UMEM Educational Pearls - Toxicology

Question

What is the name of the toxin found in this seed/bean and its mechanism of toxicity?

 

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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. 

  • Study design: cohort-cross over study (cross over at 1 year after CO poisoning)
  • Setting: South Korea
  • Data source: National Health Insurance Service database

Results

22,699 patients with CO poisoning were identified between 2004 and 2015

30 days after CO poisoning

  • Risk of PE: OR of 22.0; 95% CI: 5.33 to 90.75
  • Risk of DVT: OR of 10.33; 95% CI: 3.16 to 33.80

90 days after CO poisoning

  • Risk of PE/DVT: OR of 3.96; 95% CI: 2.5 to 6.25

No significant increase in risk > 90 days.

Conclusion

  • Patients are at highest risk of developing PE/DVT during first 30 days after CO poisoning.
  • Increased risk of PE/DVT persisted up to 90 days after CO poisoning.

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Category: Toxicology

Title: Case: 27 year old with hydroxychloroquine overdose

Keywords: hydroxychloroquine toxicity, overdose (PubMed Search)

Posted: 6/11/2020 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

Question

 

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:

 

 

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Category: Toxicology

Title: Riot Control Agents - submitted by Jake Danoff

Keywords: Riot control agent, Mace, pepper spray, tear gas (PubMed Search)

Posted: 6/4/2020 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

 

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: 

  1. Mace (2-chloroacetophenone)
  2. Pepper spray (capsaicins)
  3. Tear gas (O-chlorobenzylidene malonitrile)

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:

  • Initial management involves copious irritation of the affected area with water. 
  • There is limited evidence that decontamination with milk, milk of magnesia, or baby shampoo is better than water. 
  • Always consider projectile or blunt trauma that may be associated with the riot-control-related ED visits/complaint. 
  • Protect yourself by wearing PPE when evaluating/treating these patients.

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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:

  • Out of 6026 fatalities, 459 fatal overdose cases received ILE.
  • Majority involved either CCB or BB overdose (n=285; 62.1%)

Response to therapy (study cohort)

  • No response: 45%
  • Unknown response: 38%
  • Transient/minimal response: 7%
  • ROSC: 7.4%
  • Immediate worsening: 3%

Adverse effect (n=49)

  • ARDS with hypoxemia: 39
  • Lipemia causing delay in laboratory evaluation: 3
  • Lipemia causing failure of CRRT filter: 2
  • Worsening/new seizure: 2
  • Asystole: 2
  • Fat embolism: 1

Conclusion

  • The number of published cases of failed ILE outnumbers the published cases of ILE success.
  • Less than 5% of the patients with CCB or BB overdose had ROSC after ILE therapy.

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Question

 

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?

 

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Category: Toxicology

Title: Disinfectants!

Keywords: antiseptics, disinfectants, sterilants (PubMed Search)

Posted: 4/30/2020 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

 

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.


Category: Toxicology

Title: CYP3A4 inducing agents may cause opioid withdrawal in patients on buprenorphine

Keywords: buprenorphine, CYP3A4, induction, inhibition, metabolism (PubMed Search)

Posted: 4/23/2020 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

 

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): 

  • Reduction of plasma BUP concentration (70% reduction in area under the curve [AUC]) 
  • 50% of the study subjects (12 out of 24) experienced opioid withdrawal symptoms (OWS)
  • 4 out of 12 who experience OWS received transient increase in their BUP dose (25-100%)

 

On the contrary, exposure to voriconazole – strong 3A4 inhibitor - resulted in (n=12 health volunteers) (2):

  • Increased the plasma BUP AUC by 4.3 fold
  • Increased peak BUP concentration by 3.9 fold
  • Documented adverse effects were dizziness and nausea only

 

Cannabis use – (CBD is a CYP 3A4 inhibitor) also increased the BUP concentration by 2.7 fold. (3)

 

Bottom line:

  1. Be mindful of drug-drug interaction when initiating a new medication in patients with OUD on BUP
  2. Inquire about any recent medication change in patients who may be experiencing OWS while on steady dose of BUP for their OUD. 

