Keywords: meformin overdose, metformin associated lactic acidosis, observation period (PubMed Search)
Metformin is one of the most commonly prescribed oral hypoglycemic agents. Metformin associated lactic acidosis (MALA) is uncommon but potentially life-threatening complication of metformin overdose.
Lactic acidosis occurs due to inhibition of mitochondrial glycerophosphate dehydrogenase, resulting in decreased conversion of lactic acid to pyruvate.
A small retrospective study (using Illinois Poison Center data) attempted to characterize the development of MALA after an acute overdose.
MALA was defined as
40 cases of MALA identified between Jan. 2001 to Dec. 2014
Time to development of MALA (n=30)
Death: 1 (2.5%)
Jillian Theobald, Jamie Schneider, Navneet Cheema & Carol DesLauriers (2019) "Time to development of metformin-associated lactic acidosis," Clinical Toxicology, DOI: 10.1080/15563650.2019.1686514
Keywords: droperidol, cannabinoid hyperemesis syndrome, recurrent nausea/vomiting (PubMed Search)
Droperidol has recently become available again in select U.S. institutions. It has been used as an antiemetic and to treat agitation prior to the FDA’s black box warning (for QT prolongation) and national shortage.
Recently, a retrospective study was conducted (Melbourne, Australia) in the use of droperidol in the management of cannabinoid hyperemesis syndrome (CHS).
689 medical records were identified from January 2006 to December 2016.
76 cases met diagnostic criteria of CHS (below)
Droperidol group (DG) = 37; no droperidol group (NDG)= 39
Median length of stay:
Median time to discharge after final drug administration:
Frequency of droperidol (dose) used:
Metoclopramide and Ondansetron use in non-droperidol group was twice that of droperidol group
Keywords: VA-ECMO, drug-induced cardiogenic shock (PubMed Search)
Patients with drug-induced cardiogenic shock [DIC] (e.g. overdose of CCB/BB, membrane stabilizing agents, etc.) are often managed with medical interventions such as vasopressors, bicarbonate infusion, high-dose insulin, lipid emulsion therapy. A fraction of these patients may be refractory to the standard medical therapy. VA-ECMO (venoarterial extracorporeal membrane oxygenation) has been utilized in such situation; yet clinical experience of using VA-ECMO in DIC is limited.
A recent retrospective study of the Extracorporeal Life Support Organization’s ECMO registry showed
Clinical utility of venoarterial-extracorporeal membrane oxygenation (VA-ECMO) in patients with drug-induced cardiogenic shock: a retrospective study of the Extracorporeal Life Support Organizations’ ECMO case registry
Keywords: suicide attempt, adolescent, young adults, epidemiological trend (PubMed Search)
The rate of suicide attempt has been increasing over the past decade. A recently published article investigated the temporal trend of suicide attempts in adolescent/young adult population (10 – 25 years old) from 2000 to 2018.
Top 5 substance involved in suicide attempt
Agents associated with serious medical outcome (after 2011)
Spiller HA et al. Suicide attempts by self-poisoning in the United States among 10-25 year olds from 2000 to 2018: substances used, temporal changes and demographics. Clin Toxicol (Phila) 2019. Oct 6:1-12. doi: 10.1080/15563650.2019.1665182. [Epub ahead of print]
Keywords: e-cigarrette liquid exposure, National Poison Data System (PubMed Search)
E-cigarette (vaping) use has become increasingly popular over the past 10 years, especially among adolescents. Intentional exposure (i.e. ingestion in self harm) of nicotine (e-cigarette liquid) can be life threatening where it can produce mixture of stimulatory (early), cholinergic toxicity and muscle paralysis/respiratory failure by blocking the neuromuscular junction. However, the severity of clinical toxicity in unintentional exposure can vary widely depending on the dose/route/circumstance of their exposure.
A recently published study investigated the characteristics of e-cigarette liquid exposure between Jan 1, 2010 to Dec 31, 2018 using the National Poison Data System
Top 4 clinical/demographic characteristics are listed below.
Route of exposure
Level of care:
Clinical effects - overall
In <5 years group
Keywords: capsaicin, cannabinoid hyperemesis syndrome, marijuna use. (PubMed Search)
Cannabinoid hyperemesis syndrome [CHS] (i.e. cyclic/recurrent nausea, vomiting and abdominal pain) is associated with long-term and frequent use of marijuana. Patients with CHS often report temporary relief of symptoms with hot water/shower exposure. Emergency room providers may encounter a growing number of patients with CHS with increasing legalization of marijuana-containing products.
