Cyclic Vomiting Syndrome – Causes, Symptoms, Treatment

Cyclic vomiting syndrome (CVS) is a chronic, functional gastrointestinal debilitating illness with recurrent episodes of intense nausea and vomiting that can last from hours to days without any functional or infectious illness and absence of identifiable pathology.

Cyclic vomiting syndrome is characterized by recurrent episodes of nausea and vomiting lasting from hours to days in the absence of identifiable pathology. Cyclic vomiting syndrome is a diagnosis of exclusion, and oftentimes patients have undergone extensive, unrevealing workups over the course of months or even years. Some patients have even tried abdominal surgeries to decrease their symptoms but to no avail. Cyclic vomiting syndrome results in decreased quality of life for affected patients. Affected children often miss school, and affected adults often visit the emergency department several times per year and require time off work.

Synonyms of Cyclic Vomiting Syndrome

  • adult cyclic vomiting syndrome
  • abdominal migraine
  • childhood cyclic vomiting
  • CVS
  • cyclical vomiting
  • periodic syndrome

Phases

Symptoms of CVS in adult populations are characterized by emesis and diffusely radiated epigastric abdominal pain.,, CVS is generally regarded as having four phases: prodromal/pre-emetic, acute (also known as vomiting and hyperemesis), recovery, and remission/interepisodic.,,

Cyclic vomiting syndrome has four phases:

  • prodrome phase
  • vomiting phase
  • recovery phase
  • well phase

Causes of Cyclic Vomiting Syndrome

Experts aren’t sure what causes cyclic vomiting syndrome. However, some experts believe the following conditions may play a role:

  • problems with nerve signals between the brain and digestive tract
  • problems with the way the brain and endocrine system  react to stress
  • mutations in certain genes that are associated with an increased chance of getting CVS

Triggers for an episode of cyclic vomiting may include:

  • emotional stress
  • anxiety or panic attacks, especially in adults
  • infections, such as colds, flu, or chronic sinusitis
  • intense excitement before events such as birthdays, holidays, vacations, and school outings, especially in children
  • lack of sleep
  • physical exhaustion
  • allergies
  • temperature extremes of hot or cold
  • drinking alcohol
  • menstrual periods
  • motion sickness
  • periods without eating (fasting)
  • Eating certain foods, such as chocolate, cheese, and foods with monosodium glutamate (MSG) may play a role in triggering episodes.
  • Colds, allergies or sinus problems
  • Emotional stress or excitement, especially in children
  • Anxiety or panic attacks, especially in adults
  • Certain foods and drinks, such as alcohol, caffeine, chocolate or cheese
  • Overeating, eating right before going to bed or fasting
  • Hot weather
  • Physical exhaustion
  • Exercising too much
  • Menstruation
  • Motion sickness

Symptoms of Cyclic Vomiting Syndrome

The main symptoms of cyclic vomiting syndrome are sudden, repeated attacks—called episodes—of severe nausea and vomiting. You may vomit several times an hour. Episodes can last from a few hours to several days. Episodes may make you feel very tired and drowsy.

Each episode of cyclic vomiting syndrome tends to start at the same time of day, last the same length of time, and happen with the same symptoms and intensity as previous episodes. Episodes may begin at any time but often start during the early morning hours.

Other symptoms of cyclic vomiting syndrome may include one or more of the following

  • The main symptoms of cyclic vomiting syndrome are sudden, repeated attacks—called episodes—of severe nausea and vomiting.
  • Retching—trying to vomit but having nothing come out of your mouth, also called dry vomiting
  • Pain in the abdomen
  • Abnormal drowsiness
  • Pale skin
  • Headaches
  • Lack of appetite
  • Not wanting to talk
  • Drooling or spitting
  • Extreme thirst
  • Sensitivity to light or sound
  • Dizziness
  • Diarrhea
  • Fever

How do the symptoms vary in the phases of cyclic vomiting syndrome?