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Question

 

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?

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Category: Toxicology

Title: What is the case fatality rate after cyclopeptide-mushroom poisoning.

Keywords: cyclopeptide, mushroom poisoning, fatality rate (PubMed Search)

Posted: 4/2/2020 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

 

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:

  • Northeast 50 (33.8%)
  • West cost: 46 (31.1%)
  • Southeast: 22 (14.9%)
  • Midwest: 24 (16.2%)
  • Southcentral: 6 (4.1%)

Therapy:

  • NAC: 101 (68.2%)
  • Penicillin: 42 (28.4%)
  • Multi-dose activated charcoal: 35 (23.6%)
  • Silibinin IV: 30 (20.3%)
  • Silibinin PO: 12 (8.1%)

Case fatality

  • Overall: 8.8%
  • Treated with silibinin/silymarin: 9.5%
  • Not treated with silibinin/silymarin: 8.5%

Conclusion:

  • Overall fatality of cyclopeptide mushroom poisoning was 8.8%
  • In this retrospective study, silibinin treatment did not appear to decrease the fatality rate.

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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

  • A retrospective control (n=11) vs. prospective diazepam (2 gm/kg daily) and EPI (0.25 microgm/kg/min with titrate to SBP >= 100 mmHg) group (n=11) involving large chloroquine ingestion (> 5 mg)

Survival:

  • Combination treatment group: 91%
  • Control: 9%

 

Clemessy JL et al. Crit Care Med 1996. DOI:10.1097/00003246-199607000-00021

  • 5 year retrospective study (n=167)
  • Mean chloroquine ingestion: 4.5 gm +/- 2.8 gm
  • >5 gm ingestion: 43 (26%)

Treatment: 87% received at least one of the interventions below.

  • 79/167 (48%) received EPI infusion
  • 142/167 (85%) received diazepam
  • Mechanical ventilation: 123/167 (74%)

Mortality

  • Overall: 8.4%
  • >5 gm ingestion: 9.3%

Bottom line

  • Chloroquine and hydroxychloroquine toxicity may increase due to COVID19 pandemic
  • Limited studies show that combined therapy of high dose diazepam and epinephrine infusion may decrease mortality associated with chloroquine and hydroxychloroquine toxicity.

Category: Toxicology

Title: Can acetaminophen cause methemoglobinemia?

Keywords: acetaminophen overdose, methemoglobinemia (PubMed Search)

Posted: 3/19/2020 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

 

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:

  • Nitrites/nitrates
  • Local anesthetics (benzocaine, lidocaine)
  • Nitroglycerin
  • Nitroprusside
  • Phenazopyridine
  • Quinones
  • Sulfonamides
  • Analine
  • Naphthalene
  • Dapsone
  • Nitric oxide

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

  • pH: 7.2
  • lactic acid: 14.5 mmol/L
  • APAP: 531 mcg/mL
  • Discrepancy between pulse oximetry and arterial blood gas led to checking the methemoglobin level – 32%
  • Developed coagulopathy (INR 9.8) with AST/ALT 3487/2837

Case 2:  64 year-old man with dementia, polysubstance abuse, depression and hypertension hospitalized from nursing home for altered mental status. 

  • pH: 7.25
  • AG: 28
  • APAP: 730 mcg/mL
  • Methemoglobin level: 12%
  • AST/ALT: 44/46

Conclusion

  • It is unlikely that significant methemoglobinemia will develop in the majority of the APAP overdose.
  • However, methemoglobinemia should be considered in a large APAP overdose in select clinical scenarios (e.g. pulse oximetry and arterial blood gas discrepancy).

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Category: Toxicology

Title: Predictors of mortality in Metformin associated lactic acidosis

Keywords: mortality, predictors, MALA, pH, lactate (PubMed Search)

Posted: 2/12/2020 by Hong Kim, MD, MPH (Emailed: 2/13/2020)
Click here to contact Hong Kim, MD, MPH

 

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

  • Median age: 68.5 years
  • Median pH: 7.02
  • Median lactate: 14,45 mmol/L
  • Overall mortality: 36.2%

pH and lactate were poor predictors of mortality based upon ROC curve

  • pH: AUC of 0.430
  • lactate: AUC of 0.593

Conclusion

  • MALA was associated with high mortality in this meta-analysis: 36.2%
  • pH and lactate were poor predictors of mortality. 

