UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: Methadone is Cardioprotective?

Keywords: methadone (PubMed Search)

Posted: 10/18/2012 by Fermin Barrueto, MD (Updated: 5/29/2023)
Click here to contact Fermin Barrueto, MD

Many who work in urban EDs and have a patient population that has a high rate of methadone use have probably wondered - why don't I see many STEMIs in the ED?

One study has actually attempted to answer the question - is methadone cardioprotective? Comparing 98 decedents with known long-term methadone exposure and compared autopsy coronary artery findings to match controls without, there was significant decrease in incidence of severe CAD:

5/98 Methadone Patients post-mortem had severe CAD vs 16/97 match controls

Better than a baby ASA, who knew?

[I thank Dr. Hoffman for citing this article to me]



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Category: Toxicology

Title: The case for prehospital charcoal administration

Keywords: charcoal, prehospital, EMS, gastrointestinal decontamination (PubMed Search)

Posted: 10/9/2012 by Bryan Hayes, PharmD (Emailed: 10/11/2012) (Updated: 10/11/2012)
Click here to contact Bryan Hayes, PharmD

Activated charcoal is most effective if given within 1 hour of overdose.

Prehospital administration of charcoal can be challenging, but may save significant time compared to waiting until arrival to the ED. The patient has to be transported by EMS, registered, seen by a provider, order for charocal placed...

Two studies evaluated the time difference between prehospital and hospital administration of GI decontamination.

  • Study 1 found median time to activated charcoal in the ED was 82 minutes.
  • Study 2 found mean time to activated charcoal by EMS was 5 minutes, compared to 51 if held until arrival to ED.

Bottom line: Don't underestimate the amount of time that goes by before you evaluate non-crashing patients upon arrival to the ED. If the story supports an overdose and the patient doesn't have contraindications for receiving charcoal, recommend it be given in the prehospital setting for greatest potential benefit.

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Category: Toxicology

Title: Pharmaceutical Additives - Propylene Glycol

Keywords: propylene glycol, lorazepam, phenytoin (PubMed Search)

Posted: 10/4/2012 by Fermin Barrueto, MD (Updated: 5/29/2023)
Click here to contact Fermin Barrueto, MD

Ever have that alcholic who requires lorazapam doses that start to approach 10mg? 20mg? or even higher. The next step is usually a lorazepam infusion and then send them to the ICU. In the ICU,  the patient develops an unexplained anion gap lactic acidosis.

Check a Lactate - lorazepam has 80% propylene glycol (PG). PG is metabolized to lactate which can accumulate when a lorazepam infusion at an elevated dose is running constantly.  Hypotension, bradycardia and even other EKG changes have been reported. Simply discontinue the infusion and assess your acid-base status. 

Other IV meds that contain PG:

lorazepam - 80% PG

Phenytoin - 40% PG

Phenobarbital - 67.8%

Diazepam - 40% PG

Category: Toxicology

Title: Cannabinoid hyperemesis

Keywords: Cannabinoid,hyperemesis, marijauna (PubMed Search)

Posted: 10/4/2012 by Ellen Lemkin, MD, PharmD (Updated: 5/29/2023)
Click here to contact Ellen Lemkin, MD, PharmD


  • Is associated with chronic use of marijuana

  • Patients typically present with severe, recurrent nausea, vomiting, and abdominal pain, usually in the morning

  • Temporary relief of symptoms is achieved by taking hot showers or baths

  • Diagnostic work up is negative

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Just when you think buying organic protects you from chemicals and pesticide, along comes the studies detecting arsenic in rice products and specficially in organic foods with brown rice organic sweetener. An organic toddler milk formula reportedly had 6x EPA standards for safe drinking water limit.

The more toxic arsenic is the inorganic arsenic which can cause neuropathy but after chronic exposure can cause a classic arsenic keratosis - see attached pic. The inorganic is seen commonly in seafood and is more easily excreted by the body. Unfortunately, in the study referenced here, inorganic As was the predominant type.




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arsenickeratosis.jpg (129 Kb)

Category: Toxicology

Title: Cyanide from Smoke Inhalation in Enclosed-Space Fires

Keywords: cyanide, smoke inhalation, enclosed-space fire, carbon monoxide (PubMed Search)

Posted: 9/7/2012 by Bryan Hayes, PharmD (Emailed: 9/13/2012) (Updated: 9/13/2012)
Click here to contact Bryan Hayes, PharmD

Carbon monoxide (CO) and hydrogen cyanide (HCN) are two of the main gases causing injury and death from smoke inhalation in fire victims. During the first phase of a fire, and prior to depletion of oxygen reserves and subsequent production of CO, formation of HCN from the thermal breakdown of nitrogen-containing materials may be the primary cause of lethal poisoning in an enclosed-space fire.