The symptoms will vary as you go through the four phases of cyclic vomiting syndrome

  • Prodrome phase – During the prodrome phase, you feel an episode coming on. Often marked by intense sweating and nausea with or without pain in your abdomen this phase can last from a few minutes to several hours. Your skin may look unusually pale.
  • Vomiting phase – The main symptoms of this phase are severe nausea, vomiting, and retching. At the peak of this phase, you may vomit several times an hour. You may be
    • quiet and able to respond to people around you
    • unable to move and unable to respond to people around you
    • twisting and moaning with intense pain in your abdomen

Nausea and vomiting can last from a few hours to several days

  • Recovery phase – Recovery begins when you stop vomiting and retching and you feel less nauseated. You may feel better gradually or quickly. The recovery phase ends when your nausea stops and your healthy skin color, appetite, and energy return.
  • Well, phase – The good phase happens between episodes. You have no symptoms during this phase.

Diagnosis of Cyclic Vomiting Syndrome

  • Doctors diagnose cyclic vomiting syndrome based on family and medical history, a physical exam, pattern of symptoms, and medical tests. Your doctor may perform medical tests to rule out other diseases and conditions that may cause nausea and vomiting.

Family and medical history

  • Your doctor will ask about your family and medical history. He or she may ask for details about your history of health problems such as migraines, irritable bowel syndrome, and gastroparesis. Your doctor may also ask about your history of mental health problems, use of substances such as marijuana, and cigarette smoking.

Physical exam

During a physical exam, your doctor will

  • examine your body
  • check your abdomen for unusual sounds, tenderness, or pain
  • check your nerves, muscle strength, reflexes, and balance

Pattern or cycle of symptoms in children

A doctor will often suspect cyclic vomiting syndrome in a child when all of the following are present3:

  • at least five episodes over any time period, or a minimum of three episodes over a 6-month period
  • episodes lasting 1 hour to 10 days and happening at least 1 week apart
  • episodes similar to previous ones, tending to start at the same time of day, lasting the same length of time, and happening with the same symptoms and intensity
  • vomiting during episodes happening at least four times an hour for at least 1 hour
  • episodes are separated by weeks to months, usually with no symptoms between episodes
  • after appropriate medical evaluation, symptoms cannot be attributed to another medical condition

Pattern or cycle of symptoms in adults

A doctor will often suspect cyclic vomiting syndrome in adults when all of the following are present4:

  • three or more separate episodes in the past year and two episodes in the past 6 months, happening at least 1 week apart
  • episodes that are usually similar to previous ones, meaning that episodes tend to start at the same time of day and last the same length of time—less than 1 week
  • no nausea or vomiting between episodes, but other, milder symptoms can be present between episodes
  • no metabolic, gastrointestinal, central nervous system, structural, or biochemical disorders

A personal or family history of migraines supports the doctor’s diagnosis of cyclic vomiting syndrome.

Your doctor may diagnose cyclic vomiting syndrome even if your pattern of symptoms or your child’s pattern of symptoms do not fit the patterns described here. Talk to your doctor if your symptoms or your child’s symptoms are like the symptoms of cyclic vomiting syndrome.

Doctors use lab tests, upper GI endoscopy, and imaging tests to rule out other diseases and conditions that cause nausea and vomiting. Once other diseases and conditions have been ruled out, a doctor will diagnose cyclic vomiting syndrome based on the pattern or cycle of symptoms.

Lab tests

Your doctor may use the following lab tests:

  • Blood tests – can show signs of anemia, dehydration, inflammation, infection, and liver problems.
  • Urine tests  – can show signs of dehydration, infection, and kidney problems.
  • Blood and urine tests – can also show signs of mitochondrial diseases. Testing your blood and urine can let you and your healthcare team see how your body is working. Tracking your test results over time can show you how your kidneys are doing. Here are some common tests that are done when you have CKD:
  • Upper GI endoscopy – Your doctor may perform an upper GI endoscopy to look for problems in your upper digestive tract that may be causing nausea and vomiting.

