BACKGROUND: Classical antiemetics that target the serotonin system may not be effective in treating certain nausea and vomiting conditions like cyclic vomiting syndrome (CVS) and cannabinoid hyperemesis syndrome (CHS). As a result, there is a need for better therapies to manage the symptoms of these disorders, including nausea, vomiting, and anxiety. Cannabis is often used for its purported antiemetic and anxiolytic effects, given regulation of these processes by the endocannabinoid system (ECS). However, there is considerable evidence that cannabinoids can also produce nausea and vomiting and increase anxiety in certain instances, especially at higher doses. This paradoxical effect of cannabinoids on nausea, vomiting, and anxiety may be due to the dysregulation of the ECS, altering how it maintains these processes and contributing to the pathophysiology of CVS or CHS.
OBJECTIVE: The purpose of this review is to highlight the involvement of the ECS in the regulation of stress, nausea, and vomiting. We discuss how prolonged cannabis use, such as in the case of CHS or heightened stress, can dysregulate the ECS and affect its modulation of these functions. The review also examines the evidence for the roles of ECS and stress systems\' dysfunction in CVS and CHS to better understand the underlying mechanisms of these conditions.

Cyclic vomiting syndrome (CVS) is a disorder of gut-brain interaction which has a wide clinical spectrum. Clinical action plans have been developed to address and to facilitate treatment in the setting of complex, chronic medical conditions. The CVS Action Plan was developed to meet the chronic and acute care needs of children and adults with CVS. While this tool has not been tested for clinical efficacy as was shown with action plans for functional constipation, anecdotal and indirect evidence supports its use. The CVS Action Plan has the potential to enhance outcomes by simplifying home management and streamlining disease recognition and acute care in the emergency department.

BACKGROUND: Abdominal pain and vomiting are frequent complaints for pediatric patients presenting to the Emergency Department (ED). When a diagnosis such as chronic abdominal pain, cyclic vomiting, or abdominal migraine has previously been made, it can lead to diagnostic momentum and confirmation bias on behalf of the treating physician. Dietl\'s crisis is a commonly missed diagnosis in the pediatric population that presents with intermittent episodes of pain and vomiting. It can be readily diagnosed at the bedside by the emergency physician (EP) through the employment of point of care ultrasound (POCUS).
METHODS: We present two cases of pediatric patients with episodic abdominal pain and vomiting who were previously diagnosed with cyclic vomiting syndrome. In both cases, pediatric gastroenterology evaluations had occurred with negative diagnostic testing having been performed. Both patients also presented to their primary pediatrician and the ED multiple times with each encounter resulting in treatment of symptoms and discharge. Each patient eventually presented to the ED when an EP was present who performed a renal POCUS. In each patient, the POCUS revealed severe unilateral hydronephrosis. Subsequent workup confirmed the diagnosis of Dietl\'s crisis as the etiology of symptoms. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In pediatric patients, EPs should be wary of the diagnosis of cyclic vomiting syndrome until ureteral obstruction has been ruled out. A bedside POCUS can rapidly establish this diagnosis and potentially preclude recurrent health care visits, unnecessary diagnostic testing, and permanent loss of renal function.

Cyclic vomiting syndrome (CVS) is a chronic digestive disorder characterized by recurrent episodes of severe nausea and vomiting. The perioperative management of patients with CVS undergoing general anesthesia is challenging, especially when combined with obesity. This case report describes the successful management of a patient with CVS and obesity who underwent dental surgery under general anesthesia. A 21-year-old woman with CVS, obesity (body mass index, 35), and intellectual disability was scheduled for tooth extraction and composite resin restoration under general anesthesia. The patient was diagnosed with CVS at the age of 20 years with frequent vomiting attacks requiring hospitalization. Surgery was scheduled during the CVS remission to reduce the risk of perioperative vomiting. Preoperative laboratory test results were normal, including serum adrenocorticotropic hormone (ACTH), anti-diuretic hormone (ADH), and cortisol levels. General anesthesia was induced using remifentanil and propofol. Nasal endotracheal intubation was performed after rocuronium administration. Local anesthesia (2% lidocaine with 1:80,000 epinephrine) was used for all dental procedures. Postoperatively, midazolam was administered to control agitation. No postoperative vomiting occurred. Serum ACTH, ADH, and cortisol levels showed no significant changes before and after anesthesia, suggesting that hypothalamic-pituitary-adrenal (HPA) axis activation due to surgical stress did not occur. This case highlights the importance of careful perioperative planning and monitoring stress-related hormone levels in patients with CVS or obesity. An anesthetic approach using midazolam may effectively suppress HPA axis activation and prevent postoperative vomiting.

