UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: How to Give Physostigmine

Keywords: anticholinergic, physostigmine (PubMed Search)

Posted: 11/18/2010 by Fermin Barrueto, MD (Updated: 9/27/2022)
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In the setting of a patient suffering from an anticholinergic overdose with hallucinations/agitation, it may be beneficial to administer the antidote: Physostigmine. Many hesitate simply because they have never administered before or there may be doubt in the diagnosis. Here is the skinny:

1) Anticholinergic OD seen in following meds: diphenhydramine (Benadryl), dimenhydrinate (Dramamine), scopolamine, benztropine (Cogentin), some plants like datura stromonium (thorn apple)

2) Physostigmine 1mg IV slowly over a REAL 5 min. Administer to fast and patient may seize. Maximum dose of 2mg IV.

3) Contraindications: suspicion of TCA OD (anectdotal and from old case report) - screening EKG should be done prior to administration of physostigmine. Also glaucoma, closed angle, obstructive uropathy.

Remember your clinical endpoint needs to be measurable, thus hallucinations and agitation should be reversed. No indication if the patient is only experiencing dry mouth or other more mild anticholinergic symptoms.


Category: Toxicology

Title: Hyperbaric Therapy for Hydrogen Peroxide Poisoning

Keywords: hydrogen peroxide, embolism, hyperbaric (PubMed Search)

Posted: 11/11/2010 by Bryan Hayes, PharmD (Updated: 9/27/2022)
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  • Ingestion of concentrated hydrogen peroxide (H2O2) has been associated with venous and arterial gas embolic events, hemorrhagic gastritis, gastrointestinal bleeding, shock, and death.
  • Although H2O2 is generally considered a benign ingestion in low concentrations (OTC is 3%), case reports have described serious toxicity following high concentration exposures.
  • Hyperbaric oxygen (HBO) has been used with success in managing patients suffering from gas embolism with and without manifestations of ischemia.
  • A recent poison center case record review confirmed previous findings.
    • It identified 11 cases of portal gas embolism. In 10 cases 35% H2O2 was ingested and in 1 case 12% H2O2 was ingested. All abdominal CT scans demonstrated portal venous gas embolism in all cases. Hyperbaric treatment was successful in completely resolving all portal venous gas bubbles in nine patients (80%) and nearly resolving them in two others. Ten patients were able to be discharged home within 1 day, and one patient had a 3.5-day length of stay.
  • Bottom Line: In a patient with a history of hydrogen peroxide ingestion, have a low threshold for CT scan.  HBO therapy is an effective treatment modality.

French LK, et al. Hydrogen peroxide ingestion associated with portal venous gas and treatment with hyperbaric oxygen: a case series and review of the literature. Clinical Toxicology 2010;48:533–38.

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Category: Toxicology

Title: New anticoagulant: Dabigatran

Keywords: Dabigatran, warfarin, anticoagulant, thrombin inhibitor (PubMed Search)

Posted: 11/4/2010 by Ellen Lemkin, MD, PharmD
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Dabigatran

  • the first new ORAL anticoagulant in over 50 years
  • is a direct thrombin inhibitor
  • Indicated for reducing strokes and systemic embolism in patients with a fib
  • DOES NOT need monitoring and frequent dose adjustments
  • Has fewer drug and food interactions than warfarin
  • Costs about $8/day (more than the cost of warfarin PLUS monitoring)
  • Both warfarin and dabigatran have a similar OVERALL bleeding risk, but warfarin causes more intracranial bleeding and dabigatran more GI bleeding

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Category: Toxicology

Title: Mushroom Toxicity - Clinical Approach

Keywords: amanita, mushroom, poisoning (PubMed Search)

Posted: 10/28/2010 by Fermin Barrueto, MD (Updated: 9/27/2022)
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When a patient presents to the ED with a recent ingestion of a wild mushroom there are three very specific questions you must ask:

1) Exactly what time did you eat the mushroom?

2) Exactly what time did you begin vomiting/diarrhea/GI Sx in general?

