REVIEW
Cyclic vomiting syndrome: A common, underrecognized disorder Thais Brown Tonore, MD (Associate Professor)1,2 , Danielle C. Spree, MSN, CFNP (Pre-Admission Testing)3 , & Thomas Abell, MD (Professor)4 1
Department of Family Medicine, University of Mississippi Medical Center, Jackson, Mississippi Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 3 Division of Digestive Diseases, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 4 Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, Kentucky 2
Keywords Children; disability; migraines; pharmacotherapy. Correspondence Thomas L. Abell, MD, Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS 39216. Tel: 601-984-4548; Fax: 502-852-0846; E-mail: [email protected] Received: April 2012; accepted: August 2012 doi: 10.1002/2327-6924.12068 Disclosure
Abstract Purpose: To increase recognition and present symptom assessment strategies for treating cyclic vomiting syndrome (CVS). Data sources: Clinical experience, a range of pediatric, gastroenterological, emergency medicine research, survey, and literature review reports on CVS. Conclusions: Improved efforts to recognize, diagnose, and treat CVS will help patients manage their symptoms and may reduce both the morbidity and costs of hospitalizations associated with this illness. Implications for practice: If promptly diagnosed and appropriately treated, CVS episodes can be aborted. Patients inappropriately treated must often be hospitalized because of complications associated with symptoms. Lifestyle changes, prophylactic and abortive migraine therapy, and supportive care are important to prevention.
The authors of this clinical review have no conflicting or competing interests, nor were any funds received for the production of this manuscript.
Introduction When an excellent report on cyclic vomiting syndrome (CVS, 2010), an idiopathic syndrome of intense, episodic vomiting interspersed with periods of normal health, was electronically published (Fleisher, Gornowicz, Adams, Burch, & Feldman, 2005; Abell et al., 2008), the characterization of this illness most often referenced in differential diagnoses derived from 19th century medical texts (Dulude et al., 2011). Despite a potential prevalence rate worldwide of 2%–7% (Gunderson, 1986; Tougas et al., 1999), CVS was seldom discussed outside psychiatry, gastroenterology, and pediatrics. Such neglect is now yielding to greater awareness. For nurses, who are likely to make triage and/or treatment decisions for patients with CVS, it is particularly important to understand the disorder’s clinical course. With prompt diagnosis and timely initiation of appropriate therapeutic options, caregivers can relieve symptoms and prevent hospitalization. Symptoms and historical course are often very characteristic for CVS. Even acute symptoms, managed early, can sometimes be aborted; however, without proper management, patients with CVS are likely to be hospitalized.
Here we provide an overview of this syndrome, based on both our clinical experience and a review of historical and recent articles identified through expert peer discussions, patient advocacy, and support group websites, and searches of the term “Cyclic Vomiting Syndrome” in pediatric, adult internal medicine, and gastroenterological journals. Diagnostic criteria for children and adults, treatment approaches for CVS, and concise checklists to help facilitate prompt and accurate recognition of CVS are also included. CVS is not “all in the mind.” However, psychiatric and psychological interventions may be important for patients with CVS, as its symptomatic phases take an immense toll on patients’ lives. Acute, episodic symptoms of CVS, where frequent or prolonged, may lead to social disruption and isolation, as patients fear to assume prior levels of activity and obligation. Both medical and psychosocial interventions for patients with progressive CVS symptom patterns are likely to improve as further research strengthens our understanding of physiological parameters that can predict when and how this debilitating syndrome overwhelms healthy function.
C 2013 The Author(s) Journal of the American Association of Nurse Practitioners 00 (2013) 1–8
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Understanding the clinical course of CVS Factors that may contribute to CVS Cyclic vomiting may be associated with a variety of conditions, including irritable bowel syndrome, headache, motion sickness, and seizure disorder (Cupini et al., 2003). One subset of CVS appears to be a migraine variant; its classic episodes occur with the abruptness of a migraine headache (Pareek, Fleisher, & Abell, 2007). Circumstantial evidence for the relationship of CVS with migraine includes identification of a family member with migraine headaches for 82% of patients with CVS, as compared to only 14% of those with chronic vomiting (Venkatasubramani, Venkatesan, & Li, 2007), a higher rate of improvement with antimigraine therapy for children with CVS than for those with chronic vomiting (Pareek et al., 2007), and the development of migraine headaches among many children and adults with CVS after the cyclic vomiting episodes cease. Further, CVS appears to be more prevalent in women than in men, as is migraine, for which many studies report an incidence of 15%–18% for females and 6%–8% for males (World Health Organization: Fact Sheet, 2004). Finally, electroencephalogram changes in CVS and migraine show similar patterns, supporting their association (Dignan et al., 2001). Symptom patterns seen in CVS are thought to be associated with neuropathy. The most important factor in diagnoses is a history of recurrent cycles of nausea and vomiting, often without any known cause. Current studies of CVS etiology and symptom pathways have employed measurements of autonomic function for markers of CVS susceptibility, mitochondrial DNA studies, mapping of stress-related responses in the hypothalamus, and neuroimaging during episodes to identify regions of disorganized activity. As these studies have yet to clarify exact mechanisms for this illness, however, ideal treatment regimens remain to be developed. However, effective therapies do exist, once the disorder is recognized and distinguished from other vomiting disorders. Prevalence rates for CVS (more commonly diagnosed in children than in adults) have been suggested, but not yet confirmed and established, despite current efforts (Pareek et al., 2007). Population studies for similar disorders, such as chronic nausea and recurrent vomiting, have reported prevalence rates of 2%–7% worldwide (migraine prevalence is reported at 25%; Pareek et al., 2007; Venkatasubramani et al., 2007).
CVS in children and in adults CVS is suggested by a history of recurrent, episodic vomiting not associated with other known causes. Age 2
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of onset is reported to range from 6 days to 73 years (Li & Misiewicz, 2003). Although first described in children, adults with no childhood history of CVS may also be diagnosed with the illness (Adams, 2006). Its symptoms manifest differently in children than in adults, with children experiencing an average of 12 cycles each year, as compared to four cycles annually for adults. Children, who are diagnosed at an average age of 9.6 years, with symptom onset at an average age of 5.3 years (Tougas et al., 1994), typically experience a much shorter interval between initial symptoms and diagnosis, at 2.7 years, than do adults, at 8 years. Patients are often very ill when a cycle of CVS starts, classically vomiting continuously for protracted periods of time. Perhaps owing to the fragility of children in the context of dehydration and compromised nutrition, pediatricians recognize CVS in up to 2% of their patients (Pareek et al., 2007), and treat it far more promptly than often occurs for adults. Identifiable triggering events are more common in pediatric than in adult patients (Bullard & Page, 2005), with excitement or emotional stress often leading to symptoms, along with specific foods, overeating, hot weather, hormonal changes, motion sickness, and physical exhaustion (Venkatasubramani et al., 2007), as are seen with migraine. CVS symptom onset in adults, now reported with increasing frequency, commences at an average age of 35 years, followed by diagnosis at an average age of 41. Common triggers for adults include infections, particularly sinus infections, flu, and colds. Allergies also may precipitate an attack. In one of our recent studies, a CVSlike presentation was observed for over 50% of patients diagnosed with both diabetes mellitus and gastroparesis (Christensen, Johnson, & Abell, 2008).
