Case Report

Cannabinoid Hyperemesis Syndrome A Cause of Refractory Nausea and Vomiting in Pregnancy Veronica I. Alaniz, MD, MPH, Jill Liss, MD, Torri D. Metz, MD, MS, and Elaine Stickrath, MD BACKGROUND: Cannabinoid hyperemesis syndrome is a condition present among chronic cannabis users resulting in abdominal pain, intractable nausea and vomiting, and compulsive bathing behaviors. Given the recent legalization of marijuana in certain areas of the United States, the incidence of this condition may increase among pregnant women. CASE: We report the case of a pregnant 28-year-old woman with multiple admissions for episodic nausea and vomiting resulting in Mallory-Weiss esophageal tears, dehydration, and abdominal pain who was noted to be showering compulsively during her hospitalizations. After an extensive workup for the etiology of her intractable nausea and pain, she was diagnosed with cannabinoid hyperemesis syndrome, which is treated simply with abstinence from marijuana use. CONCLUSION: Cannabinoid hyperemesis syndrome should be considered in pregnant women with intractable nausea relieved by frequent hot bathing. By considering this diagnosis, extensive diagnostic testing can be avoided and the correct therapy, abstaining from cannabis use, can be recommended. (Obstet Gynecol 2015;125:1484–6) DOI: 10.1097/AOG.0000000000000595

From the Departments of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, and University of Colorado Anschutz Medical Campus, Anschutz, and Denver Health, Denver, Colorado. Corresponding author: Veronica Alaniz, MD, L4000 Women’s Hospital, 1500 E Medical Center Drive, SPC 5276, Ann Arbor, MI 48109; e-mail: [email protected] med.umich.edu. Financial Disclosure The authors did not report any potential conflicts of interest. © 2015 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0029-7844/15

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Teaching Points 1. Cannabinoid hyperemesis syndrome is characterized by nausea and vomiting unresponsive to traditional therapies with the hallmark behavior of frequent hot bathing. 2. The prevalence of this condition likely will increase as the legalization and use of marijuana increase around the United States. 3. Obstetricians should be aware of this condition and consider it in the differential diagnosis of nausea and vomiting in pregnancy.

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annabinoid hyperemesis syndrome, first described in 2004, is a paradoxical cyclic vomiting syndrome that develops in susceptible individuals with a history of chronic cannabis abuse.1 The classic presentation includes severe nausea, intractable vomiting, abdominal pain, and abnormal bathing behaviors. Compulsive bathing, often seen as showering in hot water for hours at a time and multiple times per day, appears to provide symptomatic relief and can be the key in identifying patients with this syndrome.1–3 The symptoms are episodic, and resolution is seen when cannabis use is stopped.2 Marijuana is the most commonly used illicit drug in and outside of pregnancy. New legislation in the states of Colorado and Washington has legalized the production, distribution, and consumption of recreational marijuana. Although the effects of these new laws are not yet known, cannabis use is expected to increase.4 It is estimated that 40% of young people in Colorado have used marijuana within the past year.5 The prevalence of cannabis use in pregnancy is limited and likely significantly underestimated as a result of variability in reporting.6 It is important for the obstetrician to consider the diagnosis of cannabinoid hyperemesis syndrome in a patient with cyclic and refractory nausea and vomiting, because failure to do so can result in expensive and futile investigations.2 We present a case of cannabinoid hyperemesis in pregnancy, a syndrome that is underreported in the obstetric literature.

CASE A 28-year-old woman, gravida 5 para 3013, was brought to the emergency department by ambulance at 30 5/7 weeks of gestation for altered mental status, loss of consciousness, persistent nausea and vomiting with hematemesis, and abdominal pain. She was monitored in our high-risk

