Keywords: flumazenil, benzodiazepine overdose, adverse events (PubMed Search)
Flumazenil is a reversal agent for benzodiazepine overdose. Adverse events including seizure, agitation and cardiac arrhythmias have been reported but the frequency of adverse events is unknown.
AE and serious AEs were defined as:
Serious AE (SAE):
A systematic review/meta-analyses of 13 randomized controlled trials showed
Most common AEs
Most common SAEs
PENNINGA E ET AL.Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication--A Systematic Review with Meta-Analyses of Randomized Trials. Basic Clin Pharmacol Toxicol. 2016
Keywords: xylazine, adulterate, heroin, fentanyl (PubMed Search)
Xylazine is a central alpha-2 agonist (similar to clonidine) that is used as a veterinary tranquilizer. It also possesses analgesic, and muscle relaxant properties. Heroin/fentanyl is increasingly being adulterated with xylazine and resulting in severe adverse effects (CNS and respiratory depression, bradycardia, and hypotension), including deaths.
According to CDC, 0.1%-5.5% of IMF death in US between 2019 – 2020 involved xylazine.
In Philadelphia, PA:
The detection of xylazine in unintentional overdose death increased from
Approximately 25% of drug seizures in Philadelphia contained xylazine in 2019
There is no effective pharmacologic agent for xylazine toxicity. Similar to clonidine toxicity, high dose naloxone may be tried. But pediatric data show that approximately 50% of pediatric clonidine toxicity response to high-dose naloxone administration. Thus, naloxone administration may not reverse the CNS/respiratory depression, bradycardia and hypotension.
O’Donnell J, Tanz LJ, Gladden RM, Davis NL, Bitting J. Trends in and Characteristics of Drug Overdose Deaths Involving Illicitly Manufactured Fentanyls — United States, 2019–2020. MMWR Morb Mortal Wkly Rep 2021;70:1740-1746. DOI: http://dx.doi.org/10.15585/mmwr.mm7050e3.
Johnson J, et al. Inj Prev 2021;27:395–398. doi:10.1136/injuryprev-2020-043968
Keywords: pediatric fatality, poisoning, US (PubMed Search)
Substance use disorder contributes significantly to pediatric exposure/poisoning. There has been an increase in the opioid overdose deaths in the US, placing pediatric population to possible exposure. A retrospective study of fatal pediatric poisoning in the US was investigated using the National Violent Death Reporting System (NVDRS) from 2012-2017.
17 US states (AK, CO, GA, KT, MD, MA, NJ, NM, NC, OH, OK, OR, RI, SC, UT, VA, WI) reported to NVDRS from 2012-2017.
Age was limited to 0-9 years
1850 violent deaths were identified: n=122 (7%) were poisoning related
Most common exposure/etiology
Hunter AA et a. An examination of fatal child poisonings in the United States using the National Violent Death Reporting System (NVDRS), 2012–2017. Clin Toxicol. 2021
Keywords: ICU requirement score, physiologic score system (PubMed Search)
There are several clinical scoring systems (SAPS II, SAPS III, SOFA, etc.) to assess the severity and/or risk of mortality in critically ill patients. However, the routinely used physiologic scoring systems are not always suitable for poisoned patient.
ICU requirement score (IRS) has been recently developed by investigators from Europe and a validation study (retrospective cohort) has been performed.
ICU requirement score (IRS) components (see inserted table)
Area under the curve for IRS ROC: 0.736 (95% CI: 0.702-0.770)
Keywords: cannabis intoxication, trend, Canada, ICU admission, legalization (PubMed Search)
Canada legalized recreational cannabis use in 2017. A retrospective study of children (0-18 years) who presented to pediatric ED with cannabis intoxication/exposure was performed between Jan 1, 2008 to Dec 21, 2019 to assess the trend/severity of intoxication.
A total of 298 patients were identified
Monthly ED visit
2.1 (IRQ: 1.9-2.5)
1.7 (IQR: 1.0-3.0)
Altered mental status
Age < 12 years
Respiratory symptoms: tachypnea/bradypnea, cyanosis, O2 sat < 92%, bronchospasm, oxygen requirement
Cohen N et al. Pediatric cannabis intoxication trends in the pre and post-legalization era. Clin Toxicol 2021. e-pub Jun 17, 2021.
Keywords: NAC, gluthathione, acetaminophen toxicity (PubMed Search)
What is the mechanism of action of N-acetylcysteine that is used to treat acetaminophen induced liver injury/toxicity?
Excess production of NAPQI via CYP 2E1 from acetaminophen overdose depletes gluthathione, which detoxifies NAPQI. Gluthathione consists of 3 amino acids: glutamate, cysteine and glycine. cysteine availability is the rate limiting step in gluthathione synthesis. hepatotoxicity occurs when gluthathione store is depleted below 30% of the baseline.
Thus NAC works by:
Goldfrank's Toxicologic Emergencies. Ch35 Acetaminophen A3: antidote in depth - N-acetylcysteine
Keywords: household spices, abuse, toxicity (PubMed Search)
There are three commonly household spices that can be abuse/misused or cause toxicity after exposure.