CVS cycles and symptom phases Once CVS is suspected, further questioning may reveal distinct phases of the illness. A single CVS cycle is comprised of four phases, the prodromal, emetic, recovery, and well intervals. The prodromal period consists of a sudden onset, lasting 1–2 h, that is often accompanied by abdominal pain, sweating, irritability, anorexia, and pallor. During the emetic phase, which may extend from 1 to 3 days in children and 6 to 9 days in adults, the patient may be unable to take medication by mouth, eat, or drink because of persistent nausea and vomiting. The emetic phase is followed by the recovery phase, during which vomiting stops and the patient’s normal color, energy, and appetite return. Within the final phase, the “well” interval, no symptoms are noted (CVS, 2010; Venkatasubramani et al., 2007). Over 90% of patients with CVS experience marked pallor and lethargy; 80% have anorexia, nausea, retching,
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Pa ent Name: ______________________________________________ DOB/Age:___________ Medica ons (Prokine cs, An eme cs, etc.): ______________________________________________________________ _____________________________________________________________________________________________________________________
T:_____ P:_____ BP:_____ RR:_____
Wt:_____ Ht:_____ BMI:_____
Rate symptoms in 1-5 and 7-10 on a scale from 0-4 (Low to high, See key on following page): 1. Severity of Nausea (0-4):
_____
Frequency of Nausea (0-4):
_____
2. Severity of Vomi ng (0-4):
_____
Frequency of Vomi ng (0-4):
_____
3. Severity of Early Sa ety (0-4):
_____
Frequency of Early Sa ety (0-4):
_____
4. Severity of Bloa ng (0-4): 5. Severity of Abdominal Pain (0-4): Sum of Items 1-5 (0 –20): 6. Upper GI Total Severity Score:
_____ _____
_____ _____
_____
Frequency of Bloa ng (0-4): Frequency of Abdominal Pain (0-4): Sum of Items 1-5 (0 –20): Upper GI Total Frequency Score:
_____
7. Severity of cons pa on (0-4):
_____
Frequency of cons pa on (0-4):
_____
8. Severity of diarrhea (0-4):
_____
Frequency of diarrhea (0-4):
_____
9. Severity, frequent urina on (0-4):
_____
Frequency, frequent urina on(0-4):
_____
Frequency, infrequent urina on(0-4): Sum of Items 1-5 (0 –20):
_____
10. Severity, infrequent urina on (0-4): _____ Sum of Items 7-10 (0 –20): 11. Lower GI Total Severity Score:
_____
Lower GI Total Frequency Score:
_____
12. IDIOMS score (QOL)? (See Pa ent Assessment form) __________________________________ 13. This year, how o en: Seen in ED? ______________ Admi ed to hospital? ______________ 14. Frequency of vomi ng (number of spates) during current episode: _____________________ 15. Number of spates of vomi ng per hour during current episode?
_____________________
16. Diarrhea with vomi ng during this episode? _________________________________________ 17. Reflux with vomi ng during this episode?
_________________________________________
18. Prodromal symptoms (aura, drowsiness, imbalance, dizziness, pallor, etc.)? _______________ ___________________________________________________________________________________________________________________________________________
19. Triggers (specific foods, such as fa y, acidic, etc.; stress, physical or emo onal; sleeplessness)? ___________________________________________________________________________________________________________________________________________
21. Overlaps (headaches, fibromyalgia, bladder problems, endometriosis, depression, autonomic disorders, cancers, learning disorders, dyslexia) __________________________________________ ___________________________________________________________________________________________________________________________ ________________
Figure 1 Acute care checklist.
and/or abdominal pain as well (Cutts et al., 2005). Other associated symptoms include fever, headache, motion sickness, photophobia, diarrhea, dehydration, excess salivation, and social withdrawal (Dulude et al., 2011). CVS episodes are usually stereotyped for length and symptoms, and characteristic for each patient over time, although they can occur without regular or predictable pat-
terns (Li & Misiewicz, 2003). Stereotypical CVS episodes begin for many patients around the same time of day, usually 2:00 a.m. to 7:00 a.m., and follow a similar course with respect to duration, symptoms, and intensity. Although adult symptoms often last longer, they occur less frequently than those of children, as earlier described (Venkatasubramani et al., 2007).
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The following key can be used in conjunc on with the Emergency Department checklist, the pa ent selfassessment form, and the Inves gator Derived Independent Outcome Measures Score (IDIOMS) quality-oflife tool to assess the severity and frequency of GI symptoms, so as to provide greater precision in quan fying symptom impact on pa ent func on. Severity
Frequency
0 = Absent
0 = Absent
1 = Mild (does not affect usual ac vi es)
1 = Rare (1 me/week)
2 = Moderate (infrequently affects usual ac vi es)
2 = Occasional (2-3 times/week)
3 = Severe (affects usual ac vi es)
3 = Frequent (4-6 mes/week)
4 = Extremely Severe (requires bed rest)
4 = Extreme (≥7 mes/week)
PaƟent Name:______________________________ Medical Records Number:______________ Date: ________________ Figure 2 Cyclic vomiting syndrome/GI symptom score key.
Diagnostic characteristics of CVS
At the history and physical examination
At presentation
Obtaining a patient history and physical examination in the context of CVS may be hampered by recurrent vomiting. A prompt, accurate diagnosis must exclude other surgical conditions associated with vomiting through abdominal radiographs or abdominal CT, and must evaluate the possibility of metabolic conditions, such as pancreatic, hepatobiliary, and endocrine disorders through laboratory tests, which are best performed during an attack (Li & Misiewicz, 2003). Although many essential clinical features of CVS have remained consistent since Samuel Gee’s 1882 description, establishing a diagnosis of CVS may now include a vomiting severity of at least four periods of emesis per hour. The following suggestions by Prakash et al. (2001), however, provide useful minimum criteria for diagnosing CVS in adults.
