Nausea and vomiting

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Vishnu Vardhan Serla M.B.B.S. [2]

Nausea (Latin: Nausea, Greek: Template:Polytonic, “sea-sickness“) is an ‘unpleasant painless subjective feeling that one will imminently vomit’. Nausea is often indicative of an underlying condition elsewhere in the body. Travel sickness, which is due to confusion between perceived movement and actual movement, is an example. The sense of equilibrium lies in the ear and works together with eyesight. When these two don’t “agree” to what extent the body is actually moving the symptom is presented as nausea even though the stomach itself has nothing to do with the situation. Nausea is also an adverse effect of many drugs. Nausea may also be an effect of a large intake of sugary foods. In medicine, nausea can be a problem during some chemotherapy regimens and following general anesthesia. Nausea is also a common symptom of pregnancy. Mild nausea experienced during pregnancy can be normal, and should not be considered an immediate cause for alarm. Vomiting (also throwing up or emesis) is the forceful expulsion of the contents of one’s stomach through the mouth and sometimes the nose resulting from contractions of gut and thoracoabdominal wall musculature. Vomiting may result from many causes, ranging from gastritis or poisoning to brain tumors, or elevated intracranial pressure (ICP). The feeling that one is about to vomit is called nausea. It usually precedes but does not always lead to vomiting. Antiemetics are sometimes necessary to suppress nausea and vomiting, and in severe cases where dehydration develops, intravenous fluid may need to be administered to replace fluid volume. The medical branch investigating vomiting, emetics, and antiemetics is called emetology.

The medical term ‘nausea’ is derived from the classical Greek terms ναυτια and ναυσια, which designated the signs and symptoms of seasickness. The descriptions of the development of seasickness in monographs from the latter half of the 19th and early 20th centuries provide a context for understanding the evolution of the demarcation of symptom clusters associated with the original term ‘nausea”. The term ‘nausea’ has been used to denote both a disorder (diagnosis of seasickness) and a symptom (or symptom cluster) associated with other disorders. This pattern also appeared for terms for vertigo, such as ‘vertigine’, dinos, scotomatikos and skotodininos. Hence, one must ask whether the term nausea denoted seasickness explicitly or whether it denoted the appearance of a ‘cluster of signs and symptoms of seasickness’ as a component of other primary disorders.

Nausea and vomiting can be classified into acute or chronic

Acute vomiting which typically lasts from a few hours to few days is the most common presentation in the emergency department. Acute vomiting needs an extensive workup to exclude life-threatening conditions like bowel obstruction, mesenteric ischemia, acute pancreatitis, and possibly myocardial infarction.

Chronic vomiting which lasts from weeks to months is initially evaluated in an outpatient setting.

It is understood that nausea and vomiting are complex and encompass psychological states, the central nervous system, the autonomic nervous system, gastric dysrhythmias, and the endocrine system. Each individual has a threshold for nausea that changes minute by minute. At any given moment, the threshold depends on the interaction of certain inherent factors of the individual with the more changeable psychological states of anxiety, anticipation, expectation, and adaptation. Stimuli giving rise to nausea and vomiting originate from visceral, vestibular, and chemoreceptor trigger zone inputs which are mediated by serotonin/dopamine, histamine/acetylcholine, and serotonin/dopamine, respectively.

Life threatening causes of nausea and vomiting include acute coronary syndrome, anaphylaxis, and heart failure. Other common causes of nausea and vomiting are food allergies, food poisoning, gastroenteritis, and gastroesophageal reflux.

ECG is done to rule out an inferior MI or arrhythmia.

Template:WH Template:WS

The medical term ‘nausea’ is derived from the classical Greek terms ναυτια and ναυσια, which designated the signs and symptoms of seasickness. The descriptions of the development of seasickness in monographs from the latter half of the 19th and early 20th centuries provide a context for understanding the evolution of the demarcation of symptom clusters associated with the original term ‘nausea”. The term ‘nausea’ has been used to denote both a disorder (diagnosis of seasickness) and a symptom (or symptom cluster) associated with other disorders. This pattern also appeared for terms for vertigo, such as ‘vertigine’, dinos, scotomatikos and skotodininos. Hence, one must ask whether the term nausea denoted seasickness explicitly or whether it denoted the appearance of a ‘cluster of signs and symptoms of seasickness’ as a component of other primary disorders.

