By: Jordan Spector, MD

Case Presentation

You are an intern in the ED at BostonCityEM, and you encounter the following patient: 28 year old male with a history of mild asthma who presents to the ED with approximately 12 hours of abdominal discomfort, nausea and recurrent emesis.  He reports diffuse abdominal pain that developed at the same time as the vomiting.  There was no blood or bile in the vomit, and the patient denied lower GI or urinary symptoms.  A brief peek into his electronic medical record shows that this man has been in your ED ten times in the last 18 months.  You note a few different discharge diagnoses; “Abdominal pain”, “Gastroenteritis”, “Vomiting”, and “Gastritis” among them.  The patient reports that the current bout of symptoms feels identical to previous occasions, he denies any undercooked foods or travel outside the area.

The patient’s past medical history is unremarkable but for asthma and GERD.  He uses albuterol as needed for respiratory symptoms, and has been prescribed ranitidine after previous ED visits.  He has no surgical history.  He is a social drinker, smokes a half pack of cigarettes and marijuana every day.

On exam, the patient is restless and uncomfortable appearing, with loud retching and small quantities of dark, non-bloody emesis produced.  His mucus membranes are moist, his neck is supple.  He has clear breath sounds with normal work of breathing.  His abdomen is soft with diffuse mild tenderness and no peritoneal features.  His neuro exam is non-focal.

As a junior house officer, you might ask, “What in the world is making this guy vomit so violently?  Is this Cyclic Vomiting Syndrome?  I never learned about cyclic vomiting in medical school!!!!  I remember a similar case last week, and my attending for that case (Dr. Slipshod) clearly told me, “You don’t need to work up cyclic vomiting!!!  Just make the patient feel better, tolerate PO, and he can go home”.  And you ask yourself, “should I send labs this time?  Do I need to do any diagnostic testing?”.  While deliberating on those questions, you attempt to be proactive…”I’ll just get started making him feel better – a liter of saline , some Zofran and a GI cocktail should do the trick!”

 

Background

Cyclic Vomiting Syndrome (CVS) was first described in the 1880s as a pediatric condition.  Patients with certain underlying mitochondrial disorders or migraine headaches may be predisposed to CVS, though many cases are idiopathic.  Though no reliable population data exists, many perceive that the incidence of CVS in adults has increased significantly in recent years1.  Adults with CVS have higher incidences of anxiety and depression than the general population2.  And a new phenomenon has arisen in recent years; CVS as result of frequent, heavy marijuana use (sometimes referred to cannabis hyperemesis syndrome)3.  In fact, though cannabis had been used as an agent to treat nausea in the past, communities that have legalized the recreational use of marijuana have seen a significant upsurge in patients presenting to the ED with CVS4,5, so much so that the lay press has taken notice6.

There is no specific test or assay to identify CVS.  In many ways, CVS is a diagnosis of exclusion.  The Rome III criteria for the diagnosis of CVS in adults stipulates that a patient must have symptoms for at least 6 months, with the following features:

  • Recurrent, episodic emesis, acute onset, lasting less than seven days
  • Three or more discreet episodes of symptoms in the prior year
  • Absence of nausea and vomiting between episodes
  • No metabolic, gastrointestinal or CNS structural biochemical disorders to explain the symptoms1

The symptoms of CVS have been described as occurring in stages; the inter-episodic ‘well-phase’, which refers to the asymptomatic timeframe between vomiting episodes.  CVS patients first feel symptomatic during the ‘prodromal phase’, where symptoms may include variable degrees of abdominal pain, anorexia, nausea and lethargy.  This phase can last minutes to hours, and should be treated aggressively in an attempt to abort the impending ‘emetic phase’.  By the time a patient presents to the ED, they are often well into the emetic phase. In this phase, the patient will experience severe nausea, recurrent vomiting, and variable degrees of pallor, abdominal pain, diaphoresis and agitation.  The emetic phase may last for hours to days.  Symptoms typically culminate in the ‘recovery phase’ when the vomiting subsides, and appetite and vigour returns7.