A recent, retrospective, observational study from Poland assessed the prevalence of toxic HCN exposure in victims of enclosed-space fires.

Important findings:

  • Of the 285 patients who died, 169 (59%) had detectable cyanide blood levels. 82% also had elevated carboxyhemoglobin (COHb) levels.
  • Of the 40 patients who survived, 20 (50%) had detectable cyanide blood levels. All 20 had elevated COHb levels.

Conclusion: The high prevalence of coincident HCN concentrations and COHb levels in victims of enclosed-space fires emphasises the need to suspect HCN as a co-toxin in all persons rescued from fire who show signs and symptoms of respiratory distress.

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Category: Toxicology

Title: Intermediate Syndrome

Keywords: organophosphates, intermediate syndrome (PubMed Search)

Posted: 9/6/2012 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD


  • Exposure to organophosphates can lead to “intermediate syndrome.”
  • It is a syndrome characterized by weakness of neck flexors and proximal limbs, cranial nerve palsies, and respiratory muscle weakness, which can lead to respiratory paralysis.
  • It follows acute cholinergic syndrome and precedes a delayed neuropathy, thus it is an “intermediate syndrome,” typically developing 24-96 hours post exposure.
  • The pathophysiology of IMS remains unclear.
  • Serum cholinesterase levels and electrophysiological studies are helpful in confirming the diagnosis.
  • With supportive therapy, including artificial ventilation, complete recovery occurs within 5-18 days.

Category: Toxicology

Title: The Toxicology of Steve Jobs

Keywords: LSD, hashish, marijuana, jobs (PubMed Search)

Posted: 8/30/2012 by Fermin Barrueto, MD (Updated: 5/29/2023)
Click here to contact Fermin Barrueto, MD

I was reading the biography of Steve Jobs looking for incredible insights into leadership and innovation. I have realized that you basically have to be a genuis and it doesn't matter what you do. His favorite drug was LSD which he believed was necessary to improve creativity and innovation. His description of the hallucinations confirm that he was taking this drug.

We describe LSD hallucinations as a crossing of the senses or "synesthesias" - you hear the color blue, you see the smell of roses.

Steve Jobs describes a moment in a wheat field while on LSD and (paraphrasing from the biography) ..." the wheat was playing Bach beautifully"

If you have a patient describing this type of hallucination you can almost be guaranteed that they have taken LSD or some other tryptamine.

Category: Toxicology

Title: L-Carnitine for Valproic Acid - not just for OD

Keywords: valproic acid, carnitine (PubMed Search)

Posted: 8/23/2012 by Fermin Barrueto, MD (Updated: 5/29/2023)
Click here to contact Fermin Barrueto, MD

Patients that experience altered mental status (specifically lethargy) and are on valproic acid - check a serum ammonia level regardless if it is an overdose or just therapeutically on VPA.

If the ammonia is elevated in combination with the mental status change consider administration of L-carnitine either po or IV. It will lower the ammonia and improve the mental status  within hours.

High risk patients for hyperammonia who therapeutically take VPA are certain pediatric patients that experience malnutrition, have seizure disorder and are on multiple seizure medications.



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Category: Toxicology

Title: Times When a Subtoxic 4-Hour Acetaminophen Level May Need Repeating

Keywords: acetaminophen, Rumack-Matthew nomogram, diphenhydramine, opioid (PubMed Search)

Posted: 8/8/2012 by Bryan Hayes, PharmD (Emailed: 8/9/2012) (Updated: 8/9/2012)
Click here to contact Bryan Hayes, PharmD

There is a growing recognition of patients who have a subtoxic acetaminophen level at the 4-hour mark, but then still go on to have a toxic level later.

This is concerning in that we usually can exclude the chance for toxicity if the 4-hour, post-ingestion level is < 150 mcg/mL following an acute ingestion (plotted on Rumack-Matthew nomogram).

It still is not clear exactly what subset of patients need to have a second level drawn, but a recurring theme seems to be ingestion of acetaminophen in combination with agents that slow GI motility, such as diphenhydramine or opioids. It may be worth ordering a second APAP level (possibly at 8 hours) in patients ingesting these prodcuts.

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Category: Toxicology

Title: Ethanol Withdrawal

Keywords: CIWA, alcohol, withdrawal (PubMed Search)

Posted: 7/26/2012 by Fermin Barrueto, MD (Updated: 5/29/2023)
Click here to contact Fermin Barrueto, MD

CIWA-Ar (Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised)

The use of a scoring system for the disposition of an ethanol withdrawal patient can be helpful. The CIWA-Ar Score can guide both treatment in the ED as well as admission versus discharge. Most studies have verified that a score of <8 can be treated outpatient; 8-15 requires treatment and >15 wil require admission/IV benzodiazepines.