Topical capsaicin has been gaining interest as a potential adjunct to the conventional management of patients with CHS (e.g. antiemetics, opioids, benzodiazepines and antipsychotics).
A small retrospective study was performed involving 43 patients who had multiple visits, and were treated with and without capsaicin. The primary outcome was the ED length of stay (LOS).
Wagner S et al. Efficacy and safety of topical capsaicin for cannabinoid hyperemesis syndrome in the emergency department. Clin Toxicol (Phila) 2019. Sep 4:1-5. doi: 10.1080/15563650.2019.1660783. [Epub ahead of print]
Keywords: ethanol, breath analyzer, mouth wash (PubMed Search)
Breath analyzers are commonly used by law enforcment officers to test for alcohol intoxication. Breath analyzer uses ethanol partition ratio between blood:breath of 1:2100 = 1 gm of ethanol in 2100 mL of breath/air.
Mouth wash products are frequently used for oral hygiene, and at times, to "mask" odor of substances. These products are readily available in any grocery stores or pharmacy and contain upto 26.9% ethanol (e.g. Listerine) (18.9% - Scope; 14.0% - Cepacol).
Recently, a small study using healthy volunteers (n=11) was published to investigate the impact of limited ethanol exposure (mouth wash and ethanol vapor) on the breath-alcohol concentration (BrAC).
Blood: No or very low levels of ethanol (0.002 mg/g) were detected in blood at all collection time for both exposures.
BrAC - first collection -- seconds after exposure
Mean time to negative BrAC level (Swedish statutory limit of 0.1 mg/L = 0.01 mg/dL in air) (FYI: US limit = 80 mg/dL)
Ernstgard L et al. Washout kinetics of ethanol from the airways following inhalation of ethnaol vapors and use of mouthwash. Clin Toxicol. 2019 Jun 19:1-7. doi: 10.1080/15563650.2019.1626868. [Epub ahead of print]
Keywords: nitrous oxide, neurotoxicity (PubMed Search)
Numerous different household products can potentially be misused/abused. One such product is whipped cream charger/propellant that contains nitrous oxide.
Acute toxicity produce dose dependent response
Chronic toxicity causes myeloneuropathy (demyelination of the dorsal and lateral columns of the spinal cord) due to vitamin B12 deficiency
Keywords: vaping, THC, e-cigarette, pulmonary injury (PubMed Search)
Center for Disease Control and Prevention (CDC) recently issued alerts regarding cases of pulmonary illnesses that may be linked to "vaping" (in 15 states with 149 possible cases). These cases are still under investigation but all cases reported vaping weeks/months prior to hospitalization.
Most cases involve young adults who have been using THC-containing products
Common complaints included
What to do:
Keywords: drug-induced liver injury (PubMed Search)
Direct hepatotoxicity from a drug is predictable and dose-dependent.
Most commonly implicated agents include:
On the contrary, idiosyncratic prescription drug-induce liver injury is rare, unpredictable and not related to dose.
Most commonly implicated agents are:
Keywords: hematologic toxicity, copperhead envenomation, bleeding (PubMed Search)
Hematologic toxicity (coagulopathy/bleeding) can occur with pit viper envenomation. Copperhead is the most commonly implicated pit viper envenomation in the U.S. However, the prevalence of hematologic toxicity from copperhead envenomation is variable, possibly due to regional variation in venom potency and species misidentification.
An observation study was performing using multi-center (Virginia Commonweath university, University of Virginia Medical Center and Eastern Virginia Medical medical center) electronic hospital/medical records (Jan 1, 2006 to Dec 31, 2016) of suspected copperhead bites. Authors state that copperhead snakes are "nearly exclusively endemic" to the VCU and UVA medical center region.
388 patients were identified but 244 met inclusion/exclusion criteria.
Hematologic toxicity: 14%
In a small sample of copperhead envenomation in Virginia, “subtle” hematologic abnormalities were observed but clinically significant hematologic toxicity was not observed (i.e. bleeding)
Wills BK et al. Prevalence of hematologic toxicity from copperhead envenomation: an observational study. Clin Toxicol. 2019. DOI: 10.1080/15563650.2019.1644346
Keywords: naloxone, pulmonary edema, aspiration, overdose (PubMed Search)
Pulmonary complications - aspiration, pulmonary edema, etc. are frequently reported in both heroin intoxication and in reversal of opioid overdose with naloxone.
