自家中毒　周期性嘔吐症
Cyclic vomiting syndrome

Author
Emily Dulude, MD
David J Desilets, MD, PhD
Richard G Boles, MD
Section Editor
Nicholas J Talley, MD, PhD
Marc C Patterson, MD, FRACP
George D Ferry, MD
Deputy Editor
Peter A L Bonis, MD



Last literature review for version 17.2: 5月 1, 2009 | This topic last updated: 5月 26, 2009



INTRODUCTION — Cyclic vomiting syndrome (CVS) is an idiopathic disorder characterized by recurrent, stereotypical bouts of vomiting with intervening periods of normal health [1]. Although it appears to primarily affect children, it is being recognized increasingly in adults.

CVS was first described in France in 1861 [2]. The first English-language publication, in 1882, described three essential clinical features of the disorder, which still hold true today [3]:

Three or more recurrent discrete episodes of vomiting
Varying intervals of completely normal health between episodes
Episodes are stereotypical with regard to timing of onset, symptoms, and duration
A critical fourth criterion that has been added subsequently includes the absence of an organic cause of vomiting [4].

This topic review will provide an overview of cyclic vomiting syndrome in adults and children. A guideline on this topic has also been published [4].

EPIDEMIOLOGY — CVS is no longer considered to be rare in children. A cross-sectional study of school-age children in Aberdeen, Scotland, estimated that 34 of 2165 children (1.6 percent) fulfilled the diagnostic criteria for CVS [5]. Their average age was 9.6 years at the time of diagnosis, while the average age at the onset of symptoms was 5.3 years. The overall gender ratio was equal, although, among younger children, it was more common in boys. A similar age distribution has been described in other reports of children, although many have suggested that it may be more common in girls [4,6-10]. A family in which CVS appears to be inherited has been described [11].

The disorder appears to be less common in adults, although there are no population-based studies from which to derive estimates of its prevalence. One of the largest studies, which included 17 adult patients seen during a 10-year period at an academic medical center, found that the CVS began at an average age of 35 (range 14 to 73 years) but was not diagnosed until patients were on average 41 years old [12]. The gender distribution was equal. The average length of episodes was six days (range 1 to 21 days), with symptom-free intervals averaging three months (range 0.5 to 6 months). Similar findings have been described in other reports in adults [13,14].

Although there appear to be similarities in CVS across age groups [7], a few differences between adults and children have been observed [12]:

Adults have on average approximately four cycles per year in contrast with 12 cycles per year in children [15].
The age of onset covers a broad span in adults, while in children the age of onset is often in the toddler or preschool years.
Adults have usually been symptomatic for longer prior to diagnosis, possibly reflecting the increased recognition of CVS by pediatricians.
Triggering events are less common in adults.
Nausea between episodes is more common in adults.
PATHOGENESIS — The pathogenesis of CVS remains unknown, although it may represent a heterogeneous group of disorders. An association between CVS and migraine headaches has been most consistently described, suggesting that there may be a common pathophysiologic process. However, CVS has also been linked to food allergy, mitochondrial, metabolic, and endocrine disorders.

CVS and migraines — CVS has been linked to migraine headaches and abdominal migraine (show table 1) [16,17]. This connection is based upon the discreteness of episodes, the progression from cyclic vomiting to migraine headaches in many patients, the presence of a strong family history of migraine headaches in affected children (approximately 80 percent), and the response to antimigraine therapy in up to 80 percent of children [4,18]. Sympathetic autonomic dysfunction may predispose children to both CVS and migraine headaches [19,20]. (See "Pathophysiology, clinical features, and diagnosis of migraine in children").

One hypothesis is that CVS may lead to abdominal migraines, which in turn lead to migraine headaches. However, more children progress directly from CVS to migraines than from CVS to abdominal migraines to migraines. Abdominal migraines can be distinguished from CVS in that the core symptom of abdominal migraines is abdominal pain, not vomiting. Both syndromes may have headache as a feature and respond to antimigraine therapy [21].

Metabolic disorders — Mitochondrial disorders of fatty acid oxidation (eg, medium-chain acyl coenzyme A dehydrogenase deficiency), respiratory chain defects (eg, MELAS: Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Syndrome), and mitochondrial DNA deletions can be associated with episodes of metabolic crisis and vomiting, usually with infection or prolonged fasting [22]. (See "Presenting features of inborn errors of metabolism" and see "Overview of the hereditary ataxias").

