Cyclical vomiting syndrome

Cyclical vomiting syndrome (CVS) is characterized by severe, recurrent, self-limited episodes of bilious or nonbilious vomiting. CVS may affect individuals of any age but is most common in children and women. Etiology is likely multifactorial, involving genetic, environmental, and neurohormonal factors. CVS is often associated with a personal or family history of migraines, and common triggers include psychological or physiological stress, certain foods, and hormonal changes such as menstruation or pregnancy. Diagnosis is clinical and involves ruling out other causes through a workup of nausea and vomiting. Treatment focuses on managing acute episodes with abortive therapies for CVS and supportive care, including hydration and antiemetics. Prevention of future episodes includes lifestyle modifications and, in some patients, prophylactic medications. Early intervention in the prodromal phase can help minimize the severity of symptoms.

• Occurs in both children and adults
• More common in female individuals than in male individuals

Epidemiological data refers to the US, unless otherwise specified.

• Likely multifactorial (genetic, environmental, neurohormonal factors) ^[3]
• Often associated with a personal or family history of migraines ^[3]
• Common triggers include: ^[1]
  • Psychologic stress
  • Physiologic stress (e.g., infection, fasting,; sleep deprivation)
  • Certain foods (e.g., dairy, soy, chocolate, red wine)
  • Hormonal changes (e.g., menstruation, pregnancy)

Recurrent, self-limited attacks of severe vomiting (bilious or nonbilious) ^[1][3]

• Prodromal phase (minutes to hours)
  • Abdominal pain and nausea
  • Autonomic symptoms (e.g., pallor, diaphoresis)
  • Irritability, sense of impending doom
• Emetic phase (hours to days; typically < 1 week)
  • Recurrent intense vomiting and retching
  • Abdominal pain, headaches, diarrhea, and/or intense thirst
  • Relief with sleep, stimuli avoidance, and/or hot showers or baths ^[1][4]
• Recovery phase (hours to days): gradual resolution of vomiting, improvement in oral intake
• Interepisodic phase (weeks to months): usually asymptomatic, though dyspepsia and nausea may occur

The emetic phase of CVS often begins in the early morning. ^[1][4]

Prodromal and emetic symptoms typically follow a consistent, recurrent pattern. ^[4]

Approach ^[3][4]

• CVS is a clinical diagnosis based on Rome IV criteria for cyclical vomiting syndrome.
• Obtain routine diagnostics for nausea and vomiting to rule out other causes of nausea and vomiting.
• Consider advanced diagnostics for nausea and vomiting if anatomic abnormalities or other underlying conditions are suspected.

Inquire about cannabinoid use to screen for cannabinoid hyperemesis syndrome, a common CVS mimic. ^[4]

Rome IV criteria for cyclical vomiting syndrome ^[5][6][7]

Adults ^[8]

All of the following criteria must be met:

• Stereotypical episodes of acute vomiting with a duration of < 1 week
• ≥ 3 episodes in the past year and ≥ 2 episodes in the past 6 months, occurring ≥ 1 week apart
• Asymptomatic intervals between episodes (mild symptoms may be present)
• Symptoms present for the past 3 months with onset ≥ 6 months prior

Children ^[6][7]

All of the following criteria must be met:

• Stereotypical episodes of unrelenting nausea and vomiting, lasting hours to days
• ≥ 2 episodes within a 6-month period
• Asymptomatic intervals (weeks to months) between episodes
• Symptoms cannot be attributed to another cause.

Laboratory studies

Obtain basic laboratory tests to identify potential causes or complications of recurrent vomiting, e.g.:

• CBC
• CMP
• Serum lipase
• Urinalysis
• Beta-HCG test for female patients

Additional studies

• Esophagogastroduodenoscopy (EGD): to exclude obstructive lesions ^[4]
• Gastric emptying scintigraphy: not routinely indicated ^[4]

Avoid repeating EGDs and other advanced studies in patients with no evidence of anatomical anomalies or other underlying conditions on initial evaluation. ^[4]

See also “Causes of nausea and vomiting” and “Differential diagnosis of infant vomiting”

• Other functional nausea and vomiting disorders
  • Chronic nausea and vomiting syndrome
  • Cannabinoid hyperemesis syndrome
• Gastrointestinal disorders
  • Gastroparesis
  • Functional bowel obstruction
  • Mechanical bowel obstruction
  • Rumination syndrome
• Pregnancy related
  • Hyperemesis gravidarum
  • Uncomplicated nausea and vomiting of pregnancy
• Others: e.g., migraine, CNS tumors, uremia

The differential diagnoses listed here are not exhaustive.