Category: Toxicology

Title: Predictors of fatality from intentional drug overdose

Keywords: risk of death, intentional drug overdose (PubMed Search)

Posted: 1/23/2020 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

 

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

  • 1.7 times higher in MALE compared to female
  • 5 times higher in age > 45 years vs. 15-24 years
  • 3 times higher in patient who ingested 2 – 5 distinct agents, 6x higher in > 6 agent vs. single agent
  • 15 times higher after TCA ingestion
  • 12 times higher after opioids ingestion
  • 4 times higher after antidepressants or illicit substance ingestion/exposure

Conclusion

  • Older age (> 45 years), male gender and ingestion of multiple agents (>2) were associated with higher risk of death from intention drug overdose.

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Category: Toxicology

Title: Risk of fatality after ED visit for non fatal opioid overdose

Keywords: non-fatal opioid overdose, risk of fatality (PubMed Search)

Posted: 1/16/2020 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

 

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

  • 11,557 patients were identified between July 1, 2011 and September 30, 2015.
  • There were 635 fatalities (5.5%) within 1 year in this cohort.
    • Of these, 428 (67.4%) died due to opioid overdose

Of those who died, 

  • 130 (20.5%) died within 1 month
  • 29 (4.6%) died within 2 days.

Manner of death

  • Natural causes: 121 (19.1%)
  • Accidental: 460 (72.4%)
  • Suicide: 13 (2.0%)
  • Other/pending investigation: 41 (6.5%)

Place of death

  • Hospital: 310 (48.8%)
  • Residence: 146 (23.0%)
  • Other/unknown/nursing home: 179 (28.2%)

Conclusion

  • There is high rate of fatality within 1 month (20.5%) after non-fatal opioid overdose ED visits.
  • Subsequent fatal opioid overdose was observed in 428 (67.4%) of the cohort.

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Category: Toxicology

Title: Pharmacobezoar formation in acetaminophen

Keywords: acetaminophen, pharmcobezoar (PubMed Search)

Posted: 1/2/2020 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

 

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

  • 25 gm (50 tablets)
  • 37.5 gm (75 tablets)
  • 50 gm (100 tablets)

Positive control group

  • ferrous sulfate (15 gm/50 tablets)

Negative control group

  • chlorpheniramine (200 mg (50 tablets)

Results

  • APAP formed clumps in 37.5 gm and 50 gm groups
  • 83% (5 out of 6) of the 25 gm APAP group did not form clumps.
  • Dissolution profile: APAP clumps released more slowly (over 60 min tested) compared to individual tablet without reaching a peak.

Conclusion

  • APAP can form pharmacobezoar at doses greater than 37.5 gm (in-vitro model) and can result in prolonged or delayed toxicity due to pharmacobezoar formation.

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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:

  • Total exposure: 72.3% 
  • Isolated intentional suicide attempt: 80.5%
  • Isolated exposure: 67.1%
  • Isolated intentional abuse/misuse: 119.9%

5 most commonly co-ingested substances with gabapentin

  • Sedative-hypnotic: 22.9%
  • Antidepressant: 12.7%
  • Antihypertensive: 9.9%
  • Opioid: 9.0%
  • Antipsychotics: 6.3%

16.7% of the isolated gabapentin exposure required hospitalization.

 

Conclusion:

  • Gabapentin abuse/misuse and ingestion with self-harm intent is increasing in the U.S.