Patients of any age with CVS may present for acute care, seeking relief from recurrent, prolonged attacks of severe nausea, vomiting, and prostration that may continue from a matter of hours to days. These episodes are often attributed to a viral gastroenteritis, but often there are no others in close contact with the patient who are ill. The attacks, interspersed with normal periods of varied duration, may or may not begin with a prodromal sign or event, such as nausea. Once begun, however, vomiting typically continues at regular intervals with great severity (Pareek et al., 2007). However, except for infants, for whom the danger of dehydration rapidly secures attention, patients with CVS may be contrasted during triage to patients with acute ischemic events, myocardial infarctions, injuries subsequent to accidents and abuse, and overdoses, and find themselves relegated to a long series of consults. They may also be misdiagnosed, a particularly worrisome possibility when the vomiting is accompanied by abdominal pain, as unnecessary surgery (e.g., appendectomy) sometimes results before the disorder is correctly identified. Diarrhea is variable, and when present, is often attributed to infectious causes. If left untreated, CVS attacks resolve spontaneously, but often result in hospitalization because of the effects of the vomiting.
4
■
■
■
Three or more recurrent, discrete episodes of nausea and vomiting. Varying periods of no symptoms between these episodes. Negative radiological and laboratory findings for other diagnoses.
In addition, as with migraines, episodes are often stereotypical in time of onset, symptoms, and duration
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Circle the score for each symptom (0 to 4) Severity
Frequency
0 = Absent 1 = Mild (does not affect usual ac vi es) 2 = Moderate (infrequently affects usual ac vi es) 3 = Severe (affects usual ac vi es) 4 = Extremely Severe (requires bed rest)
0 = Absent 1 = Rare (1 me/week) 2 = Occasional (2-3 mes/week) 3 = Frequent (4-6 mes/week) 4 = Extreme (≥7 mes/week)
How you feel now (Baseline)
Frequency
Severity
Upper Symptoms: Vomi ng 0 1 2 3 4 0 1 2 3 4 Nausea 0 1 2 3 4 0 1 2 3 4 Early Sa ety (feels full quickly) 0 1 2 3 4 0 1 2 3 4 Bloa ng 0 1 2 3 4 0 1 2 3 4 Epigastric Pain 0 1 2 3 4 0 1 2 3 4 Lower GI Symptoms: Cons pa on 0 1 2 3 4 0 1 2 3 4 Diarrhea 0 1 2 3 4 0 1 2 3 4 Frequent Urina ng 0 1 2 3 4 0 1 2 3 4 Infrequent Urina ng 0 1 2 3 4 0 1 2 3 4 Please check any symptoms experienced by yourself and your biological parents below: Symptom
You (Pa ent)
Your Biological Mother
Her Family
Your Biological Father
His Family
Headaches Fibromyalgia Bladder problem Endometriosis Depression Autonomic Disorders Cancers Learning Disorders Dyslexia 1. Please list any specific problem(s) that you are experiencing today: 2. Your last hospitaliza on was when? where? why? 3. Have there been any changes in your medica ons? 4. Are there other issues about which we should know? Figure 3 Cyclic vomiting syndrome/GI symptom patient self-assessment form.
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Severity of Illness (SoI) Mild Symptoms
1
2
Moderate Symptoms
3
4
5
Severe Symptoms
6
7
8
Very Severe Symptoms
9
10
Other Significant Illnesses (OSI) Mild Symptoms
1
2
Moderate Symptoms
3
4
5
Severe Symptoms
6
7
8
Very Severe Symptoms
9
10
Intensity of Services (IoS) Mild Symptoms
1
2
Moderate Symptoms
3
4
5
Severe Symptoms
6
7
8
Total score (the sum of the individual scores for SoI, OSI, and IoS):
Very Severe Symptoms
9
10
_____________
Comments: ________________________________________________________________________________ ________________________________________________________________________________ ________________________________________________________________________________ Modified from Form ID ID-InvesƟgator Derived Independent Outcome Measure Scores (IDIOMS) Figure 4 Quality-of-life tool.
(Dulude et al., 2011; Prakash et al., 2001). The decision about ordering additional diagnostic, for example, a head CT scan, can often be postponed from the acute setting, unless other aspects of history and/or physical suggest the need for urgent imaging. 6
Gross physical exam will confirm the history of vomiting and may also reveal dry mucous membranes, as well as a greater pallor than normal, reflecting dehydration and the shunting of blood from the periphery because of vasoconstriction. Laboratory findings consistent with
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dent Outcomes Measure Score (IDIOMS), is a Likert scale (0–4, low to high) instrument that can help in quickly assessing the impact of gastrointestinal (GI) symptoms on patient QOL, and thus assist in evaluating symptom severity (adapted from Cutts et al., 2005).
Essentials of diagnosis The role of ICD-9 coding A factor hampering the recognition of CVS as a diagnostic disorder is its lack of a distinct ICD-9 code. This issue is now being addressed by at least one CVS support group, which has an application for an ICD-9 code for the disorder pending.
Appropriate therapeutic options and management for patients with CVS Rapid access to care
Figure 5 Cyclic vomiting syndrome flow chart.
dehydration and disturbed acid–base parameters can help confirm clinical suspicion of CVS. An orthostatic drop in blood pressure, lying versus sitting, may reflect not only dehydration, but also an underlying postural defect associated with a migraine-like physiology (Rashed et al., 1999).
Readily available guidelines and checklists Published criteria for the diagnosis of children are available through the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Consensus Statement (NASPGHAN, 2008), and for adults through the Rome III Diagnostic Criteria (Rome Foundation, 2006). Here, we have provided in our Appendix an acute care checklist (Figure 1) and key (Figure 2), a patient self-assessment instrument (Figure 3), a simple, quality-of-life (QOL) tool (Figure 4), and a CVS management flow chart (Figure 5), useful in conjunction with the checklist, for use in rapidly distinguishing CVS from other causes of vomiting, as well as for patient management. The QOL tool, the Investigator Derived Indepen-
Rapid access to medical care in CVS can shorten the episode and prevent complications from prolonged vomiting. Avoidance of triggers, where they can be identified, may help in aborting an episode, and should be attempted (Forbes, 1995). Hospitalization with intravenous fluids and antiemetics may be necessary. If pain is present, analgesics are indicated. Empiric treatment with antimigraine therapy has been successful in preventing and aborting attacks for some patients, particularly those with a family history of migraines (Dulude et al., 2011). Intravenous administration of fluids to combat dehydration, and subsequent intravenous administration of agents, such as chlorpromazine (thorazine), diphenhydramine (benadryl), or lorazepam (ativan), to block the nausea may also be warranted (Forbes, 1995). These treatments can often be provided in clinics and emergency departments (Venkatesan et al., 2010); if the patient does not respond to them, however, hospital admission may be required. The patients sometimes require higher than usual doses of antiemetics because of the severity of their symptoms.
