Pediatric Emergency Medicine Follow Up: Cannabinoid Hyperemesis Syndrome
Case
“I can’t stop throwing up”
A 17 y.o. female with PMH significant for ADHD, anxiety, and depression presents to the Children’s Hospital Emergency Department with a chief complaint of vomiting, accompanied by her mother. She states that she has been vomiting for two days. Since that time, she has lost count of the number of times she has vomited. She denies seeing red or black in her emesis and tried taking Pepto-Bismol but vomited the medication.She was able to shower once which helped a little. She has diffuse abdominal tenderness with voluntary guarding, but her exam is otherwise non-revealing. She is dizzy when she stands and has had a headache, but denies changes in her vision. With her mother out of the room she endorses sexual activity with one partner and intermittent condom use. She vapes nicotine daily and consumes alcohol and marijuana “sometimes with friends”. Her menstrual cycle has been irregular her whole life, and her last period was 6 weeks ago. She denies abnormal vaginal bleeding or discharge.
Vitals:
T: 99.0
BP: 90/60
HR: 115
RR: 20
02 Sat: 96%
Differential
The differential diagnosis of vomiting and abdominal pain is large and contains multiple “can’t miss” diagnoses that often rely on complex, resource intensive imaging and laboratory evaluation . Gynecologic processes must be considered including ovarian torsion, pelvic inflammatory disease, and pregnancy, ectopic or intrauterine. Surgical pathologies including small bowel obstruction, perforated viscus, appendicitis, and biliary pathology are included as well. In addition acute coronary syndrome, aortic dissection, pulmonary embolism, pyelonephritis, gastroenteritis, substance abuse, trauma, idiopathic intracranial hypertension, and pancreatitis are valid considerations.
Laboratory studies and Imaging are undertaken:
Beta-hCG
CBC
BMP
LFTs
Lipase
Ethanol
UA
Urine toxicology
EKG
Abdominal ultrasound reveals a normal gallbladder without evidence of stones, no hydronephrosis on examination of the kidneys, the aorta is 4 mm in diameter. Importantly no intrauterine pregnancy, no free fluid in Douglas’ Pouch are identified and the appendix and bilateral ovaries are reported as normal.
EKG shows normal sinus rhythm, flattened T-waves, and mild tachycardia.
Lab Results:
Beta-hCG: <5
CBC:
WBC: 6.8
RBC: 5.0
HGB: 16.1
HCT: 44.0
MCV: 82.0
MCH: 31
MCHC: 34
RDW: 11%
PLT: 209
BMP:
Na: 142
K: 2.5
HC03-: 32
Cl: 88
BUN: 30
Cr: 1.3
Glu: 70
LFTs:
TBili: 0.1
AST: 47
ALT: 45
Albumin: 50
PT: 14
PTT: 40
INR: 1.0
Lipase: 15
UA:
Color: dark yellow
Clarity: turbid
PH: 7.0
Specific gravity: 1.010
Glucose: negative
Blood: negative
Ketones: trace!
Protein: negative
Urobili: negative
Bili: negative
Leuk Esterase: negative
Nitrites: negative
Utox:
Amphetamines: Positive!
Benzodiazepines: negative
Cannabinoids: Positive!
Cocaine: negative
Opioids: negative
Phencyclidine: negative
Ethanol: negative
Clinical Course
Based on the patient’s clinical status and laboratory results the plan is for IV access and 1 liter of Lactated Ringers. Additionally 40 mEq of potassium IV is administered to correct her hypokalemia. She is also treated with zofran 4mg for control of nausea and vomiting.
On reassessment the patient continues with nausea and dry heaves, unrelieved with treatments provided to date. Another liter of Lactated Ringers is provided and the patient now states that she feels mildly improved. Further history is obtained regarding her drug use. Patient reports she has been smoking since age 12 and that her use escalated when she started high school and moved to a new town this year. She has been a daily marijuana consumer since age 14 and now smokes multiple times a day.
Diagnosis and management
Cannabinoid Hyperemesis Syndrome is determined to be the most likely etiology of your patient’s intractable vomiting. You order Lorazepam 0.5 mg IV , Haldol 2.5mg IV and topical capsaicin cream. She is admitted for AKI, inability to tolerate PO intake, electrolyte correction, and symptomatic management.
Discussion
Cannabinoid Hyperemesis Syndrome (CHS) is a syndrome characterized by chronic cannabis use and cyclic vomiting.
The diagnosis of CHS is clinical and may be assisted by use of the imperfect ROME IV criteria [1] which are as follows:
Criteria fulfilled for at minimum three months, with symptomatic onset occurring at least six months before diagnosis
Stereotypical episodic vomiting resembling cyclical vomiting syndrome in onset, duration, and frequency
Presentation after prolonged, excessive cannabis use
Relief of vomiting by a sustained cessation of cannabis use
May be associated with “pathologic” bathing behavior, e.g., prolonged hot baths and showers.
