UMEM Educational Pearls - Toxicology

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

Category: Toxicology

Keywords: valproic acid, carnitine (PubMed Search)

Posted: 8/23/2012 by Fermin Barrueto (Updated: 12/5/2025)
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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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Title: Times When a Subtoxic 4-Hour Acetaminophen Level May Need Repeating

Category: Toxicology

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

Posted: 8/8/2012 by Bryan Hayes, PharmD (Updated: 8/9/2012)
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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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Title: Ethanol Withdrawal

Category: Toxicology

Keywords: CIWA, alcohol, withdrawal (PubMed Search)

Posted: 7/26/2012 by Fermin Barrueto (Updated: 12/5/2025)
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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:

http://www.regionstrauma.org/blogs/ciwa.pdf



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

Category: Toxicology

Keywords: cocaine, levamisole, leukoencephalopathy (PubMed Search)

Posted: 7/10/2012 by Bryan Hayes, PharmD (Updated: 7/12/2012)
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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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Title: Drug-Induced Autoimmune Thrombocytopenia

Category: Toxicology

Keywords: thrombocytopenia, sulfa, bactrim (PubMed Search)

Posted: 6/28/2012 by Fermin Barrueto (Updated: 12/5/2025)
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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



Title: Transplant Drugs - Cyclosporine and Tacrolimus

Category: Toxicology

Keywords: transplant, cyclosporine, tacrolimus (PubMed Search)

Posted: 6/21/2012 by Fermin Barrueto (Updated: 12/5/2025)
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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



Title: Azithromycin and the Risk of Cardiovascular Death

Category: Toxicology

Keywords: azithromycin, cardiovascular, death (PubMed Search)

Posted: 6/12/2012 by Bryan Hayes, PharmD (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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Title: Vitamin K: not necessary for INR 4.5 to 10?

Category: Toxicology

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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Title: Nitrous Oxide

Category: Toxicology

Keywords: Nitrous Oxide (PubMed Search)

Posted: 5/24/2012 by Fermin Barrueto (Updated: 12/5/2025)
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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.



Title: Vitamins - Which Ones Have Toxicity?

Category: Toxicology

Keywords: vitamins (PubMed Search)

Posted: 5/17/2012 by Fermin Barrueto (Updated: 12/5/2025)
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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

 

 

 



Title: Elevated Lactates in Ethylene Glycol Poisoning?

Category: Toxicology

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

Posted: 5/9/2012 by Bryan Hayes, PharmD (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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Title: Dexmedetomidine (Precedex)

Category: Toxicology

Keywords: sedation, dexmedetomidine (PubMed Search)

Posted: 4/26/2012 by Fermin Barrueto (Updated: 12/5/2025)
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Dexmedetomidine is an alpha2-agonist that has a similiar mechanism of action to clonidine. Short half-life and no respiratory depression make it possibly more effective than propofol in procedural sedation. Cost/Availability are the biggest barriers. Transient bradycardia is also possible but the actual incidence  of clinically significant bradycardia is not yet elucidated.

I am still awaiting the first emergency department study looking at dexmedetomidine for procedural sedation.

A recent article actually brought up the possibility of utilizing it intranasally which could have some tantalizing pediatric applications.

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Title: Maternal Opioid Use and Breast-Fed Infants

Category: Toxicology

Keywords: Opioid, breastfeeding, breast milk, newborn, infant (PubMed Search)

Posted: 4/5/2012 by Bryan Hayes, PharmD (Updated: 4/12/2012)
Click here to contact Bryan Hayes, PharmD

Over the last few decades, the rate of breastfeeding has increased steadily in the developed countries of the world. During this time, opioid  use in the general population has steadily increased as well. Despite this, clinicians remain unclear whether opioid use is safe during breastfeeding.

A recent article reviewed the production of breast milk, the transfer of xenobiotics from blood to milk, the characteristics that alter xenobiotic breast-milk concentrations, and the evidence of specific common opioids and infant toxicity.
 
Conclusion: The short-term maternal use of prescription opioids is usually safe and infrequently presents a hazard to the newborn.
 
 
Bonus app suggestion:
Continuing with the theme of the week, here is a nifty, free tox app for the iPhone called Emergency Toxicology. It is rudimentary and pretty basic, but it is a good starting tool.
http://itunes.apple.com/us/app/emergency-toxicology/id504893108?mt=8
iPhone Screenshot 1

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Protamine for enoxaparin overdose

  • Protamine may be used to treat severe cases of hemorrhage in enoxaparin overdose
  • Protamine reverses the prolonged aPTT, but fails to completely reverse the anti-Xa effect (reverses about 60%)
  • Administer protamine by slow IV to equal the dose of enoxaparin injected: (1:1 ratio) 
  • if < 8 hours after last dose enoxaparin, give 1 mg protamine per 1 mg enoxaparin;
  • if 8-12 hours after last dose enoxaparin, give 0.5 mg protamine per 1 mg enoxaparin;
  • if >12 hours after last dose of enoxaparin,  protamine is not required


Title: Nebulized epinephrine for Smoke Inhalation

Category: Toxicology

Keywords: epinephrine, carbon monoxide, smoke inhalation (PubMed Search)

Posted: 3/29/2012 by Fermin Barrueto (Updated: 12/5/2025)
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Animal studies can pave the way for new clinical treatment modalities. In the setting of lung injury due to smoke inhalation, one of the problems (if you can get the ET tube in) are the elevated ventilatory pressures due to the massive edema. In this sheep model of smoke inhalation, nebulized epinephrine improved ventilatory pressures, PaO2/FiO2 ratio and pulmonary shunting.

