Cyclic Vomiting Syndrome Tonya Adamiak MD Pediatric Gastroenterology

Cyclic Vomiting Syndrome
Tonya Adamiak MD
Pediatric Gastroenterology
Sanford Children’s
Objectives
• Identify the stereotypical pattern of cyclic vomiting syndrome (CVS)
• Review the consensus criteria for CVS diagnosis
• Describe the initial evaluation for patients with suspected CVS
• Review treatments for CVS including prophylactic measures,
abortive strategies, and supportive medications during acute
episodes
Patient #1
• 10 year old boy with repeated vomiting episodes
– Episodes in Dec 2010, Jan 2011, Feb 2011, April 2011, every 4-6 weeks
• Stereotypical episodes, episodes all very similar
– Starts with cold-like symptoms - sore throat, runny nose and congestion
– Repeated episodes of “violent” vomiting, about 10 times per episode
– Vomiting would start at random times of the day and would last about 24
hours
– Associated abdominal pain and headaches
– No ER visits or episodes that required IVF
– Completely well in between episodes
– No family history of migraine headaches
Patient #2
• GI clinic visit in November 2012, second opinion for presumed CVS
• 5 year old boy with 4 previous episodes of vomiting in the last 9
months, each time requiring hospitalization and IV fluids
– February, March, June, August 2012
• All episodes were very similar
–
–
–
–
Onset in the morning, between 7am and 12pm
Vomiting continued for ~4 days, vomit up to 10 times per hour
Sometimes headaches and abdominal pain, no light sensitivity or pallor
Lies down and doesn’t want to do anything, won’t talk or swallow his saliva
• In between these episodes of vomiting, he is otherwise well
• Family history: Mom has migraine headaches
Recurrent Vomiting
Cyclic vs Chronic Vomiting
• Cyclic vomiting –
– Recurrent, discrete, self-limited episodes of vomiting
• Chronic vomiting –
– Low grade, nearly daily
– For example, gastritis or reflux
•
Cyclic Vomiting Pattern
•
Chronic Vomiting Pattern
•
•
=
Cyclic vs Chronic Vomiting Pattern
Peak intensity of vomiting
Frequency of episodes
Time of onset
Dehydration
Migraine family history
Cyclic Pattern
Chronic Pattern
n = 34
n = 72
8-fold higher
12.6 +/- 1.6 emeses/per hour
1.5 +/- 0.1 emeses/hr
Bimonthly
Daily
1.9 +/- 4.8 episodes/month
36.6 +/- 0.3 episodes/month
2-fold more likely nocturnal onset
Between 1am and 7am: 56%
Between 1am and 7am: 26%
3-fold higher incidence of
dehydration requiring IVF
Increased number of relatives
with migraines
1st degree 14%, 2nd degree 8%
1st degree: 47%, 2nd degree: 35%
* Pfau BT, Li BUK, Murrary RD, et al. Differentiating Cyclic From Chronic Vomiting Patterns in Children:
Quantitative Criteria and Diagnostic Implications. Pediatrics 1996;97:364-368.
Cyclic Vomiting Syndrome
• Described by Dr. Samuel Gee in 1882:
“These cases seem to be all of the same kind, their characteristic
being fits of vomiting, which recur after intervals of uncertain length.
The intervals themselves are free from signs of disease. The
vomiting continues for a few hours or a few days. When it had been
severe, the patients are left much exhausted...”
Consensus Criteria for CVS Diagnosis
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, 2008
• 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 4X/hr for at least 1 hour
– * Task force recognizes that atypical CVS may exist with less frequent
vomiting
• At least 5 attacks in any interval, or a minimum of 3 attacks during a
6 month period
• Return to baseline health between episodes
• Not attributed to another disorder
* Li BUK, Lefevre F, Chelimsky GG, et al. North American Society for Pediatric Gastroenterology,
Hepatology, and Nutrition Consensus Statement on the Diagnosis and Management of Cyclic
Vomiting Syndrome. JPGN 2008 47:379-393.
