Chronic Nausea

Medications and toxic etiologies

Cancer chemotherapy

Aspirin

Nonsteroidal anti-inflammatory drugs

Auranofin

Antigout drugs

Digoxin

Antiarrhythmics

Antihypertensives

β-Blockers

Calcium channel antagonists

Diuretics

Oral antidiabetics

Oral contraceptives

Erythromycin

Tetracycline

Sulfonamides

Antituberculous drugs

Acyclovir

Sulfasalazine

Azathioprine

Nicotine

CNS-active drugs

Narcotics

Anti-Parkinsonian drugs

Anticonvulsants

Antiasthmatics

Theophylline

Radiation therapy

Ethanol abuse

Hypervitaminosis

Infectious causes

Gastroenteritis (Viral or Bacterial)

Otitis media

Disorders of the gut and peritoneum

Gastric outlet obstruction

Small bowel obstruction

Gastroparesis

Chronic intestinal pseudo-obstruction

Nonulcer dyspepsia

Irritable bowel syndrome

Pancreatic adenocarcinoma

Inflammatory intraperitoneal disease

Peptic ulcer disease

Cholecystitis

Pancreatitis

Hepatitis

Crohn’s disease

Mesenteric ischemia

Retroperitoneal fibrosis

Mucosal metastases

CNS causes

Migraine

Malignancy

Hemorrhage

Infarction

Abscess

Meningitis

Congenital malformation

Hydrocephalus

Pseudotumor cerebri

Seizure disorders

Demyelinating disorders

Emotional responses

Psychiatric disease

Psychogenic vomiting

Anxiety disorders

Depression

Pain

Anorexia nervosa

Bulimia nervosa

Labyrinthine disorders

Motion sickness

Labyrinthitis

Tumors

Meniere’s disease

Fluorescein angiography

Endocrinologic and metabolic causes

Pregnancy

Uremia

Diabetic ketoacidosis

Hyperparathyroidism

Hypoparathyroidism

Hyperthyroidism

Addison’s disease

Acute intermittent porphyria

Postoperative nausea and vomiting

Cyclic vomiting syndrome

Miscellaneous causes

Myocardial infarction

Congestive heart failure

Radiofrequency ablation

Starvation

Adapted from Douglas A, Drossman M., Ed. (2006). Rome III: The functional gastrointestinal disorders. McLean, Virginia: Degnon Associates

Nausea is considered chronic when it persists for >1 month. Chronic idiopathic nausea (CIN) has been recently defined as bothersome nausea occurring at least several times per week that is not associated with vomiting or an obvious metabolic or gastrointestinal disorder (see Table 7.2). For consistency purposes in this chapter, we will use the term CIN to refer to chronic nausea without an identifiable cause. When nausea is associated with vomiting, other diagnoses such as gastroparesis or cyclic vomiting syndrome need to be considered. It is not clear whether patients with CIN represent a distinct syndrome, a heterogeneous collection of different unidentified etiologies, or part of a spectrum of gastric sensorimotor dysfunction.

Table 7.2

Diagnostic criteria for chronic idiopathic nausea (CIN)

Must include all of the following
Bothersome nausea occurring at least several times per week
Not usually associated with vomiting
Absence of abnormalities at upper endoscopy or metabolic disease that explains the nausea
Criteria need to be fulfilled for past 3 months, with symptom onset at least 6 months before diagnosis

Adapted from Douglas A. Drossman, M., Ed. (2006). Rome III: The functional gastrointestinal disorders. McLean, Virginia: Degnon Associates

Epidemiology

Given the ubiquitous nature of chronic nausea, the exact incidence, prevalence, and natural history are unknown. In one study, 8 % of otherwise normal subjects reported nausea. Decreased awareness contributes to gaps in knowledge regarding demographics, age, and gender distribution of CIN. In a recent study, no differences in patient demographics, lifestyles, or anthropometric characteristics were appreciated in patients with chronic unexplained nausea and vomiting (CUNV) compared to their counterparts with gastroparesis. Similarities were also found for severity, pattern, and nature of symptoms. Forty-five percent of patients with CUNV (and 26 % of patients with gastroparesis) met Rome III criteria for the diagnosis of CIN. In addition, there appeared to be stability in the disorder, as little change in diagnosis was noted over the course of a year. At present, there are no published quality of life studies for CIN; however, studies of other disorders associated with nausea have demonstrated decreased activity, increased fatigue, sleep disturbance, and irritability. Furthermore, increased nursing care and health-care expenses and lost productivity have been demonstrated in patients with chronic nausea.

Pathophysiology

The exact mechanisms underlying CIN remain unclear but are likely to be multiple given the variety of its causes. Indeed, CIN may arise due to central or peripheral abnormalities or a combination of both. To better approach its evaluation and management, it is helpful to have a basic understanding of the functional anatomy and physiology involved in the pathogenesis of nausea and vomiting (see Fig. 7.1). Motor and sensory function of the gut is controlled by the interaction among the extrinsic nervous system (parasympathetic and sympathetic), central nervous system, and gut smooth muscle cells. The area postrema, located on the floor of the fourth ventricle, is sensitive to neurotransmitters, peptides, drugs, and toxins. The nucleus tractus solitarius (NTS) in the medulla serves a central role, receiving input from visceral afferents (via the vagus nerve) and humoral factors (via the area postrema). Neurons from the NTS project into paraventricular nuclei of the hypothalamus and limbic and cortical regions, impacting electromechanical events, sensation, and emotion. Afferent neural pathways also arise from non-digestive locations such as the pharynx, heart, bile ducts, and vestibular apparatus. Aberrant afferent signaling of vagal or splanchnic nerves, altered neuronal communication, environmental triggers, gut inflammation, alterations in the gut microbiome, visceral hypersensitivity, and numerous medications can impact this intricate network and lead to the generation of nausea and vomiting and the emotional experience of those symptoms.