Diagnostic Approach

Though not specifically stipulated in most formal descriptions of CVS, most EM providers consider cyclic vomiting as a diagnosis of exclusion.  Dr. Slipshod’s expertise notwithstanding, most seasoned EM providers will tell you that every patient presenting with abdominal pain and vomiting requires a thoughtful evaluation.  That is because abdominal pain and vomiting has a scary differential.  Patients with nausea and vomiting may have a massive ST elevation MI.  Or severe sepsis.  Or DKA.  Or perforated appendicitis.  The differential for vomiting is so long, it’s almost nauseating!  And it’s littered with conditions that could kill your patient. Do NOT be misled by Dr. Slipshod, every patient presenting with abdominal pain and vomiting warrants a thoughtful evaluation.  Now in some cases, a detailed history, a comprehensive exam, and a quick review of past records are sufficient for a thoughtful evaluation, but it is important that ED providers don’t cut corners with these patients.

For patients with prolonged symptoms, we suggest a low threshold for checking a metabolic panel to assess the anion gap and renal function, which can help guide resuscitation efforts.  A point-of-care glucose level is quick and cheap, and will help if you are considering DKA or HHS.  For patients with a history of alcohol abuse, or any significant epigastric or right upper quadrant tenderness, a liver function panel is indicated as well. An inferior wall MI may present with epigastric symptoms, so consider an EKG in the work-up.  Mesenteric ischemia classically presents with significant GI discomfort and an unremarkable abdominal exam, consider a venous lactate level in patients at risk for atherosclerotic and/or embolic disease.  The presence of focal tenderness on exam, fever, leukocytosis or an obstructive pattern on LFTs are a few of the reasons you might consider advanced imaging of the abdomen as well in these patients.   It is only after having considered (and ruled out) the high acuity conditions that a provider should feel comfortable diagnosing and treating vomiting as a flare of CVS.

 

Therapeutic Approach

Of course, Dr. Slipshod did offer one piece of helpful advice – we want to help a patient with CVS to feel better.  How best to accomplish this?  Practically every reference on CVS advocates ‘supportive treatment’ without any particulars of which agent to use, and for what indications.  Amongst all patients presenting to an ED with nausea and vomiting, there is no evidence to support the superiority of any one antiemetic versus another, and patients receiving simple volume resuscitation and placebo often report improvement8.  But anyone who has treated a patient with CVS can tell you these patients often require a ‘cocktail’ of multiple medications to experience relief.  Especially for patients presenting in the prodromal phase, aggressive treatment can sometimes can abort the emetic phase, and reduce the time and resources required in the care of these patients.  The ‘GI cocktail’ is a common treatment offered in the ED and can be effective for treatment of discomfort associated with acid reflux, but it is not the ideal pharmaceutical option for a patient with recurrent, severe emesis.  Our subject intern should rather consider parenteral therapies, and we recommend starting with an intravenous dose of an antiemetic and an antacid at minimum for these patients.  Volume resuscitation is a must, though no formal recommendations exist to decide which type of crystalloid is best.  We recommend that you consider a crystalloid containing dextrose, as analogous to that which occurs in pregnant patients with hyperemesis gravidarum, supplemental dextrose can reverse ketosis, reduce nausea and aid in recovery2.  For a patient with frequent recurrent symptoms, or those at risk for malnutrition, you likely ought to provide a dose of thiamine prior to the dextrose.  Along with IV fluids, there are many antiemetics readily available in most North American EDs, and there is no telling which may work for the patient in front of you.  Phenothiazines (such as promethazine and prochlorperazine), metoclopramide and ondansetron are all considerations for treatment of the prodromal or the emetic phase of CVS.  Some have suggested that ondansetron is only effective at higher doses (as is given to patients with emesis after chemotherapy or general anesthesia), and as such, the standard dose in the ED (4 mg IV) may not provide relief as desired9.  In CVS, higher doses of ondansetron may be indicated, or perhaps you should consider a different agent altogether.