We may have these sheep to thank for this new treatment.

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Title: Had enough of coumadin and clopidogrel wannabe's?

Category: Toxicology

Keywords: ticagrelor, brillinta, xarelto, pradaxa (PubMed Search)

Posted: 3/15/2012 by Fermin Barrueto (Updated: 12/5/2025)
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Coumadin Wannabe's - have indication non-valvular atrial fibrillation

1) Dabigatran (Pradaxa) 

2) Rivaroxaban (Xarelto)

Clopidogrel Wannabe's - both are antiplatelets

1) Ticagrelor (Brilinta)

2) Prasugrel (Effient)

If you were looking for the first case reports of lethal hemorrhage due to pradaxa that could not be reversed - look no further. One patient fall from standing dies from ICH and another death in a spine trauma patient on pradaxa. I am waiting for the first epidural hematoma due to pradaxa, xarelto, etc in ED. Watch out! :

 

  1: Garber ST, Sivakumar W, Schmidt RH. Neurosurgical complications of direct  thrombin inhibitors-catastrophic hemorrhage after mild traumatic brain injury in  a patient receiving dabigatran. J Neurosurg. 2012 Mar 6.       2: Truumees E, Gaudu T, Dieterichs C, Geck M, Stokes J. Epidural Hematoma &  Intra-operative Hemorrhage in a Spine Trauma Patient on Pradaxa® [Dabigatran].  Spine (Phila Pa 1976). 2012 Feb 16. 

 



Title: Pressure Immobilization for Crotalid snake envenomation

Category: Toxicology

Keywords: crotalinae, snake, pressure immobilization, envenomation (PubMed Search)

Posted: 3/4/2012 by Bryan Hayes, PharmD (Updated: 3/8/2012)
Click here to contact Bryan Hayes, PharmD

Pressure immobilization involves wrapping the entire extremity with a bandage and then immobilizing the extremity with a splint. It is a technique routinely employed in the pre-hospital management of neurotoxic snakes in Australia.

A position statement was recently published by several international toxicology societies regarding the utility of pressure immobilization after North American Crotalinae snake envenomation (e.g., Copperheads, Timber rattlesnakes, Cottonmouths).

"Available evidence fails to establish the efficacy of pressure immobilization in humans, but indicates the possibility of serious adverse events arising from its use. The use of pressure immobilization for the pre-hospital treatment of North American Crotalinae envenomation is NOT recommended."

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Title: Octreotide for sulfonylurea overdose- updated

Category: Toxicology

Keywords: Octreotide, sulfonylurea, glucose, insulin (PubMed Search)

Posted: 3/1/2012 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

 

  • Sulfonyurea overdose is associated with hypoglycemia, which may be delayed and prolonged.
  • Treatment with dextrose results in hyperglycemia, which potentiates insulin release from the pancreas, resulting in recurrent hypoglycemia.
  • Octreotide mimics somatostatin, which suppresses the secretion of glucagon and insulin, among others.
  • Octreotide binds with somatostatin receptors, closing calcium channels, preventing the influx of calcium and subsequent insulin release.
  • The dose is 100 mcg SUBCUTANEOUSLY, repeated every 8 hours as needed.

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Title: IM Midazolam vs IV Lorazepam for Seizure Pre-Hospital

Category: Toxicology

Keywords: midazolam, lorazepam (PubMed Search)

Posted: 2/23/2012 by Fermin Barrueto (Updated: 12/5/2025)
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You have seen the study comparing diazepam to lorazepam IV for the cessation of seizures. Lorazepam one that one. Now, for prehospital status epilepticus midazolam IM went head to head with IV lorazepam to see which would stop seizure more quickly.

This study was more about the practicality of starting an IV than it was of the pharmacokinetics or onset of action of a particular benzodiazepine. It was a large enough study to warrant publication in New Engl J Med last month and is worth noting.

Subjects whose seizures ceased before ED arrival (median):

Time to active treatment: 1.2 min IM Midazolam group;  4.8 min IV Lorazepam group

Median times active treatment to cessation of SZ:  3.3 min IM Midazolam and 1.6 min IV Lorazepam

Safety was equal in both groups. This study validates EMS initiating therapy with IM midazolam for the cessation of seizures while intravenous access is being attempted. 

 

 

 

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