How should cyclic vomiting syndrome be diagnosed and managed acutely and prophylactically?

Cyclic Vomiting Syndrome: Diagnosis and Management

Diagnose CVS using Rome IV criteria (stereotypical vomiting episodes <7 days, ≥3 episodes/year with 2 in prior 6 months, separated by ≥1 week of wellness), then classify severity to determine treatment intensity: mild CVS requires only abortive therapy with sumatriptan plus ondansetron during prodrome, while moderate-severe CVS requires both prophylactic amitriptyline (75-150 mg nightly) and abortive therapy. 1, 2

Diagnostic Approach

Clinical Diagnostic Criteria

• Apply Rome IV criteria: stereotypical episodes of acute-onset vomiting lasting <7 days, at least 3 discrete episodes in the past year (with 2 in the prior 6 months), episodes separated by at least 1 week of baseline health, and absence of vomiting between episodes 1, 3
• Recognize key diagnostic features: approximately 65% of patients experience prodromal symptoms (impending doom, panic, anxiety, diaphoresis, mental fog, restlessness) lasting a median of 1 hour before vomiting onset 1, 3
• Do not exclude CVS based on abdominal pain—it is present in most patients during episodes 1, 3
• Note the stereotypical pattern: each patient has an identical onset, duration, and symptom cluster that repeats with every episode 1, 3

Essential Screening and Testing

• Screen all patients for cannabis use (≥4 times weekly for >1 year suggests cannabinoid hyperemesis syndrome rather than CVS) before confirming diagnosis 2, 4, 3
• Obtain basic laboratory evaluation: complete blood count, serum electrolytes, glucose, liver function tests, lipase, urinalysis, and urine drug screen 2, 3
• Obtain baseline ECG before starting amitriptyline due to QTc prolongation risk 2
• Screen for psychiatric comorbidities (anxiety, depression, panic disorder) present in 50-60% of CVS patients 2, 4, 3

Severity Classification

• Mild CVS: <4 episodes/year, each lasting <2 days, without ED visits or hospitalizations 1, 2
• Moderate-severe CVS: ≥4 episodes/year, each lasting >2 days, requiring at least 1 ED visit or hospitalization 1, 2

Acute Episode Management (Emetic Phase)

Emergency Department Treatment

• Place patient in quiet, dark room immediately to minimize sensory stimulation, as patients are often agitated and unable to communicate effectively 1, 4
• Administer aggressive IV fluid replacement with dextrose-containing fluids for rehydration and metabolic support 2, 4
• Give ondansetron 8 mg IV as first-line antiemetic, repeat every 4-6 hours 2, 4
• Use IV ketorolac 15-30 mg every 6 hours (maximum 5 days, 120 mg/day) as first-line non-narcotic analgesia for severe abdominal pain—avoid opioids as they worsen nausea and carry addiction risk 2, 4
• Provide sedation with IV benzodiazepines in a quiet, dark room 2, 4
• For refractory cases, use droperidol or haloperidol 2, 4

Critical Caveats for Ketorolac Use

• Exercise caution in patients >60 years, with compromised fluid status, history of peptic ulcer disease, or significant alcohol use due to GI and renal toxicity risk 2
• Discontinue NSAIDs if BUN or creatinine doubles or if hypertension develops or worsens 2

Abortive Therapy (Prodromal Phase)

The highest probability of aborting an episode occurs when medications are taken immediately at prodromal symptom onset—educate patients to recognize their stereotypical prodrome and act immediately. 1, 2, 4

Standard Abortive Regimen

• Sumatriptan 20 mg intranasal spray (can repeat once after 2 hours, maximum 2 doses per 24 hours) administered in head-forward position to optimize nasal receptor contact 2
• Ondansetron 8 mg sublingual every 4-6 hours during the episode 2
• Alternative sumatriptan route: subcutaneous injection in patients who cannot tolerate intranasal administration 2