Etiology of CVS
• Etiology and Pathogenesis unknown:
• Strong link between CVS and migraines
–
–
–
–
Similar symptoms
Common coexistence of both conditions in the same individual
High family prevalence of migraine in patients with CVS
Effectiveness of anti-migraine therapy in CVS
• Mitochondrial DNA mutations that cause defects in energy
production
– May predispose patients to vomiting episodes during periods of
heightened energy demands, for example stress or excitement
– Mitochondrial DNA is maternally derived and there is a striking
predominance of migraines on maternal side compared to paternal side
• Hypothalamic-pituitary-adrenal axis activation
– Heightened hypothalamic stress response that activates the emetic
response
– Corticotropin releasing factor (CRF) from the hypothalamus  anterior
pituitary secretes ACTH  activation hypophyseal pituitary adrenal axis
and the stress response
– Circadian CRF peaks in the early morning hours between 4-8am
• Autonomic dysfunction
– Many CVS symptoms are mediated by autonomic nervous system
• Pallor, flushing, fever, lethargy, excessive salivation, vomiting, diarrhea
– Predominance of sympathetic adrenergic over parasympathetic
cholinergic tone
– Greater sympathetic response to postural changes
CVS Demographics
• Pediatric prevalence: 0.04% to ~2%
– 0.04% in Pediatric GI referral center in Ohio
* Li BUK, Misiewicz L. Cyclic vomiting syndrome: a brain-gut disorder. Gastroenterol Clin N Am
2003;32:997-1019.
– ~2% in population surveys Turkey and Scotland
* Ertekin V, Selimoglu MA, Altinkaynak S. Prevalence of Cyclic Vomiting Syndrome in a Sample of
Turkish School Children in an Urban Area. J Clin Gastroenterol 2006;40:896-898.
* Abu-Arafeh I, Russell G. Cyclical vomiting syndrome in children: a population-based study. J
Pediatr Gastroenterol Nutr 1995;21:454-458.
• Slight predominance of girls over boys: 55:45
– 214 children who met consensus criteria for CVS
* Li BUK, Murrary RD, Heitlinger LA, et al. Is cyclic vomiting syndrome related to migraine? J
Pediatr 1999;134:567-72.
– Observations of 71 children with CVS
* Fleisher DR, Matar M. The cyclic vomiting syndrome: a report of 71 cases and literature review.
JPGN 1993;17:361-9.
• Most commonly begins in preschool or early school aged children
– Median age of onset of symptoms is 5-6 years old
– Adult onset cases have been reported but are rare
• Median interval from onset of symptoms to diagnosis is 2.5 years
– Often misdiagnosed as acute gastroenteritis or food poisoning initially
• 82% have a family history of migraine headaches
* Li BUK, Balint J. Cyclic vomiting syndrome: the evolution of understanding of a brain-gut
disorder. Adv Pediatr 2000;47:117-60.
* Li BUK, Murray RD, Heitlinger LA, et al. Is cyclic vomiting syndrome related to migraine? J
Pediatr 1999;134:567-72.
• Early morning onset:
• Vomiting begins most commonly during the
night (2-4am) or upon awakening (6-8am)
•
Could possibly be related to the surge of CRF
in the early morning
• 76% of patients had one or two characteristic
times of onset of episodes
• 24% had no characteristic time of onset
* Fleisher DR, Matar M. The cyclic vomiting syndrome: a report of
71 cases and literature review. JPGN 1993;17:361-9.
• Episode last most commonly 24-48 hours
– Some patients have episodes that are less than 6 hours, other patients
have episodes that last 5-7 days
– 85% of episodes are of fairly uniform length,15% of patients have attacks
of variable length
* Fleisher DR, Matar M. The cyclic
vomiting syndrome: a report of 71
cases and literature review. JPGN
1993;17:361-9.
• Some patients have a short prodrome, consisting of nausea,
lethargy, anorexia, and pallor before the onset of vomiting
• The vomiting usually reaches its peak intensity within the first hour
and begins to decline after the first 4-8 hours
• Intense vomiting
– Emeses per episode: median 11, mean 22
– Median peak vomiting 6 times per hour
• The recovery period from the end of vomiting to the point of turning
the corner and being able to eat is often described “like turning off a
switch”
* Li BUK, Balint J. Cyclic vomiting syndrome: the evolution of understanding of a brain-gut
disorder. Adv Pediatr 2000;47:117-60.