N/V: 0-7 (None to Constant N/V)

Tremor: 0-7 (None to Severe even with arms not extended)

Sweats: 0-7 (None to Drenching Sweats)

Anxiety: 0-7 (None to panic attack/delirium)

Agitation: 0-7 (None to pacing/thrashing during interview)

Tactile Disturbance: 0-7 (Mild itching to Continuous Hallucinations)

Auditory Disturbances: 0-7 (None to Continuous Hallucinations)

Visual Disturbances: 0-7 (None to Continuous Hallucinations)

Headache: 1-7 (Miild to Extremely Severe)

Orientation: 0-4

Go to this website to see the actual tool and how it should be administered:

Category: Toxicology

Title: Leukoencephalopathy from levamisole adulterant in cocaine (and heroin)

Keywords: cocaine, levamisole, leukoencephalopathy (PubMed Search)

Posted: 7/10/2012 by Bryan Hayes, PharmD (Emailed: 7/12/2012) (Updated: 7/12/2012)
Click here to contact Bryan Hayes, PharmD

Levamisole is a pharmaceutical with anthelminthic and immunomodulatory properties that was previously used in both animals and humans to treat inflammatory conditions and cancer.

It has been identified as a cocaine adulterant in the U.S. since 2003, with the DEA estimating that by 2009 up to 70% of cocaine seized contained levamisole.

Leukopenia, agranulocytosis, and vasculitis are well known complications of levamisole use.

One important complication to keep in mind is the possibility of multifocal inflammatory leukoencephalopathy (MIL). Although no formal case of leukoencephalopathy in the setting of cocaine use has yet been reported, various neurological side effects were described with levamisole therapy, the most concerning complication being MIL.

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No one treatment has demonstrated consistency of pain relief from jellyfish stings over all species; conversely, a treatment for one species may worsen an envenomation from another.

Deionized water, seawater, meat tenderizer, and urea treatment do not appear to produce any improvement in pain sensation.

Ammonia, acetic acid, and ethanol may cause an increased stinging sensation, and in most species vinegar may cause nematocyst discharge.

Application of topical lidocaine reduced the local sensation of pain (10% and 15% produced immediate pain relief), and hot water results in pain relief in the majority of patients tested.

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Category: Toxicology

Title: Drug-Induced Autoimmune Thrombocytopenia

Keywords: thrombocytopenia, sulfa, bactrim (PubMed Search)

Posted: 6/28/2012 by Fermin Barrueto, MD (Updated: 5/29/2023)
Click here to contact Fermin Barrueto, MD

Though an uncommon event, Drug-Induced Autoimmune thrombocytopenia occurs in a variety of drugs. Having recently diagnosed a patient that was receiving the "double-dose" bactrim for an MRSA abscess, it is worth mentioning the other drugs that have been reported to do it. Platelet count can go down to lethal levels and result in death due to the coagulopathy. Treatment is effective with platelets and no contraindication like in TTP.

Drugs that have been reported to do it:

abciximab, acetaminophen, amiodarone, amphotericin B

Carbamazepine, danazol, diclofenac, digoxin

Methyldopa, procainamide

Rifampin, trimethoprim-sulfamethoxazole, vancomycin

Category: Toxicology

Title: Transplant Drugs - Cyclosporine and Tacrolimus

Keywords: transplant, cyclosporine, tacrolimus (PubMed Search)

Posted: 6/21/2012 by Fermin Barrueto, MD (Updated: 5/29/2023)
Click here to contact Fermin Barrueto, MD

Transplant patients are the norm now in the ED. Their drug lists are immense and are usually on some form of immunosuppression to prevent rejection of the transplanted organ. Two common medications are cyclosporine and tacrolimus. They share many adverse effects like hepatotoxicity, nephrotoxicity and hypertension. Here is the mechanism of action and some unique adverse effects to these powerful immunosuppressants (there are many more so be wary):

1) Cyclosporine - suppresses T-cell activation and growth. Unique toxicity - painful neuropathy of the fingertips and toes, cortical blindness

2) Tacrolimus - simiar to cyclosporine but actually hampers T-cell communication/signal transduction. Unique toxicity - can also cause cortical blindness but is also known to cause diabetes/hyperglycemiad

Category: Toxicology

Title: Azithromycin and the Risk of Cardiovascular Death

Keywords: azithromycin, cardiovascular, death (PubMed Search)

Posted: 6/12/2012 by Bryan Hayes, PharmD (Emailed: 6/14/2012) (Updated: 6/15/2012)
Click here to contact Bryan Hayes, PharmD