Suspected opioid overdose victims (N=1831) who received naloxone from EMS providers were studied retrospectively. Pulmonary complications were defined as pulmonary edema, aspiration pneumonia and aspiration pneumonitis.
Higher out of hospital naloxone administration is associated with increased odds of developing pulmonary complications
Keywords: push dose pressor, phenylephrine, epinephrine, human error (PubMed Search)
“Push dose pressors” – administration of small doses of vasopressors in the emergency room has become a common practice. A recently published study investigated the incidence of human error and adverse hemodynamic events.
Push dose pressors were defined as:
Adverse hemodynamic event was defined as:
249 out of 1522 patients were identified and analyzed from Jan 2010 to November 2017
Cole JB et al. human errors and adverse hemodynamic events related to "push dose pressors" in the emergency department. J Med Toxicol. 2019 Jul 3. doi: 10.1007/s13181-019-00716-z. [Epub ahead of print]
Keywords: Sudden sniffing death, Inhalants, Fluoridated Hydrocarbons (PubMed Search)
Volatile inhalants such as glue, lighter fluid, spray paint are abused by "sniffing" (from container), "huffing" (poured into rag), or "bagging" (poured into bag). "Dusting" is the abuse of canned air dust removal products. These inexpensive easliy accessible products are so dangerous that manufacturers include product warnings regarding lethal consequences from misuse and even may indicate that a bitterant is added to discourage use. Common duster gases include the halogenated hydrocarbons, 1,1-difluoroethane or 1,1,1-trifluroethane which are highly lipid soluble and rapidly absorbed by alveolar membranes and distributed to CNS. Desired effect of euphoria and disinhibition rapidly occur but unwanted side effects include confusion, tremors, ataxia, pulmonary irritation, asphyxia and, rarely, coma.
"Sudden sniffing death" is seen within minutes to hours of use and is due to ventricular arrhythmias and cardiovascular collapse. Available experimental evidence postulates the following mechanisms: Inhibition of cardiac sodium, calcium, and repolarizing potassium channels hERG and I(Ks) causing reduced conduction velocity and altered refractory period leading to reentry arrythmias or myocardial "sensitiization" to catecholamines resulting in after depolarizations and enhanced automaticity. Treatment should include standard resuscitation measures but refractory arrythmias to defibrillation have been reported and use of amiodarone and beta blockers should be considered.
Sudden death involving inhalation of 1, 1-difluoroethane (HFC-152a) with spray cleaner: three case reports. K Sakai, K Maruyama-Maebashi, et.al. Forensic science Int. Volume 206, Issues 1–3, 20 March 2011.
Esmolol in treatment of severe arrhythmia after tricholoroethylene poisoning. Mortiz F. de La Chapelle, et al. Intensive Care Med. 2000 Feb;26(2):256.
Deaths Involving 1,1-Difluoroethane at the San Diego County Medical Examiner's OfficeVance C., Swalwell C., et al. Journal of Analytical Toxicology, Volume 36, Issue 9, November/December 2012.
Keywords: cyanide toxicity, sodium tetrathionate, (PubMed Search)
Cyanide poisoning, while uncommon, is frequently fatal. Current antidotes include methemoglobinemia inducers (nitrites), sulfur donators (thiosulfate), and hydroxocobalamin. Each has risks and benefits that must be considered. Three new potential antidotes, including sodium tetrathionate, have recently been evaluated in swine models.
Intramuscular sodium tetrathionate1
Hendry-Hofer TB, Witeof AE, Ng PC, et al. Intramuscular sodium tetrathionate as an antidote in a clinically relevant swine model of acute cyanide toxicity. Clin Toxicol (Phila). 2019;105:1-7. doi:10.1080/15563650.2019.1602272.
Keywords: intranasal naloxone, opioid overdose, reversal (PubMed Search)
Naloxone distribution programs have been expanding to promote the naloxone adminstration by laypersons, usually intranasal (IN) device, to victims of opioid overdose. A recent study analyzed the reports of prehospital naloxone administration reported to a regional poison center.