Pure vanilla extract contains at least 35% ethanol by volume per US Food and Drug Administration standards
Nutmeg contains myristicin – serotonergic agonist that possess psychomimetic properties.
Cinnamon contains cinnamaldehyde and eugenol – local irritants.
Johnson-Arbor K et al. Stoned on spices: a mini-review of three commonly abuse housenold spices. Clin Toxicol (Phila) 2020
Keywords: diphenhydramine overdose, seizure, ventricular dysrhythmia, severe toxicity (PubMed Search)
Diphenhydramine is commonly involved in overdose or misused. Although it is primarily used for its anti-histamine property, it also has significant antimuscarinic effect.
A recent retrospective study investigated the clinical characteristics associated with severe outcomes in diphenhydramine overdose using the multi-center Toxicology Investigators Consortium (ToxIC) Registry.
Severe outcomes were defined as any of the following:
863 cases of isolated diphenhydramine ingestion were identified between Jan 1, 2010 to Dec 31, 2016
Most common symptoms:
Factors associated with severe outcome
Hughes AR et al. Clinical and patient characteristics associated with severe outcome in diphenhydramine toxicity. Clin Toxicol (Phila) 2021.
Keywords: occupational poisoning (PubMed Search)
There are different occupational hazards depending on the nature of one’s trade/skill/employment. Although healthcare providers may not always inquire about patient’s occupation, knowledge of a patient’s occupation may provide insightful information when caring for patients with acute poisoning.
From a recent retrospective study of National Poison Data System, the top 10 occupational toxicants were:
Top 10 occupational toxicants associated with fatalities were:
Downs JW et al. Descriptive epidemiology of clincally signifcant occupational poisonings, United States, 2008-2018. Clin Toxicol (Phila). 2021. PMID: 33703981
Keywords: massive acetaminophen overdose, standard NAC, hepatotoxicity (PubMed Search)
Recently, there has been questions if standard n-acetylcysteine (NAC) dose is adequate for massive acetaminophen (APAP) overdose (ingestion of > 32 gm or APAP >300 mcg/mL).
A retrospective study from a single poison center (1/1/2010 to 12/31/2019) investigated the clinical outcome of massive APAP overdose (APAP > 300 mcg/mL at 4 hour post ingestion) treated with standard dosing of NAC.
1425 cases of APAP overdose identified; 104 met the criteria of massive APAP overdose.
Among cases that received NAC within 8 hours post ingestion (n=44)
Among cases that received NAC > 8 hours post ingestion (n=60)
Odds of hepatotoxicity
Keywords: Haloperidol, ondansetron, cannabis hyperemesis syndrome (PubMed Search)
Patients with cannabis hyperemesis syndrome experience recurrent/protracted nausea/vomiting. Cases of cannabis hyperemesis syndrome may increase as cannabis use becomes more common in the United States.
A randomized control trial (triple-blind) was conducted to compare haloperidol (0.05 or 0.1 mg/kg) IV or ondansetron 8 mg IV. Primary outcome was reduction of abdominal pain and nausea from baseline (on a 10 cm visual analog scale) 2 hours after treatment.
Ruberto AJ. et al. Intravenous haloperidol versus ondansetron for cannabis hyperemesis syndrome (HaVOC): a randomized controlled trial. Annals of Emergency Medicine. Nov 2020
Keywords: alcoholic ketoacidosis, toxic alcohol ingestion, anion gap metabolic acidosis (PubMed Search)
Anion gap metabolic acidosis is often found in ED patients. It can be difficult to distinguish between toxic alcohol (TA) ingestion and alcoholic ketoacidosis (AKA). A retrospective study attempted to identify risk factors associated with AKA when TA ingestion was the alternative diagnosis.
New York City poison center data was reviewed from Jan 1, 2000 to April 30, 2019.
Case definition of AKA included
Case definition of TA ingestion
Univariate analysis showed following variables to be associated with AKA diagnosis
Multivariate logistic regression showed elevated ethanol concentration was associated with increased odd of AKA diagnosis
Keywords: Serum insulin level table (Attachment) (PubMed Search)
Keywords: high dose insulin. insulin kinetic (PubMed Search)
High dose insulin (HDI) therapy is commonly used in patients with severe beta-adrenergic antagonist and calcium channel antagonist overdose. Hypoglycemia and hypokalemia are commonly known complication of HDI therapy. However, kinetics of insulin in patients who received HDI therapy is unknown.
A 51 year-old man with amlodipine overdose was infused HDI (10 unit/kg/hr) for 37 hours; Serial serum insulin levels were drawn after discontinuation of HDI.
Serum insulin levels are shown in below table
The serum insulin level remained significantly elevated during the first 24 hours (normal range: 2.6-24.9 microU/mL) and gradually decreased over 6 days.
Corcoran JN et al. Persistent hyperinsulinemia following high-dose insulin therapy: a case report. J Med Toxicol 2020;16:465-469.
Keywords: physostigmine, lorazepam, anticholinergic toxicity, delirium (PubMed Search)
Antimuscarinic agents (e.g. diphenhydramine) are one of the commonly ingested substances in the US. Lorazepam is frequently used to treat delirium and agitation associated with antimuscarinic toxicity. Although physostigmine is also effective, its use is infrequent due to concerns of safety and provider’s limited experience with physostigmine.