• Associated signs and symptoms:
– Common: lethargy (91%), pallor (87%), abdominal pain (80%), retching
(76%), nausea (72%), anorexia (74%), diarrhea (36%), fever (29%)
– About 30-40% have headaches and photophobia
– Nausea is often identified by patients as the most persistent and
distressing symptom unrelieved by vomiting
– “Conscious coma”, lethargic, listless, withdrawn
– Child usually oriented and able to respond appropriately to commands,
but prefers not to because of incapacitating nausea
* Li BUK, Balint J. Cyclic vomiting syndrome: the evolution of understanding of a brain-gut
disorder. Adv Pediatr 2000;47:117-60.
Quotes from Patients with CVS
• “…as the attack progresses, the nausea becomes constant. Nothing
will relieve it… I am utterly exhausted, and all I want to do is sleep…
I am not aware of the nausea and the pain while sleeping… I am
aware of incredible discomfort and pain…”
• “…The telling symptom for me is extreme nausea, which is
worsened by the slightest movement or faintest odor. The nausea is
an extremely controlling, dominating force… During these episodes,
I am also extremely lethargic and have a difficult time talking, as the
nausea consumes every ounce of strength. It is an extremely difficult
experience to articulate, sick or well.”
* Fleisher D. Cyclic vomiting syndrome. In: Hyman P, DiLorenzo C (eds). Pediatric Gastroenterology
Motility Disorders. New York: Academy Professional Information Services; 1994. pp. 89-104.
• Approximately half of patients have regular intervals between
attacks - most often monthly
* Fleisher DR, Matar M. The cyclic vomiting syndrome: a report of 71 cases and literature review.
JPGN 1993;17:361-9.
* Li BUK, Balint J. Cyclic vomiting syndrome: the evolution of understanding of a brain-gut
disorder. Adv Pediatr 2000;47:117-60.
• Seasonal in 30%
– More frequent in winter while remitting in summer
– Possibly related to exposure to infections, allergies, school related
stressors, and less sleep
CVS Triggers
• Triggering events: 68% of patients can identify a trigger for their
episodes
– Psychological (34%)
• 2/3 positive stress (birthday, holidays, vacations), 1/3 school or family related
– Infections (41%)
• URI, sinusitis, strep pharyngitis
– Physical exhaustion or lack of sleep (18%)
– Dietary (26%)
• Chocolate, aged cheese, MSG
– Other: motion sickness, atopy, weather changes, fasting, menses
* Li BUK, Balint J. Cyclic vomiting syndrome: the evolution of understanding of a brain-gut
disorder. Adv Pediatr 2000;47:117-60.
High Morbidity Related to CVS
High degree of medical morbidity
• 50% children with CVS require IVF, 28% require IVF each episode
• School age children >7yo missed 20 days of school in the past year
• Estimated average annual cost of care for child with CVS $17,035
– Clinic visits, ER, hospitalization, tests, missed work days for parents
* Li BUK, Balint J. Cyclic vomiting syndrome: the evolution of understanding of a brain-gut
disorder. Adv Pediatr 2000;47:117-60.
CVS episodes worse than rotavirus
• Dehydration requiring IVF: 75X more likely than rotavirus
* Li BUK, Misiewicz L. Cyclic vomiting syndrome: a brain-gut disorder. Gastroenterol Clin N Am
2003;32:997-1019.
Summarizing the Characteristic
CVS Patient
• Vomiting episodes start at 5-6 years of age
• Intense stereotypical vomiting episodes occurring monthly and
lasting 24-48 hours
• Vomiting starts in the middle of the night or right when waking up in
the morning
• Peak emeses 6 times an hour
• Associated nausea, abdominal pain, lethargy, and pallor
• Family history of migraine headaches
Patient #1
• 10 year old boy with repeated vomiting episodes
– Episodes in Dec 2010, Jan 2011, Feb 2011, April 2011, every 4-6 weeks
• These episodes all very similar
– Starts with cold-like symptoms - sore throat, runny nose and congestion
– Repeated episodes of “violent” vomiting, about 10 times per episode
– Vomiting would start at random times of the day and would last about 24
hours
– Associated abdominal pain and headaches
– No ER visits or episodes that required IVF
– Completely well in between episodes
– No family history of migraine headaches
Evaluation
• There are no specific laboratory markers to diagnose CVS
• The diagnosis of CVS is based upon the fulfillment of the consensus
diagnostic criteria in the absence of another explanation for the
symptoms
Key Diagnostic Questions
• Has your child had 3 or more attacks of vomiting like this before?