OBSTETRICS & GYNECOLOGY

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obstetrics clinic for severe hyperemesis gravidarum. Her medical history was significant only for asthma, and her social history was significant for chronic marijuana use since age 16 years. She estimated smoking up to “20 bowls” of marijuana daily. The history at presentation was obtained from the patient’s fiance´, who reported that she awoke that morning with nausea, vomiting, and abdominal cramping. The patient was taking a warm bath as he left for work, and when he returned later that day, she was still in the bath, but was now lethargic and surrounded by coffee ground emesis. He reported that the patient frequently took long, warm baths to relieve her symptoms. On evaluation in the emergency department, the patient’s vital signs were normal; however, she was lethargic and intermittently lost consciousness for periods of 20–30 seconds. Her abdomen was soft with mild diffuse tenderness but no rebound or guarding. She received a comprehensive workup, which revealed normal liver function and lactate, lipase, and electrolyte levels; a magnetic resonance image of her brain and abdomen showed no acute intracranial or intraabdominal processes. Her mental status improved with intravenous resuscitation, and she was admitted to the obstetric service for further treatment. She was placed on intravenous antiemetics and antacids. The medical team and nursing staff found it challenging to care for the patient because she was often showering and unavailable for evaluation. She was discharged home 2 days later with the diagnosis of hyperemesis gravidarum and associated Mallory-Weiss tears. The patient re-presented at 31 4/7 weeks of gestation for another acute episode of nausea, vomiting, and abdominal pain. She reported that her symptoms returned 3–4 days after discharge. Again, the patient was often found in the bathroom taking a warm shower or bath. She almost always had to be asked to come out of the shower for rounds or nursing administration of medications. In fact, she admitted that this was the only thing that provided symptomatic relief. Given her severe symptoms, the gastroenterology team was consulted. They suggested that, in the setting of normal laboratory values, chronic marijuana use, recurrent nausea and vomiting, abdominal pain, and frequent warm bathing behaviors, her symptoms were most consistent with cannabinoid hyperemesis syndrome. She was transitioned to oral antacids and antiemetics and advised to abstain from marijuana. The patient reduced her marijuana use to once daily for the remainder of the pregnancy, which resulted in resolution of her symptoms. At 39 weeks of gestation, she delivered an appropriatefor-gestational-age (3,435 g) male neonate with Apgar scores of 8 at 1 minute and 8 at 5 minutes. The neonate required a brief period of observation in the neonatal intensive care unit for intermittent hypoxia, with the need for blow-by oxygen administration to maintain normal saturations. His urine and meconium screenings both were positive for marijuana but no other drugs. He was discharged on day of life 2 in good condition.

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DISCUSSION The patient in this case report had a classic presentation of cannabinoid hyperemesis syndrome. Although widely recognized in the gastroenterology and psychiatry literature, its report in pregnancy is limited to only two prior case reports (PubMed search from 2004 to 2014 using the search terms “pregnancy” and “marijuana,” “cannabinoid hyperemesis syndrome,” or “cannabinoid”).7,8 Obstetricians are likely familiar with antiemetic properties of cannabis but may not recognize the potential for certain chronic users to develop this paradoxical reaction. The characteristic features of cannabinoid hyperemesis include history of heavy marijuana use, episodic nausea and vomiting that is unresponsive to antiemetics, abdominal pain, and compulsive bathing with hot water. Additional symptoms may include agitation, diaphoresis, tachycardia, postural hypotension, subjective fevers and chills, and weight loss.2,3,7,9 Hyperemesis gravidarum is a common diagnosis among pregnant women with severe nausea and vomiting. Symptoms that are not relieved by antiemetics should trigger the obstetrician to inquire about drug use, which is information not usually volunteered by the pregnant patient.7 Patients also should be asked about relief of symptoms with hot water bathing, which is a unique feature not seen with other vomiting syndromes.3 The pathophysiology of cannabinoid hyperemesis syndrome is not well understood. Toxic levels are thought to result from marijuana’s lipophilic properties and long half-life. Cannabinoid type 1 receptors found in the central nervous system are responsible for the antiemetic effects of cannabinoids. These receptors also are found in the gut and, when stimulated, result in delayed gastricemptying and peristalsis. At toxic levels, it is hypothesized that hyperemesis develops when the peripheral effects at the gut override the centrally mediated antiemetic effects.3,10,11 The learned behavior of compulsive bathing is interesting and essentially pathognomonic for cannabinoid hyperemesis syndrome. There are several proposed mechanisms that may explain this behavior. The psychoactive component of cannabis is hypothermic and hot water bathing may be a reaction to changes in core body temperature. Alternatively, the behavior might be resulting from direct activation of cannabinoid type 1 receptors near the thermoregulatory center of the hypothalamus.9,10 Others suggest that symptom relief is related to redistribution of blood flow from the gut to the skin.11

