide, which appears to be more effective than droperidol alone for outpatient gynecologic procedures.

Although a full stomach is best avoided before any operative procedure, with situations such as emergencies, in which danger from vomiting is acute, a rapid sequence of administering anesthesia (induction) and clearing the air passage (intubation) remains the method of choice to avoid nausea and vomiting in patients with a full stomach. After the procedure, it is recommended that the patient minimize movement in order to avoid nausea and vomiting. Also, it has been found that avoiding eating solid food for at least eight hours after a surgical procedure is helpful in preventing postoperative nausea and vomiting.

PERSPECTIVE AND PROSPECTS

Though it has existed for as long as there have been human beings, the symptom of nausea has never received much attention in health care practice or research. In fact, until the early 1970s the sensation of nausea was frequently dismissed as merely a passing phenomenon. The rationale for this dismissal was most likely the understanding that nausea is self-limiting (it always passes with time), is never life-threatening in itself, is probably psychogenic in nature (at least to some degree), and, being subjective, is very difficult to measure. In addition, in the past the most predictable nausea was related to pregnancy, which may also explain the lack of attention given to nausea.

Until the late 1980s, there was still little research being conducted on the nausea associated with pregnancy, although it is a common symptom. The historical lack of interest in nausea and vomiting during pregnancy may be traced to the fact that, since the symptoms generally persist only through the first trimester, health care professionals have viewed the problem as relatively insignificant. As more pregnant women work outside the home in demanding positions, however, these women have exhibited less tolerance for illness. Demands upon the health care industry and upon personal physicians for more research and effective treatment have become more widespread.

While it is surprising that nausea has received scant attention in the history of clinical research, it is even more astonishing that vomiting, an observable behavior, has received so little attention as well. Although vomiting is a primitive neurologic process that has remained almost unchanged in the evolution of animals, the mechanisms that regulate the behavior remain virtually unknown.

One reason for the paucity of information on the subject of nausea in particular stems from the lack of a reliable animal model. This fact has hampered research aimed at establishing the etiological basis for nausea and its relationship to vomiting. While some species of lower animals, for example rats, cannot vomit, it is not known whether rats experience the phenomenon of nausea. Thus no effective means of measuring nausea in lower animals has been devised.

Since the early 1970s, there has been a noticeable increase in research on nausea as a drug side effect because it was so frequently seen in cancer chemotherapy clinical trials sponsored by the National Cancer Institute and the American Cancer Society. As more powerful chemotherapy agents and aggressive combinations were clinically investigated, patients began to experience severe, potentially life-threatening nausea and vomiting. Older drugs such as antihistamines, phenothiazines, and benzodiazepines are still used for their antiemetic characteristics, but they are augmented by newer agents such as benzamides, neurokinin-1-receptor antagonists, and serotonin antagonists.

Aside from the pharmacological investigations of new drugs and drug combinations in the treatment of nausea and vomiting, an interesting branch of scientific investigation has begun the process of exploring alternative ways of managing these symptoms. Behavioral interventions, such as progressive muscle relaxation, biofeedback, imagery, or music therapy, have been used to alleviate postchemotherapy anxiety. These methods may also be used to treat other patients suffering from the symptoms of nausea and vomiting, such as pregnant women.

Another noninvasive, nonpharmacologic measure that has been considered in the relief of nausea and vomiting is transcutaneous electrical nerve stimulation (TENS). Several research studies indicate that TENS may be useful in alleviating chemotherapy-related nausea and vomiting, including delayed nausea and vomiting. Side effects from using TENS units are negligible, and with further study they may prove to be an acceptable, helpful relief measure.

See also Acid reflux disease; Anesthesia; Appetite loss; Botulism; Bulimia; Chemotherapy; Colitis; Crohn’s disease; Diaphragm; Digestion; Eating disorders; Esophagus; Food biochemistry; Food poisoning; Gastroenteritis; Gastroenterology; Gastroenterology, pediatric; Gastrointestinal disorders; Gastrointestinal system; Heartburn; Indigestion; Influenza; Lactose intolerance; Motion sickness; Multiple chemical sensitivity syndrome; Noroviruses; Poisoning; Poisonous plants; Pregnancy and gestation; Radiation sickness; Rotavirus; Salmonella infection; Stomach, intestinal, and pancreatic cancers; Ulcer surgery; Ulcers; Vagotomy.