Management strategies Strategies for managing CVS include avoidance therapy, pharmacologic prophylaxis, abortive therapy (once the nausea or vomiting has begun), supportive care during an episode, and family support. Avoidance of dietary triggers (e.g., cheese, chocolate, monosodium glutamate), as well as improved psychological stress management skills, may help with prevention of the attacks. If attacks occur more than once a month, pharmacologic therapy with antimigraine agents, prokinetic agents, and neuroleptics may be indicated for 7
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prophylaxis. Erythromycin has been used as a prokinetic agent. Propranolol (inderal), cyproheptadine (periactin), and amitriptyline (elavil) have also been found to decrease the frequency and severity of episodes. Antimigraine agents and antiemetics can be used to abort an attack, and may be given parenterally at the onset of symptoms. Ondansetron (zofran) has been 62% effective in decreasing the symptoms. Transnasal administration of sumatriptan succinate (imitrex) has a 51% efficacy (Fleisher et al., 2005; Venkatesan, Marcus, Sundaram, & Li, 2002). As mentioned above, higher than commonly used doses of some medications, for example, ondansetron may be needed, often approaching the doses used for the GI symptoms of cancer chemotherapy.
Enlisting the patient and family for management and support Accessible descriptions and empiric guidelines for managing the symptoms of CVS can be found on the website of Dr. David Fleisher, University of Missouri Health Care (Fleisher, 2013). In addition, patients and their families may find information and support from patient groups, such as the CVS Association, which since 1993 has provided information on treatment, research and patient support networks, newsletters and online links, phone support, regional conferences, and provider information (CVS, 2010).
Conclusion A prompt and accurate diagnosis, often based on classic presentation, and timely institution of appropriate treatment, as well as the attention of empathetic medical personnel can greatly help patients with CVS to manage their symptoms, and may reduce both the morbidity and costs of hospitalization associated with this illness.
Acknowledgments The authors would like to thank Drs. Namita Pareek and Archana Kedar of the Division of Digestive Diseases, Joy Hughes of the School of Medicine, and Jo Anne Fordham and Jane Free of the Division of Digestive Diseases for their assistance with this article.
References Abell, T. L., Adams, K. A., Boles, R. G., Bousvaros, A., Chong, S. K. F., Fleisher, D. R., . . . Vakil, N. (2008). Cyclic vomiting syndrome in adults. Neurogastroenterology & Motility, 20, 269–284. Adams, K. (2006). President’s message. Code ‘V’: Newsletter of the Cyclic Vomiting Syndrome Association, 14(2), 2.
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Bullard, J., & Page, N. E. (2005). Cyclic vomiting syndrome: A disease in disguise. Pediatric Nursing, 31(1), 27–29. Christensen, C., Johnson, W., & Abell, T. L. (2008). Comparison of diabetic gastropathy with or without cyclic vomiting syndrome (CVS). Scandinavian Journal of Gastroenterology, 3(9), 1076–1081. Cupini, L., Santorelli, F., Iani, C., Fariello, G., & Calabresi, P. (2003). Cyclic vomiting syndrome, migraine and epilepsy; a common underlying disorder. Headache, 43, 407–409. Cutts, T. F., Luo, J., Starkebaum, W., Rashed, H., & Abell, T. L. (2005). Is gastric electrical stimulation superior to standard pharmacologic therapy in improving GI symptoms, healthcare resources and long-term healthcare benefits? Neurogastroenterology & Motility, 17, 35–43. Cyclic Vomiting Syndrome (CVS): National Digestive Diseases Information Clearinghouse. (2010). Code ‘V’: Newsletter of the Cyclic Vomiting Syndrome Association—USA/Canada, 12(2), 1–4. Dignan, F., Symon, D., AbuArefeh, I., & Russell, G. (2001). The prognosis of cyclical vomiting syndrome. Archives of Disease in Childhood, 84, 55–57. Dulude, E., Desilets, D. J., & Boles, R. G. (2011). Cyclic vomiting syndrome. UpToDate. “Cyclic vomiting syndrome.” Retrieved from http://www. uptodate.com/contents/cyclic-vomiting-syndrome Fleisher, D. R. (2013). University of Missouri School of Medicine: David R. Fleisher. Retrieved from http://medicine.missouri.edu/childhealth/ fleisher.html. Fleisher, D. R., Gornowicz, B., Adams, K., Burch, R., & Feldman, E. J. (2005). Cyclic vomiting syndrome in 41 adults: The illness, the patients, and problems of management. BMC Medicine. Retrieved from http://www. biomedcentral.com/content/pdf/1741--7015--3--20.pdf Forbes, D. (1995). Cyclic vomiting syndrome. Journal of Paediatric Child Health, 31(2), 67–69. Gunderson, C. (1986). Management of the migraine patient. American Family Physician, 33(1), 137–143. Li, B. U. K., & Misiewicz, L. (2003). Cyclic vomiting syndrome: A brain-gut disorder. Gastroenterology Clinics of North America, 32(3), 997–1019. Retrieved from http://home.mdconsult.com North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN). (2008). Consensus statement on the diagnosis and management of cyclic vomiting syndrome. Journal of Pediatric Gastroenterology and Nutrition, 47, 379–393. Pareek, N., Fleisher, D., & Abell, T. L. (2007). Cyclic vomiting syndrome: What a gastroenterologist needs to know. American Journal of Gastroenterology, 102, 1–9. Prakash, C., Staiano, A., Rothbaum, R., & Clouse, R. E. (2001). Similarities in cyclic vomiting syndrome across age groups. American Journal of Gastroenterology, 69(3), 684–688. Rashed, H., Abell, T. L., Familoni, B., & Cardoso, S. (1999). Autonomic function in cyclic vomiting syndrome and classic migraine. Digestive Diseases and Sciences, 44(8), 74S–78S. Rome Foundation. Rome III Diagnostic Criteria. (2006). Cyclic vomiting syndrome. Gastroenterology, 20(5), 1377–1556. Retrieved from http://www.romecriteria.org/criteria/ Tougas, G., Chen, Y., Hwang, P., Liu, M. M., & Eggelston, A. (1999). Prevalence and impact of upper gastrointestinal symptoms in the Canadian population: Findings from the DIGEST study. American Journal of Gastroenterology, 94(10), 2845–2854. Venkatasubramani, N., Venkatesan, T., & Li, B. U. K. (2007). Extreme emesis: Cyclic vomiting syndrome. Practical Gastroenterology, 21(9), 21–34. Venkatesan, T., Marcus, S., Sundaram, S., & Li, B. U. K. (2002). Cyclic vomiting syndrome. eMedicine. Retrieved from http://www.emedicine.com/ ped/topic2910.htm Venkatesan, T., Tarbell, S., Adams, K., McKanry, J., Barribeau, T., Beckmann, K., . . . Li, B. U. K. (2010). A survey of emergency department use in patients with cyclic vomiting syndrome. BMC Emergency Medicine. Retrieved from http://www.biomedcentral.com/content/pdf/1471--227x-10--4.pdf World Health Organization. Headache disorders: Fact sheet no. 277. Retrieved from http://www.who.int/mediacentre/factsheets/fs277/en/
Cyclic vomiting syndrome: A common, underrecognized disorder Thais Brown Tonore, MD (Associate Professor)1,2 , Danielle C. Spree, MSN, CFNP (Pre-Admission Testing)3 , & Thomas Abell, MD (Professor)4 1
Department of Family Medicine, University of Mississippi Medical Center, Jackson, Mississippi Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 3 Division of Digestive Diseases, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 4 Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, Louisville, Kentucky 2
Keywords Children; disability; migraines; pharmacotherapy. Correspondence Thomas L. Abell, MD, Division of Digestive Diseases, University of Mississippi Medical Center, Jackson, MS 39216. Tel: 601-984-4548; Fax: 502-852-0846; E-mail: [email protected] Received: April 2012; accepted: August 2012 doi: 10.1002/2327-6924.12068 Disclosure
Abstract Purpose: To increase recognition and present symptom assessment strategies for treating cyclic vomiting syndrome (CVS). Data sources: Clinical experience, a range of pediatric, gastroenterological, emergency medicine research, survey, and literature review reports on CVS. Conclusions: Improved efforts to recognize, diagnose, and treat CVS will help patients manage their symptoms and may reduce both the morbidity and costs of hospitalizations associated with this illness. Implications for practice: If promptly diagnosed and appropriately treated, CVS episodes can be aborted. Patients inappropriately treated must often be hospitalized because of complications associated with symptoms. Lifestyle changes, prophylactic and abortive migraine therapy, and supportive care are important to prevention.