One group suggested that about one-half of patients with cyclic vomiting syndrome have evidence for maternal inheritance of a mitochondrial DNA sequence variation [23]. Compared with controls, mothers of patients with cyclic vomiting syndrome were more likely to have a history of migraine, depression, irritable bowel syndrome, and hypothyroidism, disorders that the researchers hypothesized may segregate with cyclic vomiting syndrome in families due to predisposing mitochondrial DNA sequence variants. The authors speculated that cyclic vomiting syndrome represents a rare clinical presentation in individuals who carry the predisposing mitochondrial variants that are more commonly associated with migraine, depression, irritable bowel syndrome, hypothyroidism, and other functional/dysautonomic conditions [24,25].

Dysautonomia — Patients who have a hereditary sensory autonomic neuropathy (such as Riley Day Syndrome) can also have clinical features resembling CVS. (See "Hereditary sensory autonomic neuropathies").

Hypothalamic-pituitary-adrenal axis defects — Elevated corticotropin, cortisol, vasopressin, prostaglandin E2, and catecholamines have been described in a group of children with cyclic vomiting, profound lethargy, and hypertension [26]. Animal studies suggest that CVS may be a brain-gut disorder in which corticotropin-releasing factor induces gastric stasis and vomiting by vagal stimulation [27].

Food allergy — Sensitivity to cow's milk, soy, and egg white protein may be related to CVS in children [6]. Other food triggers include chocolate, cheese, and monosodium glutamate. The relationship between food allergy and CVS is uncertain.

Catamenial CVS — Similar to menstrual migraine headaches, some girls develop catamenial CVS at the onset of their menstrual period. Some respond to treatment with a low-dose estrogen or progesterone-only birth control pill, although oral contraceptives and other steroids can also precipitate vomiting episodes and other symptomatology in some. An association between symptoms and menses has also been described in adults [12].

Chronic cannabis use — Cessation of chronic cannabis use has been associated with resolution of cyclic vomiting in case reports suggesting a causal association [28-30]. In one series, the association was characterized by repetitive washing behavior during vomiting cycles [28]. However, many adults with CVS self-medicate with cannabis to alleviate the nausea.

CLINICAL MANIFESTATIONS — Each of the proposed diagnostic criteria suggests two essential features of cyclic vomiting syndrome. (See "Diagnosis" belowSee "Diagnosis" below).

Stereotypical episodes of vomiting regarding onset (acute) and duration (hours to days)
The absence of nausea and vomiting between episodes
Supportive criteria for the diagnosis of CVS include a history or family history of migraine headaches, the self-limited nature of the attacks, associated symptoms of nausea, abdominal pain, headache, motion sickness, photophobia, and lethargy, and associated signs of fever, pallor, diarrhea, dehydration, excess salivation, and social withdrawal. In children, nausea and possibly lethargy are considered to be key diagnostic features.

The specific pattern of vomiting episodes is variable among patients but, importantly, is stereotypical for an individual patient [31]. In general, CVS episodes tend to begin in the early morning hours (2:00 to 7:00 AM) and may involve a prodromal period of pallor, anorexia, nausea, abdominal pain, and/or lethargy (show table 2). In children, the attacks last an average of 24 to 48 hours. Approximately one-half of children have attacks at regular intervals, commonly occurring every two to four weeks, while the others have an unpredictable temporal pattern of vomiting. Approximately two-thirds of parents can identify a trigger, which is usually infectious (upper respiratory) or psychological (negative or positive) [32].

As noted above, episodes tend to be longer in adults (approximately three to six days) with longer intervening intervals of normal health (approximately three months) [12-14]. Intervening episodes of normal health are important for distinguishing CVS from functional nausea and vomiting in which symptoms are present continuously or nearly continuously (show figure 1).

The characteristics on presentation (and difficulty establishing the diagnosis) were illustrated in a group of 17 adults [12]:

Each patient had been evaluated by at least two physicians (typically with repeated imaging and endoscopic studies) and had been hospitalized at least once. Three patients (18 percent) required nutritional support.
Three patients had undergone surgical exploration and partial gastrectomy, pyloroplasty, or fundoplication without improvement.
Abdominal pain was present during episodes in approximately two-thirds of patients.
Only 20 percent of patients had a psychiatric diagnosis (either anxiety or another affective disorder).
Erosive esophagitis was observed in 50 percent of patients during or shortly after a vomiting episode (including one patient who had a Mallory-Weiss tear). However, in no patients did vomiting episodes improve with antireflux measures.
Only one-third of patients described a prodrome of nausea, epigastric pain, or both, while the others reported the onset of symptoms without warning.
Four of seven reproductive age women described a link to their menstrual cycle; two had severe episodes precipitated by pregnancy.
Sleep was beneficial in relieving symptoms in four patients (23 percent).
A history of migraine headaches was described in only four patients (23 percent).
NATURAL HISTORY — Many children outgrow CVS by their preteen or early teenage years. However, some authors have observed that up to 75 percent of children with CVS will go on to develop migraine headaches by age 18 [18]. A minority of children who progress from CVS to migraine headaches will first pass through a phase of abdominal migraines [33]. One retrospective study of 51 children followed for up to 13 years found that vomiting resolved in 60 percent [34]. However, 42 percent continued to have regular headaches and 37 percent had abdominal pain; these features were present even in patients whose vomiting had resolved.

The natural history in adults has not been well studied. In the series of 17 adults described above [12], 13 had at least a partial response to antidepressant therapy while an additional 3 responded to other types of treatment. One patient had persistent symptoms during two years of follow-up.

DIAGNOSIS — Cyclic vomiting syndrome remains a diagnosis based upon the history and exclusion of alternative diagnoses. At least two sets of criteria have been proposed based upon a consensus of experts.

Rome III criteria — Rome III criteria include the presence of all of the following [35]:

Stereotypical episodes of vomiting regarding onset (acute) and duration (less than one week)
Three or more discrete episodes in the prior year
Absence of nausea and vomiting between episodes
The criteria should be fulfilled for the last three months with symptom onset at least six months before diagnosis.

Supportive criteria include:

History or family history of migraine headaches.
North American Society for Pediatric Gastroenterology Hepatology and Nutrition — A consensus statement issued by the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN) suggests the following diagnostic criteria (all of which must be met) [4]. These recommendations apply to children and adolescents:

At least five attacks in any interval, or a minimum of three attacks during a six-month period
Episodic attacks of intense nausea and vomiting lasting 1 hour to 10 days and occurring at least one week apart
Stereotypical pattern and symptoms in the individual patient
Vomiting during attacks occurs at least four times per hour for at least one hour
Return to baseline health between episodes
Not attributed to another disorder
The recommendations for diagnosis and treatment from NASPGHAN (which apply to children and adolescents) are summarized in the algorithms (show algorithm).

Warning signs — Warning signs alerting to an alternative diagnosis include the presence of severe headaches, altered mental status, gait disturbances or other new "neurological signs", gastrointestinal bleeding, unilateral abdominal pain, weight loss, failure to respond to treatment, progressive worsening, prolonged episodes requiring hospitalization, and a change in pattern or symptoms [4]. An upper gastrointestinal series should be performed in children to exclude intestinal malrotation. (See "Intestinal malrotation"). Ureteropelvic junction obstruction has been reported to be an overlooked mimic of CVS in a case series of four children [36]. CVS should be considered among other diagnoses in patients presenting with nausea and vomiting. (See "Approach to the adult patient with nausea and vomiting" and see "Approach to the infant or child with nausea and vomiting").

One approach to excluding other disorders of recurrent vomiting includes a complete, extensive evaluation of standard blood work (electrolytes, glucose, ALT, GGTP, amylase, lipase), urinalysis, and (in children) evaluation for metabolic disorders (eg, lactate, ammonia, amino acids, urine organic acids) during an acute episode. (See "Approach to the infant or child with nausea and vomiting"). An upper gastrointestinal series with small bowel follow-through X-ray (UGI/SBFT), CT/MRI of the head, and endoscopy can be performed between episodes. As noted above, the presence of esophagitis on endoscopy (performed during or near an episode) does not necessarily imply that reflux is an underlying cause, since as many as one-half of patients will have esophagitis but will not respond to antireflux measures.

Only one in eight children with cyclical episodes of vomiting who were evaluated with this approach has been found to have another underlying disorder that required intervention [4]. However, the cost of initial diagnostic testing and annual ambulatory and hospital treatment of CVS using the above approach was estimated to be $17,035 per child in one report [21]. A decision-analysis concluded that a more cost-effective diagnostic strategy in children was to obtain a UGI/SBFT to rule out malrotation with volvulus, followed by a two-month trial of antimigraine therapy, with further studies reserved for those with continued symptoms [37]. In adults, a CT scan of the abdomen and pelvis has been suggested to exclude malignancy and other structural disorders.