3) Are there are more mushrooms that can be brought to ED for identification?

The reason the first two questions are critically important is it determines the total time of onset of toxicity. As a very general rule of thumb, delayed GI symptoms >6hrs is predictive of a possible lethal ingestion of a cyclopeptide containing mushroom like Amanita Phalloides. Immediate symptoms < 6hrs and even more so if within 2 hrs usually indicates ingestion of a nonlethal mushroom that causes GI distress (many mushrooms like Clitocybe nebularis)

Website with pics of the most poisonous mushrooms: 

http://scienceray.com/biology/botany/13-deadliest-mushrooms-on-the-planet/

There is a saying:

"There are old mushroom pickers and wise mushroom pickers but no old and wise mushroom pickers"


Category: Toxicology

Title: Intralipid - It Works Video

Keywords: intralipid (PubMed Search)

Posted: 10/21/2010 by Fermin Barrueto, MD (Updated: 9/27/2022)
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Take a look at this link - an incredible video of how effective Intralipid can be:
 
http://www.youtube.com/watch?v=B3au3aKU4oE
 

Category: Toxicology

Title: Intralipid for Drug Overdose

Keywords: Intralipid, fat emulsion (PubMed Search)

Posted: 10/14/2010 by Bryan Hayes, PharmD (Updated: 9/27/2022)
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Emerging evidence supports using intravenous fat emulsion (Intralipid) therapy for various drug overdoses, particularly those that are lipophilic.  Within seconds to minutes of administration, toxic cardiovascular effects are reversed, including return of spontaneous circulation in cardiac arrest patients.  Central nervous system effects also tend to improve.

Lipophilic agents for which there has been success include:

  • Calcium channel blockers (verapamil, diltiazem, amlodipine)
  • Beta blockers
  • Bupropion
  • Quetiapine
  • Lamotrigine
  • Sertraline
  • TCA's
  • Diphenhydramine

Bottom line: Consider intralipid therapy early in the course of a hemodynamically unstable patient with suspected overdose.  Give a bolus of 1.5 mL/kg of 20% lipid emulsion over 1-2 minutes.


Category: Toxicology

Title: Shellfish Poisoning

Keywords: amnestic, neurotoxic, paralytic, shellfish (PubMed Search)

Posted: 9/30/2010 by Fermin Barrueto, MD
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Although we may not be able to eat as much shellfish after the oil spill, there are still some left that can cause some interesting toxicity here in the USA. Shellfish act as vectors for the bacteria, virus etc that produces toxin thus not specific to one species of shellfish. There is a map attached that shows where shellfish poisoning occurs most. In the picture CFP=ciguatera, PSP=Paralytic and ASP=AmnesticC. Surprising the distribution and it will be interesting how the oil spill affects the distribution. Treatment for all of these is supportive with no known antidote and incidence increases during Red Tide months:

Tox Fish Map

  • Paralytic Shellfish Poisoning
    • Saxitoxin, potent, heat-stable, blocks fast sodium channels
    • Symptoms: Paresthesias, weakness, bulbar symptoms, blindness and paralysis (30m-2hrs after meal)
  • Amnestic Shellfish Poisoning (my favorite excuse for why I forget my anniversary)
    • Domoic acid build up created from Nitzchia spp (a marine diatom). This causes release of gluatamate thus causing excitotoxic nerve damage.
    • 1987 outbreak in Canada saw GI Sx in 24 hrs followed by HA, SZ, memory loss - has been fatal

Attachments

US-toxinmap-circles-2009-web_86265.jpg (86 Kb)


Category: Toxicology

Title: Fentanyl Patch Abuse

Keywords: fentanyl (PubMed Search)

Posted: 9/16/2010 by Fermin Barrueto, MD (Updated: 9/18/2010)
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A fentanyl patch contains 100-fold more fentanyl in the reservoir than what is posted on the patch. For instance, 100mcg/hr patch will have over 10mg - thats milligrams - of fentanyl. This provides a rather large source for potential abuse. Overdose and deaths have occurred by patients in the following ways:

  1. Ingesting
  2. Placing in a cigarette and inhaling
  3. Inadvertent overdose by sleeping with an electric heating blanket and increasing absorption through the skin
  4. Steeping the patch in hot water
  5. Actually stealing the patches off of dead bodies in the morgue

 

It is the many

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Category: Toxicology

Title: Diagnosing Cyanide Poisoning with Lab Tests

Keywords: cyanide, lactate (PubMed Search)

Posted: 9/9/2010 by Bryan Hayes, PharmD (Updated: 9/27/2022)
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In the setting of acute cyanide poisoning, it is virtually impossible to obtain a timely cyanide level to help assess toxicity.  However, there are two diagnostic tests that can help confirm your diagnosis.

  1. Anion gap metabolic acidosis with elevated lactate
  2. Narrowing of the venous-arterial PO2 gradient

Remember cyanide halts cellular respiration meaning the cells cannot utilize oxygen.  Therefore, the venous PO2 should be about the same as the arterial PO2.  The cells then switch to anaerobic metabolism, thereby producing lactate.


Category: Toxicology

Title: Epinephrine Digital Injections

Keywords: Epinephrine, epi-pen, digital block, finger, ischemia (PubMed Search)

Posted: 9/2/2010 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

A recent study examined the effects of accidental digital epinephrine injection from auto-injectors. 127 cases with complete follow-up had the following effects:

  • no effects were reported in 10%
  • minor effects in 77%
  • moderate effects in 13%
  • major effects in 1 case

Pharmacologic vasodilators were used in 23%. Four patients had possible digital ischemia. All patients had complete resolution of symptoms, most within 2 hours. No patient was admitted, received hand surgery consultation, or had surgical care. 

Although this speaks for the safety of digital anesthesia using epinephrine, it underscores the importance of providing education to patients who are prescribed epinephrine auto-injectors.

 


 

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Category: Toxicology

Title: Caustic Exposures - Continued

Keywords: caustic (PubMed Search)

Posted: 8/26/2010 by Fermin Barrueto, MD (Updated: 9/27/2022)
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In a previous pearl we were discussing the need to perform EGD for any suicidal patient with a history of ingestion of a caustic to grade injury and assess chance of perforation and/or stricture formation. Suicidal patients are intentionally ingesting the caustic and can thus justify the risk/benefit ratio more easily than the pediatric unintentional ingestion. The concerned parent will bring the child in with a possible ingestion of a caustic. The container could be simply in the same room, spilled on the child and never be ingested. Even if ingested, the amount is less if the child tastes the caustic and will reflexively cause spitting. The literature is scant in regards to this type of patient but seems to point to this general algorithm:

Child displays 2 or more of the following symptoms there is enough evidence from case series that there will be a clinically signficant lesion found on EGD.

Vomiting, Drooling, Stridor, Presence of Oropharyngeal Burns

That being said, many clinicians would elect for EGD and assessment of airway with stridor alone. Do not be fooled into thinking if you see no oral lesions that there is no way the child ingested the caustic. Each case series showed a lack of correlation of physical exam findings to EGD findings.

 

 

 

 

 

 

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Category: Toxicology

Title: Sulfonylureas

Keywords: sulfonylureas,hypoglycemia (PubMed Search)

Posted: 8/19/2010 by Fermin Barrueto, MD (Updated: 9/27/2022)
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We will all get the patient presenting with low blood glucose on a regular basis. In general, barring any underlying infection, those who are insulin dependent can be corrected with IV dextrose and/or food and be discharged. Those on a sulfonylurea may experience repeated hypoglycemic episodes and require admission - perhaps even treatment with the antidote: octreotide.