BACKGROUND: Cannabis use in the general population is prevalent and is rising because of increased acceptance of its use, legalization in most US states, and perceived health benefits. Cannabis product potency has dramatically increased with higher delta-9-tetrahydrocannabinol content. Cannabis has documented antiemetic properties and cannabinoid pharmaceuticals are used in disorders like chemotherapy-induced nausea and vomiting.
OBJECTIVE: Forty to eighty percent of cyclic vomiting syndrome (CVS) patients use cannabis products, which reportedly reduce stress as well as nausea and vomiting. Cannabinoid hyperemesis syndrome (CHS) has a presentation similar to CVS, but is associated with longstanding, high dose cannabis use, and is thought to be relieved by sustained cannabis abstinence. Most CHS patients have used cannabis on a daily or near-daily basis for more than 2 years. Compulsive hot-water bathing behaviors are reported by most CHS patients, but are not specific for this disorder as they are also noted by about half of CVS patients. Episodic vomiting associated with cannabis use contributes to extensive health resource use, including emergency department visits and inpatient hospitalizations, and impacts patients and their families negatively. Treatment for CHS overlaps with CVS although cannabis abstinence remains the cornerstone of its management. Challenges associated with cannabis use cessation in CHS include patient skepticism of the role of cannabis as a cause of symptoms, perceived benefits of cannabis, and a lack of other effective therapies. In this review, we highlight cannabis use patterns in the US and discuss diagnosis and management of CHS and gaps in knowledge about this disorder.

BACKGROUND: Cyclic vomiting syndrome (CVS) and cannabinoid hyperemesis syndrome (CHS) are both characterized by episodic, acute transitions from asymptomatic states to highly symptomatic states of nausea, repetitive vomiting, and often severe abdominal pain. Patients with CVS and CHS face significant challenges to abort or mitigate episodes at home and often require emergency department (ED)-based care.
OBJECTIVE: This paper reviews the current treatment approach to abort acute CVS and CHS episodes at home and in ED settings. Multiple pharmacologic and nonpharmacologic interventions have been demonstrated to potentially abort CVS or CHS episodes. Systemic pharmacologic agents often used as abortive therapy include triptans, antiemetics, anxiolytics, NK-1 receptor antagonists, antipsychotics, sedatives in general, and various analgesic / anti-inflammatory medications. Nonsystemic, nonpharmacologic approaches include reducing external stimuli (quiet room, dim lights, etc.), and hot water bathing or the application of topical capsaicin cream. More research is needed to develop evidence-based, individualized abortive treatment plans, as well as to determine whether the abortive treatment for CVS requires a fundamentally different approach than for CHS. When home-based approaches fail, all patients with CVS or CHS should receive nonjudgmental, informed, and compassionate care in the ED to abort their episode. Patients with more severe forms of CVS/CHS who require more frequent ED utilization should develop care plans with their ED to assure predictable and effective treatment.

Here, we report an individual, eventually diagnosed with HMG-CoA synthase deficiency, who presented with a cyclic vomiting phenotype. HMG-CoA synthase deficiency is a rare disorder affecting ketone body synthesis in which affected individuals typically present at a young age with hypoketotic hypoglycemia, lethargy, encephalopathy, and hepatomegaly, usually triggered by catabolism (e.g., infection or prolonged fasting). This individual presented with recurrent episodes of vomiting and lethargy, often associated with hypoglycemia or hyperglycemia, at 3 years of age. Metabolic labs revealed nonspecific abnormalities in her urine organic acids (showing mild elevation of dicarboxylic acids with relatively low excretion of ketones) and a normal acylcarnitine profile. Given her clinical presentation, as well as a normal upper gastrointestinal series, esophagogastroduodenoscopy with biopsies, and abdominal ultrasound, she was diagnosed with cyclic vomiting syndrome at 3 years of age. Molecular testing completed at 7 years of age revealed a previously reported pathogenic sequence variant (c.1016+1G>A) and a novel likely pathogenic deletion (1.57 kB deletion, including exon 1) within HMGCS2 consistent with HMG-CoA synthase deficiency. This individual\'s presentation, mimicking cyclic vomiting syndrome, widens the clinical spectrum of HMG-CoA synthase deficiency. In addition, this case highlights the importance of molecular genetic testing in such presentations, as this rare disorder lacks specific metabolic markers.

