UMEM Educational Pearls - By Hong Kim

Title: What's in that unlabeled container?

Category: Toxicology

Keywords: chemical transfer, unlabeled bottle, poison center (PubMed Search)

Posted: 10/29/2020 by Hong Kim, MD
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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.

  • Median age: 30 years (interquartile range: 6 – 53)
  • Female: 52%

Most commonly involved products included

  • Cleaning products: 38.2%
    • Bleach, 18.8%
    • Peroxides, 5.7%
    • Anionic cleaners, 4.6%
  • Disinfectants: 17.3%
  • Hydrocarbons: 5.0%

These exposures led to 

  • ED visits: 9,369 (20.6%) 
  • Hospitalization: 1,856 (4.1%) 
  • Deaths: 23 (0.1%)

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:

  • Pesticides: 10.3%
  • Prescription medications: 9.8%
  • Herbicides: 7.6%

Deaths

  • Hydrofluoric acid and herbicides accounted for 13 of 23 deaths (57%), followed by cleaning products (7/23).

 

Conclusion

  • Transfer of a chemical to unlabeled/different container is a well-recognized risk factor of poisoning.
  • Although small in number, the annual reported cases to the regional poison center are increasing.

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Title: Co-ingestion of dihydropyridine with ARBs/ACEIs can cause more significant hypotension

Category: Toxicology

Keywords: dihydropyridine, ARBs, ACEIs, co-ingestion, hypotension, toxicity (PubMed Search)

Posted: 10/15/2020 by Hong Kim, MD
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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

  • 68 mixed overdoses of dihydropyridines with ARBs/ACEIs
  • 21 single agent overdose (dihydropyridines)

Mixed overdose group had:

  • Lower median nadir mean arterial pressure: 62 vs. 75 mmHg (p<0.001)
  • Higher OR for hypotension: OR 4.5, (95% CI: 1.7 – 11.9)
  • Higher OR for bradycardia: OR 8.8 (95% CI: 1.1 – 70) 
  • Lower minimum systolic blood pressure by 11.5 mmHg (95% CI: 4.9 – 18.1)

Higher proportion of the mixed overdose group received:

  • IV fluids: OR 5.7, (95% CI: 1.8-18.6)
  • Antidotes and/or vasopressor: OR 2.9 (95% CI: 1.004 – 8.6)

Conclusion

Combined overdose of dihydropyridines with ARBs/ACEIs can result in more significant hypotension.

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Title: Black urine!

Category: Toxicology

Keywords: Black urine, toxicological cause (PubMed Search)

Posted: 9/24/2020 by Hong Kim, MD
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Question

 

What medication ingestion can lead to black urine?

 

Black urine due to cresol intoxication | Postgraduate Medical Journal

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Title: Trend of ECMO use for poisoning in the US: 2000 to 2018

Category: Toxicology

Keywords: ECMO, poisoning, trend in US (PubMed Search)

Posted: 9/10/2020 by Hong Kim, MD (Updated: 12/13/2024)
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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

  • Median age: 27 years (IQR: 15-39)
  • Male: 52.6%
  • Single substance exposure: 51.5%
  • Median number of exposures: 3 (IQR: 2-4)
  • Overall survival: 70%

Intentional exposure

  • Age > 12 years: 72.6%
  • Age < 12 years: 9.3%

Most common class of drug/poison exposure in adults

  • Sedative/hypnotic: 26%
  • Antidepressants: 25%
  • Calcium channel blockers: 19%
  • Opioids: 17%

Most common class of drug/poison exposure in children

  • Hydrocarbons: 37%
  • Antiarrhythmics: 15%
  • Antihistamine: 8%
  • Unknown: 8%

Most common states that used ECMO for poisoning

  • Pennsylvania: 45
  • Texas: 27
  • Minnesota: 24
  • Maryland: 22
  • Michigan: 20
  • New York: 20

 

Conclusion

  • Increase in EMCO use was most notable in patients with age > 12 years
  • There was no significant trend in mortality during the study period
  • ECMO cases were mostly reported from urban areas 


Title: Baclofen clearance: hemodialysis or kidneys?