• Is each episode similar to the others?
• Does the vomiting occur more than every 15 minute at its peak?
• Is there associated pallor, lethargy, abdominal pain, anorexia, or
nausea?
• Is your child completely normal in between?
• Is there a family history of migraine headaches?
Heterogeneity of Diagnoses Presenting
with Cyclic Vomiting Pattern
• 225 children with at least 3 discrete episodes of vomiting between
which the child was free of symptoms
• 88% idiopathic CVS
• 12% had specific disorders that, based on complete resolution after
specific therapy, were thought to be the probable cause of vomiting
– GERD/esophagitis (4), duodenitis, IBS, duplication cyst, malrotation (3),
chronic appendicitis (2), adhesions, choledochal cyst, cholelithiasis,
chronic sinusitis, asthma, nephrolithiasis, VLCAD +/- SCAD, acute
intermittent porphyria, suspected mitochondriopathies (2), epilepsy,
brainstem glioma, cerebellar medulloblastoma, astrocytoma, VP shunt
dysfunction
* Li BUK, Murray RD, Heitlinger LA. Heterogeneity of Diagnoses Presenting as Cyclic Vomiting.
Pediatrics 1998;102:583-587.
Red Flags in a Child with
Cyclic Vomiting Pattern
• Abnormal neurological exam
• i.e. severe alteration of mental status, abnormal eye movements,
papilledema, motor asymmetry, and/or gait abnormality
– Brain MRI  Posterior fossa or hypothalamic tumor, Chiari
malformation, hydrocephalus, subdural hematoma, etc
• Altered mental state, “conscious coma” in CVS patients
• In CVS, the child is usually oriented and able to respond appropriately
to commands, but prefers not to because of incapacitating nausea
• In metabolic encephalopathy, the child is frequently disoriented,
confused, excessively irritable, and/or difficult to arouse
• Vomiting attacks precipitated by intercurrent illness, fasting, and/or
high protein meal
– Disorders of fatty acid oxidation, urea cycle, organic and amino acid
metabolism, and mitochondrial energy metabolism can follow a
catabolic state induced by acute illness, fasting, or a high protein meal
– Although severe enzyme deficiencies generally present immediately
after birth, partial enzyme defects present later
– Altered mental status, severe anion gap metabolic acidosis, substantial
ketosis, and/or an unusual odor
– Obtain labs before IVF administered: lactate, ammonia, serum AA, urine
OA, carnitine, acylcarnitine, urine ketones, glucose, electrolytes
– Labs may be normal if obtained either while asymptomatic or after
several hours of IV dextrose
* Rinaldo P. Mitochondrial fatty acid oxidation disorders and cyclic vomiting syndrome. Dig Dis
Sci 1999;44 (8 Suppl):97S-102S.
• Bilious vomiting, and/or severe abdominal pain
– Bilious emesis (83%) and severe abdominal pain (80%) common in
CVS, but serious surgical disorders can present similarly
– Evaluate for malrotation with UGI study
• Progressively worsening episodes or conversion to a continuous or
chronic pattern
Cost Benefit Analysis of CVS
Evaluation and Treatment
• Cost and benefit of three initial treatment strategies compared:
– Extensive diagnostic evaluation $3017
• UGI SBFT, EGD, Sinus films, Head CT or MRI, Abd US, metabolic lab tests
– Upper GI SBFT plus empiric treatment $1602
• 2 month trial of prophylactic anti-migraine therapy
– Empiric treatment alone $1825
– Extensive evaluation performed in all children who failed to respond to
empiric therapy
• The cost of complications of a missed malrotation with volvulus was
higher than that of adding a UGI SBFT to each evaluation
• Most cost effective to do UGI SBFT and two month trial of
prophylactic therapy
* Olson AD, Li BUK. The diagnostic evaluation of children with cyclic vomiting: A cost-effectiveness
assessment. J Pediatr 2002;141:724-8.