Classically, CHS involves three phases: prodromal, cyclic vomiting, and resolution. [2] The prodromal phase can last months to years and is associated with nausea, normal eating, and fear of emesis. The cyclic vomiting phase is characterized by periods of frequent emesis, often as many as 5 episodes per hour, abdominal pain, and poor PO intake. The resolution phase occurs across months and is associated with absence of pain and return of normal eating habits, usually following a decrease in cannabis consumption. Individuals with mood disorders, males, and people who begin consuming cannabis in their teenage years may be at greater risk for developing CHS relative to the population. [3]
The mechanism by which bioactive compounds in cannabis produce emesis is not well defined. Cannabis consumption is observed to produce a dose-dependent biphasic effect, with low doses often decreasing nausea and stimulating appetite and higher levels of exposure producing intractable vomiting. Neuronal dysregulation following over-agonism of CB-1 and CB-2 receptors in the brainstem and hypothalamic–pituitary–adrenal (HPA) axis likely drives the clinical syndrome of nausea and vomiting. [4] CB receptor agonism causes changes in glutamate, GABA, and dopamine signaling as well, which may all contribute to CHS pathophysiology. .
Patients are typically hemodynamically stable but may experience hypotension and electrolyte derangement secondary to large volume emesis. Patients are typically young with a prolonged history of cannabis use with several years between the onset of cannabis consumption and CHS symptom onset, with daily marijuana use being characteristic. Misdiagnosis is common, as the differential diagnosis of nausea and vomiting is large. Work up should begin by excluding alternative life threatening causes of cyclic vomiting prior to establishing a diagnosis of CHS.
Treatment
Zofran
First line treatment may include medications such as Zofran, which achieve their antiemetic effect by antagonism of serotonergic receptors. The GI tract releases serotonin in response to noxious stimuli and inhibiting the brain from receiving this information may alleviate symptoms. Efficacy, however, has been reported to be limited and many report requiring additional medications for treatment of CHS. [5]
Compazine and Haldol
Blockade of D2 and D3 receptors in the chemoreceptor trigger zone of the medulla is often an effective means of emesis control. Compazine can be effective in treating CHS and is frequently favored over haldol as it is less sedating. [6] Haldol has anecdotally been reported to be highly effective in treating CHS and has been noted to be clinically superior to Zofran in treating CHS in at least one randomized control trial. [7] Of importance, both Zofran and Haldol may prolong the QTc, patients are at particular risk in the setting of electrolyte abnormality for progression to V-tach and TdP. As such, obtain an EKG prior to administration.
Lorazepam
Lorazepam and other benzodiazepines have been shown to decrease emesis by neuronal inhibition in the medulla and vestibular nuclei by their action at the GABA receptor producing neuronal hyperpolarization. These medications may be effective in treatment of CHS, however the sedating and respiratory depressant effects must be considered, particularly if used in combination with antidopaminergic drugs. [8]
Capsaicin
Capsaicin is a chemical found in many peppers that binds to transient receptor potential vanilloid-1 (TRPV 1) receptors. TRPV1 receptors are found in many locations, including in the gut, and may regulate CB receptor function as well as the release of substance P from sensory nerves to produce an antiemetic effect. CHS has been treated with the application of topical capsaicin cream to the Epigastrium successfully in a number of cases. Patient discomfort is frequently a barrier to treatment, with many describing the application of capsaicin as painful. [9]
Steroids
Steroids are frequently used to treat emesis and nausea, though the exact mechanism by which their effect is achieved is not well described. The use of steroids in treatment of CHS may be undertaken, however there is a paucity of data on their efficacy, and side effects including adrenal and immunosuppression must be considered. [10]
Cannabis Cessation
While life threatening hypovolemia, hypoglycemia, and electrolyte abnormalities may be corrected in the hospital setting, the patient is at-risk for symptom recurrence in the absence of a change in pattern of consumption. Cannabis use reduction and/or cessation are the definitive treatment. [11]
The incidence and nature of cannabis consumption has changed rapidly in the 21st century as many states have legalized or decriminalized cannabis. In 2015 in the United States, 22 million used marijuana and in 2011 there were 456,000 cannabis related Emergency Department visits. [12] CHS is noted to be a particular concern for those involved in the treatment of adolescents. [13] In addition, cultivation and consumption technologies have advanced in parallel. The concentration and potency of biochemically active cannabinoids have increased with commercial strains frequently containing THC concentrations in excess of 20%. In addition, e-cigarette technology and the ability to produce hyperconcentrated THC tinctures allows cannabis users to ingest cannabinoids at concentrations of >90%, something historically not accessible to the majority of consumers Legal, technologic, and sociopolitical trends may act as primary drivers of increasing rates of Cannabis Hyperemesis Syndrome observed in emergency departments. [14]
Author: Keaton Cameron-Burr, MD is a second-year emergency medicine resident at Brown Emergency Medicine Residency.
Faculty Reviewer: Kristina McAteer, MD is an attending physician at Rhode Island Hospital & Newport Hospital.
ReferenceS
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