Stimulant drugs are associated with violent and penetrating trauma.

BACKGROUND: Substance abuse is associated with traumatic injuries. Prior studies of drug use and injury have relied on urine drug of abuse screens, which have false positives, false negatives and inability to detect novel drugs. Our study characterizes the relationship between injury mechanism and drugs of abuse detected in serum via confirmatory testing. METHODS: This prospective observational study was conducted from Jan-Sept 2012 at a level 1 trauma center on trauma patients > 13 years who had blood drawn for routine tests. Demographic, injury and standard laboratory data were abstracted from patient charts. Comprehensive serum drug testing was done using liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS, LC1200-TOF/MS 6230, Agilent, Santa Clara, CA). RESULTS: Of 272 patients, 71.0% were male, 30.5% had violent injury type and 32.4% had a penetrating injury mechanism. Violent injury type and penetrating injury mechanisms were more frequent in patients who were male, younger age, Black, or Hispanic (p < 0.05 for all). LC-TOF/MS showed that 46.0% were positive for at least one drug. Stimulant drugs were associated with violent injury type (OR 2.9; 95% CI 1.64-5.15) and penetrating injury mechanism (OR 3.3; 95% CI 1.86-5.82). Tobacco use was associated with violent injury type (OR 3.9; 95% CI 2.25-6.77) and penetrating injury mechanism (OR 4.14; 95%CI 2.4-7.14). CONCLUSIONS: Many drugs are present in trauma patients that are not routinely detected on urine drug of abuse tests. Both stimulant drugs and cigarette smoking are indicators of multidimensional hazardous behaviors, which were associated with more violent and penetrating trauma.

Fentanyl and a Novel Synthetic Opioid U-47700 Masquerading as Street "Norco" in Central California: A Case Report.

In 2013 and 2014, more than 700 deaths were attributed to fentanyl and fentanyl analogues in the United States. Of recent concern is the cluster of unintentional fentanyl overdoses because of tablets thought to be "Norco" purchased on the street in Northern California. U-47700 (trans-3,4-dichloro-N-[2-(dimethyl-amino)cyclohexyl]-N-methylbenz-amide) is a nonfentanyl-based synthetic opioid with 7.5 times the binding affinity of morphine to µ-opioid. We report a case of fentanyl and U-47700 intoxication from what was thought to be illicitly purchased Norco. A 41-year-old woman presented to the emergency department (ED) for altered mental status shortly after ingesting 3 beige Norco pills bearing a Watson imprint. She had pinpoint pupils and respiratory depression, which reversed after 0.4 mg naloxone administration intravenously. She had complete recovery and was discharged from the ED after a 4-hour observation period. Serum testing with liquid chromatography-quadrupole time-of-flight mass spectrometry (LC 1260 QTOF/MS 6550; Agilent, Santa Clara, CA) confirmed the presence of the medications the patient reported receiving, and additionally fentanyl (15.2 ng/mL) and U-47700 (7.6 ng/mL). In this case report, street Norco purchased in Central California resulted in altered mental status requiring naloxone reversal because of fentanyl and the novel synthetic opioid U-47700. Because these compounds are not detected by routine urine drug testing and physical examination findings are similar to those of a traditional opioid toxidrome, emergency providers should use the patient's history and other circumstantial details to aid in diagnosis. In cases with suspicion of opioid or opioid analogue cause, we recommend that emergency providers contact their local poison control center, medical toxicologist, or public health department to aid in the investigation.

Hot and Cold Drugs: National Park Service Medication Stability at the Extremes of Temperature.