BACKGROUND: Cyclic vomiting syndrome (CVS) is identified as one of the \"episodic syndromes that may be associated with migraine,\" along with benign paroxysmal torticollis, benign paroxysmal vertigo, and abdominal migraine. It has been proposed that CVS and migraine may share pathophysiologic mechanisms of hypothalamic activation and altered dopaminergic signaling, and impaired sensorimotor intrinsic connectivity. The past decade has brought groundbreaking advances in the treatment of migraine and other headache disorders. While many of these therapies have yet to be studied in episodic syndromes associated with migraine including CVS and abdominal migraine, the potential shared pathophysiology among these conditions suggests that use of migraine-specific treatments may have a beneficial role even in those for whom headache is not the primary symptom.
OBJECTIVE: This manuscript highlights newer therapies in migraine. Calcitonin gene-related peptide (CGRP) and its relation to migraine pathophysiology and the therapies that target the CGRP pathway, as well as a 5HT1F receptor agonist and neuromodulation devices used to treat migraine are briefly discussed as they may potentially prove to be useful in the future treatment of CVS.

UNASSIGNED: To quantify the indirect burden of cyclic vomiting syndrome (CVS), we assessed work-related productivity loss in patients with CVS and caregivers using large-sized databases in the United States.
UNASSIGNED: Patients aged 18-64 years with full-time employment in MarketScan Commercial and Health and Productivity Management Databases were selected if they had ≥1 inpatient or ≥2 outpatient claims for CVS between 2008 and 2018 and continuous enrollment of ≥6 months before and ≥3 months after the initial CVS diagnosis. CVS caregivers were adults with full-time employment and also having dependent(s) with CVS. Propensity scores via multivariable regressions were used to match patients with CVS and their caregivers to non-CVS controls. Productivity loss was assessed by short-term disability (STD) and absenteeism (ABS) days, and the associated costs were also calculated. Differences between the matched cohorts were regarded as the burden attributable to CVS.
UNASSIGNED: Patients with CVS had longer annualized STD (21.1 vs 7.0, P < .001) and ABS days (26.4 vs 22.8, P < .05) than their matched controls. CVS caregivers had more annualized STD (3.9 vs 2.6, P < .001) and ABS days (20.9 vs 19.5, P < .05) than controls. Productivity loss costs for STD or ABS days were greater for patients with CVS and caregivers. Annualized health-care resource utilization (inpatient, emergency room, outpatient) was 5.2-6.0 times higher in patients with CVS (P < .001).
UNASSIGNED: CVS is associated with higher productivity loss due to STD/ABS and, therefore, greater indirect costs for patients and caregivers. Further research is needed to assess the full societal burden of CVS. More effective interventions may reduce the disease burden.

OBJECTIVE: This study aimed to estimate the extent of US health care resource use (HRU) and direct cost burden of cyclic vomiting syndrome (CVS).
UNASSIGNED: We selected patients in the MarketScan Commercial and Medicare Supplemental databases with ≥1 inpatient (IP) or ≥2 outpatient (OP) claims for CVS between October 1, 2015 and June 30, 2019, and continuous insurance enrollment for ≥12 months before (baseline) and ≥3 months after first CVS diagnosis (index). Using propensity scores based on baseline characteristics, each patient with CVS was matched to ∼3 non-CVS controls. We annualized HRU and costs to accommodate varying follow-up periods. Multivariable regressions further balanced CVS and non-CVS groups, and differences in HRU and costs between the matched cohorts were compared to quantify the direct cost burden of CVS.
UNASSIGNED: Patients with CVS incurred significantly higher average annualized HRU, with the largest differences in emergency room (1.9 vs 0.4) visits and hospital IP (0.9 vs 0.1) stays (P < .001). Patients with CVS had significantly higher annual total health care costs ($57,140 vs $14,912), with IP spending as the primary driver ($28,522 vs $3250) of the cost difference (all P < .001). After multivariable regression adjustments, total health care costs remained 4.1 times higher for patients with CVS relative to non-CVS controls, with IP costs 12.3 times higher, emergency room costs 5.8 times higher, OP visit costs 2.9 times higher, and OP pharmacy costs 1.5 times higher (all P < .001).
UNASSIGNED: Newly diagnosed patients with CVS have greater health care utilization and higher costs than matched non-CVS counterparts, suggesting substantial economic burden of CVS on the US health care system.