Opioid toxicity revesal:
However, between 2015 and 2017, the reversal rate decreased (82.1% to 76.4%) while mean administered naloxone dose increased (2.12 mg to 3.63 mg). The cause of this trend is unknown but the dose of commercially available IN naloxone kit increased from 2 mg to 4 mg in 2016.
Mahonski SG et al. Prepacked naloxone administration for suspected opioid overdose in the era of illicitly manufactured fentanyl: a retrospective study of regional poison center data. Clin Toxicol 2019.
Keywords: opioid use disorder, fentanyl exposure, baltimore, (PubMed Search)
Since 2013, the availability of fentanyl has been increasing in the illicit drug supply, especially in heroin supply. Fentanyl and its analogs have been responsible for the dramatic increase in opioid overdose death over the past 5 years.
Two recent cross-sectional studies screened ED patients with opioid use disorder for fentanyl exposure.
Bach H et al. Prevalence of fentanly exposure among emergency department patients with history of opioid abuse. Clin Toxicol 2019 May https://doi.org/10.1080/15563650.2019.1598646 (Abstract presented at the EAPCCT 2019, Naples, Italy)
Dezman ZDW et al. Evidence of fentanyl use is common and frequently missed in a cross-sectional study of emergency deparmtne patients in Baltimore, Maryland. Clin Toxicol 2019 April 17. https://doi.org/10.1080/15563650.2019.1605078
Keywords: toxic substance, online retailers, amazon.com, (PubMed Search)
Many chemicals and substances - both legal and illegal - can be purchased from an online retailer. A recent study searched Amazon.com to see if any of the "extremely hazardaous substances" identified by Environmental Protection Agency (EPA) were available for purchase.
Amazon.com was searched over 10-month period.
Toxic substances are readily available from many online retailers that can potentially cause serious toxicity. Online retailers should consult with experts and governmental agencies to limit the availability of such products.
Learnoad JB et al. Prime eligible poisons: identification of extremely hazardous substances available on Amazon.com. 2019 Clin Toxicol (Phila). 2019 Apr 30:1-4. doi: 10.1080/15563650.2019.1594870. [Epub ahead of print]
Keywords: Hypoglycemia, Drug induced (PubMed Search)
Drug-induced hypoglycemia is an important cause of hypoglycemia which should be considered in any patient presenting with altered mental status. In one study, drug-induced hypoglycemia represented 23% of all hospital admissions attributed to adverse drug events. Risk factors for developing hypoglycemia include older age, renal or hepatic insufficiency, concurrent use of insulin or sulfonylureas, infection, ethanol use, or severe comorbidities. The most commonly cited drugs associated with hypoglycemia include:
*In Glipizide users, there was 2-3 fold higher odds of hypoglycemia with concurrent use of sulfamethoxale-trimethoprim, fluconazole, and levofloxacin compared with patients using Cephalexin.
**Tramadol potentially induces hypoglycemia by effects on hepatic gluconeogenesis and increasing insulin release and peripheral utlizilation. Was seen in elderly at initiation of therapy within first 30 days.
Take care in prescribing drugs known to increase risk of hypoglycemia in elderly patients, with comorbidities, or those already taking medications associated with hypoglycemia.
Drug induced hypoglycemia, A Systematic Review. Hassan M. et al. J Clin Endo & Metab. 94(3) March 2009. 741-45.
Hypogylcemia after antimicrobial drug prescription for older patients using sulfonylureas. Parekh TM, Raji M, et al. JAMA Intern Med. 2014. 1605-12.
Tramadol Use and the Risk of Hospitalization for Hypoglycemia in Patients with Noncancer Pain. Fournier J, Azoulay L. et al. Jama Intern Med. 2015;175(2):186-193.
Hypoglycemic effects of tramadol analgesia in hospitalized patients: a case-control study. Golightly LK. Simendinger BA. et al. J Diabetes Metab Disord. 2017;16:30.
Keywords: guanfacine, ADHD, pediatric, toxicity (PubMed Search)
Guanfacine is a presynaptic alpha-2 adrenergic receptor agonist (similar to clonidine) that is FDA approved to treat ADHD in pediatric patients 6 years of age and older. A recently published study characterized the pediatric exposure to guanfacine between 2000 and 2016.
Most frequently reported clinical effect (n=10927)
Severe clinical effects (n=10927)
Duration of clinical effect