The study was approved by the Loma Linda University Institutional Review Board.The most common symptoms reported in our study were cough, shortness of breath, and vomiting, each occurring separately in five patients. Three patients presented with chest pain. Two patients presented with altered mental status in the form of unresponsiveness, with one patient requiring intubation. The other unresponsive patient, a 16-year-old male, returned to a normal mentation with bag-valve-mask ventilation and naloxone but required high-flow nasal cannula for shortness of breath. On physical examination, accessory muscle use was the most common finding, reported in four patients. Rales were appreciated in two patients, while no patients were found to have wheezing . In our study, six patients presented with respiratory failure. Four required HFNC. One patient was intubated; one patient required simple nasal cannula oxygen at two liters per minute; and one patient maintained normal oxygen saturations in room air during his ED visit and was discharged home. A brief clinical presentation, summary of findings on imaging, and type of respiratory support needed are summarized in Table 2. Five patients were admitted to the pediatric intensive care unit, and one patient was admitted to the normal pediatric unit. The median hospital length of stay was six days . All patients were discharged with no comorbidities or deaths reported. Six patients were treated with steroids. The median duration of treatment with steroids during admission and after discharge was nine days . Our patients had a variety of laboratory tests ordered. Most common were complete blood count, respiratory virus panel, respiratory cultures,microgreen rack for sale and urine drug screen. All patients had a complete blood count, and the median for white cell count was 16 thousand cells per cubic millimeter . A respiratory virus panel was collected from five patients and it was negative in all of them .
Respiratory cultures were collected from two patients and both resulted negative. A urine drug screen was performed for six patients and was positive for cannabinoids in all six . Three patients followed up at different intervals in the pulmonology clinic . Spirometry showed normal results in all three patients at that time. Case 1 followed up one week after discharge, at which time spirometry showed evidence of obstructive lung disease, which returned to normal at three-month follow-up visit. No repeat imaging was performed for that patient. Case 2 followed up six weeks after discharge with near-complete resolution of ground-glass appearance on repeat CT and normal spirometry. Case 4 followed up two weeks after discharge with improvement in lung opacities on repeat radiograph and normal spirometry. All three patients had received steroids for 10 days when they were originally diagnosed with EVALI. No follow-up data was available for the remaining four patients.EVALI was an emerging disease entity in 2019. In our case series, we describe adolescents diagnosed with EVALI and their clinical course in the ED and the hospital. In our study, the most common symptoms of cough, shortness of breath, and vomiting presented with an equal frequency of 71%. In a study by Layden et al, shortness of breath and cough was noticed in 85% of patients and vomiting in 61%; whereas, according to Belgaev et al, 90% of patients in their study presented with gastrointestinal and respiratory symptoms.In a report by the CDC, 85% of the EVALI population had respiratory symptoms and 57% had GI symptoms.The results of our study are similar to previous literature in suggesting that respiratory and GI symptoms are common in patients with EVALI. According to Balgaev et al, 67% of patients had clinical and radiological improvement with residual findings on radiological and pulmonary function tests at time of follow up.In our study, the three patients who had documented follow-up visits had normal spirometry without residual deficits. Only two of those patients had repeat imaging, and both showed improvement without residual abnormalities. E-cigarette liquids and aerosols have been shown to contain a variety of chemical constituents including flavors that can be cytotoxic to human pulmonary fibroblasts and stem cells.Exposure to heavy metals such as chromium, nickel, and lead has also been reported.
None of our patients were tested for heavy metal exposure. Most of the delivery systems have nicotine in them, with one cartridge providing the nicotine equivalent to a pack of cigarettes.In addition to nicotine, e-cigarette devices can be used to deliver THC-based oils.According to Trivers et al, one-third of the adolescents who used e-cigarettes had used cannabinoids in their e-cigarettes.In our patients with EVALI, urinary drug screen was positive for cannabinoids in all patients. One caveat is that we do not know whether our patients used only THC-containing products or a combination of nicotine and THC-containing products. In our case series, the majority of patients presented with pulmonary disease requiring respiratory support and intensive care unit admission. None of these patients developed acute respiratory distress syndrome . We likely did not see this disease process due to our small sample size, as Layden et al reported ARDS development in several of their examined cases.6 In our series, we did not evaluate the pathologic pulmonary changes in different patients. In other case reports, different pathophysiologic patterns of pulmonary involvement, in the form of diffuse alveolar hemorrhage, exogenous lipoid pneumonia, acute eosinophilic pneumonia, or hypersensitivity pneumonitis have been identified.Although the mechanism of EVALI is not clearly understood, the CDC suggests the use of steroids for treatment.According to a series of patients in Illinois, 51% of those patients had improvement in symptoms after the administration of steroids.6 In another study, patients showed clinical and radiological improvement following the use of antibiotics and steroids.In our study, six patients received steroids and six patients received antibiotics; three of those patients followed up in clinics with normal spirometry. But this evidence is not sufficient to establish that use of steroids or antibiotics is beneficial in EVALI. There are several limitations of our study. First, because it was a retrospective chart review we could not establish causation. Second, all data may not have been recorded on all patients . We might have missed some if the ICD-10 codes were not correct on the chart. Only three had documented follow-up, so we don’t know whether the other four had any comorbidities after their hospitalization. Third, we had a small number of patients. Fourth, this was a single-center study; so results may not be generalizable to other hospitals with different patient demographics.