TREATMENT — Patients may require supportive care during severe bouts of cyclic vomiting, which may include admission to a hospital, intravenous fluids, antiemetics, and occasionally analgesics. Children should be referred to a pediatric gastroenterologist, neurologist, or metabolic specialist. Recognized precipitating factors (more commonly observed in children) should be avoided whenever feasible. Examples include physical exhaustion, motion (car rides, amusement park rides), fasting, and certain foods (eg, chocolate, cheese).

No specific therapy has been proven to be effective for CVS in controlled trials. However, several empiric treatments have been effective in case series. Treatment with medications should be guided by three considerations [22]:

Whether there is a family history of migraines
Frequency of episodes
Severity of episodes
Treatment can also be considered as abortive, prophylactic, and supportive.

A trial of antimigraine medications is reasonable in patients with a family history of migraine headaches. Some authors recommend antimigraine therapy even in the absence of a personal or family history of migraines if, after careful evaluation, the diagnosis of CVS seems certain.

The decision to administer abortive and/or prophylactic antimigraine medications depends upon the frequency and severity of the attacks, similar to the principles that guide treatment of patients with migraine headaches. Prophylactic daily therapy with antimigraine medications is warranted if attacks occur more than once every one to two months or are severe enough to require hospitalization or substantial disability. In contrast, abortive therapy can be used if episodes occur less than once every one to two months or are mild. The choice of specific agents is discussed separately. (See "Management of migraine headache in children" and see "Acute treatment of migraine in adults" and see "Preventive treatment of migraine in adults").

Agents that have been used empirically (with variable success) in children include sumatriptan, erythromycin, carnitine, propranolol, cyproheptadine, and tricyclic antidepressants [38-40]. Some authorities advocate use of amitriptyline for prophylaxis in children older than five even if there is no history of headache or a family history of migraine [25]. A common starting dose is 0.5 mg/kg per day at bedtime, although many patients require a higher dose, often 1 mg/kg per day at bedtime. It typically takes one to three months for the effects of amitriptyline to become evident.

Some CVS patients who do not respond to 1 mg/kg per day have very low or undetectable blood levels of amitriptyline, and respond when the amitriptyline dosage is further increased. As a general rule, a blood amitryptyline level should be obtained before attempting to exceed 1 mg/kg/ per day to avoid a toxic level.

Use of amitriptyline may be limited in infants and toddlers under 5 years of age due to side effects (such as personality changes, anticholinergic effects, and tachyarrhythmias). The EKG (particularly the QTc interval) and electrolytes (K+, Mag+) should be monitored. Cyproheptadine and propranolol are often used as alternatives. Cyproheptadine is recommended as first-line treatment in children under age 5 years. Therapies of unproven efficacy that have been used include topiramate and co-enzyme Q10.

Sumatriptan, ketorolac, prochlorperazine, and tricyclic antidepressants have been used in case reports in adults [13,39,41,42]. Low-dose estrogen or progesterone-only birth control pills can be used as directed in females with catamenial CVS in whom vomiting attacks occur at the time of menses; however, birth control pills can also exacerbate symptoms in CVS patients [4,43]. (See "Estrogen-associated migraine"). A variety of antiemetic medications have been used unsuccessfully, including high dose dexamethasone, metoclopramide, ondansetron, and naloxone [42].

A clinical response to tricyclic antidepressants was observed in 13 of 17 adults in the report described above (although only three patients had a complete response) [12]. Antidepressants used included amitriptyline, doxepin, and nortriptyline (median dose for each is 50 mg daily). Two other patients responded to fluoxetine or cyproheptadine. Another report described improvement with zonisamide or levetiracetam (antiepileptic drugs) in adults who had symptoms refractory to tricyclic antidepressants [44]. However, side-effects (such as fatigue, confusion, headache, and poor concentration) were common.

During vomiting episodes, the goal is to abort or shorten the episode. Anecdotal experience in children suggests that intravenous administration of a 10 percent dextrose solution can decrease the frequency and duration of vomiting episodes [25] in about one-half of patients. Between episodes, frequent low fat feedings have been advocated to decrease the frequency of episodes. These observations may have a pathophysiologic basis in the impaired carbohydrate and fat metabolism that has been described in children with mitochondrial variants that may predispose to cyclic vomiting syndrome. (See "Metabolic disorders" above).