Imaging tests

A doctor may perform one or more of the following imaging tests:

  • Ultrasound of the abdomen – An ultrasound is an imaging test that uses sound waves to create a picture (also known as a sonogram) of organs, tissues, and other structures inside the body. Unlike ultrasounds don’t use any radiation. An ultrasound can also show parts of the body in motion, such as a heart beating or blood flowing through blood vessels.
  • Gastric emptying test – also called gastric emptying scintigraphy. This test involves eating a bland meal, such as eggs or an egg substitute, that contains a small amount of radioactive material. An external camera scans the abdomen to show where the radioactive material is located. A radiologist can then measure how quickly the stomach empties after the meal. Health care professionals perform gastric emptying tests only between episodes.
  • Upper GI series – An upper GI series is a procedure in which a doctor uses x-rays, fluoroscopy, and a chalky liquid called barium to view your upper GI tract. The barium will make your upper GI tract more visible on an x-ray.
  • MRI scan – Magnetic resonance imaging (MRI) uses a large magnet and radio waves to look at organs and structures inside your body. Health care professionals use MRI scans to diagnose a variety of conditions, from torn ligaments to tumors. MRIs are very useful for examining the brain and spinal cord.
  • CT scan of the brain – Computed tomography (CT) is an imaging procedure that uses special x-ray equipment to create detailed pictures, or scans, of areas inside the body. It is sometimes called computerized tomography or computerized axial tomography (CAT).

North American Society for Pediatric Gastroenterology Hepatology and Nutrition(NASPGHAN)

A consensus by the NASPGHAN suggests the following diagnostic criteria(all of which must be met). These recommendations apply to children and adolescents.

  • At least five attacks in any interval or a minimum of three attacks during a 6 month period
  • Episodic attacks of intense nausea and vomiting lasting 1 hour to 10 days and occurring at least 1 week apart
  • Stereotypical pattern and symptoms in the individual patient
  • Vomiting during attacks occurs at least four times per hour for at least 1 hour
  • Return to baseline health between episodes
  • Not attributed to another disorder

Treatment of Cyclic Vomiting Syndrome

Treatment can be divided into three categories: prophylactic, abortive and supportive. Supportive treatment is the mainstay in emergency departments whether or not there has been a diagnosis of CVS.

  • Intravenous fluids and nausea medications such as ondansetron or prochlorperazine are given. Ketorolac is often given for pain.
  • Sometimes sedation with lorazepam or diphenhydramine is effective. Rest and a quiet, dark environment are recommended.
  • Amitriptyline has been tried in low doses for prophylactic therapy.
  • Other medications that have been studied to prevent CVS are cyproheptadine, propranolol, topiramate, and erythromycin.

Drugs used in the treatment of cyclic vomiting syndrome, and their suggested dosages

Setting Drug Suggested dosage
Terminating the acute episode ▸ Sumatriptan ▸ Intranasally: 20 mg as a single dose, maximum dose of 40 mg per day.
Subcutaneous: 6 mg as a single dose, maximum dose of 12 mg per day.
▸ Lorazepam ▸ 0.5–2 mg up to four times daily.
▸ Ondansetron ▸ 8 mg three times daily.
Prolonging the interepisodic phase with prophylactic therapy ▸ Tricyclic antidepressants (eg, amitriptyline) ▸ 10–150 mg per day.
▸ Zonisamide ▸ 100–700 mg per day.
▸ Levetiracetam ▸ 500 mg–3 g per day.
▸ Coenzyme Q10 ▸ 300–500 mg per day.
▸ L-carnitine ▸ 990 mg three times daily.
▸ Propranolol ▸ 80 mg per day.
▸ Erythromycin ▸ 250 mg three times daily.
▸ Cyproheptadine ▸ 4–8 mg three times daily.
▸ Aprepitant ▸ 40–125 mg per day twice weekly.