A small blinded randomized clinical trial was conducted to compare physostigmine vs lorazepam for the treatment of antimuscarinic toxicity -delirium/agitation.
Plus administration of lorazepam (0.05 mg/kg) IV bolus (max 2 mg) every 2 hours as needed for continued agitation or delirium (at the discretion of treatment team)
Delirium and agitation were assessed by Confusion Assessment Method for the Intensive Care Unit score (CAM-ICU) and Richmond Agitation Sedation Score
Study duration: March 20, 2017 to June 30, 2020
Antimuscarinic agent ingested
Proportion of subject with delirium by CAM-ICU
Prior to first bolus (p >0.99)
After 1st bolus (p=0.01)
End of 4 hr infusion (p <0.001)
No adverse events noted in both group
Wang GS et al. A randomized trial comparing physostigmine vs lorazepam for treatment of antimuscarinic (anticholinergic) toxidrome. Clin Toxicol (Phila.) 2020. Dec 9. Online ahead of print. https://doi.org/10.1080/15563650.2020.1854281
Keywords: ethanol exposure, infant, national poison data system. (PubMed Search)
Ethanol exposure among young children can result in significant morbidity. Infants and young children can be exposed to ethanol in many different ways: exploratory ingestion, mixed in formula-both intentionally and unintentionally, etc.
A recently published study used national poison data system to characterize the ethanol exposure among infants < 12 months of age.
Between 2009-2018, 1,818 ethanol exposures among infants were reported. Oral ingestion was the most common (96.7%; n=1738). Annual number of ethanol exposure increased by 37.5% each year.
Clinically significant effects
563 infants (31%) were evaluated at hospital
38% (n=214) of the exposures were hospitalized
0-5 months of age
Ethanol exposure among infants is increasing each year and associated with serious clinical effects.
Gaw CE et al. Beverage ethanol exposure among infants reported to United States pison control centers 2020 Clin Toxicol (Phila) https://doi.org/10.1080/15563650.2020.1843658
Keywords: mad honey poisoning (PubMed Search)
What is the cause of Mad honey poisoning?
Grayanotoxin is a neurotoxin that is found in honey contaminated with nectar of Rhododendron plants. It binds to activated/open neuronal sodium channels and prevents inactivation of sodium channels. Case reports of mad honey poisoning is often reported in the eastern Black Sea region of Turkey. Commercial honey producers frequently mix honeys from multiple sources to decrease the grayanotoxin contamination.
Mad honey poisoning is rarely fatal and generally resolves within 24 hours. Commonly reported symptoms include dizziness, weakness, impaired consciousness/disorientation, excessive perspiration, nausea/vomiting, and paresthesia. In severe intoxication, patients can experience complete AV block, bradycardia/asystole, hypotension, and syncope.
Management is primarily supportive with atropine and IV fluids.
Keywords: chemical transfer, unlabeled bottle, poison center (PubMed Search)
Transfer of chemical from their original container to an unlabeled or different container (e.g. Gatorade bottle) is one of the common causes of unintentional poisoning.
A retrospective study of National Poison Data System from 2007 – 2017 identified 45,512 cases of unintentional exposure/ingestion of chemicals contained in unlabeled/incorrectly labeled containers.
Annual reported cases increased from 3,223 in 2007 to 5,417 in 2017.
Most commonly involved products included
These exposures led to
The majority of these exposures were non-toxic in nature (72%) but serious outcomes were noted in 4.4% of the cases, including 23 deaths.
Highest morbidity was associated with:
Carpenter JE et al. Poisonings due to storage in a secondary container reported to the National Poison Data System, 2007-2017. Clin Toxicol (Phila) 2020.
Keywords: dihydropyridine, ARBs, ACEIs, co-ingestion, hypotension, toxicity (PubMed Search)
Dihydropyridine (calcium channel blocker) overdose is one of the leading causes of death from cardiovascular drug poisoning. In contrast, angiotensin-II receptors blockers (ARBs) and angiotensin converting enzyme inhibitor (ACEIs) causes minimal toxicity in overdose. Frequently, these medications are co-ingested with dihydropridines.
Recently, a retrospective study was conducted to evaluate the hemodynamic impact of dihydropyridines with ARBs/ACEIs co-ingestion.
Mixed overdose group had:
Higher proportion of the mixed overdose group received:
Combined overdose of dihydropyridines with ARBs/ACEIs can result in more significant hypotension.
Huang J et al. Angiotensin axis antagonists increase the incidence of haemodynamic instability in dihydropyridine calcium channel blocker poisoning. Clint Toxicol (Phila) 2020. Epub. https://doi.org/10.1080/15563650.2020.1826504
Keywords: Black urine, toxicological cause (PubMed Search)
What medication ingestion can lead to black urine?
There are many medical disorder and ingestion that can lead to change in urine colors.
Black discoloration of urine can be caused by:
Aycock, RD et al. Abnormal Urine Color. Southern Medical Journal 2012;105;43-47.