In addition to 10 percent intravenous dextrose, anecdotal experience suggests that high dose ondansetron (0.3 to 0.4 mg/kg/dose, maximum about 20 mg/dose), sedation (eg, with diphenhydramine or lorazepam), and a quiet, dark room are often helpful. Drinking water to induce vomiting (and thus lessening nausea) is common, and does not indicate a factitious or psychiatric etiology [45].

SUMMARY AND RECOMMENDATIONS

Definition —

Cyclic vomiting syndrome (CVS) is an idiopathic disorder characterized by recurrent, stereotypical bouts of vomiting with intervening periods of normal health. Although it appears to affect primarily children, it is being recognized increasingly in adults. (See "Introduction" above).
Pathogenesis —

The pathogenesis of CVS remains unknown, although it may represent a heterogeneous group of disorders. An association between CVS and migraine headaches has been most consistently described, suggesting that there may be a common pathophysiologic process. However, CVS has also been linked to food allergy, mitochondrial, metabolic, and endocrine disorders. (See "Pathogenesis" aboveSee "Pathogenesis" above).
Diagnosis — Diagnostic criteria have been proposed based upon consensus of experts. The specific pattern of vomiting is variable among patients but, importantly, is stereotypical for an individual patient. Cyclic vomiting syndrome remains a diagnosis based upon the history and exclusion of alternative diagnoses. (See "Diagnosis" aboveSee "Diagnosis" above).

Treatment — Treatment can be considered as abortive, prophylactic, and supportive. Most treatments have been based upon observational data or clinical experience, forming the basis for the following suggested approach (Grade 2C).

In adults, we generally start antimigraine therapy, especially if there is a family history of migraine headaches. If episodes occur more often than monthly, or if they are prolonged or debilitating, we start daily prophylactic therapy. If episodes are less frequent or are mild, we will usually try abortive therapy at the onset of episodes. If abortive therapy fails after two or three attempts, we switch to prophylactic therapy. (See "Management of migraine headache in children" and see "Acute treatment of migraine in adults" and see "Preventive treatment of migraine in adults").
In children, some authorities advocate use of amitriptyline (0.5 mg/kg per day increased as needed to 1 mg/kg or higher per day at bedtime) for prophylaxis even if there is no history of headache or a family history of migraine. However, its use may be limited due to side effects in infants and toddlers under age 5 years. The EKG (particularly the QTc interval) should be monitored. Cyproheptadine and propranolol are often used as alternatives. (See "Management of migraine headache in children"). In children under age 5 years, cyproheptadine is the first choice (or pizotifen outside of the United States).
Topiramate and coenzyme Q10 are unproven therapies that are gaining in popularity due to anecdotal experiences of efficacy. Abortive therapy with intravenous dextrose (10 percent) and high-dose ondansetron have been found to be helpful in anecdotal reports in children. Comfort measures during episodes include a dark quiet room, and sedation as appropriate. In addition, patients should be instructed to avoid fasting.

Support — Support and counseling may be helpful for selected patients. The Cyclic Vomiting Syndrome Association (CVSA), a national and international organization, was established in 1993 to provide phone support, support groups, regional conferences, a newsletter, and a web site.

For more information on the CVSA, contact:
Cyclic Vomiting Syndrome Association (CVSA-USA/Canada)
2819 West Highland Blvd.
Milwaukee, WI 53208
Phone: 414-342-7880
Fax: 414-342-8980
E-mail: cvsa@cvsaonline.org
Website: www.cvsaonline.org

Additional resources that might be useful are listed in the table (show table 3).

Guidelines — The above recommendations are similar to those issued by the North American Society of Pediatric Gastroenterology Hepatology and Nutrition, which apply to children and adolescents (show algorithm).



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GRAPHICS


Profile of symptoms in cyclic vomiting syndrome, abdominal migraine, and migraine headaches
Percentage of patients with symptom
CVS Abdominal migraine Migraine headache
Core symptoms
Vomiting 100 39-72 40-69
Abdominal pain 3-81 100 10-55
Headache 38-59 31-50 100
Associated symptoms
Lethargy 91
Pallor 87 90-100 23-88
Anorexia 74 91-98 13-93
Nausea 72 73-91 46-100
Photophobia 32 1-42 27-81

Adapted from: Li, BU, Balint, JP. Cyclic vomiting syndrome: Evolution in understanding of a brain-gut disorder. Adv Pediatr 2000; 47:117.