Unfortunately, many patients with CVS do not feel better with conventional antiemetics.  As a result, EM providers have explored different pharmaceutical options to bring relief where the usual antiemetics may fail.  Any emergency medicine provider who has been in practice since the 1990’s likely recalls droperidol fondly. Droperidol has been shown to be significantly more effective for the treatment moderate-severe emesis of all causes, though with an increased rate of extrapyramidal effects9.  Unfortunately, due to the rare but statistically significant association between droperidol and QTc prolongation/torsade de pointes, the US Food and Drug Association applied a ‘black-box’ warning to this medication, and it is largely unavailable in most EDs in 2017.  However, droperidol’s ‘cousin’ haloperidol is widely stocked in most US hospital, and available for use.  There is ample literature to suggest that haloperidol is effective for the management of emesis after anesthesia or during palliative care in cancer patients10–12.  Perhaps as a result of these data, EM providers have begun providing haloperidol for cannabinoid hyperemesis, and with good success13–15.  For patients with cyclic vomiting in whom conventional agents are ineffective, you may consider 2 to 5 mg of IV haloperidol for treatment of emesis.  Please note that haloperidol can lengthen the QTc interval, and you may need to do an EKG prior to giving the med to be certain that the QTc is not already so long as to put the patient at risk for malignant dysrhythmia due to your intervention.  In addition, patients who receive this agent should be placed on a cardiac monitor while in the ED.

Along with the antipsychotics, some EM providers have begun to provide benzodiazepines to treat cyclic vomiting16,17.  Given their antiemetic and anxiolytic properties, benzos can quell the nausea as well as the psychomotor agitation that CVS patients experience during the emetic phase.  Benzos are a good option to consider in patients who you note to have a long QTc on the EKG.  If you are considering benzos, we would suggest IV lorazepam or midazolam, starting at a low dose, and titrating to comfort.

Interestingly, EM providers have identified that patients presenting with cannabinoid hyperemesis may experience transient relief from their symptoms with hot water bathing18,19.  The mechanism for this is poorly understood, but thought to arise in part due to the cannabinoid receptors that exist in the hypothalamus near the thermoregulatory centers of the brain18.  The relief of emesis after a cutaneous intervention (from bathing) may have persuaded physicians that cyclic vomiting is possible with topical therapy. Recent literature suggests that topical capsaicin cream (0.1%) applied liberally to the thorax and abdomen can ameliorate vomiting and help abort the emetic phase of CVS20,21.  Given the low risk and potential benefits of this topical therapy, EM providers may consider adding this to the armamentarium.

 

Case Resolution

After a thorough patient evaluation and a careful review of the electronic health records, you decide this 28 year old gentleman is presenting with an uncomplicated flare of his chronic, recurrent emetic syndrome, with low suspicion for other malignant processes.  You send a basic metabolic panel, and all lab values return within normal limits.  An EKG shows no ischemic features and a normal QTc.  You have the nurse place a peripheral IV, and provide this patient a parenteral dose of antacids, 5 mg of IV haloperidol and two liters of crystalloid (one liter of normal saline to correct hypovolemia, one liter of D5 half-normal saline to provide dextrose to treat ketosis).  The patient experiences relief within 5 minutes of the medication, and after a ninety-minute nap in the ED, awakens to say he feels “SO MUCH BETTER!”.  He is able to tolerate a PO trial, and is discharged in improved condition.

Emesis as Nemesis no longer!!!!

 