  • Several macrolide antibiotics can cause QTc prolongation and dysrhythmias (e.g., erythromycin), but azithromycin is thought to have little cardiotoxicity.
  • A cohort of patients taking azithromycin was compared to those taking no antibiotics, amoxicillin, ciprofloxacin, or levofloxacin.
  • When compared to no antibiotics, amoxicillin, and ciprofloxacin, azithromycin was associated with a small but significant increased risk of cardiovascular death. Azithromycin was similar to levofloxacin.
  • Important points:
    • Increased risk translates to 47 additional deaths per 1 million prescriptions.
    • Increased risk only occurs during the 5 day course and does not carry on after discontinuation.
    • Patients most likely to die were in the highest risk category based on preexisting cardiovascular diseases (245 deaths per 1 million prescriptions).
  • Bottom line: Patients may start asking about this study finding when given a prescription for azithromycin. Although a small risk, it may be prudent to prescribe an alternative if patients have preexisting cardiovascular disease.


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Category: Toxicology

Title: Vitamin K: not necessary for INR 4.5 to 10?

Keywords: Warfarin,vitamin K,coagulation,INR,supratherapeutic (PubMed Search)

Posted: 6/7/2012 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

It may not be necessary to give oral vitamin K to patients that are not bleeding that have INRs between 4.5 and 10.

Patients who were supratherapeutic on warfarin were randomized to vitamin K 1.25 mg (n=355) versus placebo (n=369).

In the 90 days after enrollment, 15.8% of patients allocated to vitamin K and 16.3% allocated to placebo had a bleeding event. Major bleeding events occurred in 9 patients in the vitamin K group and 4 in the placebo.

Thromboembolic events occurred in 1.1% of patients in the vitamin K group, compared to 0.8% of patients in the placebo group. An equal number of patients died in each group (n=7).

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Category: Toxicology

Title: Nitrous Oxide

Keywords: Nitrous Oxide (PubMed Search)

Posted: 5/24/2012 by Fermin Barrueto, MD (Updated: 5/29/2023)
Click here to contact Fermin Barrueto, MD

Nitrous Oxide(N2O) is a common gas utilized to assist with procedural sedation especially in the pediatric population and dental offices. It has a long track history of safety but also has been abused.

N2O is 35x more solube in blood than N2. This means any air-filled space can have pressure increase thus complications like pneumothorax, TM rupture and bowel distention can occur.

When abused chronically can cause bone marrow suppression, B12 deficiency and resulting in polyneruopathy.

On the street, "whip its" are N2O from whipped cream containers. Balloons filled with N2O are inhaled which combine nitrous oxide and hypoxia effects.

Category: Toxicology

Title: Vitamins - Which Ones Have Toxicity?

Keywords: vitamins (PubMed Search)

Posted: 5/17/2012 by Fermin Barrueto, MD (Updated: 5/29/2023)
Click here to contact Fermin Barrueto, MD

More and more people are going to holistic medicine and "naturopaths". These have been an interesting source of toxicology case reports due to therapeutic misadventures. Vitamins have been an ever increasing adjunct to these health philosophies. The following are the vitamins and their related toxicity in overdose:

Vitamin A: Pseudotumor cerebri, increase ICH, hair thinning, hepatotoxicity

Vitamin D: Hypercalcemia

Vitamin E: can antagonize vitamin K particularly in vitamin K deficient people, could result in coagulopathy

Vitamin K: problem if supplement contains this and patient on coumadin, ask patient

Vitamin C: Association with increased kidney stones though controversial




Category: Toxicology

Title: Elevated Lactates in Ethylene Glycol Poisoning?

Keywords: lactate, lactic acid, ethylene glycol (PubMed Search)

Posted: 5/9/2012 by Bryan Hayes, PharmD (Emailed: 5/10/2012) (Updated: 6/15/2012)
Click here to contact Bryan Hayes, PharmD

  • Ethylene glycol can result in elevated lactate concentrations secondary to hypotension and organ failure in severely poisoned patients. However, lactate production by these mechanisms tends to result in serum concentrations less than 5 mmol/L.

  • Unfortunately, higher lactate levels don't necessarily rule out ethylene glycol. The glycolate metabolite causes a false-positive lactate elevation when measured by some analyzers, particularly with whole blood arterial blood gas analyzers. Specific models implicated include: ABL 625, Radiometer ABL 700, Beckman LX 20, Chiron 865, Bayer (formerly Chiron) 860, Rapidlab (Bayer) 865, Integra and to a lesser extent, Hitachi 911 analyzers, but not the Vitros 950 or Vitros 250.

  • The degree of lactate elevation directly correlates with the concentration of glycolate present, and the artifact probably results from the lack of specificity of the lactate oxidase enzyme used in these machines.

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