• In 1830, Marshall Hall was the first to discover the reflex theory and the association between nervous mechanisms and the development of nausea and vomiting
• In 1865, Gianuzzi speculated on the possible existence of a regulating center of the emetic reflex in the brain .
• In 1881, Thumas, pointed to an area on the floor of the fourth ventricle in animals which, if damaged, made apomorphine’s emetic action impossible
• In 1889, Clarke described a case of an 8-year-old boy with uncontrollable hiccups and vomiting. The outcome of the case was the death of the patient, and a tumorin the middle of the fourth ventricle was found at the postmortem examination, leaving the author curious about the absence of manifestations other thanvomiting.
• Retzius produced the most important work on the macroscopic anatomy of the encephalon and he described a structure on thefloor of the fourth ventricle, adjacent to the nucleus of the solitary tract, named it as the area postrema (AP), in Latin meaning, the hindmost area. ^[1]

• In 1906, Wilson in a descriptive work on the human bulb, mentioned the AP as being richly vascularized, as well as detailing histological aspects and pointing out the high density of neurons in area postrema.
• In 1924, Wislocki and Putnam speculated about the postrema region as an area of diffusion between blood andcerebrospinal fluid, after observing dye granules deposited in the perivascular space, especially amongependymal cells.
• In 1942, Dow and Berglund, in an article on the vascular patterns ofmultiple sclerosis lesions, also described the case of a 38-year-old woman with some of the symptoms involving incessantvomiting, and showing postmortem plaques on the pons andmedulla oblongata.
• In 1951, Borison and Brizzee while studying the medulla oblongata of cats, identified the AP as a chemoreceptor zone sensitive to the vomiting reflex, integrating the hypothesis of the researchers of late 19 th century, and in 1974, Borison published a review article condensing the advances made by countless other researchers since the early 1950s, concluding that the AP acted primarily as a chemoreceptor trigger zone to the emetic response.
• In 1979, McFarling and Susac13, reported on patients with multiple sclerosis with intractablehiccups, a symptom not reported within their clinical manifestations, relating to probable disinhibition of the hiccup reflex by the multiple sclerosisplaques.
• In 1986, Leslie published a meticulous comparative study between several animal species and humans, detailing the microscopic ultrastructure of the AP, and demonstrating that it was an area of permeability of the blood-brain barrier serving as a zone of fine control of autonomic and neurochemical information.
• In the 2000s, a profusion of papers correlated area postrema syndrome cases to neuromyelitis optica spectrum disorders, with AP in a central role as the target of anti-aquaporin 4 antibodies.^[2]

Template:WH Template:WS

Nausea and vomiting can be classified into acute or chronic

Acute vomiting which typically lasts from a few hours to few days is the most common presentation in the emergency department. Acute vomiting needs an extensive workup to exclude life-threatening conditions like bowel obstruction, mesenteric ischemia, acute pancreatitis, and possibly myocardial infarction.

Chronic vomiting which lasts from weeks to months is initially evaluated in an outpatient setting. Cyclical vomiting syndrome is the most common cause of chronic nausea and vomiting.

Based on the duration of symptoms it can be classified as

Acute nausea and vomiting can be caused by food allergies, viral gastroenteritis etc

It typically lasts from few hours to few days

Chronic nausea, vomiting can last from weeks to months. ^[1]

Chemotherapy is one of the most common cause of nausea and vomiting, and

Acute Chemotherapy induced nausea and vomiting (CINV) occur with in 24 hours of chemotherapy administration

Delayed CINV can occur at least 24 hours after chemotherapy and peaks between 48-72 hours ^[2]

Nausea and vomiting that is triggered by stimuli associated withchemotherapy and can be due to prior poor control of nausea and vomiting during chemotherapy ^{[3] [4]}

CINV that occurs despite maximum antiemetics

CINV that occurs within 5 days of chemotherapy despite of antiemetics. May require rescue therapy

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Vishnu Vardhan Serla M.B.B.S. [2]

The physiology of nausea and vomiting encompass psychological states, the central nervous system, the autonomic nervous system, gastric dysrhythmias, and the endocrine system. Each individual has a threshold for nausea that changes minute by minute. Stimuli giving rise to nausea and vomiting originate from visceral, vestibular, and chemoreceptor trigger zone inputs which are mediated by serotonin/dopamine, histamine/acetylcholine, and serotonin/dopamine, respectively.