Category: Toxicology

Title: Safety of Droperidol use for agitation in the emergency department

Keywords: droperidol, agitation, sedation, QT prolongation (PubMed Search)

Posted: 12/5/2019 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

 

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

  • Study period: August 2009 to April 2013 in 6 EDs in Australia
  • Intervention: droperidol 10 – 20 mg IM or IV (if available)
  • EKG performed within 2 hours of droperidol administration.
  • QT was manually measured and plotted against the heart rate on the QT nomogram – if above “at-risk line” = abnormal

Results

  • Droperidol was administered in 1,403 ED patients
  • EKG available in 1,009 ED patients
  • Median age: 34 years (IQR: 25-44)
  • Men: 59.9%

Four leading reason for ED presentation

  1. Alcohol intoxication: 421
  2. Deliberate or threatened self-harm: 200
  3. Psychostimulant use: 130
  4. Mental illness/psychosis: 142
  • Median droperidol dose: 10 mg (IQR: 10 to 17.5 mg) 
  • Abnormal QT interval: 13 (1.3%, 95% CI: 0.3% to 2.3%)
    • 7 patient had other potential contributing factors: methadone, escitalopram, Amiodarone or preexisting condition. 
  • Median time to sedation: 20 min (IQR: 10 to 30 min)

Adverse events

  • Desaturation (<90%): 22 (1.6%)
  • Airway obstruction: 8 (0.6%)
  • Hypotension: 28 (2.0%)
  • Extrapyramidal symptoms: 7 (0.5%)
  • Arrhythmia: 1 (0.1%)
  • Hypoventilation (RR < 12 breaths/min): 4 (0.2%)
  • Seizure: 1 (0.1%)
  • No adverse events: 1,333 (95.0%)

Conclusion

  • Droperidol is a safe sedating agent with no evidence of increased risk for QT prolongation with the doses used. 

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As of November 20, 2019:

2290 cases of e-cigarette, or vaping, product use-associated lung injury (EVALI) from 49 states (except Alaska), District of Columbia and 2 U.S. territories.

  • Largest number of cases (150-199) reported from CA, TX and IL
  • 47 deaths

Analysis of 29 bronchoalveolar lavage (BAL) fluid samples from EVALI patients submitted to CDC from 10 states showed:

  • Vitamin E acetate in all samples 
  • THC: 82%
  • Nicotine: 62%
  • No other chemicals of concern were identified (e.g. plant oil, mineral oil, terpenes, etc.) 

*** Vitamin E acetate appears to be associated with EVALI but the investigation is continuing.*** 

  • Oral ingestion of vitamin E acetate does not cause harm.
  • High dose vitamin E supplementation (>2000 IU/day [2000 mg/day]) can cause GI symptoms: nausea, vomiting, diarrhea and abdominal pain.

Some research has suggested that oral vitamin E use has potential beneficial effects (i.e. anti-inflammatory/antioxidant) in the lung (e.g. asthma and allergic lung disease), cardiovascular disease and prostate cancer (Cook-Mills JM et al. 2013; Jiang Q et al. 2001)

Common uses of vitamin E

  • Topical cosmetic skin products (skin cream) for antioxidant effect.
  • Essential dietary vitamin (fat soluble) found in many food items and as dietary supplement.
  • In vaping products: vitamin E is used as an additive/thickening agent in THC containing e-cigarette, or vaping products.

There is limited to no data on pulmonary effect of vitamin E from inhalation in the scientific literature.

Stay tuned for additional updates from CDC.

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Category: Toxicology

Title: Observation for the development of metformin associated lactic acidosis after an acute metformin overdose

Keywords: meformin overdose, metformin associated lactic acidosis, observation period (PubMed Search)

Posted: 11/14/2019 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

 

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 

  • Lactate: > 5 mmol/L
  • Acidemia: (HCO3< 20 mmol/L or pH < 7.35)

Results

40 cases of MALA identified between Jan. 2001 to Dec. 2014

  • Meadian age: 41 year
  • Female: 55%
  • Acute on chronic ingestion: 62.5%
  • Hypoglycemia: 3 (7.5%)

Time to development of MALA (n=30)

  • <=6 hours: 18 (60%)
  • 6-12 hours: 9 (30%)
  • >12 hours: 3 (10%)
  • Unknown: 10

Death: 1 (2.5%)

 

Conclusion

  1. The majority of MALA developed within 6 hours. However, delayed onset of MALA can occur, up to 12 hours post ingestion.
  2. Minimum of 12 hour of observation is recommended after an acute metformin overdose.

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