Category: Toxicology

Keywords: baclofen overdose, hemodialysis, renal elimination (PubMed Search)

Posted: 8/20/2020 by Hong Kim, MD
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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:

  • Coma/CNS depression
  • Tonic-clonic seizure
  • Transient hypotension (95/47 mmHg – resolved with IV fluids)
  • Flaccid extremities
  • Initially intubated for airway protection --> no spontaneous breathing on mech. ventilation.

Baclofen level: 882 ng/mL (therapeutic range: 80 – 400 ng/mL)

Baclofen clearance from hemodialysis vs. urine

  • 24 hour urine output: 2810 mL --> total baclofen urinary elimination: 42 mg
  • 3 hours of HD #1: 3.05 mg removed. Total of 3 HD session performed.

Patient’s mental status improved on hospital day 6 and was extubated. She was discharged to psychiatry on hospital day 14.

 

 Conclusion:

  • Although this is a single case report, it appears that hemodialysis does not remove baclofen effectively.

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Title: Physical exam findings in chronic nitrous oxide abuse

Category: Toxicology

Keywords: nitrous oxide abuse, neurologic findings, physical exam (PubMed Search)

Posted: 8/13/2020 by Hong Kim, MD
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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: 

  1. Truncal ataxia
  2. Decreased vibratory sensation and proprioception in lower extremities
  3. Impaired coordination and rapid alternative movements
  4. Lhermitte’s sign: paresthesia of the upper and lower extremities associated with flexion of the head/neck.
  5. Rossolimo’s sign: exaggerated flexion of the toes when the tips of the toes are percussed


Title: "Tianna Red" - Tianeptine, a new medication of abuse?

Category: Toxicology

Keywords: tianeptine, clinical characteristics, poison center (PubMed Search)

Posted: 7/23/2020 by Hong Kim, MD
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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

  • 48 cases of tianeptine exposure were identified from January 1, 2015 to March 15, 2020 from a single poison center
  • 37 cases (77%) occurred from May 2019 to March 2020.

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

  • Tianeptine exposure is increasing in the US .
  • Intoxication frequently results in lethargy and/or agitation.

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Question

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

 

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Title: Carbon monoxide poisoning increases the risk of PE/DVT

Category: Toxicology

Keywords: Carbon monoxide poisoning, PE, DVT (PubMed Search)

Posted: 6/25/2020 by Hong Kim, MD
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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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Title: Case: 27 year old with hydroxychloroquine overdose

Category: Toxicology

Keywords: hydroxychloroquine toxicity, overdose (PubMed Search)

Posted: 6/11/2020 by Hong Kim, MD
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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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Title: Riot Control Agents - submitted by Jake Danoff

Category: Toxicology

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

Posted: 6/4/2020 by Hong Kim, MD
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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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Title: What is the cause of his burn?

Category: Toxicology

Keywords: Tox image, skin (PubMed Search)

Posted: 5/14/2020 by Hong Kim, MD
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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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Title: Disinfectants!

Category: Toxicology

Keywords: antiseptics, disinfectants, sterilants (PubMed Search)

Posted: 4/30/2020 by Hong Kim, MD
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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.



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

Category: Toxicology

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

Posted: 4/23/2020 by Hong Kim, MD
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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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Title: What is the case fatality rate after cyclopeptide-mushroom poisoning.

Category: Toxicology

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

Posted: 4/2/2020 by Hong Kim, MD
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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.


Title: Can acetaminophen cause methemoglobinemia?

Category: Toxicology

Keywords: acetaminophen overdose, methemoglobinemia (PubMed Search)

Posted: 3/19/2020 by Hong Kim, MD
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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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Title: Predictors of mortality in Metformin associated lactic acidosis

Category: Toxicology

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

Posted: 2/12/2020 by Hong Kim, MD
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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.