Abortive therapy for prodromal CVS ^[4][9]

Administer an oral, intranasal, or subcutaneous agent as soon as possible during the prodromal phase.

• Adults
  • First-line agents: A combination of ≥ 2 medications is typically required (e.g., usually a triptan PLUS an antiemetic agent)
    • Triptans: e.g., sumatriptan (off-label) ^[4]
    • Serotonin receptor antagonists: e.g., ondansetron (off-label) ^[4]
    • Dopamine receptor antagonists: e.g., prochlorperazine ^[4]
    • Antihistamines: e.g., promethazine ^[4], diphenhydramine (off-label) ^[4]
    • Sedatives: e.g., lorazepam (off-label) ^[4]
  • Second-line: aprepitant (off-label) ^[1][3][9]
• Children: Data on abortive therapy in children is limited. Seek expert advice. ^[10][11][12]
  • Sumatriptan (off-label) may be considered in children ≥ 12 years of age. ^[10][11]
  • Other: ondansetron (off-label), aprepitant (off-label)

Abortive therapy for CVS prevents the transition to the emetic phase or reduces its severity.

Acute management of emetic CVS ^[3][4][9]

Emetic CVS often requires hospital-based care (See “Disposition.”)

Parenteral antiemetics

• Options in adults
  • Ondansetron (off-label) ^[9]
  • Diphenhydramine (off-label) ^[9]
  • Metoclopramide (off-label) ^[9]
  • Fosaprepitant (off-label) ^[9]
• Option in children ondansetron (off-label) ; for refractory nausea and vomiting, consider adding a sedative, e.g., diphenhydramine (off-label) . ^[10]

Supportive care

• Nonpharmacological management
  • Place the patient in a dark, quiet environment.
  • Provide initial fluids for dehydration and start dextrose-containing maintenance fluids (e.g., IV D5NS).
• Pharmacological management: Consider additional symptomatic treatment as needed in adults and children.
  • Anxiety and/or agitation: parenteral sedatives, e.g., IV lorazepam (off-label) ^[9][10]
  • Significant abdominal pain persisting ≥ 60 minutes: parenteral analgesics ^[9]
    • Use non-narcotic medications, e.g., IV ketorolac . ^[9][10]
    • Use opioids sparingly for refractory pain.
    • Evaluate for other causes of acute abdominal pain.
    • See also “Pain management in children.”
  • Migraine-like symptoms: sumatriptan (off-label) ^[9][10][11]

Long-term management ^[1][4][9]

• Consider specialist referral (e.g., psychiatry, psychology, neurology) to manage comorbidities. ^[1][4]
• Manage triggers (see “Etiology”).
• Provide counseling on sleep hygiene and stress reduction techniques (e.g., biofeedback, meditation).
• Consider prophylactic pharmacotherapy.
  • Adults: a tricyclic antidepressant, anticonvulsant, or neurokinin receptor antagonist in selected patients ^[4]
  • Children ^[10][11][13]
    • < 5 years old: cyproheptadine or propranolol
    • ≥ 5 years old: amitriptyline or propranolol

• Severe or prolonged (> 24 hours) emetic episodes: Refer to emergency department (ED). ^[4]
• Inability to tolerate oral intake despite ED therapy: Admit to hospital. ^[4]
• Clinical improvement after ED therapy: Consider discharge with outpatient therapy. ^[4]
  • Oral ondansetron and/or lorazepam for 24–48 hours if initially effective
  • Oral NSAIDs as needed for pain
  • Electrolyte-rich fluids (e.g., oral rehydration solution)