STUDY OBJECTIVE: National Park Service (NPS) Parkmedics provide medical care in austere environments. The objective of this study was to evaluate the stability of specific medications used by Parkmedics at extremes of temperatures likely to be faced in the field. METHODS: This is a bench research study conducted in the laboratory setting over a 4-week period. Parenteral medications were separated into 4 temperature exposure groups: A) 45°C (hot); B) -20°C (cold); C) hot then cold temperatures alternating weekly; and D) cold then hot temperatures alternating weekly. At study start and the end of each week, three aliquots from each group were sampled to determine the remaining drug concentration through liquid chromatography-quadrupole time-of-flight mass spectrometry (Agilent LC 1260- QTOF/MS 6550). Quantitative analysis was done using Agilent MassHunter Quantitative Analysis software. The mean drug concentration from triplicate aliquots was expressed as percentage of its baseline concentration to monitor the drug's stability during storage. RESULTS: Eight medications were analyzed (atropine, diphenhydramine, fentanyl, hydromorphone, midazolam, morphine, naloxone, ondansetron). Hydromorphone, morphine, and ondansetron showed the greatest stability, at above 90% of original concentration in all study arms. Diphenhydramine, fentanyl and midazolam showed heat independent degradation, degrading the same way regardless of heat exposure. By the end of the study period, 51-56% midazolam remained in all groups. Atropine and naloxone showed heat dependent degradation, degrading more when exposed to heat. Atropine had the most degradation, being undetectable after 4 weeks of heat exposure. CONCLUSIONS: We recommend that EMS providers replace atropine, naloxone, diphenhydramine, fentanyl, and midazolam frequently if they are practicing in low call volume or high-temperature environments. Further studies will be needed to determine if re-dosing midazolam, naloxone, and atropine is the appropriate clinical strategy in this setting if adequate clinical effect is not reached with a single dose.

Ketamine as a first-line treatment for severely agitated emergency department patients.

OBJECTIVE: Emergency physicians often need to control agitated patients who present a danger to themselves and hospital personnel. Commonly used medications have limitations. Our primary objective was to compare the time to a defined reduction in agitation scores for ketamine versus benzodiazepines and haloperidol, alone or in combination. Our secondary objectives were to compare rates of medication redosing, vital sign changes, and adverse events in the different treatment groups. METHODS: We conducted a single-center, prospective, observational study examining agitation levels in acutely agitated emergency department patients between the ages of 18 and 65 who required sedation medication for acute agitation. Providers measured agitation levels on a previously validated 6-point sedation scale at 0-, 5-, 10-, and 15-min after receiving sedation. We also assessed the incidence of adverse events, repeat or rescue medication dosing, and changes in vital signs. RESULTS: 106 patients were enrolled and 98 met eligibility criteria. There was no significant difference between groups in initial agitation scores. Based on agitation scores, more patients in the ketamine group were no longer agitated than the other medication groups at 5-, 10-, and 15-min after receiving medication. Patients receiving ketamine had similar rates of redosing, changes in vital signs, and adverse events to the other groups. CONCLUSION: In highly agitated and violent emergency department patients, significantly fewer patients receiving ketamine as a first line sedating agent were agitated at 5-, 10-, and 15-min. Ketamine appears to be faster at controlling agitation than standard emergency department medications.

Unintentional Pediatric Cocaine Exposures Result in Worse Outcomes than Other Unintentional Pediatric Poisonings.

BACKGROUND: Unintentional pediatric cocaine exposures are rare but concerning due to potentially serious complications such as seizures, dysrhythmias, and death. OBJECTIVES: The objectives were to assess the demographic and clinical characteristics of pediatric cocaine exposures reported to the California Poison Control System. METHODS: This is a retrospective study of all confirmed pediatric (< 6 years of age) cocaine exposures reported to the California Poison Control System from January 1, 1997-September 30, 2010. Case narratives were reviewed for patient demographics, exposure details, clinical effects, therapy, hospitalization, and final outcome. RESULTS: Of the 86 reported pediatric cocaine exposures, 36 had positive urine drug testing and were included in the study cohort. The median age at presentation was 18 months (range: 0-48 months), and 56% were male (n = 20). The most common clinical manifestations were tachycardia and seizures. The most common disposition was admission to an intensive care unit (n = 14; 39%). Eleven cases (31%) were classified as having a major effect as per American Association of Poison Control Centers case coding guidelines. One child presented in asystole with return of spontaneous circulation after cardiopulmonary resuscitation and multiple vasoactive medications. The proportion of cocaine exposures with serious (moderate or major) outcomes (66.7%; 95% confidence interval 50.3-79.8%) was higher than other pediatric poisonings reported to the American Association of Poison Control Centers during the study period (0.88%; 95% confidence interval 0.87-0.88). CONCLUSIONS: Although pediatric cocaine exposures are rare, they result in more severe outcomes than most unintentional pediatric poisonings. Practitioners need to be aware of the risk of recurrent seizures and cardiovascular collapse associated with cocaine poisoning.

