Bupropion associated cardiac toxicity widens the QRS complex by inhibiting the cardiac gap junction, not cardiac Na channel blockade. NaHCO3 is often administered when EKG changes are noted. But the effectiveness of NaHCO3 in bupropion toxicity is not well established.
A retrospective study between 2010-2020 showed, that administration of NaHCO3 only decreased QRS duration by 2 msec (median). The median NaHCO3 administered was 100 mEq. Although this study was limited by the fact that it only had a small sample size of 13, NaHCO3 administration may provide limited clinical benefit in patients with QRS widening from bupropion overdose.
Medical Cannabis is permitted in 39 states and Washington DC while 18 sates and Washington DC has legalized recreational cannabis use. As cannabis products become more available, pediatric exposure has also increased.
A retrospective study of National Poison Data System involving children < 6 years from 2017 and 2021 showed: Pre-COVID (2017-2019) & COVID (2020-2021)
Common Clinical effects
Disposition
Conclusion
Calcium channel blocker (CCB) overdose can lead to severe shock/hypotension. A small study was conducted to compare the hemodynamic effects of high-dose insulin (HDI) for two classes of CCB (dihydropyridines vs. non-dihydropyridines) that work differently to manage hypertension.
Study design:
Study sample:
Result
Median number of maximum concomitant vasopressors (p=0.04)
Median difference in max concomitant vasopressors: 1 (95% CI: 0 – 2)
Median max epinephrine dosing
Use of rescue methylene blue (p=0.009)
Conclusion:
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:
AE:
Serious AE (SAE):
A systematic review/meta-analyses of 13 randomized controlled trials showed
Most common AEs
Most common SAEs
Conclusion
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.
Conclusion
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
Results
1850 violent deaths were identified: n=122 (7%) were poisoning related
Characteristics
Region
Most common exposure/etiology
Conclusion
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)
Retrospective cohort
Results
N=1503
Area under the curve for IRS ROC: 0.736 (95% CI: 0.702-0.770)
IRS <6
Conclusion
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.
Methods
Result
A total of 298 patients were identified
|
| Pre-legalization | Peri-post legalization | P value |
| Monthly ED visit | 2.1 (IRQ: 1.9-2.5) | 1.7 (IQR: 1.0-3.0) | 0.69 |
| ICU admission | 4.7% | 13.6% | 0.02 |
| Respiratory symptoms | 50.9% | 65.9% | 0.05 |
| Altered mental status | 14.2% | 28.8% | <0.01 |
| Age < 12 years | 3.0% | 12.1% | 0.04 |
| Unintentional exposure | 2.8% | 14.4% | 0.02 |
| Edible ingestion | 7.8% | 19.7% | 0.02 |
Respiratory symptoms: tachypnea/bradypnea, cyanosis, O2 sat < 92%, bronchospasm, oxygen requirement
Conclusion
What is the mechanism of action of N-acetylcysteine that is used to treat acetaminophen induced liver injury/toxicity?
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.
Clinical effects:
Cinnamon contains cinnamaldehyde and eugenol – local irritants.
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:
Results
863 cases of isolated diphenhydramine ingestion were identified between Jan 1, 2010 to Dec 31, 2016
Most common symptoms:
Factors associated with severe outcome
Conclusion
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:
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.
Results
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
Conclusion
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.
Results
Conclusion
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
Results
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
Conclusion
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.
Conclusion
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.
Inclusion criteria
Intervention
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
Result
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
Conclusion
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.
Results:
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.
Exposure site
Age
Clinically significant effects
563 infants (31%) were evaluated at hospital
38% (n=214) of the exposures were hospitalized
0-5 months of age
Conclusion
Ethanol exposure among infants is increasing each year and associated with serious clinical effects.
What is the cause of Mad honey poisoning?
Grayanotoxin
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.