Synthetic cannabinoids first made their appearance in the United States in 2008 and are sold under numerous names including “K2,” “Spice,” and “Black Magic.” These drugs have long evaded law enforcement due to the drug manufacturers’ ability to quickly alter chemical formulas and generate novel products that have yet to be made illegal under the Controlled Substances Act. In addition, most of these are packaged and sold as herbal products and labeled as “not for human consumption” to further circumvent drug laws.After being dissolved in solvent, synthetic cannabinoids are typically formulated and sprayed onto an herbal product that is then smoked and inhaled.A wide array of symptoms has been associated with ingestion from these compounds. While some users report similar euphoric effects to that of marijuana,cannabis grow facility layout there have been other significant adverse reactions reported. Most common adverse symptoms reported include paranoid delusions, psychosis, supraventricular tachycardia, seizures, and altered sensorium.Additionally, there are many reports describing associations of synthetic cannabinoids with acute medical conditions including ischemic and hemorrhagic strokes, thrombotic microangiopathy, disseminated intravascular coagulation, immune thrombocytopenic purpura, rhabdomyolysis, and death.Illicit drugs are often adulterated with other products to increase profits and/or to enhance or alter the drugs’ effects on the body. Several substances including both legal and illegal compounds have been used to achieve these effects.Interestingly, there are numerous case reports surrounding the use of warfarin as an adulterant “lacing compound.”The addition of warfarin or long-acting anticoagulant rodenticides may alter CYP P450 metabolism of the psychoactive compound and act to enhance the high. We surmise drug manufacturers and distributors have exploited this pharmacological interaction in the past based on several other reported cases. During the spring of 2018, a large influx of patients presented to area hospitals in Illinois with unfounded coagulopathy and bleeding. The outbreak began in mid-March 2018 with over 160 reported cases in Illinois across 15 counties through June 2018.Through July 2018 the number of cases increased to 255 with eight reported deaths.By the end of July, over 55% of the documented cases had occurred in Peoria, Tazewell, and surrounding counties in Illinois. Due to symptoms of significant, prolonged bleeding and lack of known exposure to vitamin K1 antagonists there was concern that these patients had been inadvertently exposed to a long-acting anticoagulant. A large, interdisciplinary task force composed of members of the US Centers for Disease Control and Prevention, Illinois Poison Center, Illinois Department of Public Health, law enforcement agencies, and health departments was convened to elucidate the cause of this unexplained coagulopathy. It was promptly discovered that poisoned patients had been exposed to tainted synthetic cannabinoids that largely tested positive for brodifacoum, a LAAR.Other researchers have described a similar population at a single Illinois academic center.While those studies concentrated on the inpatient population, treatment and long-term therapy, our focus is to address the emergency department presentation, diagnosis, and treatment.
While the populations are similar, we feel the difference in focus is substantive as the emergency physician is tasked with diagnosis, stabilization, and treatment initiation prior to the patient’s hospital stay. Our goal is to help readers recognize and diagnose patients suffering from bleeding diathesis in the ED as well as to identify potential resuscitative treatment strategies via descriptive data from a recent LAAR outbreak. This study was conducted at two Illinois academic urban EDs with annual patient visits of approximately 85,000 and 120,000, respectively. We performed chart review of all patients with suspected brodifacoum-related coagulopathy from contaminated synthetic cannabinoids presenting to the ED. Patients with reported exposure who presented to either of these ED between March 29–April 23, 2018 were included in this study. Patients were identified from internal and public health registries, from patients themselves self identifying as having an exposure, or who were identified by hospital providers as having an exposure. Using defined variables, we abstracted ED and hospital charts, and all data was deidentified prior to analysis. The institutional review boards of the University of Illinois College of Medicine at Peoria and Oregon State University reviewed and approved this study prior to initiation. All data remained deidentified throughout.A total of 38 patients met criteria for inclusion in this study. Of the patients included, 24 males and 14 females were identified as being exposed to tainted synthetic cannabinoids. Ages ranged between 23-65 years with a mean age of 37 years at time of presentation. Of these patients, 76% were identified as White. This cohort experienced high admission rates to the hospital with 92% of patients being admitted. The three patients not admitted to the hospital left the ED against medical advice . Mean length of stay for those admitted was 4.1 days, with a range of 1-11 days. Readmission rates were also very high for this group as 30% of patients were readmitted within 30 days of their initial presentation. Among the wide variety of presenting symptoms the most common presenting complaint was back and or flank pain and the most common site of bleeding was from the urinary tract . On average, patients had significantly elevated INR values at time of presentation. The INRs ranged from 1 to >20. The mean INR at presentation was 14.5. At time of discharge from the hospital, the mean INR was 2.5. Reversal of LAAR-related coagulopathy was at the treating physician’s discretion. Several therapeutic decisions were made in consultation with Illinois Poison Control. Patients were treated with a combination of oral vitamin K1 , intravenous vitamin K1 , and fresh frozen plasma . Two patients left AMA before being treated. Of those treated, 25% received 10 milligrams IV vitamin K1 ; 41% received 50 mg oral vitamin K1 as monotherapy, and 34% received a combination of 50 mg oral vitamin K1 and 10 mg IV vitamin K1 . In addition to vitamin K1 , 48% of patients also received FFP with a dose range of 1-4 units while in the ED .