Below is the duration of action and half-life of the sulfonylureas which illustrates the need for admission:

  • Chlorpropamide (Diabinase): Duration: 24-27hrs; t 1/2: 36hrs
  • Glipizide (Glucatrol): Duration 16-24hrs; t 1/2: 7hrs
  • Glipizide XL (Glucatrol XL): Duration 24hrs
  • Glyburide (Micronase others): Duration <24hrs; t 1/2 10hrs
  • Glimepride (Amaryl): Duration 16-24hrs; t1/2: 5-9hrs

Duration of action is the physiologic effect whereas the half-life is the pharmacokinetics of elimination of the drug. Often these two numbers are different for drugs. Do not let the half-life fool you into thinking it is safe to discharge a hypoglycemic patient on a sulfonylurea.


Category: Toxicology

Title: Cyproheptadine for Serotonin Syndrome

Keywords: serotonin syndrome, cyproheptadine (PubMed Search)

Posted: 8/12/2010 by Bryan Hayes, PharmD (Updated: 9/27/2022)
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If benzodiazepines and supportive care fail to improve agitation and correct vital signs, several case reports indicate the successful use of cyproheptadine, an antihistamine with nonspecific antagonist effects at 5-HT1A and 5-HT2A receptors.

Cyproheptadine is available in 4 mg tablets or 2 mg/5 mL syrup. When administered as an antidote for serotonin syndrome, an initial dose of 8-12 mg is recommended, followed by 2 mg every two hours until clinical response is seen. Cyproheptadine is only available in an oral form, but it may be crushed and given through a nasogastric tube.

Cyproheptadine may lead to sedation, but this effect is consistent with the goals of management. It may also produce transient hypotension due to the reversal of serotonin-mediated increases in vascular tone. Such hypotension usually responds to IV fluids. Cyproheptadine is rated category B for safety in pregnancy by the FDA.


Category: Toxicology

Title: Caustic Injury

Keywords: caustic (PubMed Search)

Posted: 7/29/2010 by Fermin Barrueto, MD (Updated: 9/27/2022)
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Ingestion of caustics can lead to immediate burns to mouth, esophagus, stomach as well as possible perforation. Months and years later, further complications are esophageal stenosis and increased incidence of esophageal carcinoma. The main benefit to EGD is to determine extent of injury within the esophagus. The lesions are graded much like a burn: 

Grade I: Mild burn, no risk for esophageal stenosis

Grade II: Moderate, if circumferential, patient is at risk for esophageal stenosis

Grade II: Eschar present, high risk of perforation as well as esophagel stenosis

You can make a case that all intentional-suicidal ingestions of caustics should undergo EGD since there should be some injury if ingestion truly occurred or at the least a higher probability. The difficult case is the pediatric unintentional ingestion. Utilizing clinical exam and history will assist with that determination - there is a little research to guide this decision (next pearl)

The attached picture is the post-mortem of a caustic injury showing grade II linear lesions in esophagus with eschar distally and in stomach (Grade III).


Category: Toxicology

Title: Anticholinergic or Sympathomimetic

Keywords: anticholinergic, sympathomimetic, pupil (PubMed Search)

Posted: 7/22/2010 by Michael Bond, MD (Updated: 7/24/2010)
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A patient arrives via EMS agitated with VS: P 140, BP 155/100, R 18, T 101F. There is an admitted drug exposure and you examine his eyes which are dilated. You shine the light in the eyes - if the pupil reacts, would that be consistent with anticholinergic or sympathomimetic toxidrome?

Answer: Anticholinergic exposure paralyzes pupillary constrictor muscles and causes dilated pupils that do not react to light. Think about when you go to the eye doctor's office. They put homoatropine in your eyes so that when they look with the slit lamp they can see the retina without interference from pupillary constriction. Sympathomimetic exposure like cocaine activates pupillary dilator muscles, the constrictors are still intact and will give a reflexive constriction to light.  This patient has reactive pupils and by the mere fact is in Baltimore probability dictates a sympathomimetic exposure like cocaine.

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Category: Toxicology

Title: Valproic Acid and the Antidote

Keywords: valproic acid, carnitine, ammonia (PubMed Search)

Posted: 7/15/2010 by Fermin Barrueto, MD (Updated: 9/27/2022)
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Valproic Acid (Depakote) is a drug that uniquely has the ability to raise serum ammonia concentrations. It is able to do this without raising liver er enzymes and it can occur in overdose or at therapeutic levels. Do not think of this in the context of hepatic encephalopathy. This a metabolic derangement caused by VPA.