Antimigraine

  • Amitriptyline – start at 0.5 mg/kg and advance to 1–2 mg/kg per day QHS (adults 10–100 mg QHS). Monitor electrocardiogram QTc interval prior to starting. 1st choice >5 yrs old. SE: sedation, anticholinergic
  • Propranolol – 0.25–1 mg/kg per day BID or TID (adults 40 mg BID). Monitor resting heart rate. SE: hypotension, bradycardia, fatigue.
  • Cyproheptadine – 0.25–0.5 mg/kg per day BID or TID. 1st choice <5 yrs old. SE: sedation, weight gain, anticholinergic.
  • Alternatives – nortriptyline, imipramine.

Anticonvulsants

  • Phenobarbital – 2 mg/kg per day QHS. SE: sedation, cognitive impairment.
  • Valproate – 500–1,000 mg ER QHS. SE: somnolence, hepatotoxicity.
  • Carbamazepine – 5–10 mg/kg per day BID. SE: sedation, anticholinergic.
  • Alternatives – gabapentin, topiramate, levetiracetam, zonisamide.

Antimigraine

  • Sumatriptan: 20 mg intranasally at episode onset and can repeat once or 25 mg orally once. SE: chest and neck burning, coronary vasospasm, headache.
  • Alternatives: frovatriptan, rizatriptan, zolmitriptan.

Antiemetics

  • Ondansetron: 0.3–0.4 mg/kg per dose every 4–6 hours intravenously/orally. SE: headache, drowsiness, dry mouth.
  • Alternatives: granisetron, aprepitant.

Sedatives

  • Lorazepam: 0.05–0.1 mg/kg per dose every 6 hours intravenously/orally. A useful adjunct to ondansetron. SE: sedation, respiratory depression.
  • Chlorpromazine: 0.5–1 mg/kg per dose every 6 hours intravenously/orally. SE: drowsiness, hypotension, seizures.
  • Diphenhydramine: 1.25 mg/kg per dose every 6 hours intravenously/orally. A useful adjunct to chlorpromazine. SE: hypotension, sedation, dizziness.

Analgesics

  • Ketorolac: 0.5–1 mg/kg per dose every 6 hours intravenously/orally. SE: gastrointestinal bleeding, dyspepsia.
  • Alternatives: opioids.

Supplements

  • L-carnitine – 50–100 mg/kg per day BID or TID (adults 660 mg–1 g BID or TID). SE: diarrhea, fishy body odor.
  • CoenzymeQ10 – 10 mg/kg per day BID or TID.

How do doctors treat cyclic vomiting syndrome?

How doctors treat cyclic vomiting syndrome depends on the phase. Your doctor may

  • prescribe medicines
  • treat health problems that may trigger the disorder
  • recommend
    • staying away from triggers
    • ways to manage triggers
    • getting plenty of sleep and rest

Prodrome phase

Taking medicines early in this phase can sometimes help stop an episode from happening. Your doctor may recommend over-the-counter medicines or prescription medicines such as

  • ondansetron  (Zofran) or promethazine (Phenergan) for nausea
  • sumatriptan (Imitrex) for migraines
  • lorazepam (Ativan) for anxiety
  • ibuprofen for pain

Your doctor may recommend over-the-counter medicines to reduce the amount of acid your stomach makes, such as

  • famotidine (Pepcid)
  • ranitidine (Zantac)
  • omeprazole  (Prilosec)
  • esomeprazole  (Nexium)

Vomiting phase

During this phase, you should stay in bed and sleep in a dark, quiet room. You may have to go to a hospital if your nausea and vomiting are severe or if you become severely dehydrated. Your doctor may recommend or prescribe the following for children and adults:

  • medicines for
    • nausea
    • migraines
    • anxiety
    • pain
  • medicines that reduce the amount of acid your stomach makes

If you go to a hospital, your doctor may treat you with

  • intravenous (IV) fluids for dehydration
  • medicines for symptoms
  • IV nutrition if an episode continues for several days

Recovery phase

During the recovery phase, you may need IV fluids for a while. Your doctor may recommend that you drink plenty of water and liquids that contain glucose and electrolytes, such as

  • broths
  • caffeine-free soft drinks
  • fruit juices
  • sports drinks
  • oral rehydration solutions, such as Pedialyte

If you’ve lost your appetite, start drinking clear liquids and then move slowly to other liquids and solid foods. Your doctor may prescribe medicines to help prevent future episodes.