NASPGHAN Consensus Recommendations
Li BUK et al. JPGN 2008 47:379-393
• UGI to exclude malrotation/volvulus
• Consider labs during episode of vomiting, before administering IVF
– CBC, ESR, Electrolytes, Glucose, AST, ALT, GGT, Amylase, Lipase,
Lactic Acid, Ammonia, Carnitine, Serum AA, Pyruvate, Acylcarnitine
profile, Celiac panel, UA/UC, Urine OA
• Routine endoscopy if chronic symptoms between episodes that are
suggestive of a specific disorder or in patients with hematemesis
– But routine endoscopy not required in every patient
• Screen and treat empirically for 2 months if no alarm findings
– If patient responds to therapy with at least 50% reduction in episode
frequency and/or severity, further evaluation not required
– If patient does not improve with initial therapy during the 2 month period,
further evaluation is recommended: Labs, EGD, renal US, brain MRI
CYCLIC VOMITING
SYNDROME
TREATMENT
CVS Treatment
• Treatment of CVS requires an individually tailored plan that takes
into consideration:
– Clinical course
– Frequency and severity of attacks
– Resultant disability balanced against the potential side effects of
treatment
Treatment Goals
PHASE
WELL
PRODROME
EPISODE
RECOVERY
THERAPEUTIC
GOAL
Prevent
Episodes
Abort
Episode
Terminate Episode
Refeed
without
causing
relapse
Identify and
Avoid
Triggers
Support at home or
in the hospital –
dark, quiet room;
TREATMENT
GOALS
Abortive meds
Or, if Unsuccessful:
sedate until
episode passes
Anti-emetic and
sedative
Provide early energy
substrate 10%
glucose/fluids;
Prophylactic
therapy if abortive
therapy fails
and/or severe or
frequent episodes
Treatment – Education
• Reassurance and anticipatory guidance
– Fleisher reported that 70% of patients initially
respond by reduced episode frequency following
consultation alone without drug therapy
• Improvement may be from alleviation of known
precipitating factors
• Reduction in stress due to a positive diagnosis,
knowledge that effective therapies are available,
and learning that CVS typically improves with age
* Fleisher D. Cyclic vomiting syndrome. In: Hyman P, DiLorenzo C
(eds). Pediatric Gastroenterology Motility Disorders. New York:
Academy Professional Information Services; 1994. pp. 89-104.
• Support Group: Cyclic Vomiting Syndrome Association (CVSA),
www.cvsaonline.org
Treatment – Well Phase
Prophylactic Measures – Lifestyle Changes
• Avoidance of triggers
– Careful history and/or detailed vomiting diary can help identify
potentially avoidable triggers in ~2/3 of children
– Episodes can be precipitated by common infections, exciting occasions
such as birthdays and holidays, lack of sleep and/or overexertion
– Triggering foods: chocolate, cheese, hot dogs, aspartame, monosodium
glutamate, alcohol, food allergens
– Recommend regular sleep schedules, exercise, and meal schedules;
good hydration, moderation or avoidance of caffeine (30mg/day)
Treatment – Abortive Therapy
• Treatment with abortive therapy as early as possible in the
prodrome or vomiting phase may terminate the attack
– Early intervention more effective than later intervention
• Treatment options that can be done at home:
– Sumatriptan (Imitrex):
• Anti-migraine medication
• 20mg intranasally at episode onset
– Ondansetron ODT (Zofran):
• Anti-emetics to lessen nausea and vomiting
• If positive personal or family history of migraine, 79% will respond to
some form of anti-migraine treatment
– Compared to 36% response in patients without a personal or family
history of migraines
* Li BUK, Murray RD, Heitlinger LA, et al. Is cyclic vomiting syndrome related to migraine? J
Pediatr 1999;134:567-72.