Analysis of Gastric Lavage Reported to a Statewide Poison Control System.

BACKGROUND: As decontamination trends have evolved, gastric lavage (GL) has become a rare procedure. The current information regarding use, outcomes, and complications of GL could help refine indications for this invasive procedure. OBJECTIVES: We sought to determine case type, location, and complications of GL cases reported to a statewide poison control system. METHODS: This is a retrospective review of the California Poison Control System (CPCS) records from 2009 to 2012. Specific substances ingested, results and complications of GL, referring hospital ZIP codes, and outcomes were examined. RESULTS: Nine hundred twenty-three patients who underwent GL were included in the final analysis, ranging in age from 9 months to 88 years. There were 381 single and 540 multiple substance ingestions, with pill fragment return in 27%. Five hundred thirty-six GLs were performed with CPCS recommendation, while 387 were performed without. Complications were reported for 20 cases. There were 5 deaths, all after multiple ingestions. Among survivors, 37% were released from the emergency department, 13% were admitted to hospital wards, and 48% were admitted to intensive care units. The most commonly ingested substances were nontricyclic antidepressant psychotropics (n = 313), benzodiazepines (n = 233), acetaminophen (n = 191), nonsteroidal anti-inflammatory drugs (n = 107), diphenhydramine (n = 70), tricyclic antidepressants (n = 45), aspirin (n = 45), lithium (n = 36), and antifreeze (n = 10). The geographic distribution was clustered near regions of high population density, with a few exceptions. CONCLUSIONS: Toxic agents for which GL was performed reflected a broad spectrum of potential hazards, some of which are not life-threatening or have effective treatments. Continuing emergency physician and poison center staff education is required to assist in patient selection.

Illicit Distribution of Prescription Drugs: Report of Inadvertent Chloroquine Toxicity and a Market Survey of Businesses Serving Ethnic Minority Populations.

OBJECTIVE: To report a case of life-threatening cinchonism from illicit purchase of chloroquine and survey local ethnic markets to determine what medications are sold without a prescription. CASE REPORT: A 44-year-old Hmong woman presented with abdominal pain and vomiting 30 minutes after ingesting 20 presumed acetaminophen pills in a self-harm gesture. Initial vital signs were normal, and an electrocardiogram (ECG) showed normal sinus rhythm, QRS = 130 ms, and QTc = 455 ms. Her systolic blood pressure dropped to 84 mm Hg, which was unchanged after 3 L normal saline, but improved after 150 mEq NaHCO3. A repeat ECG showed QRS = 114 ms and QTc = 588 ms. Serum labs were significant for K 2.8 mmol/L and Mg 1.8 mg/dL; 2.5 hours later, the family brought in the medication, which was 250 mg tablets of chloroquine phosphate. K and Mg were repleted, and she was admitted to the intensive care unit with complete recovery. Serum chloroquine level 9 hours after ingestion was 530 ng/mL (therapeutic = 20-400 ng/mL). METHODS: We identified local ethnic markets through patient and hospital employee referrals and Internet searches. RESULTS: In our survey, 3 of 4 ethnic markets sold prescription medications: 35 were identified, of which 5 are discontinued by the FDA (diphenidol, phenacetin, metamizole, phenylbutazone, and sibutramine). CONCLUSIONS: A variety of prescription medications, including 5 discontinued by the FDA, were available in markets serving our community's ethnic minorities. Health care workers should be aware of this public health risk, which can result in serious toxicity, as described in this case of chloroquine overdose.

The electric Kool-Aid NBOMe test: LC-TOF/MS confirmed 2C-C-NBOMe (25C) intoxication at Burning Man.

Designer drugs are constantly evolving, with the NBOMe derivatives of the 2C class of phenethylamines recently emerging in the US market. Cases of 2C-I-NBOMe toxicity have recently been reported in the literature. No reports to date describe the clinical effects 2C-C-NBOMe toxicity.