Clinical/epidemiological features of cyclic vomiting syndrome
Feature Characterization
Female:male ratio 55:45
Age of onset 5.3 years
Morbidity 20 d of missed school/year, 50 percent of patients require intravenous hydration
Symptoms:
Vomiting 6 times/hr at peak, with bile (76 percent) and blood (32 percent)
Autonomic Lethargy (91 percent), pallor (87 percent), fever (29 percent), salivation (13 percent)
GI Abdominal pain (80 percent), retching (78 percent), anorexia (74 percent), nausea (72 percent), diarrhea (36 percent)
Neurologic Headache (40 percent), photophobia (32 percent), phonophobia (28 percent), vertigo (22 percent)
Temporal pattern 24-48 h duration; 47 percent of patients have episodes at regular intervals, usually 2-4 weeks; episodes occur at night or early morning in 34-60 percent of patients; 98 percent of patients show a stereotypical pattern
Precipitating events Infection (41 percent), psychological stress (34 percent), dietary (26 percent), menstrual (13 percent), some trigger identified in 68 percent of patients
Natural history 3.4 yr duration; 28 percent of patients progress to migraine headaches; predicted 75 percent progress to migraines by age 18 yrs
Family history of migraine Present in 82 percent of patients

Adapted from: Li, BU, Balint, JP. Cyclic vomiting syndrome: Evolution in understanding of a brain-gut disorder. Adv Pediatr 2000; 47:117 and Li, BU. Cyclic vomiting: New understanding of an old disorder. Contemp Pediatr 1996; 17:48.


Differences between cyclic and chronic temporal patterns of vomiting

Differences between cyclic and chronic temporal patterns of vomiting can be compared when the number of emeses is plotted over a two-month period. The chronic pattern (red line) is characterized by low-grade, nearly daily episodes whereas the cyclic pattern (black line) is marked by high-intensity episodes every several weeks. Adapted from Li, BU. New hope for children with cyclic vomiting syndrome. Contemp Pediatr 2002; 19:121.

NASPGHN evaluation CVS


Evaluation of cyclic vomiting pattern in children older than 2 years

* May not need metabolic evaluation.
Reproduced with permission from: Li, BU, 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. J Pediatr Gastroenterol Nutr 2008; 47:379. Copyright ©2008 Lippincott Williams & Wilkins.

Lifestyle changes in CVS


Lifestyle changes in CVS
Lifestyle changes (for 1-2 months or 1-2 cycles)
Reassurance (eg, episodes are not self-induced) and anticipatory guidance (eg, natural history)
Avoidance of triggers
Keep a "vomiting diary" of potential precipitating factors
Avoid fasting
Recognize the potential role of excitement as a trigger (eg, downplay big events)
Maintain good sleep hygiene (eg, avoid sleep deprivation)
Avoid triggering foods: chocolate, cheese, monosodium glutamate, antigenic foods
Avoid excessive energy output
Supplemental carbohydrate: for fasting-induced episodes
Provide fruit juices, other sugar-containing drinks
Provide extra snacks between meals, before exertion, or at bedtime
Migraine headache lifestyle interventions
Regular aerobic exercise (avoid overexercising)
Regular meal schedules (ie, avoid skipping meals)
Moderation in consuming or avoidance of caffeine

Reproduced with permission from: Li, BU, 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. J Pediatr Gastroenterol Nutr 2008; 47:379. Copyright ©2008 Lippincott Williams & Wilkins.