• If episodes ≤24 hours, better response to abortive anti-migraines
(sumatriptan) and prophylactic propranolol
(Li unpublished)
Acute Treatment
• If vomiting progresses despite abortive therapies, then supportive
care at home or in the hospital is focused on providing relief from
nausea, vomiting, abdominal pain
Acute Management – ER/inpatient:
• Dark, quiet non-stimulating environment
• Replacement of fluids, electrolytes, and energy
– NS bolus, then D10 ½ NS +/- KCL at 1.5 X maintenance
• D10W at 1X maintenance and “Y” in NS at 0.5X maintenance
– 10% dextrose concentration to lessen any possible metabolic crisis that
can be worsened by catabolism
– IVF stop ketosis, replaces electrolytes and lost volume
• Glucose may be most effective component by terminating ketosis
• Antiemetic and sedative are most effective combination
– Scheduled Ondansetron (Zofran) and Lorazepam (Ativan) for first 24
hours, then as needed
– Antiemetic: Ondansetron reduces vomiting, but usually does not abort
the episode
• Ondansetron 0.3-0.4mg/kg/dose (up to 20mg) IV q6 hours
– Sedation: sleep may be the only mode that provides relief and may
shorten the vomiting episode
• Lorazepam 0.05 – 0.1 mg/kg IV q6 hours
• Alternative:
– Chlorpromazine (Thorazine) 0.5-1mg/kg IV q6 hours +
Diphenhydramine (Benadryl) 1-1.25mg/kg IV q6 hours
– Provides less antiemetic and more sedative effect compared to
Ondansetron and Lorazepam
• Pain management
– Ketorolac (Toradol) 0.5-1mg/kg IV/IM, then 0.2-0.5mg/kg q6-8 hours (up
to 30mg q6 hours)
– Morphine or hydromorphone if needed
– If epigastric pain/dyspepsia, then IV H2 blocker or PPI may help
Recovery Phase
• Recovery phase: from the last emesis to the point of being able to
retain foods typically lasts a few hours
• Once children state they are hungry and want to eat food, they can
generally resume a normal diet, “like turning off a switch”
– But some children require stepwise reintroduction of foods to prevent
the recurrence of nausea
Patient #2 Follow Up
• 5 year old boy with 4 previous episodes of vomiting in the last 9
months, each time requiring hospitalization and IV fluids
– February, March, June, August 2012
• Stereotypical episodes, well in between the episodes
– Hospitalized ~4 days with each episode, vomit up to 10 times per hour
– Sometimes associated headaches and abdominal pain
– Lies down and doesn’t want to do anything, won’t talk or swallow his
saliva
• Review of his evaluation:
– Labs: normal CBC, CMP, GGT, amylase, lipase, celiac panel, ammonia,
acylcarnitine panel; essentially normal lactic acid and pyruvic acid;
serum amino acids with decreased concentration of several amino
acids, but not indicative of specific disorder; urine organic acids
consistent with physiologic ketosis
– UGI study: normal anatomy, no malrotation
– MRI brain: normal
– EGD: Normal duodenum biopsies, focal moderate gastritis (negative H.