The physiology of nausea and vomiting encompass psychological states, the central nervous system, the autonomic nervous system, gastric dysrhythmias, and the endocrine system. Each individual has a threshold for nausea that changes minute by minute. At any given moment, the threshold depends on the interaction of certain inherent factors of the individual with the more changeable psychological states of anxiety, anticipation, expectation, and adaptation. Stimuli giving rise to nausea and vomiting originate from visceral, vestibular, and chemoreceptor trigger zone inputs which are mediated by serotonin/dopamine, histamine/acetylcholine, and serotonin/dopamine, respectively. These relationships between these areas are the basis of the pharmacotherapy.^[1]

The vomiting center lies in the medulla oblongata and comprises the reticular formation and the nucleus of the tractus solitarius.

When there is stimulus, it activates motor pathways descend from this center and trigger vomiting.

These efferent pathways travel within the 5th, 7th, 9th, 10th, and 12th cranial nerves to the upper gastrointestinal tract, within vagal and sympathetic nerves to the lower tract, and within spinal nerves to the diaphragm and abdominal muscles.

The vomiting center can be activated directly by irritants or indirectly following input from gastrointestinal tract, cerebral cortex and thalamus, vestibular region, and chemoreceptor trigger zone (CRTZ). ^[2]

The CRTZ is closest in proximity, lying between the medulla and the floor of the fourth ventricle, and it is not protected by the blood-brain barrier.

The chemoreceptor trigger zone at the base of the fourth ventricle has numerous dopamine D₂ receptors, serotonin 5-HT₃ receptors, opioid receptors, acetylcholine receptors, and receptors for substance P. Stimulation of different receptors are involved in different pathways leading to emesis, in the final common pathway substance P appears to be involved.^[3]

The vestibular system which sends information to the brain via cranial nerve VIII (vestibulocochlear nerve). It plays a major role in motion sickness and is rich in muscarinic receptors and histamine H₁ receptors.

Cranial nerve X (vagus nerve), which is activated when the pharynx is irritated, leading to a gag reflex.

Vagal and enteric nervous system inputs that transmit information regarding the state of the gastrointestinal system. Irritation of the GI mucosa by chemotherapy, radiation, distention or acute infectious gastroenteritis activates the 5-HT₃ receptors of these inputs.

The CNS mediates vomiting arising from psychiatric disorders and stress.

The act of vomiting consists of 3 steps:^[4]

• ”’Nausea”’ is an unpleasant and difficult to describe psychic experience. Physiologically,nausea is typically associated with decreased gastric motility and increased tone in the small intestine. Also, there is often reverse peristalsis in the proximal small intestine.
• ”’Retching”’ (“dry heaves”) refers to spasmodic respiratory movements conducted with a closedglottis. While this is occurring, the antrum of the stomach contracts and the fundus and cardia relax.
• ”’Emesis”’ is when gastric and often small intestinal contents are propelled up to and out of the mouth.

and is caused by three types of outputs initiated by themedulla:Motor, parasympathetic nervous system (PNS) and sympathetic nervous system (SNS).

• Increased salivation to protect the enamel of teeth from stomach acids (excessive vomiting leads to caries). This is part of the PNS output.
• Reverse peristalsis, starting from the middle of the small intestine, sweeping up the contents of the digestive tract into the stomach, through the relaxed pyloric sphincter.
• A lowering of intrathoracic pressure (by inspiration against a closed glottis), coupled with an increase in abdominal pressure as the abdominal muscles contract, propels stomach contents into the esophagus without involvement of the reverse peristalsis. The lower esophageal sphincter relaxes.
• Vomiting also initiates a SNS response causing both sweating and increased heart rate.