The authors of this clinical review have no conflicting or competing interests, nor were any funds received for the production of this manuscript.
Introduction When an excellent report on cyclic vomiting syndrome (CVS, 2010), an idiopathic syndrome of intense, episodic vomiting interspersed with periods of normal health, was electronically published (Fleisher, Gornowicz, Adams, Burch, & Feldman, 2005; Abell et al., 2008), the characterization of this illness most often referenced in differential diagnoses derived from 19th century medical texts (Dulude et al., 2011). Despite a potential prevalence rate worldwide of 2%–7% (Gunderson, 1986; Tougas et al., 1999), CVS was seldom discussed outside psychiatry, gastroenterology, and pediatrics. Such neglect is now yielding to greater awareness. For nurses, who are likely to make triage and/or treatment decisions for patients with CVS, it is particularly important to understand the disorder’s clinical course. With prompt diagnosis and timely initiation of appropriate therapeutic options, caregivers can relieve symptoms and prevent hospitalization. Symptoms and historical course are often very characteristic for CVS. Even acute symptoms, managed early, can sometimes be aborted; however, without proper management, patients with CVS are likely to be hospitalized.
Here we provide an overview of this syndrome, based on both our clinical experience and a review of historical and recent articles identified through expert peer discussions, patient advocacy, and support group websites, and searches of the term “Cyclic Vomiting Syndrome” in pediatric, adult internal medicine, and gastroenterological journals. Diagnostic criteria for children and adults, treatment approaches for CVS, and concise checklists to help facilitate prompt and accurate recognition of CVS are also included. CVS is not “all in the mind.” However, psychiatric and psychological interventions may be important for patients with CVS, as its symptomatic phases take an immense toll on patients’ lives. Acute, episodic symptoms of CVS, where frequent or prolonged, may lead to social disruption and isolation, as patients fear to assume prior levels of activity and obligation. Both medical and psychosocial interventions for patients with progressive CVS symptom patterns are likely to improve as further research strengthens our understanding of physiological parameters that can predict when and how this debilitating syndrome overwhelms healthy function.
C 2013 The Author(s) Journal of the American Association of Nurse Practitioners 00 (2013) 1–8
C 2013 American Association of Nurse Practitioners
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Cyclic vomiting syndrome
Understanding the clinical course of CVS Factors that may contribute to CVS Cyclic vomiting may be associated with a variety of conditions, including irritable bowel syndrome, headache, motion sickness, and seizure disorder (Cupini et al., 2003). One subset of CVS appears to be a migraine variant; its classic episodes occur with the abruptness of a migraine headache (Pareek, Fleisher, & Abell, 2007). Circumstantial evidence for the relationship of CVS with migraine includes identification of a family member with migraine headaches for 82% of patients with CVS, as compared to only 14% of those with chronic vomiting (Venkatasubramani, Venkatesan, & Li, 2007), a higher rate of improvement with antimigraine therapy for children with CVS than for those with chronic vomiting (Pareek et al., 2007), and the development of migraine headaches among many children and adults with CVS after the cyclic vomiting episodes cease. Further, CVS appears to be more prevalent in women than in men, as is migraine, for which many studies report an incidence of 15%–18% for females and 6%–8% for males (World Health Organization: Fact Sheet, 2004). Finally, electroencephalogram changes in CVS and migraine show similar patterns, supporting their association (Dignan et al., 2001). Symptom patterns seen in CVS are thought to be associated with neuropathy. The most important factor in diagnoses is a history of recurrent cycles of nausea and vomiting, often without any known cause. Current studies of CVS etiology and symptom pathways have employed measurements of autonomic function for markers of CVS susceptibility, mitochondrial DNA studies, mapping of stress-related responses in the hypothalamus, and neuroimaging during episodes to identify regions of disorganized activity. As these studies have yet to clarify exact mechanisms for this illness, however, ideal treatment regimens remain to be developed. However, effective therapies do exist, once the disorder is recognized and distinguished from other vomiting disorders. Prevalence rates for CVS (more commonly diagnosed in children than in adults) have been suggested, but not yet confirmed and established, despite current efforts (Pareek et al., 2007). Population studies for similar disorders, such as chronic nausea and recurrent vomiting, have reported prevalence rates of 2%–7% worldwide (migraine prevalence is reported at 25%; Pareek et al., 2007; Venkatasubramani et al., 2007).
CVS in children and in adults CVS is suggested by a history of recurrent, episodic vomiting not associated with other known causes. Age 2
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of onset is reported to range from 6 days to 73 years (Li & Misiewicz, 2003). Although first described in children, adults with no childhood history of CVS may also be diagnosed with the illness (Adams, 2006). Its symptoms manifest differently in children than in adults, with children experiencing an average of 12 cycles each year, as compared to four cycles annually for adults. Children, who are diagnosed at an average age of 9.6 years, with symptom onset at an average age of 5.3 years (Tougas et al., 1994), typically experience a much shorter interval between initial symptoms and diagnosis, at 2.7 years, than do adults, at 8 years. Patients are often very ill when a cycle of CVS starts, classically vomiting continuously for protracted periods of time. Perhaps owing to the fragility of children in the context of dehydration and compromised nutrition, pediatricians recognize CVS in up to 2% of their patients (Pareek et al., 2007), and treat it far more promptly than often occurs for adults. Identifiable triggering events are more common in pediatric than in adult patients (Bullard & Page, 2005), with excitement or emotional stress often leading to symptoms, along with specific foods, overeating, hot weather, hormonal changes, motion sickness, and physical exhaustion (Venkatasubramani et al., 2007), as are seen with migraine. CVS symptom onset in adults, now reported with increasing frequency, commences at an average age of 35 years, followed by diagnosis at an average age of 41. Common triggers for adults include infections, particularly sinus infections, flu, and colds. Allergies also may precipitate an attack. In one of our recent studies, a CVSlike presentation was observed for over 50% of patients diagnosed with both diabetes mellitus and gastroparesis (Christensen, Johnson, & Abell, 2008).