pylori), ulcerative esophagitis distal esophagus, proximal esophagus
with occasional eosinophils suggestive of reflux
•  Omeprazole (Prilosec) 20mg daily
• Admitted again in December 2012 and January 2013 for vomiting
– Woke up with vomiting at 2am on Christmas Eve
– In January the vomiting started at 6:45am
• January episode: at home gave Sumatriptan nasal spray and
Ondansetron, initially slept for 3 hours, but then had ongoing
vomiting, complaints of abdominal pain, pale appearing  admitted
• January hospital admission:
– NS bolus and then D10 1/2 NS with 20 mEq/L KCl at 1.5 times
maintenance
– Scheduled Ondansetron 0.3mg/kg IV q6 hours
– Scheduled Diphenhydramine 25mg IV q6 hours
• Lorazepam not given because parents felt he “freaked out” with it previously
– IV Esomeprazole (Nexium)
– Keep the room quiet and dark and with as few interruptions as possible
CVS Prophylaxis
• Preventive prophylactic pharmacotherapy if:
– Frequent episodes - occurring more than once a month
– Severe episodes - causing repeated hospitalizations and school
absences
• >15 emesis per episodes or >2 days in length
• Most commonly used medications for CVS prophylaxis are:
– Cyproheptadine
– Amitriptyline
– Propranolol
CVS Prophylaxis
• Cyproheptadine (Periactin)
– First choice for children 5 years old or younger
– 0.25-0.5mg/kg/day div BID–QHS; giving QHS may reduce effect of sedation
– Side effects: increased appetite, weight gain, sedation
• Amitriptyline
–
–
–
–
First choice for child >5yo
0.25-0.5mg/kg QHS and gradually increase weekly until 1-1.5 mg/kg QHS
Higher response rate when given at adequate dose for at least 4 weeks
Side effects: constipation, sedation, arrhythmia, behavioral changes
• Propranolol
–
–
–
–
2nd choice in children of all ages
0.25-1mg/kg/day, most often 10mg BID or TID
Side effects: lethargy, reduced exercise intolerance
Contraindications: asthma, diabetes, heart disease, depression
Effective Prophylactic Therapy for Cyclic Vomiting Syndrome in
Children Using Amitriptyline or Cyproheptadine
Andersen JM, Sugerman KS, Lockhart JR, Weinberg WA; Pediatrics 1997;100;977-981
• Retrospective chart review of 27 children with CVS
– 22 children treated with amitriptyline and 6 treated with cyproheptadine
(both=1), follow up ranged from 5 months to 10 years
• Mean interval between onset of symptoms and diagnosis was 2 years (range
3 months to 8 years)
• Vomiting frequency varied from weekly to q 3 months (most every 4-6 weeks)
• 50% of children had a parent or sibling with migraine history
• Treatment outcomes:
– 73% treated with amitriptyline and 66% treated with cyproheptadine
achieved complete remission
– If also including patients with partial response (50% or greater reduction
in frequency of attacks), 91% in amitriptyline group and 83% in
cyproheptadine group improved
– No patients experienced significant side effects to either medication
– Family history of migraine not predictive of response to either med
Cyclic Vomiting Syndrome in Children: Experience
with 181 Cases from Southern Iran
Haghighat M, Rafie SM, Dehghani SM et al. World J Gastroenterol 2007;13:1833
• 181 children diagnosed with CVS
–
–
–
–
88 boys and 93 girls
Mean age of onset of symptoms 4.9 yrs, mean age at diagnosis 6.9 yrs
Mean duration attack 4.2 days, mean interval between attacks 1.8 mo
Follow up ranged from 6 months to 12 years
• Patients randomly selected for prophylactic treatment with propranolol
or amitriptyline
– Amitriptyline was effective in 56%
– Propranolol was effective in 92%
– Patients who were non-responsive to amitriptyline were treated with
propranolol and most of them had a satisfactory response
– More side effects in patients on amitriptyline (irritability, agitation,
insomnia, or lethargy), propranolol without significant side effects
• If not responding to prophylactic medications, if episode pattern is
changing, or new symptoms appearing:
– Consider need for additional diagnostic testing to evaluate for diagnoses
other than CVS
• Obtain Abd U/S and UGI during episode, MRI, EGD
– Was an adequate trial administered (appropriate dose), was there lack
of adherence?
– Does the patient need combination therapy of two medications?
– Consider complementary therapy
• Alternative Prophylactic Medications
– L-Carnitine
• Serves as a transport cofactor for long chain fatty acids into mitochondria,
may help patients with suspected mitochondrial or metabolic dysfunction
• 50-100mg/kg/day div BID-TID up to 1g TID
* Van Calcar SC, Harding CO, Wolff JA: L-carnitine administration reduces number of
episodes in cyclic vomiting syndrome. Clin Pediatr 2002;41(3):171-174.