The neurotransmitters that regulate vomiting are poorly understood, but inhibitors of dopamine, histamine and serotonin are all used to suppress vomiting, suggesting that these play a role in the initiation or maintenance of a vomiting cycle. Vasopressin and neurokinin may also be involved.

As the stomach secretes acid, vomit contains a high concentration of hydronium ions and is thus strongly acidic. Recent food intake will be reflected in the gastric vomit.

The content of the vomitus (vomit) may be of medical interest.

Fresh blood in the vomit is called hematemesis (“blood vomiting”).

Old blood bears resemblance to coffee grounds (as the iron in the blood is oxidized), and is termed “coffee ground vomiting”.

Bile can enter the vomit during subsequent heaves due to duodenal contraction if the vomiting is severe.

Fecal vomiting is often a consequence of intestinal obstruction, and is treated as a warning sign of this potentially serious problem (“signum mali ominis”); such vomiting is sometimes called “miserere”. If food has recently been consumed, then partly digested food may show up in the vomit.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vishnu Vardhan Serla M.B.B.S. [2] Kiran Singh, M.D. [3]

Life threatening causes of nausea and vomiting include acute coronary syndrome, anaphylaxis, and heart failure. Other common causes of nausea and vomiting are food allergies, food poisoning, gastroenteritis, and gastroesophageal reflux.

• Acute Coronary Syndromes^[1]
• Anaphylaxis
• Angina pectoris
• Heart failure

• Chemotherapy^[2]

• Food allergies
• Food poisoning
• Migraine
• Morning sickness
• Rotavirus
• Viral gastroenteritis

Template:WH Template:WS

Differential diagnosis of vomiting may be a result of a range of causes, including GI (obstructive and inflammatory) etiologies, CNS disease, pulmonary problems, renal disease, endocrine/metabolic disorders, drugs (either as side effects or in over dosages), psychiatric disorders, strep throat, pregnancy or stress.^[1]

The causes of nausea and vomiting can be differentiated as GI and Non GI causes:

Esophagitis

Gastritis

Hepatitis

Enteritis

Pancreatitis

Esophageal malignancies

Gastric outlet obstruction , may be due tomalignancy

Pyloric stenosis

Strangulated hernias

Small bowel obstruction due toadhesion,intussusception orvolvulus

Diverticulitis

Esophageal dysmotility

Achalasia Cardia

Gastroparesis due to autonomic dysfunction

Ileus–Hypokalemia

Ogilvie Syndrome

Migraine

Pseudotumor cerebri^[2]

Meningitis

Space occupying lesions

Labrynthitis

Acidosis- DKA, Lactic acidosis

Alcoholism

Chemotherapy^[3]

Opiate therapy

Antibiotics

Pregnancy

Sea sickness

Template:WH Template:WS

• In population studies, at least one episode of nausea was reported in more than 50% of adults, and one episode of vomiting in more than 30% of adults within the preceding 12 months, with nausea seen more in women than men. ^{[1] [2]}
• A significant psychological and economic impact of nausea and vomiting is seen with an estimated economic burden of $4-16 billion on US economy. ^[2]
• Only 25% of people with acute symptoms of nausea and vomiting seek medical help. ^[3]

• Incidence of nausea and vomiting varies with the underlying cause.
• Nausea and vomiting of pregnancy effects 70% to 80% of all pregnant women. ^[4]
• Approximately 40% of patients experience nausea and 15%-25% patients experience vomiting with opioid use. ^[5]
• Incidence of postoperative nausea and vomiting varies from 8%-92%. ^[5]

• In population studies, at least one episode of nausea was reported in more than 50% of adults, and one episode of vomiting in more than 30% of adults within the preceding 12 months, with nausea seen more in women than men. ^[1]
• Only 25% of people with acute symptoms of nausea and vomiting seek medical help. ^[3]
• The exact prevalence of idiopathic nausea and vomiting is not known. ^[2]

• In a study of patients with nausea and vomiting in Australia, between April 2000 and March 2006. vomiting was more often presented in children aged <15 years and decreased steadily with age. ^[6]
• Nausea was more often presented in age 15-25 years and less frequently in all other age groups.