CVS cycles and symptom phases Once CVS is suspected, further questioning may reveal distinct phases of the illness. A single CVS cycle is comprised of four phases, the prodromal, emetic, recovery, and well intervals. The prodromal period consists of a sudden onset, lasting 1–2 h, that is often accompanied by abdominal pain, sweating, irritability, anorexia, and pallor. During the emetic phase, which may extend from 1 to 3 days in children and 6 to 9 days in adults, the patient may be unable to take medication by mouth, eat, or drink because of persistent nausea and vomiting. The emetic phase is followed by the recovery phase, during which vomiting stops and the patient’s normal color, energy, and appetite return. Within the final phase, the “well” interval, no symptoms are noted (CVS, 2010; Venkatasubramani et al., 2007). Over 90% of patients with CVS experience marked pallor and lethargy; 80% have anorexia, nausea, retching,
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Pa ent Name: ______________________________________________ DOB/Age:___________ Medica ons (Prokine cs, An eme cs, etc.): ______________________________________________________________ _____________________________________________________________________________________________________________________
T:_____ P:_____ BP:_____ RR:_____
Wt:_____ Ht:_____ BMI:_____
Rate symptoms in 1-5 and 7-10 on a scale from 0-4 (Low to high, See key on following page): 1. Severity of Nausea (0-4):
_____
Frequency of Nausea (0-4):
_____
2. Severity of Vomi ng (0-4):
_____
Frequency of Vomi ng (0-4):
_____
3. Severity of Early Sa ety (0-4):
_____
Frequency of Early Sa ety (0-4):
_____
4. Severity of Bloa ng (0-4): 5. Severity of Abdominal Pain (0-4): Sum of Items 1-5 (0 –20): 6. Upper GI Total Severity Score:
_____ _____
_____ _____
_____
Frequency of Bloa ng (0-4): Frequency of Abdominal Pain (0-4): Sum of Items 1-5 (0 –20): Upper GI Total Frequency Score:
_____
7. Severity of cons pa on (0-4):
_____
Frequency of cons pa on (0-4):
_____
8. Severity of diarrhea (0-4):
_____
Frequency of diarrhea (0-4):
_____
9. Severity, frequent urina on (0-4):
_____
Frequency, frequent urina on(0-4):
_____
Frequency, infrequent urina on(0-4): Sum of Items 1-5 (0 –20):
_____
10. Severity, infrequent urina on (0-4): _____ Sum of Items 7-10 (0 –20): 11. Lower GI Total Severity Score:
_____
Lower GI Total Frequency Score:
_____
12. IDIOMS score (QOL)? (See Pa ent Assessment form) __________________________________ 13. This year, how o en: Seen in ED? ______________ Admi ed to hospital? ______________ 14. Frequency of vomi ng (number of spates) during current episode: _____________________ 15. Number of spates of vomi ng per hour during current episode?
_____________________
16. Diarrhea with vomi ng during this episode? _________________________________________ 17. Reflux with vomi ng during this episode?
_________________________________________
18. Prodromal symptoms (aura, drowsiness, imbalance, dizziness, pallor, etc.)? _______________ ___________________________________________________________________________________________________________________________________________
19. Triggers (specific foods, such as fa y, acidic, etc.; stress, physical or emo onal; sleeplessness)? ___________________________________________________________________________________________________________________________________________
21. Overlaps (headaches, fibromyalgia, bladder problems, endometriosis, depression, autonomic disorders, cancers, learning disorders, dyslexia) __________________________________________ ___________________________________________________________________________________________________________________________ ________________
Figure 1 Acute care checklist.
and/or abdominal pain as well (Cutts et al., 2005). Other associated symptoms include fever, headache, motion sickness, photophobia, diarrhea, dehydration, excess salivation, and social withdrawal (Dulude et al., 2011). CVS episodes are usually stereotyped for length and symptoms, and characteristic for each patient over time, although they can occur without regular or predictable pat-
terns (Li & Misiewicz, 2003). Stereotypical CVS episodes begin for many patients around the same time of day, usually 2:00 a.m. to 7:00 a.m., and follow a similar course with respect to duration, symptoms, and intensity. Although adult symptoms often last longer, they occur less frequently than those of children, as earlier described (Venkatasubramani et al., 2007).
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The following key can be used in conjunc on with the Emergency Department checklist, the pa ent selfassessment form, and the Inves gator Derived Independent Outcome Measures Score (IDIOMS) quality-oflife tool to assess the severity and frequency of GI symptoms, so as to provide greater precision in quan fying symptom impact on pa ent func on. Severity
Frequency
0 = Absent
0 = Absent
1 = Mild (does not affect usual ac vi es)
1 = Rare (1 me/week)
2 = Moderate (infrequently affects usual ac vi es)
2 = Occasional (2-3 times/week)
3 = Severe (affects usual ac vi es)
3 = Frequent (4-6 mes/week)
4 = Extremely Severe (requires bed rest)
4 = Extreme (≥7 mes/week)
PaƟent Name:______________________________ Medical Records Number:______________ Date: ________________ Figure 2 Cyclic vomiting syndrome/GI symptom score key.
Diagnostic characteristics of CVS
At the history and physical examination
At presentation
Obtaining a patient history and physical examination in the context of CVS may be hampered by recurrent vomiting. A prompt, accurate diagnosis must exclude other surgical conditions associated with vomiting through abdominal radiographs or abdominal CT, and must evaluate the possibility of metabolic conditions, such as pancreatic, hepatobiliary, and endocrine disorders through laboratory tests, which are best performed during an attack (Li & Misiewicz, 2003). Although many essential clinical features of CVS have remained consistent since Samuel Gee’s 1882 description, establishing a diagnosis of CVS may now include a vomiting severity of at least four periods of emesis per hour. The following suggestions by Prakash et al. (2001), however, provide useful minimum criteria for diagnosing CVS in adults.