Additional Abortive Agents

• Promethazine 12.5-25 mg oral/rectal every 4-6 hours 2
• Prochlorperazine 5-10 mg every 6-8 hours or 25 mg suppository every 12 hours 2
• Sedatives (alprazolam, lorazepam, diphenhydramine) to truncate the episode, with caution in adolescents with substance abuse risk 2

Prophylactic Therapy (Moderate-Severe CVS Only)

First-Line: Amitriptyline

• Start amitriptyline 25 mg at bedtime, titrate by 10-25 mg every 2 weeks to target dose of 75-150 mg nightly (goal: 1-1.5 mg/kg) 2, 4
• Response rate: 67-75% in clinical studies 2, 4
• Administer at night to reduce daytime sedation and anticholinergic effects (dry mouth, blurred vision, constipation, weight gain) 2
• Slow titration is associated with better tolerability compared to rapid dose escalation 2

Second-Line Prophylactic Options

• Topiramate: start 25 mg daily, titrate to 100-150 mg daily in divided doses; monitor electrolytes and renal function twice yearly 2
• Levetiracetam: start 500 mg twice daily, titrate to 1000-2000 mg daily in divided doses; monitor CBC 2
• Zonisamide: start 100 mg daily, titrate to 200-400 mg daily; monitor electrolytes and renal function twice yearly 2
• Aprepitant (neurokinin-1 antagonist): 80 mg 2-3 times weekly for adolescents 40-60 kg, 125 mg 2-3 times weekly for adolescents >60 kg 2

Essential Lifestyle Modifications and Trigger Management

• Maintain regular sleep schedule and avoid sleep deprivation 2, 4
• Avoid prolonged fasting 2, 4
• Implement stress management techniques, as stress triggers episodes in 70-80% of patients (including positive stressors like birthdays and vacations) 1
• Identify and avoid individual triggers: hormonal fluctuations (menstrual cycle), travel, motion sickness, acute infections, surgery, intense exercise 1

Management of Psychiatric Comorbidities

Treating underlying anxiety and depression decreases CVS episode frequency—this is a critical component of comprehensive management. 2, 4, 3

• Screen all patients for anxiety, depression, and panic disorder (present in 50-60% of CVS patients) 2, 4, 3
• Personal or family history of migraine is present in 20-30% of CVS patients and supports diagnosis 2, 3
• Consider referral to psychiatry, psychology, or counseling services for cognitive-behavioral therapy and pharmacologic management of psychiatric comorbidities 2

Critical Diagnostic Distinction: CVS vs. Cannabinoid Hyperemesis Syndrome

• Cannabis use ≥4 times weekly for >1 year suggests cannabinoid hyperemesis syndrome (CHS) rather than CVS 2, 4, 3
• Hot water bathing is present in 48% of CVS patients without cannabis use, so this behavior alone does not distinguish CHS from CVS 2, 4
• If cannabis criteria are met, change working diagnosis to CHS and require 6 months of cannabis cessation to differentiate 2

Common Pitfalls to Avoid

• Missing the prodromal window dramatically reduces abortive therapy effectiveness—patient education on immediate medication administration is imperative 1, 2, 4
• Misinterpreting self-soothing behaviors (excessive water drinking, self-induced vomiting) as malingering—these are characteristic coping responses specific to CVS that provide temporary relief 1, 4
• Overlooking retching and nausea, which are equally disabling as vomiting itself and require aggressive treatment 2, 4
• Underestimating severity: approximately one-third of adults with CVS become disabled, and one-half visit the ED at least annually 4, 3
• Failing to recognize the stereotypical pattern of episodes, which is the key to diagnosis 3
• Dismissing abdominal pain as excluding CVS—it is present in most patients 1, 3

Special Population: Coalescent CVS

• A distinct subgroup experiences progressively longer and more frequent episodes, eventually leading to daily nausea and vomiting with few asymptomatic days 2
• Manage with prophylactic therapy comparable to moderate-severe CVS (amitriptyline), acknowledging the heightened therapeutic challenge 2
• History typically reveals years of episodic nausea/vomiting preceding the coalescent phase 2