• White/African-Americans experience less nausea than Asian/Asian-American subjects. ^{[7] [8]}

• Prevalence of nausea is more in females than males. ^[9]
• Nausea and vomiting associated with gastroenteritis is significantly more in males than in females. ^[6]
• Undiagnosed cases of nausea and vomiting are more commonly seen in females than males. ^[6]

• In a study, nausea and vomiting was reported more commonly by less educated pregnant females (hence less common in developed countries due to high literacy rate) ^[10]

• Developing countries may have more cases of nausea and vomiting due to low literacy and low socioeconomic status according to a study that involved cases of nausea and vomiting in pregnant females. ^[10]

Template:WH Template:WS

• Risk factors for nausea and vomiting vary with underlying cause.

• Well established risk factors for postoperative nausea and vomiting include: ^[1]
  • female gender post puberty
  • nonsmoking status
  • history of postoperative nausea and vomiting
  • history of motion sickness
  • childhood after infancy and younger adulthood
  • increasing duration of surgery
  • use of volatile anesthetics, nitrous oxide, large-dose neostigmine, or intraoperative or postoperative opioids
• Possible risk factors for postoperative nausea and vomiting include: ^[1]
  • history of migraine
  • history of postoperative nausea and vomiting or motion sickness in a child’s parent or sibling
  • intense preoperative anxiety
  • certain ethnicities or surgery types
  • decreased perioperative fluids
  • crystalloid versus colloid administration
  • increasing duration of anesthesia
  • general versus regional anesthesia or sedation
  • balanced versus total IV anesthesia
  • use of longer-acting versus shorter-acting opioids

• Risk factors for nausea and vomiting in pregnancy include: ^[2]
  • increased number of prior miscarriages
  • increased gravidity
  • risk decreased with increasing age
  • twin births
  • Increased risk of nausea and vomiting after first trimester is seen in women who are less well educated, have lower incomes, and more likely in black women.

• Risk factors for chemotherapy induced nausea and vomiting: ^{[3] [4]}
  • age less than 50 years
  • female gender
  • history of nausea and vomiting or motion sickness
  • type of antineoplastic agent and how it is used

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Vishnu Vardhan Serla M.B.B.S. [2]

• Nausea starts as an urge of vomiting. There is a diffuse sensation of unease and discomfort (often described as feeling sick or queasy feeling). Discomfort in chest, upper abdomen or back of throat might be present. It is often accompanied by excessive salivation. If vomiting follows, there is involuntary expulsion of stomach contents through mouth and sometimes nose. If nausea and vomiting are left untreated, the general feeing of distress can progress to life threatening complications.

• aspiration of gastric content ^[1]
• dehydration ^[2]
• electrolyte imbalance leading to metabolic alkalosis (increased blood pH), showing hypokalemia and hypochloremia ^{[2] [1]}

• cachexia due to loss of intake of food ^[2]
• antepartum hemorrhage of indeterminate origin in early pregnancy ^[3]
• callus formation and abrasions on skin of hands in case of self induced vomiting ^[1]

• pressure on ear, nose and eyes sometimes leading to subconjunctival hemorrhage and nose bleeds due to prolonged retching ^[1]

• dental erosion, discoloration and sensitivity of teeth, gum disease due to acidic gastric content ^[1]

• cracking of corners of lips ^[1]

• mucositis of hard palate and throat ^[1]

• hoarseness ^[1]

• salivary gland enlargement and parotid gland hypertrophy in bulimics ^{[1] [4]}

• GERD in case of frequent vomiting ^[1]

• Mallory-Weiss tear ^[1]

• Boerhaauve’s syndrome ^[1]

• elevated amylase level in case of repeated vomiting ^{[1] [4]}

• Cardiovascular symptoms including hypotention, sinus tachycardia, arrythmias and orthostasis in bulimic patients ^[1]

Prognosis for nausea and vomiting depends on the underlying cause.

Template:WH Template:WS