References

  1. Hejazi RA, McCallum RW. Review article: Cyclic vomiting syndrome in adults – Rediscovering and redefining an old entity. Aliment Pharmacol Ther. 2011;34(3):263-273. doi:10.1111/j.1365-2036.2011.04721.x.
  2. Abell TL, Adams KA, Boles RG, et al. Cyclic vomiting syndrome in adults. Neurogastroenterol Motil. 2008;20(4):269-284. doi:10.1111/j.1365-2982.2008.01113.x.
  3. Pattathan MB, Hejazi RA, McCallum RW. Association of marijuana use and cyclic vomiting syndrome. Pharmaceuticals. 2012;5(7):719-726. doi:10.3390/ph5070719.
  4. Kim, Howard S. and Monte AA. Colorado Cannabis Legalization and Its Effect on Emergency Care. Ann Emerg Med. 2016;68(1):71-75. doi:10.1016/B978-0-12-386043-9.00005-0.New.
  5. Kim HS, Anderson JD, Saghafi O, Heard KJ, Monte AA. Cyclic vomiting presentations following marijuana liberalization in Colorado. Acad Emerg Med. 2015;22(6):694-699. doi:10.1111/acem.12655.
  6. Heany K. Does Marijuana Cause Cyclic Vomiting Syndrome? – The Atlantic. Atl. August 2017. http://www.theatlantic.com/health/archive/2017/08/cyclic-vomiting-syndrome/538398/.
  7. Venkatesan, Thangam. Samuel EA. Cyclic vomiting syndrome. In: Rao SSC, Parkman HP MR, ed. Handbook of Gastointestinal Motility and Functional Disorders. ; 2015:131-140. http://aplicacionesbiblioteca.udea.edu.co:4560/contents/cyclic-vomiting-syndrome?source=search_result&search=vomito+ciclico&selectedTitle=1~17.
  8. Furyk JS, EgertonWarburton D, Meek RA. Drugs for the treatment of nausea and vomiting in adult patients in the emergency department setting. 2012;(9). doi:10.1002/14651858.CD010106.pub2.
  9. Patanwala AE, Amini R, Hays DP, Rosen P. Antiemetic therapy for nausea and vomiting in the emergency department. J Emerg Med. 2010;39(3):330-336. doi:10.1016/j.jemermed.2009.08.060.
  10. Roldan CJ, Chambers KA, Paniagua L, et al. Randomized Controlled Double-Blind Trial Comparing Haloperidol Combined with Conventional Therapy to Conventional Therapy Alone in Patients with Symptomatic Gastroparesis. 2017:1-8. doi:10.1111/ijlh.12426.
  11. Lee Y, Wang PK, Lai HY, Yang YL, Chu CC, Wang JJ. Haloperidol is as effective as ondansetron for preventing postoperative nausea and vomiting. Can J Anaesth. 2007;54(5):349-354. doi:10.1007/BF03022656.
  12. Hardy JR, O’Shea A, White C, Gilshenan K, Welch L, Douglas C. The efficacy of haloperidol in the management of nausea and vomiting in patients with cancer. J Pain Symptom Manage. 2010;40(1):111-116. doi:10.1016/j.jpainsymman.2009.11.321.
  13. Witsil JC, Mycyk MB. Haloperidol, a Novel Treatment for Cannabinoid Hyperemesis Syndrome. Am J Ther. 2017;24(1):e64-e67. doi:10.1097/MJT.0000000000000157.
  14. Hickey JL, Witsil JC, Mycyk MB. Haloperidol for treatment of cannabinoid hyperemesis syndrome. Am J Emerg Med. 2013;31(6):1003.e5-1003.e6. doi:10.1016/j.ajem.2013.02.021.
  15. Inayat F, Virk HUH, Ullah W, Hussain Q. Is haloperidol the wonder drug for cannabinoid hyperemesis syndrome? BMJ Case Rep. 2017;2017:bcr2016218239. doi:10.1136/bcr-2016-218239.
  16. PALMER GM, CAMERON DJ. Use of intravenous midazolam and clonidine in cyclical vomiting syndrome: a case report. Pediatr Anesth. 2005;15(1):68-72. doi:10.1111/j.1460-9592.2005.01369.x.
  17. Shadowfax. Dealing With Cyclic Vomiting Syndrome Given How Little Is Known About The Condition – Better Health – Better Health. Get Better Health: Smart Health Commentary. http://getbetterhealth.com/dealing-with-cyclic-vomiting-syndrome-given-how-little-is-known-about-the-condition/2011.11.29. Published 2011. Accessed September 29, 2017.
  18. Patterson DA, Smith E, Monahan M, et al. Cannabinoid Hyperemesis and Compulsive Bathing: A Case Series and Paradoxical Pathophysiological Explanation. J Am Board Fam Med. 2010;23(6):790-793. doi:10.3122/jabfm.2010.06.100117.
  19. Warner A Ben, B ASC, C AS. Lesson of the month 1: A rare case of cannabis hyperemesis syndrome relieved by hot water bathing. . 2014;14(1):86-87. doi:10.1136/bcr.01.2010.2605.Address.
  20. Dezieck L, Hafez Z, Conicella A, et al. Resolution of cannabis hyperemesis syndrome with topical capsaicin in the emergency department: a case series. Clin Toxicol. 2017;55(8):908-913. doi:10.1080/15563650.2017.1324166.
  21. Sorensen CJ, DeSanto K, Borgelt L, Phillips KT, Monte AA. Cannabinoid Hyperemesis Syndrome: Diagnosis, Pathophysiology, and Treatment—a Systematic Review. J Med Toxicol. 2017;13(1):71-87. doi:10.1007/s13181-016-0595-z.

 

Faculty Author: Jordan Spector, MD
Resident Editor: Keya Rahnemoon, MD

Photo Credit: https://www.flickr.com/photos/yatil/6298370857