– Coenzyme Q10
• Serves as the electron shuttle between complexes of the mitochondrial
respiratory chain
• 5-10mg/kg/day div BID-TID up 100mg TID
Treatment of cyclic vomiting syndrome with co-enzyme
Q10 and amitriptyline, a retrospective study
Boles RG, Lovett-Barr MR, Preston A, et al. BMC Neurology 2010:10:10
• Retrospective questionnaire of 184 children and adults with CVS
diagnosis
– 22 took Co-Q and 162 took amitriptyline
• Queried episode frequency, episode duration, number of emeses, and
nausea severity
– Reduction of at least 50% was scored as positive
– Compound measure of “episode improvement” was scored as positive if
at least one of the four parameters were scored as positive
• Results:
– No difference between amitriptyline and CoQ in the compound measure
of episode improvement (72% amitriptyline and 68% Co-Q)
– Side effects were frequently reported with amitriptyline (50%) and not
recorded with Co-Q
• 21% discontinued amitriptyline because of side effects
• Erythromycin as a prokinetic agent
* Vanderhoof JA, Young R, Kaufman SS, et al. Treatment of Cyclic Vomiting in Childhood with
Erythromycin. J Pediatr Gastroent Nutr 1993;17:387-91.
• Low estrogen oral contraceptives – has been used to treat girls with
menstrual related CVS
– Attenuates estrogen drop before onset of menses
• Acupuncture at the P6 (pericardial) point may attenuate the severity
of CVS attacks
Johnston W. Acupuncture may treat cyclic vomiting syndrome. Anesth News 2000;5.
• Psychotherapy, especially stress reduction, may help as an
adjunctive therapy
* Magagna J. Psychophysiologic treatment of cyclic vomiting. J Pediatr Gastroenterol Nutr
1995;21 (Suppl.1):S31-6.
Natural History of CVS
• Most children suffer from CVS episodes for about 4-6 years
– As children get older, their episodes become less severe
• BUK Li, unpublished data
– Median age of resolution of vomiting episodes was 10 years old
– The younger the age of onset correlated with a longer duration
• Age at CVS onset <3yo  length of illness 5.8 years, 3-8yo  4.9 years,
>8yo  2.9 years
– 28% of children underwent the transition from CVS to migraine
headaches at 9.6 years old
– Projection analysis estimated that 75% of CVS patients will develop
migraine headaches by age 18
* Li BUK, Hayes JR. Unpublished data, 1999.
* Li BUK, Kagalwalla A. Unpublished data, 2002.
Cited by Li, BUK and Misiewicz L. Cyclic vomiting: A brain gut disorder. Gastroenterol Clin N Amer
2003;32:997-1019.
Patient #2 Follow Up
• Prophylactic medications:
– Following 4th episode in August 2012 tried amitriptyline - stopped after
~6 weeks because parents felt he had worsening of his behavior
– Then started cyproheptadine but parents again felt he had worsening of
his behavior so this was stopped
– After hospitalization in January 2013 he was started on CoQ10 100mg
BID and L-carnitine 1000mg BID
• Admitted for vomiting in February 2013, but this episode was different
– Vomiting started in the middle of the day
– Sudden onset of vomiting without any warning, felt completely well prior to
the onset of the vomiting
– No improvement with Ondansetron and Sumatriptan at home
– Episode otherwise similar in that he wouldn’t talk or swallow his saliva
– However vomiting was significantly less frequent and only lasted ~28 hours
• Most recent clinic appointment May 2013:
– Overall doing well on CoQ10, L-carnitine, and Omeprazole
– One episode in April 2013 when parents were away on vacation, but this
episode was much less severe
• Tired, not talking, spitting out his saliva, intermittent abd pain and headaches, but he didn’t
vomit and he didn’t require hospitalization
Summary
• CVS is characterized by stereotypical episodes of repeated vomiting
separated by periods where the patient feels completely well
• The “average” CVS patient starts having vomiting episodes in early
school age years, has monthly episodes of intense vomiting with
associated nausea, abdominal pain, pallor and lethargy that lasts
24-48 hours
• Initial evaluation in patients with recurrent vomiting should include
detailed history, exam, and UGI study
– If any red flags and/or continued episodes despite empiric CVS
treatment  consider labs, brain MRI, renal US, and/or EGD
• The goals of treatment of CVS are to prevent episodes from
occurring with prophylactic medications, use abortive therapies at
the onset of an episode to try to stop the episode from progressing,
and then supportive treatment when episodes do occur