Question
What is the name of the toxin found in this seed/bean and its mechanism of toxicity?
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?
Cyclopeptides (Amatoxin)-containing mushroom poisoning results in delayed development of gastrointestinal symptoms that may progress to liver failure. There is no established antidotal treatment for cyclopeptide-induced hepatic failure; silibinin is currently under investigation.
There is a wide range of case fatality reported from cyclopeptides-containing mushroom poisoning: 4.8% to 47%.
National Poison Data System was reviewed from 1/1/2008 to 12/31/2018 for all suspected cyclopeptides containing mushroom poisoning. Out of 8953 suspected cases, 148 cases were included in the study.
Results:
Therapy:
Case fatality
Conclusion:
COVID-19 pandemic has brought two old medications – chloroquine and Hydroxychloroquine – back from the past.
A couple in Arizona self-medicated with chloroquine this week and experienced chloroquine toxicity; the man died and his wife was admitted to the ICU.
https://www.cnn.com/2020/03/23/health/arizona-coronavirus-chloroquine-death/index.html
Chloroquine and hydroxychloroquine overdose result in cardiotoxicity by Na and K channel blockade (similar to other membrane stabilizing agents such as TCAs, loperamide, etc.). Onset of toxicity is usually within 1 – 3 hours after ingestion.
Other symptoms of toxicity include: nausea/vomiting, respiratory depression/apnea, altered mental status and seizure. Hypokalemia is often encountered.
Use of sodium bicarbonate is controversial due to worsening of hypokalemia. Instead, administration of high dose diazepam and epinephrine (EPI) infusion has shown to decrease mortality (see below).
Riou B et al. NEJM 1988 DOI: 10.1056/NEJM198801073180101
Survival:
Clemessy JL et al. Crit Care Med 1996. DOI:10.1097/00003246-199607000-00021
Treatment: 87% received at least one of the interventions below.
Mortality
Bottom line
Methemoglobinemia occurs when iron in the hemoglobin is converted from ferrous (2+) to ferric (3+) state, frequently by substance exposure. There are many medications and chemicals that can induce methemoglobinemia.
Common agents that induce methemoglobinemia include:
Acetaminophen has not been associated with methemoglobinemia. However, two cases of methemoglobinemia in massive acetaminophen overdose were recently reported. Both patients were not on any medication known to cause methemoglobinemia.
Case 1: 54 year-old man with DM, HTN, cognitive impairment and no hx of G6PD deficiency hospitalized for altered mental status
Case 2: 64 year-old man with dementia, polysubstance abuse, depression and hypertension hospitalized from nursing home for altered mental status.
Conclusion
Metformin associated lactic acidosis (MALA) has a high rate of mortality, ranging from 25% to 50%. Lactate level and acidemia are frequently associated with poor clinical outcome in many disease/medical conditions (e.g. sepsis).
A study investigated, via meta-analysis, if lactate level and pH were predictive of mortality in MALA.
Results
44 studies were identified from PubMed, EMBASE and Web of Science.
170 cases of MALA were included
pH and lactate were poor predictors of mortality based upon ROC curve
Conclusion
Intentional drug overdose (IDO) can lead to significant morbidity and can increased patient's risk of death. A study was recently performed to identify the predictors of death in a cohort of patient who intentionally overdose on drug(s).
National Self-Harm Registry and National Drug-Related Death Index were reviewed (between January 1st, 2007 and December 31st, 2014) to identify the study cohort.
Results
|
| Non fatal IDO | Fatal IDO |
| Number of cases | 63,831 | 364 |
| Incidence | 148.8/100,000 | 1.01/100,000 |
| Male | 42.0% | 55.2% |
| Age, years (median) | 35 | 44 |
| Multiple drug ingestion | 48.5% | 78.3% |
Risk of death
Conclusion
Many patients are treated in the emergency room for non-fatal opioid overdose. However, it is unknown what proportion of these patient population experience subsequent fatality after their ED visit.
A recent study investigated the 1-year mortality rate among Massachusetts ED patients who were treated and discharged from ED for non-fatal opioid overdose.
Results
Of those who died,
Manner of death
Place of death
Conclusion
Pharmacobezoars (clumps of medication/pills) formation has been demonstrated in few medications such as aspirin, and ferrous sulfate tablets. Their presence can alter management due to prolonged absorption and may cause GI obstruction.
Acetaminophen (APAP) is a commonly available over-the-counter medication that is often implicated in an acute overdose event. A recently published in-vitro study (using pig stomach) investigated whether APAP can form a pharmacobezoar.
APAP group/dosage
Positive control group
Negative control group
Results
Conclusion
Non-opioid medications such as gabapentin are frequently prescribed for the management of pain.
A retrospective study of the National Poison Data System (data collected by the U.S. Poison Centers) from 2013 – 2017 showed increasing trend of gabapentin exposure.
Gabapentin exposure increased between 2013 and 2017 by:
5 most commonly co-ingested substances with gabapentin
16.7% of the isolated gabapentin exposure required hospitalization.
Conclusion:
After many years of national shortage and FDA’s black box warning in 2001 (QT prolongation) droperidol is slowing becoming available.
In 2015, a prospective observational study was published involving ED patients who received droperidol for agitation (acute behavioral disturbance).
Method
Results
Four leading reason for ED presentation
Adverse events
Conclusion