Well phase

During the good phase, your doctor may prescribe medicines to help prevent episodes and how often and how severe they are, such as

  • amitriptyline (Elavil)
  • cyproheptadine (Periactin)
  • propranolol (Inderal)
  • topiramate (Topamax)
  • zonisamide (Zonegran)

Your doctor may also recommend coenzyme Q10, levocarnitine (L-carnitine), or riboflavin as dietary supplements to help prevent episodes.

Preventive management

Preventive management is primarily avoidance of triggers; adequate sleep to prevent exhaustion; treating allergies and sinus problems and instituting measures for reducing stress and anxiety. Feeding advice should include avoidance of foods with additives and those known to trigger episodes [].

  • Eating small carbohydrate-containing snacks between meals, before exercise, and at bedtime should be advised. Prophylactic treatment options include medications and supplements during symptom-free periods. For children 5 years old or less, the medication of choice is cyproheptadine at 0.25-0.5 mg/kg/day, dose divided two or three times a day.
  • The second choice is propranolol at 0.25-1.0 mg/kg/day, dose divided two or three times a day. For those above 6 years of age, amitriptyline at 1.0 to 1.5 mg/kg at bedtime is the first choice, followed by propranolol.
  • Pizotifen, phenobarbital, topiramate, valproic acid, gabapentin, and levetiracetam have also been reportedly tried with mixed results [,].
  • Supplements that have been shown to help include L-carnitine 50-100 mg per day divided into 2 or 3 doses to a maximum of 1 gm thrice a day, and coenzyme Q-10, 10 mg per kg per day in two or three divided doses up to a maximum of 100 mg thrice a day [,].
  • At the onset of an episode, abortive therapy should be instituted as soon as possible. Sleeping and resting in a quiet and darkroom during the episode is helpful. Ondansetron may be used initially for milder symptoms.
  • Early use of intranasal sumatriptan can abort an attack in a third of patients and use of subcutaneous sumatriptan in over half of them (54%) [].
  • Clonidine alone as a pill (0.1 or 0.2 mg) or as a transdermal patch (0.2 or 0.3 mg per day) may also be tried. Alternatively, a combination of clonidine with a benzodiazepine (midazolam or lorazepam) can be administered in more severe cases [,].
  • Another option is alternating promethazine suppository (12.5, 25, or 10 mg) with diazepam rectal gel (2.5, 5, or 10 mg) every 4-6 hours. If the symptoms persist beyond 24 hours and the child is unable to maintain hydration, intravenous fluids may be indicated.

Prevention

Knowing and managing your triggers can help prevent cyclic vomiting syndrome, especially during the good phase. You should also

  • get enough sleep and rest
  • treat infections and allergies
  • learn how to reduce or manage stress and anxiety
  • avoid foods and food additives that trigger episodes

You should seek medical help if

  • the medicines your doctor recommended or prescribed for the prodrome phase don’t relieve your symptoms
  • your episode is severe and lasts more than several hours
  • you are not able to take in foods or liquids for several hours

You should seek medical help right away if you have any signs or symptoms of dehydration during the vomiting phase. These signs and symptoms may include

  • extreme thirst and dry mouth
  • urinating less than usual
  • dark-colored urine
  • dry mouth
  • decreased skin turgor, meaning that when your skin is pinched and released, the skin does not flatten back to normal right away
  • sunken eyes or cheeks
  • light-headedness or fainting

If you are a parent or caregiver of an infant or child, you should seek medical care for them right away if they have any signs and symptoms of dehydration during the vomiting phase. These signs and symptoms may include

  • thirst
  • urinating less than usual, or no wet diapers for 3 hours or more
  • lack of energy
  • dry mouth
  • no tears when crying
  • decreased skin turgor
  • sunken eyes or cheeks
  • unusually cranky or drowsy behavior

References

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