Clinical guidelines highlight for the hospitalist: Management of cyclic vomiting syndrome in children

Cyclic vomiting syndrome is characterized by recurrent attacks of nausea and vomiting lasting from a few hours up to 1 week, which affects quality of life and incurs substantial healthcare costs. The yearly incidence of CVS is 3.2 per 100,000 children/year,1 with the peak being amongst school-aged children. The exact pathophysiology is unclear, and evidence-based treatment algorithms are lacking. Known subgroups of CVS include migraine-like presentations; catamenial subtype, where vomiting episodes are triggered by menstrual periods; a subgroup characterized by a predictable calendar-type pattern; and the sato-variant group with symptoms associated with an overreactive-hypothalamic-pituitary-adrenal axis. Cannabinoid hyperemesis syndrome (CHS) is considered another probable subtype of CVS. The North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) released a clinical practice guideline2 for the management of CVS in children, which replaces the prior 2008 NASPGHAN expert consensus statements.3 There were 16 recommendations condensed into 10 applicable to the hospitalist. A suggested CVS management algorithm summarizes these recommendations (Figure 1).2 Recommendation 1: Anti-migraine medications (e.g., nonsteroidal anti-inflammatory drug [NSAIDs] and triptans) can be used for treatment of acute CVS in patients with a personal or family history of migraines (strong recommendation, moderate certainty). Data demonstrates pain relief with NSAIDs alone, but the strongest evidence supports a combination of naproxen and sumatriptan.4 Rizatriptan is the only triptan approved for children as young as 6 years old. If a patient needs triptans more than 9 days/month or NSAIDs greater than 14 days/month, they may benefit from a change to their prophylactic regimen. Recommendation 2: NK-1 receptor antagonist (e.g., aprepitant) for 3 consecutive days or 5-hydroxytryptamine 3 (5-HT3) receptor antagonists (e.g., ondansetron) can be used for treatment of acute CVS episodes (conditional recommendation, very low certainty). In patients who could tolerate oral aprepitant, one retrospective study5 (n = 25) demonstrated a significant decrease in frequency and duration of CVS episodes, and doubling of symptom free days. Notably, aprepitant can cause decreased efficacy of oral contraceptives. Recommendation 3: Early presentation to obtain IV hydration is recommended for acute treatment of CVS episodes that are unresponsive to outpatient therapies (conditional recommendation, very low certainty). The type of IV fluid rehydration should be guided based on age, severity, and degree of dehydration (conditional recommendation, very low certainty). Delayed emergency department presentation (>24 h after symptom onset) is the greatest independent predictor for hospital admission.6 Other factors included male sex, younger age, and prolonged wait time in ED before antiemetic administration. The decision to use dextrose 10% or dextrose 5% for hydration should be based on clinician assessment of age, severity, possibly underlying metabolic disorders, and specific patient presentation. The panel was unable to judge the benefits of D10 versus D5 given lack of evidence. Recommendation 4: IV NK-1 receptor antagonist (e.g., fosaprepitant) or IV 5-HT3 receptor antagonists (e.g., ondansetron) can be helpful in the acute treatment of CVS for patients who failed outpatient abortive therapies (conditional recommendation, very low certainty). The addition of either fosaprepitant or aprepitant to ondansetron has been shown to be more effective than ondansetron alone. NK-1 receptor antagonists may interact with hormonal contraceptives, benzodiazepines, and serotonergic antidepressants. Recommendation 5: Nonpharmacologic therapies such as neuromodulation, acupuncture, noninvasive vagal nerve stimulator, and behavioral interventions may be helpful in patients who prefer nonpharmacologic methods or cannot tolerate medication side effects (conditional recommendation, very low certainty). Topical capsaicin may also be considered for patients presenting with CHS. Recommendation 6: Trigger avoidance should be utilized to help prevent CVS episodes (Conditional recommendation, very low certainty). Recommendation 7: Psychological therapies, lifestyle management, and treatment adherence interventions are suggested for preventing episodes and treating comorbidities in pediatric patients with CVS (conditional recommendation, very low certainty). Triggers for CVS episodes may include fasting, dehydration, sedentary lifestyle, and certain foods. Recommendation 8: Supplements such as coenzyme Q10, riboflavin, and magnesium may be helpful to prevent CVS episodes (conditional recommendation, very low to moderate certainty). Coenzyme Q10, Riboflavin (200 mg BID), and Magnesium (400 mg/day) had small desirable effects with decreased CVS or migraine episode frequency, duration, and severity. The mild possibility of improvement with these supplements warrants trial usage with a timed re-evaluation. Magnesium glycinate is preferred to other forms of magnesium as it has less bowel movement side effects. Vitamin D (200 IU daily for 2 months) can be used as an adjunct to other pharmacologic therapies in those with reduced blood levels. Recommendation 9: Beta blockers (e.g., propranolol), 5-hydroxytryptamine 2A (5-HT2A) receptor antagonists (e.g., cyproheptadine), NK-1 receptor antagonist (e.g., aprepitant), and tricyclic antidepressants (TCAs) (e.g., amitriptyline) can all be used to help prevent pediatric CVS episodes (conditional recommendation, low and very low certainty). Recommendation 10: Anticonvulsants (e.g., topiramate or valproate) should only be used for pediatric CVS prevention in patients with refractory disease (conditional recommendation, very low certainty). We recommend subspecialist consultation before prescribing prophylactic medications to ensure safety and outpatient follow-up as needed. The majority of these prophylactic pharmacologic agents have at least a small therapeutic benefit citing very low certainty evidence. Therefore, caution must be given to minimize harm. Consider side effect profiles and perform trials of the medications accordingly with the help of subspecialty consultants. For instance, choose cardio-selective beta-blockers such as metoprolol for patients with asthma. 5-HT2A receptor antagonists can cause appetite increase and weight gain in up to 21% of children7 which should be discussed before starting. TCA standard dosing is 1.0-1.5 mg/kg/day and should be used with caution due to the side effect profile of sedation, cognitive dysfunction, weight gain, QTc prolongation, behavioral changes, and suicidality. Anticonvulsants have a large potential for side effects so should only be considered in patients with severe refractory symptoms such as monthly episodes requiring ED visits and hospitalizations. The purpose of this guideline was to provide updated, evidence-based recommendations that supersede the prior 2008 NASPGHAN expert consensus regarding management of pediatric CVS. The guideline panel was made up of emergency medicine, gastroenterologists, metabolic genetics, neurologists, psychiatrists and a patient representative, but notably does not include general pediatrician or hospitalist input. The target audience was clearly defined to include patients, general and subspecialty pediatricians, and policy makers. The panel followed best practices for guideline development and stated clear methods for their comprehensive search and grading of evidence. The outcomes included many functional needs such as symptom reduction, quality of life, health equity, and feasibility of interventions. With most of the recommendations coming from low-certainty evidence or extrapolating from parallel migraine studies, the authors focus on improving function and minimizing harm. The recommendations are specific and identifiable. Considering the low-quality evidence, there were many options for brief medication trials to balance the financial impact and side effects with the potential for clinical benefit. Finally, the panel did not have influence from competing interests, and it underwent independent peer review. The panel highlighted the need for prospective, controlled, multicenter treatment trials on efficacy and safety that account for the substantial placebo effect in CVS and the natural time course of disease resolution. Both nonpharmacologic and pharmacologic therapies need to be studied to improve the strength of the recommendations. The authors declare no conflicts of interest.