Prophylactic medication CVS


Prophylactic or preventive medications* in CVS
Children 2 to 5 years old
Antihistamines: cyproheptadine (first choice) and pizotifen (available in UK, Canada)
Cyproheptadine 0.25-0.5 mg/kg/day orally divided twice daily or three times daily (maximum 12 mg per 24 hours). (Available in 2 mg/5 mL liquid).
Side effects: increased appetite, weight gain, sedation
Alternatives: pizotifen (available in UK, Canada)
Beta-blockers: propranolol (second choice)
Propranolol 0.25-1 mg/kg/day orally divided twice daily or three times daily, most often 10 mg twice daily or three times daily. Initiate at 0.25 mg/kg/day and increase every 1-4 weeks in increments of 0.25 mg/kg/day as needed and tolerated. (<35 kg maximum 60 mg per 24 hours. 35 kg maximum 120 mg per 24 hours). (Available in liquid). Monitor: resting heart rate maintain 60 bpm Side effects: lethargy, reduced exercise intolerance Contraindications: asthma, diabetes, heart disease, depression Discontinuation: tapered for 1-2 weeks Children older than 5 years Tricyclic antidepressants: amitriptyline (first choice) Amitriptyline begin at 0.25-0.5 mg/kg/day orally at bedtime, increase every 1-4 weeks as needed and tolerated by 5-10 mg, until 1-1.5 mg/kg/day (maximum 75 mg per 24 hours). (For dose >1 mg/kg/day, divide twice daily).
Monitor: EKG QTc interval before starting and 10 days after peak dose
Side effects: constipation, sedation, arrhythmia, behavioral changes (especially in young children)
Alternatives: nortriptyline (available in 10 mg/5 mL liquid)
Beta-blockers: propranolol (second choice) - see above
Other agents
Anticonvulsants: phenobarbital
Phenobarbital 2 mg/kg/day orally administered at bedtime (maximum 40 mg per 24 hours)
Side effects: sedation, cognitive impairment
Alternatives: topiramate, valproic acid, gabapentin, levetiracetam - consult Pediatric neurologist
Supplements
L-carnitine 50-100 mg/kg/day orally divided twice daily or three times daily (maximum 1 g three times daily)
Coenzyme Q10 10 mg/kg/day orally divided twice daily or three times daily (maximum 100 mg three times daily)
Side effects: diarrhea, fishy body odor (for L-carnitine)

* All medication recommendations are made for off-label use.
Limited or no published experience regarding efficacy.
Adapted from: Li, BU, 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. J Pediatr Gastroenterol Nutr 2008; 47:379. Copyright ©2008 Lippincott Williams & Wilkins.

Supportive abortive Rx CVS


Supportive and abortive treatment approaches in CVS
Supportive care
Fluid, electrolyte and nutritional management
Infuse 10% dextrose, 0.45% (half normal) saline solution and potassium chloride as appropriate at 1.5 times maintenance fluid rates OR through a Y-connector 10% dextrose infusion at one times maintenance and normal saline at 0.5 times maintenance
If no enteral intake for 3-5 days, initiate peripheral parenteral nutrition with 1.5 g of amino acids/kg/day and energy units above the catabolic threshold of 55-70 kcal/kg/day
Antiemetic (5HT3 antagonist) agents
Ondansetron 0.3-0.4 mg/kg/dose intravenously every 4-6 hours (maximum 20 mg per dose)
Side effects: constipation
Alternatives: granisetron
Sedatives
Diphenhydramine 1-1.25 mg/kg/dose intravenously every 6 hours (maximum 50 mg per dose)
Lorazepam 0.05-0.1 mg/kg/dose intravenously every 6 hours (maximum 2 mg per dose)
Side effects: respiratory depression, hallucinations
Chlorpromazine 0.5-1 mg/kg/dose intravenously every 6 hours + diphenhydramine (see above) intravenously:
<5 years or <23 kg maximum 10 mg per dose, 40 mg per 24 hours chlorpromazine >5 years or 23 kg maximum 18 mg per dose, 75 mg per 24 hours chlorpromazine
Side effects: dystonic reactions with chlorpromazine alone
Analgesics (nonsteroidal and narcotic) agents
Ketorolac 0.4-1 mg/kg intravenously every 6 hours x 48 hours (maximum 30 mg per dose, maximum 120 mg per 24 hours); avoid in renal insufficiency or dehydration
Side effects: gastrointestinal hemorrhage
Alternatives: narcotics, intravenous morphine or fentanyl by bolus or by patient-control infusion
Treatment of specific signs and symptoms: epigastric pain, diarrhea, and hypertension
Epigastric pain: acid suppression by H2RAs or PPIs, (eg, intravenous ranitidine, pantoprazole)
Diarrhea: antidiarrheals (eg, loperamide)
Hypertension: short-acting ACE inhibitors (eg, captopril)
Treatment of specific complications
Dehydration and electrolyte deficit: replace calculated deficits
Metabolic acidosis: determine cause and treat accordingly
SIADH: restrict free water intake
Hematemesis: intravenous H2RAs or PPIs
Weight loss: nasogastric or parenteral nutrition
Abortive care
Antimigraine (triptan) agents
Sumatriptan: 20 mg once intranasally as early as possible at episode onset for children 12 years and older (maximum 40 mg / 24 hours)
Side effects: neck pain/burning, coronary vasospasm
Contraindications: basilar artery migraine
Recovery and refeeding
Feed ad libitum when child declares episode is over

H2RAs: histamine-2 receptor antagonists. PPIs: proton pump inhibitors; ACE: angiotensive converting enzyme; SIADH: syndrome of inappropriate antidiuretic hormone.
Adapted from: Li, BU, 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. J Pediatr Gastroenterol Nutr 2008; 47:379. Copyright ©2008 Lippincott Williams & Wilkins.