Multiple MDMA (Ecstasy) overdoses at a rave event: a case series.

Twelve patients with 3,4-methylenedioxymethamphetamine (MDMA) toxicity from a single rave event presented to multiple San Francisco Bay area hospitals with various life-threatening complications including seizures and hyperthermia. Eight required emergent endotracheal intubation and six had hypotension. Hyperkalemia, acute kidney injury, and rhabdomyolysis were present in most of the patients. In all, 2 patients died, 4 survived with permanent neurologic, musculoskeletal, and/or renal sequelae, and 6 survived without any apparent lasting deficits. Hyperthermia was present in 10 patients and was severe (40.9-43° C) in 7. Using multiple cooling methods, the average time to achieve cooling was 2.7 hours. Serum drug analysis was performed on 3 patients, demonstrating toxic MDMA concentrations without the presence of other xenobiotics. Two capsules confiscated by police at the event contained 82% and 98% MDMA, respectively, without other pharmacologically active compounds. Capsule #2 contained 270 mg MDMA, which is more than twice the amount of MDMA usually contained in 1 dose. The MDMA-induced hyperthermia significantly contributed to the morbidity and mortality in this case series. Factors contributing to the severity of the hyperthermia include ingestion of large doses of MDMA, a warm ambient environment, and physical exertion.

Catecholaminergic polymorphic ventricular tachycardia found in an adolescent after a methylenedioxymethamphetamine and marijuana-induced cardiac arrest.

OBJECTIVE: To illustrate the challenges of managing patients with acute, undiagnosed arrhythmias through a case that demonstrates a possible association between catecholaminergic polymorphic ventricular tachycardia, a genetically determined severe arrhythmia disorder that often presents as either syncope or sudden death, and 3,4-Methylenedioxymethamphetamine ("Ecstasy") combined with marijuana, which are often considered safe drugs by users. DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENT: A 15-yr-old male collapsed suddenly after ingesting an unknown substance and smoking marijuana. He was successfully resuscitated by first-responder chest compressions and rescue breaths along with a single 100-J shock by paramedics. He was intubated and transferred to a pediatric intensive care unit. Initial cardiac workup was negative but severe instability on vasopressors and a family history of intermittent palpitations and syncope in his brother raised suspicion for catecholaminergic polymorphic ventricular tachycardia. Identification of the unknown substance required coordination with a toxicology laboratory. INTERVENTIONS: The patient had extremely labile cardiovascular responses to vasopressors. On day 5, his blood pressure was stable and he was extubated. A full cardiac workup, including a catheterization (preadmission to pediatric intensive care unit), electrocardiogram, cardiac magnetic resonance imaging were done to screen out most structural arrythmogenic diseases. A specific genetic test for catecholaminergic polymorphic ventricular tachycardia was sent. MEASUREMENTS AND MAIN RESULTS: The patient's methylenedioxymethamphetamine blood level was 87 ng/mL approximately 12 hrs after ingestion. Given the 3-8 hr half-life of methylenedioxymethamphetamine, it is likely that levels were toxic at the time of ingestion (>110 ng/mL). Marijuana may have provided a synergistic critical catecholamine release to trigger an arrhythmia. Genetic testing showed a ryanodine receptor-2 mutation that was consistent with catecholaminergic polymorphic ventricular tachycardia. CONCLUSIONS: While an initial cardiac workup for an acute, undiagnosed arrhythmia may be negative, family history may be a simple, essential component of patient management and disease diagnosis. This case demonstrates a possible association between methylenedioxymethamphetamine, marijuana, and catecholaminergic polymorphic ventricular tachycardia. All genetic and structural arrythmogenic disorders should be considered when working up a patient with presumed toxin-induced arrhythmias.

5-oxoprolinemia causing elevated anion gap metabolic acidosis in the setting of acetaminophen use.

