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.
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.
Result
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:
Deaths
Conclusion
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.
Results
Cohort
Mixed overdose group had:
Higher proportion of the mixed overdose group received:
Conclusion
Combined overdose of dihydropyridines with ARBs/ACEIs can result in more significant hypotension.
Extracorporeal membrane oxygenation use is increasing in the US for acute poisoning.
A retrospective study of the National Poison Data System from 2000 to 2018 identified 407 ECMO cases (332 adults – age > 12 years, 75 pediatric – age < 12 years). Increase in ECMO use were more notable in adult population.
Characteristics
Intentional exposure
Most common class of drug/poison exposure in adults
Most common class of drug/poison exposure in children
Most common states that used ECMO for poisoning
Conclusion
Baclofen is a presynaptic GABA-B receptor agonist in the spinal cord that is primarily used for muscle spasms/spasticity. In large overdose, baclofen can produce CNS depression, respiratory depression, bradycardia/hypotension, hypothermia, seizure and coma.
Baclofen is primarily eliminated by the kidney. In patients with end-stage kidney disease/acute kidney failure, hemodialysis (HD) has been used to enhance baclofen clearance. However, it is unclear if there is a benefit of using HD in patients with normal kidney function.
In a recently published case report, HD was implemented in an attempt to shorten the anticipated prolonged ICU course.
Case: 14 year old (51 kg) woman ingested 60 tablets of baclofen (20 mg tablets)
Her symptoms were:
Baclofen level: 882 ng/mL (therapeutic range: 80 – 400 ng/mL)
Baclofen clearance from hemodialysis vs. urine
Patient’s mental status improved on hospital day 6 and was extubated. She was discharged to psychiatry on hospital day 14.
Conclusion:
What physical exam findings are associated with nitrous oxide abuse?
Nitrous oxide (NO) inhalation abuse, also called “whip-its” or “whippets”, inactivates vitamin B12 and create a vitamin B12 deficiency state. Chronic abuse of nitrous oxide can result in neurologic deficits/findings affecting the posterior/dorsal column of the spinal cord.
Physical exam findings:
Tianeptine is an antidepressant with mu-opioid receptor agonism. It is available in several European countries for therapeutic use, but not available in the US.
There has been an increase in tianeptine exposure in the US since August 2019. Recently a retrospective observation study was done to characterize the clinical features associated with tianeptine exposure.
Result
| Intoxication (n=11) | Withdrawal (n=27) |
| Symptoms · Lethargy: 7 (63%) · Agitation: 3 (27%) · Tachycardia: 3 (27%) · GI distress: 2 (18%) · Myoclonic/hallucination: 2 (18) | Symptoms · Anxiety: 12 (44%) · GI distress: 3 (33%) · Hypertension: 8 (30%) · Agitation: 8 (30%) · Tachycardia: 7 (26%) |
| Treatment · Naloxone: 3 (27%) · Benzodiazepines: 2 (18%) · Antipsychotics: 2 (18%) · Antimuscarinic: 1 (9%)
| Treatment · Benzodiazepine: 10 (37%) · Opioids: 6 (22%) · Alpha-2-agonist: 5 (19%) · Antipsychotics: 5 (19%) · Antimuscarinic: 5 (19%) |
| Disposition · ICU: 6 (55%) · Non-ICU: 2 (18%) · Discharged home: 2 (18%)
| Disposition · ICU: 4 (15%) · Non-ICU: 7 (26%) · Psych: 1 (4%) · Discharged home: 10 (37%) |
Conclusion
What is the name of the toxin found in this seed/bean and its mechanism of toxicity?
Carbon monoxide is an odorless gas that can cause neurologic and cardiovascular toxicity. It is produce by combustion of organic materials/fuel such as natural gas (furnace, gas stove, water heater, space heater) or gasoline. DVT/PE has been reported among victims of CO poisoning.
A recently published article investigated the risk of DVT/PE after CO poisoning.
Results
22,699 patients with CO poisoning were identified between 2004 and 2015
30 days after CO poisoning
90 days after CO poisoning
No significant increase in risk > 90 days.