Patients of any age with CVS may present for acute care, seeking relief from recurrent, prolonged attacks of severe nausea, vomiting, and prostration that may continue from a matter of hours to days. These episodes are often attributed to a viral gastroenteritis, but often there are no others in close contact with the patient who are ill. The attacks, interspersed with normal periods of varied duration, may or may not begin with a prodromal sign or event, such as nausea. Once begun, however, vomiting typically continues at regular intervals with great severity (Pareek et al., 2007). However, except for infants, for whom the danger of dehydration rapidly secures attention, patients with CVS may be contrasted during triage to patients with acute ischemic events, myocardial infarctions, injuries subsequent to accidents and abuse, and overdoses, and find themselves relegated to a long series of consults. They may also be misdiagnosed, a particularly worrisome possibility when the vomiting is accompanied by abdominal pain, as unnecessary surgery (e.g., appendectomy) sometimes results before the disorder is correctly identified. Diarrhea is variable, and when present, is often attributed to infectious causes. If left untreated, CVS attacks resolve spontaneously, but often result in hospitalization because of the effects of the vomiting.
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Three or more recurrent, discrete episodes of nausea and vomiting. Varying periods of no symptoms between these episodes. Negative radiological and laboratory findings for other diagnoses.
In addition, as with migraines, episodes are often stereotypical in time of onset, symptoms, and duration
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Circle the score for each symptom (0 to 4) Severity
Frequency
0 = Absent 1 = Mild (does not affect usual ac vi es) 2 = Moderate (infrequently affects usual ac vi es) 3 = Severe (affects usual ac vi es) 4 = Extremely Severe (requires bed rest)
0 = Absent 1 = Rare (1 me/week) 2 = Occasional (2-3 mes/week) 3 = Frequent (4-6 mes/week) 4 = Extreme (≥7 mes/week)
How you feel now (Baseline)
Frequency
Severity
Upper Symptoms: Vomi ng 0 1 2 3 4 0 1 2 3 4 Nausea 0 1 2 3 4 0 1 2 3 4 Early Sa ety (feels full quickly) 0 1 2 3 4 0 1 2 3 4 Bloa ng 0 1 2 3 4 0 1 2 3 4 Epigastric Pain 0 1 2 3 4 0 1 2 3 4 Lower GI Symptoms: Cons pa on 0 1 2 3 4 0 1 2 3 4 Diarrhea 0 1 2 3 4 0 1 2 3 4 Frequent Urina ng 0 1 2 3 4 0 1 2 3 4 Infrequent Urina ng 0 1 2 3 4 0 1 2 3 4 Please check any symptoms experienced by yourself and your biological parents below: Symptom
You (Pa ent)
Your Biological Mother
Her Family
Your Biological Father
His Family
Headaches Fibromyalgia Bladder problem Endometriosis Depression Autonomic Disorders Cancers Learning Disorders Dyslexia 1. Please list any specific problem(s) that you are experiencing today: 2. Your last hospitaliza on was when? where? why? 3. Have there been any changes in your medica ons? 4. Are there other issues about which we should know? Figure 3 Cyclic vomiting syndrome/GI symptom patient self-assessment form.
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Severity of Illness (SoI) Mild Symptoms
1
2
Moderate Symptoms
3
4
5
Severe Symptoms
6
7
8
Very Severe Symptoms
9
10
Other Significant Illnesses (OSI) Mild Symptoms
1
2
Moderate Symptoms
3
4
5
Severe Symptoms
6
7
8
Very Severe Symptoms
9
10
Intensity of Services (IoS) Mild Symptoms
1
2
Moderate Symptoms
3
4
5
Severe Symptoms
6
7
8
Total score (the sum of the individual scores for SoI, OSI, and IoS):
Very Severe Symptoms
9
10
_____________
Comments: ________________________________________________________________________________ ________________________________________________________________________________ ________________________________________________________________________________ Modified from Form ID ID-InvesƟgator Derived Independent Outcome Measure Scores (IDIOMS) Figure 4 Quality-of-life tool.
(Dulude et al., 2011; Prakash et al., 2001). The decision about ordering additional diagnostic, for example, a head CT scan, can often be postponed from the acute setting, unless other aspects of history and/or physical suggest the need for urgent imaging. 6
Gross physical exam will confirm the history of vomiting and may also reveal dry mucous membranes, as well as a greater pallor than normal, reflecting dehydration and the shunting of blood from the periphery because of vasoconstriction. Laboratory findings consistent with
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dent Outcomes Measure Score (IDIOMS), is a Likert scale (0–4, low to high) instrument that can help in quickly assessing the impact of gastrointestinal (GI) symptoms on patient QOL, and thus assist in evaluating symptom severity (adapted from Cutts et al., 2005).
Essentials of diagnosis The role of ICD-9 coding A factor hampering the recognition of CVS as a diagnostic disorder is its lack of a distinct ICD-9 code. This issue is now being addressed by at least one CVS support group, which has an application for an ICD-9 code for the disorder pending.
Appropriate therapeutic options and management for patients with CVS Rapid access to care
Figure 5 Cyclic vomiting syndrome flow chart.
dehydration and disturbed acid–base parameters can help confirm clinical suspicion of CVS. An orthostatic drop in blood pressure, lying versus sitting, may reflect not only dehydration, but also an underlying postural defect associated with a migraine-like physiology (Rashed et al., 1999).
Readily available guidelines and checklists Published criteria for the diagnosis of children are available through the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Consensus Statement (NASPGHAN, 2008), and for adults through the Rome III Diagnostic Criteria (Rome Foundation, 2006). Here, we have provided in our Appendix an acute care checklist (Figure 1) and key (Figure 2), a patient self-assessment instrument (Figure 3), a simple, quality-of-life (QOL) tool (Figure 4), and a CVS management flow chart (Figure 5), useful in conjunction with the checklist, for use in rapidly distinguishing CVS from other causes of vomiting, as well as for patient management. The QOL tool, the Investigator Derived Indepen-
Rapid access to medical care in CVS can shorten the episode and prevent complications from prolonged vomiting. Avoidance of triggers, where they can be identified, may help in aborting an episode, and should be attempted (Forbes, 1995). Hospitalization with intravenous fluids and antiemetics may be necessary. If pain is present, analgesics are indicated. Empiric treatment with antimigraine therapy has been successful in preventing and aborting attacks for some patients, particularly those with a family history of migraines (Dulude et al., 2011). Intravenous administration of fluids to combat dehydration, and subsequent intravenous administration of agents, such as chlorpromazine (thorazine), diphenhydramine (benadryl), or lorazepam (ativan), to block the nausea may also be warranted (Forbes, 1995). These treatments can often be provided in clinics and emergency departments (Venkatesan et al., 2010); if the patient does not respond to them, however, hospital admission may be required. The patients sometimes require higher than usual doses of antiemetics because of the severity of their symptoms.