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Patients with cannabinoid hyperemesis syndrome usually have a history of several visits to the emergency department. As with the patient in this case report, they are dehydrated on presentation and undergo extensive diagnostic workup, including laboratory and imaging studies.12 The treatment for cannabinoid hyperemesis syndrome may require hospitalization for supportive care with fluid resuscitation and electrolyte replacement.2,13 The antiemetics used commonly in pregnancy, such as vitamin B6, ondansetron, promethazine, and metoclopramide, typically do not relieve symptoms.13 Episodes usually last for 24–48 hours at a time and will recur if cannabis use is continued.2,12 Some patients cannot accept the idea that marijuana is causing their symptoms and may in fact increase their use to treat episodes.1,12 Although the pathophysiology of cannabinoid hyperemesis syndrome is not well-understood, the clinical characteristics have been reported in the literature. Given the increasing medical and recreational uses of cannabis, particularly with the recent legalization of recreational marijuana in some states, obstetricians should recognize cannabinoid hyperemesis syndrome as a possible etiology of refractory nausea and vomiting in the pregnant patient. REFERENCES 1. Allen JH, de Moore GM, Heddle R, Twartz JC. Cannabinoid hyperemesis: cyclical hyperemesis in association with chronic cannabis abuse. Gut 2004;53:1566–70.

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2. Sullivan S. Cannabinoid hyperemesis. Can J Gastroenterol 2010;24:284–5. 3. Simonetto DA, Oxentenko AS, Herman ML, Szostek JH. Cannabinoid hyperemesis: a case series of 98 patients. Mayo Clin Proc 2012;87:114–9. 4. United Nations Office on Drug and Crime. World drug report 2014. Available at: www.unodc.org/documents/wdr2014/ World_Drug_Report_2014_web.pdf. Retrieved July 15, 2014. 5. Center for Behavioral Health Statistics and Quality. Results from the 2010 national survey on drug use and health: summary of national findings. Available at: http://www.samhsa.gov/data/ NSDUH/2k10NSDUH/2k10Results.pdf. Retrieved July 15, 2014. 6. Jaques SC, Kingsbury A, Henshcke P, Chomchai C, Clews S, Falconer J, et al. Cannabis, the pregnant woman and her child: weeding out the myths. J Perinatol 2014;34:417–24. 7. Schmid S, Lapaire O, Huang DJ, Jurgens FE, Güth U. Cannabinoid hyperemesis syndrome: an underreported entity causing nausea and vomiting of pregnancy. Arch Gynecol Obstet 2011; 284:1095–7. 8. Swanson M, Epperly T. Vomiting, abdominal pain, compulsive bathing—Dx? J Fam Pract 2014;63:257–9. 9. Lacopetti CL, Packer CD. Cannabinoid hyperemesis syndrome: a case report and review of pathophysiology. Clin Med Res 2014;12:65–7. 10. Chang YH, Windish DM. Cannabinoid hyperemesis relieved by compulsive bathing. Mayo Clin Proc 2009;84:76–8. 11. Patterson DA, Smith E, Monahan M, Medvecz A, Hagerty B, Krijger L, et al. Cannabinoid hyperemesis and compulsive bathing: a case series and paradoxical pathophysiological explanation. J Am Board Fam Med 2010;23:790–3. 12. Galli JA, Sawaya RA, Friedenberg FK. Cannabinoid hyperemesis syndrome. Curr Drug Abuse Rev 2011;4:241–9. 13. Sun S, Zimmermann AE. Cannabinoid hyperemesis syndrome. Hosp Pharm 2013;48:650–5.

OBSTETRICS & GYNECOLOGY

Copyright ª by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

Cannabinoid hyperemesis syndrome: a cause of refractory nausea and vomiting in pregnancy.

Cannabinoid hyperemesis syndrome is a condition present among chronic cannabis users resulting in abdominal pain, intractable nausea and vomiting, and...
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