Sample treatment protocol order sheet for a child having an acute attack of CVS
In Emergency Department and in-hospital settings, an example of a regimen would include:
Darkened, quiet room, take vital signs every 4-6 hours
If child is dehydrated, rehydrate with initial intravenous fluid bolus of 10 mL/kg normal 0.9% saline and repeat as clinically necessary
Infuse 10% dextrose 0.45% (half normal) saline solution with potassium chloride as appropriate at 1.5 times maintenance rates
Intravenous ondansetron 0.3 mg/kg/dose every 6 hours x 24 hours (maximum 20 mg per dose)
Intravenous lorazepam 0.05 mg/kg/dose every 6 hours x 24 hours (maximum 2 mg per dose)
If child has moderate to severe abdominal pain, intravenous ketorolac 0.5 to 1 mg/kg/dose (maximum 30 mg per dose) every 6 hours x 24 hours (avoid in renal insufficiency or prior to hydration if dehydrated)
Admit child if >5 percent dehydrated, no urine output >12 hours, Na+ <130 mEq/L, anion gap >18 mEq/L, or inability to stop emesis
Allow oral fluid intake

Adapted from: Li, BU, 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. J Pediatr Gastroenterol Nutr 2008; 47:379. Copyright ©2008 Lippincott Williams & Wilkins.


Grade 2C recommendation
A Grade 2C recommendation is a very weak recommendation; other alternatives may be equally reasonable.
Explanation:
A Grade 2 recommendation is a weak recommendation. It means "this is our suggestion, but you may want to think about it." It is unlikely that you should follow the suggested approach in all your patients, and you might reasonably choose an alternative approach. For Grade 2 recommendations, benefits and risks may be finely balanced, or the benefits and risks may be uncertain. In deciding whether to follow a Grade 2 recommendation in an individual patient, you may want to think about your patient's values and preferences or about your patient's risk aversion.
Grade C means the evidence comes from observational studies, unsystematic clinical experience, or from randomized, controlled trials with serious flaws. Any estimate of effect is uncertain.

Recommendation grades
1. Strong recommendation: Benefits clearly outweigh the risks and burdens (or vice versa) for most, if not all, patients
2. Weak recommendation: Benefits and risks closely balanced and/or uncertain

Evidence grades
A. High-quality evidence: Consistent evidence from randomized trials, or overwhelming evidence of some other form
B. Moderate-quality evidence: Evidence from randomized trials with important limitations, or very strong evidence of some other form
C. Low-quality evidence: Evidence from observational studies, unsystematic clinical observations, or from randomized trials with serious flaws

For a complete description of our grading system, please see the UpToDate editorial policy which can be found by clicking "About UpToDate" and then selecting "Policies".


Family support and informational resources
Cyclic Vomiting Syndrome Association (CVSA)
2819 W Highland Blvd, Milwaukee, WI 53208

Phone: 414-342-7880

Fax: 414-342-8980

cvsa@cvsaonline.org, www.cvsaonline.org

Gastroparesis and Dysmotilities Association (GDPA)
5520 Dalhart Hill NW, Calgary, AB, Canada T3A 1S9

Phone: 403-247-3215

www.gpda.net

International Foundation for Functional Gastrointestinal Disorders (IFFGD)
PO Box 170864, Milwaukee, WI 53217

Phone: 414-964-1799

Children: http://www.aboutkidsgi.org

Adults: http://www.iffgd.org

Migraine Awareness Group (MAGNUM)
113 S Saint Asaph, Suite 300, Alexandria, VA 22314

Phone: 703-739-9384

www.migraines.org

National Organization for Rare Disorders
55 Kenosia Ave, PO Box 1968, Danbury, CT 06813-1968

Phone: 203-744-0100, 800-999-6673

TDD number: 203-797-9590

Fax: 203-798-2291

www.nord-rdb.com

United Mitochondrial Disease Foundation
PO Box 1151, Monroeville, PA 15146-1151

Phone: 412-793-8077




Reproduced with permission from: Li, BU, 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. J Pediatr Gastroenterol Nutr 2008; 47:379. Copyright ©2008 Lippincott Williams & Wilkins.
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