Management strategies Strategies for managing CVS include avoidance therapy, pharmacologic prophylaxis, abortive therapy (once the nausea or vomiting has begun), supportive care during an episode, and family support. Avoidance of dietary triggers (e.g., cheese, chocolate, monosodium glutamate), as well as improved psychological stress management skills, may help with prevention of the attacks. If attacks occur more than once a month, pharmacologic therapy with antimigraine agents, prokinetic agents, and neuroleptics may be indicated for 7
Cyclic vomiting syndrome
prophylaxis. Erythromycin has been used as a prokinetic agent. Propranolol (inderal), cyproheptadine (periactin), and amitriptyline (elavil) have also been found to decrease the frequency and severity of episodes. Antimigraine agents and antiemetics can be used to abort an attack, and may be given parenterally at the onset of symptoms. Ondansetron (zofran) has been 62% effective in decreasing the symptoms. Transnasal administration of sumatriptan succinate (imitrex) has a 51% efficacy (Fleisher et al., 2005; Venkatesan, Marcus, Sundaram, & Li, 2002). As mentioned above, higher than commonly used doses of some medications, for example, ondansetron may be needed, often approaching the doses used for the GI symptoms of cancer chemotherapy.
Enlisting the patient and family for management and support Accessible descriptions and empiric guidelines for managing the symptoms of CVS can be found on the website of Dr. David Fleisher, University of Missouri Health Care (Fleisher, 2013). In addition, patients and their families may find information and support from patient groups, such as the CVS Association, which since 1993 has provided information on treatment, research and patient support networks, newsletters and online links, phone support, regional conferences, and provider information (CVS, 2010).
Conclusion A prompt and accurate diagnosis, often based on classic presentation, and timely institution of appropriate treatment, as well as the attention of empathetic medical personnel can greatly help patients with CVS to manage their symptoms, and may reduce both the morbidity and costs of hospitalization associated with this illness.
Acknowledgments The authors would like to thank Drs. Namita Pareek and Archana Kedar of the Division of Digestive Diseases, Joy Hughes of the School of Medicine, and Jo Anne Fordham and Jane Free of the Division of Digestive Diseases for their assistance with this article.
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Bullard, J., & Page, N. E. (2005). Cyclic vomiting syndrome: A disease in disguise. Pediatric Nursing, 31(1), 27–29. Christensen, C., Johnson, W., & Abell, T. L. (2008). Comparison of diabetic gastropathy with or without cyclic vomiting syndrome (CVS). Scandinavian Journal of Gastroenterology, 3(9), 1076–1081. Cupini, L., Santorelli, F., Iani, C., Fariello, G., & Calabresi, P. (2003). Cyclic vomiting syndrome, migraine and epilepsy; a common underlying disorder. Headache, 43, 407–409. Cutts, T. F., Luo, J., Starkebaum, W., Rashed, H., & Abell, T. L. (2005). Is gastric electrical stimulation superior to standard pharmacologic therapy in improving GI symptoms, healthcare resources and long-term healthcare benefits? Neurogastroenterology & Motility, 17, 35–43. Cyclic Vomiting Syndrome (CVS): National Digestive Diseases Information Clearinghouse. (2010). Code ‘V’: Newsletter of the Cyclic Vomiting Syndrome Association—USA/Canada, 12(2), 1–4. Dignan, F., Symon, D., AbuArefeh, I., & Russell, G. (2001). The prognosis of cyclical vomiting syndrome. Archives of Disease in Childhood, 84, 55–57. Dulude, E., Desilets, D. J., & Boles, R. G. (2011). Cyclic vomiting syndrome. UpToDate. “Cyclic vomiting syndrome.” Retrieved from http://www. uptodate.com/contents/cyclic-vomiting-syndrome Fleisher, D. R. (2013). University of Missouri School of Medicine: David R. Fleisher. Retrieved from http://medicine.missouri.edu/childhealth/ fleisher.html. Fleisher, D. R., Gornowicz, B., Adams, K., Burch, R., & Feldman, E. J. (2005). Cyclic vomiting syndrome in 41 adults: The illness, the patients, and problems of management. BMC Medicine. Retrieved from http://www. biomedcentral.com/content/pdf/1741--7015--3--20.pdf Forbes, D. (1995). Cyclic vomiting syndrome. Journal of Paediatric Child Health, 31(2), 67–69. Gunderson, C. (1986). Management of the migraine patient. American Family Physician, 33(1), 137–143. Li, B. U. K., & Misiewicz, L. (2003). Cyclic vomiting syndrome: A brain-gut disorder. Gastroenterology Clinics of North America, 32(3), 997–1019. Retrieved from http://home.mdconsult.com North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN). (2008). Consensus statement on the diagnosis and management of cyclic vomiting syndrome. Journal of Pediatric Gastroenterology and Nutrition, 47, 379–393. Pareek, N., Fleisher, D., & Abell, T. L. (2007). Cyclic vomiting syndrome: What a gastroenterologist needs to know. American Journal of Gastroenterology, 102, 1–9. Prakash, C., Staiano, A., Rothbaum, R., & Clouse, R. E. (2001). Similarities in cyclic vomiting syndrome across age groups. American Journal of Gastroenterology, 69(3), 684–688. Rashed, H., Abell, T. L., Familoni, B., & Cardoso, S. (1999). Autonomic function in cyclic vomiting syndrome and classic migraine. Digestive Diseases and Sciences, 44(8), 74S–78S. Rome Foundation. Rome III Diagnostic Criteria. (2006). Cyclic vomiting syndrome. Gastroenterology, 20(5), 1377–1556. Retrieved from http://www.romecriteria.org/criteria/ Tougas, G., Chen, Y., Hwang, P., Liu, M. M., & Eggelston, A. (1999). Prevalence and impact of upper gastrointestinal symptoms in the Canadian population: Findings from the DIGEST study. American Journal of Gastroenterology, 94(10), 2845–2854. Venkatasubramani, N., Venkatesan, T., & Li, B. U. K. (2007). Extreme emesis: Cyclic vomiting syndrome. Practical Gastroenterology, 21(9), 21–34. Venkatesan, T., Marcus, S., Sundaram, S., & Li, B. U. K. (2002). Cyclic vomiting syndrome. eMedicine. Retrieved from http://www.emedicine.com/ ped/topic2910.htm Venkatesan, T., Tarbell, S., Adams, K., McKanry, J., Barribeau, T., Beckmann, K., . . . Li, B. U. K. (2010). A survey of emergency department use in patients with cyclic vomiting syndrome. BMC Emergency Medicine. Retrieved from http://www.biomedcentral.com/content/pdf/1471--227x-10--4.pdf World Health Organization. Headache disorders: Fact sheet no. 277. Retrieved from http://www.who.int/mediacentre/factsheets/fs277/en/