Conclusion
A 27 year-old man with history of rheumatoid arthritis presents to the emergency department after ingestion of hydroxychloroquine (20 tablets of 200 mg/tablet). He complains of nausea/vomiting. He appears lethargic. What is the anticipated hydroxychloroquine toxicity and management?
VS: Temp: afebrile, BP: 95/55 mmHg, RR: 23 breaths/min, O2 saturation: 99%
ECG:
Over the past several days, riot control agents have been used against the protest participants (related to Mr. George Floyd’s death). There are 3 widely used riot control “lacrimating” agents:
These agents (irritants) primarily affect the eye, skin, and respiratory tract.
| Organ | Effect | Management |
| Eyes | · Lacrimination · Blepharospasm · Conjunctiva irritation/conjunctivitis · Periorbital edema · Corneal abrasions | · Copious H20/saline irrigation with Morgan Lensor Nasal Cannula jury-rig · Slit lamp exam for corneal abrasions |
| Skin | · Burning sensation · Blister · Contact dermatitis · 2nd degree burns (mace) | · Wash with soap and water · Wound care |
| Airway/respiratory tract | · Respiratory tract irritation · Rhinorrhea · Laryngospasm · Bronchospasm · Chemical pneumonitis | · B2-agonists for bronchospasm · Steroids if worsening underlying reactive airway disease · CXR to evaluate for possible pneumonitis · Supplementary oxygen as needed |
Mangement:
ILE is considered as one of the “last resort” therapy in cases of life-threatening drug-induced cardiogenic shock or cardiac arrest. Although there are numerous case reports and case series that showed “successful” or “positive” outcome with ILE, here is no clear evidence that lipid emulsion therapy is effective.
A group of researcher reviewed the National Poison Data System (NPDS) to investigate the failure of ILE therapy by reviewing the overdose fatalities reported to NPDS between 2010 and 2015.
Result:
Response to therapy (study cohort)
Adverse effect (n=49)
Conclusion
A 19 year old man presents with a scalp lesions/burns after an exposure to incendiary agent. His wounds were smoking and they flouresce under UV light.
What is the causative agent?
Recently, “disinfectants,” or germicides, has gain public attention during COVID-19 pandemic. So, what types of agents are considered as “disinfectants?”
Germicides as classified into three broad categories
1. Antiseptics – chemicals applied to living tissue to kill or inhibit microorganisms
a. Iodine & iodophors (e.g. Povidone-iodine; aka Betadine)
b. Chlorine, bleach (sodium hypochlorite)
c. Chlorhexidine
d. Hydrogen peroxide
e. Alcohols (ethanol and isopropanol)
2. Disinfectants – chemicals applied to inanimate objects to kill or inhibit microorganisms
a. Formaldehyde
b. Phenol (aka carbolic acid)
c. Substituted phenols (e.g. hexachlorophene; aka pHisoHex)
d. Quaternary ammonium compounds (benzalkonium chloride; aka Zephiran)
3. Sterilants – chemicals applied to inanimate objects to kill all microorganisms including spores
a. Ethylene oxide
b. Glutaraldehyde
Although ethanol is frequently found in alcoholic beverage and consumable, no other chemicals should be ingested or injected.
Buprenorphine (BUP) is increasingly prescribed/used to treat opioid use disorder (OUD) in the United State. BUP is mainly metabolized by CYP3A4 where its enzymatic activity can be either induced or inhibited by many agents.
For example, a study showed that Rifampin administration for 15 days, a potent 3A4 inducer, resulted in (1):
On the contrary, exposure to voriconazole – strong 3A4 inhibitor - resulted in (n=12 health volunteers) (2):
Cannabis use – (CBD is a CYP 3A4 inhibitor) also increased the BUP concentration by 2.7 fold. (3)
Bottom line:
A 7 year-old Spanish speaking female presents to the emergency room after ingestion of 2 – 3 tablets of her sister’s medication. She complains of nausea/vomiting with diarrhea, periorbital/facial swelling, and flushing of her skin. Her urine is reddish but there is no blood is shown in urinalysis/urine microscopic analysis. The patient's sister is taking the medication for a respiratory condition.
Which medication did she take?