BACKGROUND: Anion gap metabolic acidosis is typically encountered in the emergency department (ED) setting as the result of shock, other endogenous metabolic derangements, or from exogenous toxicants. The differential diagnosis for toxicant-related acidosis (exemplified by common mnemonics) emphasizes acute overdose. CASE REPORT: The case we present manifested an anion gap (AG) metabolic acidosis due to a chronic intoxication: acetaminophen (APAP) overuse over a period of weeks. Lactic acidemia did not account for the AG. In this case, chronic APAP overuse, combined with decreased caloric intake and weight loss, was associated with excess 5-oxoproline (pyroglutamic acid), an organic acid accounting for the AG metabolic acidosis. Overproduction of 5-oxoproline is attributed to depleted glutathione stores, leading to perturbation in the γ-glutamyl cycle. The patient was treated with supportive care and with N-acetylcysteine (NAC). By repleting glutathione, NAC may facilitate the resolution of excess 5-oxoproline. CONCLUSIONS: The ED differential diagnosis of AG metabolic acidosis in chronic APAP overuse, especially with concomitant nutritional compromise, should include 5-oxoprolinemia.

Refractory vasodilatory shock secondary to metformin overdose supported with VA ECMO.

Metformin overdose may result in vasodilatory shock, lactic acidosis and death. Hemodialysis is an effective means of extracorporeal elimination, but may be insufficient in the shock setting. We present a case of a 39 yo male who presented with hypotension, coma, hypoglycemia, and lactate of 6.5 mmol/L after ingesting an unknown medication. Metformin overdose was suspected, and he was started on hemodialysis. He developed profound vasoplegia refractory to high doses of norepinephrine, vasopressin, epinephrine and phenylephrine. Venoarterial extracorporeal membrane oxygenation (VA ECMO) was initiated and he had full recovery. Serum analysis with high resolution liquid chromatography mass spectrometry revealed a metformin level of 678 µg/mL and trazodone level of 2.1 µg/mL. This case is one of only a handful of reported cases of metformin overdose requiring ECMO support, and we report the highest serum metformin levels in the literature to date. We recommend early aggressive hemodialysis and vasopressor support in all suspected cases of metformin toxicity as well as VA ECMO if refractory to these therapies. OBJECTIVE: We present a case of vasodilatory shock secondary to metformin overdose requiring venoarterial extracorporeal membrane oxygenation (VA ECMO) support. This case is one of only a handful of reported cases of metformin overdose requiring ECMO support, and we report the highest serum metformin levels in the literature to date. DATA SOURCES: University of San Francisco, Fresno. STUDY DESIGN: Case report. DATA EXTRACTION: Clinical records and high resolution liquid chromatography mass spectroscopy analysis. DATA SYNTHESIS: None. CONCLUSIONS: Venoarterial ECMO provided an effective means of hemodynamic support for a patient with severe metformin toxicity.

Two Decades of Ecstasy: Shifting Demographic Trends in Decedents using MDMA.

Deaths with a toxicology finding of the party drug, 3,4-Methylenedioxymethamphetamine (MDMA), over the 20-year period from 2000-2019 in San Francisco are presented to identify shifting demographic trends. Of the 148 cases, 129 (87.2%) were male with mean and median ages of 30 and 28, respectively. The most common manner of death (MOD) in males was homicide (65 of 129) and accident (49 of 129). The most common MOD in females was accident (15 of 19). Regarding racial demographics, Black homicide deaths accounted for 59 of 67 (88.1%) of total homicides. The most prevalent cause of death for homicides was gunshot wounds (63 of 67, 94.0%). Homicide prevalence was high in the first decade of the study (53 of 88, 60.2%), sharply dropping off after 2011. White accidental deaths made up most of the accidental deaths (45 of 64, 70.3%). Since 2015, accidental deaths with MDMA began to rise (40 of 60, 66.7%), most with other coingestants. MDMA concentrations (median, mean ± SD) between homicide (290, 450 ± 490 ng/mL) and accidental (250, 680 ± 1120 ng/mL) deaths were similar. MDMA concentrations were elevated in central blood compared to peripheral blood from unmatched cases. MDMA was detected in a variety of decedents during the two decades, with primarily young Black male gunshot wound homicide victims in the first decade and primarily young White male accidental polydrug victims in the second decade. This study demonstrates that MDMA is no longer confined to a party setting, but can also be found in different socio-economic strata, including its association with violent homicidal deaths.