Case
A 23-year-old Hispanic woman with no past medical history is brought to the ED for the second time in one day. On her first presentation, which was for a fever and a headache, meningitis was excluded with normal laboratory tests that included a lumbar puncture. She was administered acetaminophen for fever and pain control, and was discharged with a diagnosis of viral illness. On this second visit, 10 hours after being discharged, she presented because her family noted convulsions that began 3 hours after taking an herbal headache remedy given to her by a naturopath.
The patient arrived to the ED with a persistent seizure that terminated following administration of 2 mg of lorazepam. Her initial vital signs were: blood pressure, 115/51 mm Hg; heart rate, 121 beats/minute; respiratory rate, 24 breaths/minute; temperature, 97.6oF. Oxygen (O2) saturation was 100% with 2 L of O2 administered via nasal cannula. Her neurological examination was significant for a depressed mental status, pupils that were 6 mm and minimally reactive, clonus, and hyperreflexia. Repeat laboratory evaluation found a leukocytosis of 22.0 x 103/µL, serum bicarbonate of 9 mEq/L, and an anion gap of 22 with a normal serum lactate.
What is the differential diagnosis of this patient?
The history of medicinal plant ingestion raises the possibility of a toxicologic etiology. However, because the patient took the “medication” to treat another disorder, a search for an alternate cause should be performed. The differential diagnosis of a toxin-induced seizure is broad and includes pharmaceuticals (eg, tramadol, antihistamines), which may be surreptitiously added to herbal medication to assure efficacy. Plants associated with seizures include those containing antimuscarinic tropane alkaloids such as Jimsonweed (though a rare side effect from this plant product) or the water hemlock (Cicuta maculata). Contaminants of the plant itself may include pesticides such as organophosphates.
Although unlikely in a 21 year old, withdrawal from benzodiazepines, ethanol, baclofen, or gamma hydroxybutyrate are other possible etiologies. In addition to pharmaceutical and plant-derived causes, carbon monoxide poisoning should be a consideration in any patient with headache and flu-like illness.
This patient also presented with a constellation of other findings that included hyperreflexia, clonus, tachycardia, and altered mental status. Together these signs are expected in patients with serotonin toxicity (also referred to as serotonin syndrome), neuroleptic malignant syndrome, exogenous thyrotoxicosis, and lithium poisoning.
Case Continuation
The naturopathic practitioner arrived at the ED concerned about the patient, informing the ED team that she had given the patient 2 ounces of ayahuasca tea.
What is ayahuasca? What is the mechanism by which it exerts toxic effects?
Ayahuasca is a plant-derived psychotropic beverage that is used for religious purposes by members of two Brazilian churches—Centro Espírita Beneficente União do Vegetal (UDV) and Santo Daime. The ayahuasca beverage consists of two pharmacologically active compounds that together, but not individually, are psychoactive. The desired active effects for church participants include hallucinations, and vomiting to bring about a “religious purge.”1
Ayahuasca is prepared by combining two plants indigenous to the Amazon Basin area: Banisteriopsis caapi and either Psychotria viridis or Diplopterys cabrerana. B caapi contains the β-carboline alkaloids harmine, harmaline, and tetrahydroharmine. These alkaloids act as reversible inhibitors of the monoamine oxidase A (MAO-A) enzyme. The bark and stems of B caapi are boiled along with either P viridis or D cabrerana, both of which contain the potent hallucinogen N-N dimethyltryptamine (DMT).2 Normally, DMT is not active orally because it is enzymatically metabolized by MAO-A. However, when taken in the presence of the B caapi-derived MAO-A–inhibiting harmine alkaloids, DMT reaches the systemic circulation and produces its clinical effects.3
What are the clinical findings of serotonin toxicity?
Serotonin toxicity is a collection of clinical findings that fall under three main categories: autonomic hyperactivity, altered mental status, and muscle rigidity.5 The autonomic findings may include tachycardia, hypertension, hyperthermia, shivering, diaphoresis, or mydriasis. Altered mental status ranges from mild agitation and hypervigilance to agitated delirium to obtundation. Other neurological findings may include tremor, myoclonus, hyperreflexia, or seizures. The onset of these signs is rapid, usually occurring within minutes after exposure to one or more serotonergic compounds. Although rare, severe serotonin toxicity may be associated with hypotension and shock, leading to death.4