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.

Pharmacist dispensed naloxone: Knowledge, availability, participation and cost in selected California counties.

BACKGROUND: In 2014, California signed into law AB1535 permitting pharmacists to dispense naloxone upon request and without physician or midlevel provider prescription. OBJECTIVE: We sought to determine pharmacist knowledge of AB1535, participation, availability of naloxone, future plans for participation, and out-of-pocket charges to consumers amongst outpatient pharmacies in selected California counties. METHODS: All pharmacies in Plumas, Lake, Lassen, Humboldt, Shasta, Fresno, and San Diego Counties were identified. Between January 30 and March 30, 2017, pharmacies meeting inclusion criteria were contacted and the pharmacist-on-duty were queried regarding knowledge, participation, availability, and cost of naloxone. RESULTS: A total of 2296 pharmacies were identified in the 7 counties. Twenty-six were unwilling or unable to participate and an additional 1648 were excluded because of licensing or special pharmacy status. Six-hundred-twenty-two pharmacies completed the survey. There was variation in knowledge of AB1535, participation in, immediate availability of naloxone, charge, and expressed future interest in participation identified. Charge to consumers was similarly variable amongst surveyed pharmacies within counties. CONCLUSIONS: Despite considerable public health and political support, the passage of CA AB1535 has not resulted in broad current, future planned participation, or availability of naloxone in selected counties. Out-of-pocket costs to the consumer remain highly variable.

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.

Intoxication from the novel synthetic cannabinoids AB-PINACA and ADB-PINACA: A case series and review of the literature.

Synthetic cannabinoids (SC), are a novel class of designer drugs which emerged as a drug of abuse in the late 2000's. We report a case series of 6 patients who may have smoked a synthetic cannabinoid product in a remote wilderness setting. They presented with varying degrees of altered mental status, agitation, and seizures. Two were confirmed to have AB-PINACA, ADB-PINACA and their respective pentanoic acid metabolites in biological specimens via liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS). Both compounds had DEA Schedule I classification at the time of case presentation, and 22 SCs are currently temporary or permanent DEA Schedule I. More than 150 SCs are known to date, and new compounds are appearing at a rapid rate on darknet and surface web e-commerce websites, marketed as "research chemicals" or "legal highs." The scale and rapidity of SC evolution make legal control and analytical detection difficult. Nontargeted testing with liquid chromatography high resolution mass spectrometry (LC-HRMS), examining both parent compounds and metabolites, is the ideal method for novel SC identification and confirmation. Due to full agonism at the cannabinoid receptors CB1 and CB2, clinical effects are more severe than marijuana, which is a partial cannabinoid receptor agonist. They include agitated delirium, lethargy and coma, seizures, tachycardia, hypertension, and hallucinations, among other findings. Treatment is primarily symptomatic and aimed at airway protection and control of agitation and seizures. SCs do not appear to be abating anytime soon and require the cooperation of law enforcement, analytical scientists, and clinicians to adequately control. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'

Fentanyl, fentanyl analogs and novel synthetic opioids: A comprehensive review.

Deaths from opioid use are increasing in the US, with a growing proportion due to synthetic opioids. Until 2013, sporadic outbreaks of fentanyl and fentanyl analogs contaminating the heroin supply caused some deaths in heroin users. Since then, fentanyl has caused deaths in every state and fentanyl and its analogs have completely infiltrated the North American heroin supply. In 2014, the first illicit pills containing fentanyl, fentanyl analogs, and other novel synthetic opioids such as U-47700 were detected. These pills, which look like known opioids or benzodiazepines, have introduced synthetic opioids to more unsuspecting customers. As soon as these drugs are regulated by various countries, new compounds quickly appear on the market, making detection difficult and the number of cases likely underreported. Standard targeted analytical techniques such as GC-MS (gas chromatography mass spectrometry) and LC-MS/MS (liquid chromatography tandem mass spectrometry) can detect these drugs, but novel compound identification is aided by nontargeted testing with LC-HRMS (liquid chromatography high resolution mass spectrometry). Fentanyl, fentanyl analogs and other novel synthetic opioids are all full agonists of varying potencies at the µ-opioid receptor, leading to typical clinical effects of miosis and respiratory and central nervous system depression. Due to their high affinity for µ-opioid receptors, larger doses of naloxone are required to reverse the effects than are commonly used. Synthetic opioids are an increasingly major public health threat requiring vigilance from multiple fields including law enforcement, government agencies, clinical chemists, pharmacists, and physicians, to name a few, in order to stem its tide. This article is part of the Special Issue entitled 'Designer Drugs and Legal Highs.'

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.

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.

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.

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.

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.

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.

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.