  • Any patient with somnolence, lethargy, decreased responsiveness - order a serum ammonia level as well as Valproic acid level
  • If the serum ammonia is elevated in conjunction with altered mental status consider a trial of carnitine
  • L-carnitine is a safe drug that is used in nutritional supplementation. VPA and other anticonvulsants cause carnitine deficiency
  • Most effective dose is unknown but from a recent review: IV 100 mg/kg once, followed by infusions of 50 mg/kg (to a maximum of 3 g per dose) every 8 hours until patient improves, ammonia decreases

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Category: Toxicology

Title: Toxin-Induced Bradycardia with Hypotension

Keywords: bradycardia, hypotension, beta blocker, calcium channel blocker, clonidine (PubMed Search)

Posted: 7/7/2010 by Bryan Hayes, PharmD (Emailed: 7/8/2010) (Updated: 9/27/2022)
Click here to contact Bryan Hayes, PharmD

In a patient with toxin-induced bradycardia and hypotension, here is a quick differential to help identify the responsible substance:

  • Beta blockers
  • Calcium channel blockers
  • Cholinergics
  • Clonidine (and other alpha-2 agonists)
  • Digoxin (and other cardiac glycosides)
  • Opioids
  • Sedative hypnotics (such as benzodiazepines and barbiturates)

Less commonly seen causes include: magnesium, propafenone, and plant toxins (aconitine, andromedotoxin, veratrine).


Category: Toxicology

Title: Copperhead Snakebite

Keywords: copperhead, crofab (PubMed Search)

Posted: 6/24/2010 by Fermin Barrueto, MD (Updated: 9/27/2022)
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In the state of Maryland, the most common venomous snake is the copperhead. Though not as dangerous as the rattlesnake, it can still cause loss of function of limb and mortality in the pediatric patient.

Treatment has involved the use of CroFab (Protherics, Atlanta). This ovine derived monovalent immunoglobolin is actually made against the following snakes:

  • Eastern diamondback rattlesnake
  • Western diamondback rattlesnake
  • Mojave rattlsnake
  • Cottonmouth (Water moccasin)

Though efficacy has been shown with these snakes, we are hoping for cross-reactivity when we treat copperheads. There are case series and case reports (1) that have shown anectdotal improvement. We are still awaiting a real randomized controlled trial - may never happen.

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Category: Toxicology

Title: Physostigmine for Anticholinergic Poisoning

Keywords: physostigmine, anticholinergic (PubMed Search)

Posted: 6/10/2010 by Bryan Hayes, PharmD (Updated: 9/27/2022)
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Physostigmine has been used extensively in the fields of anesthesiology and emergency medicine.  The only use of physostigmine with sound scientific support is for the management of patients with an anticholinergic syndrome, particularly those without cardiovascular compromise who have an agitated delirium.  In this population, physostigmine has an excellent risk-to-benefit profile.

  • Try benzodiazepines first.  They last longer and may diminish the need for physostigmine.
  • Obtain ECG.  If there are signs of sodium channel blockade (QRS prolongation), do not use physostigmine.
  • Administer 1-2 mg via slow IV push/infusion over at least 5 minutes.
  • Have atropine available at the bedside.
  • Effects last about 1 hour.

Category: Toxicology

Title: Deadly in a Single Dose

Keywords: pediatrics, toxicology, antidepressant, antimalarial, antipsychotic, calcium channel, aspirin (PubMed Search)

Posted: 6/4/2010 by Ellen Lemkin, MD, PharmD (Updated: 9/27/2022)
Click here to contact Ellen Lemkin, MD, PharmD

There are a several classes of medications that can kill a toddler with a single dose. Toddlers are particularly susceptible due to their low weights and propensity to place everything in their mouths.


1. Calcium channel blockers
2. Camphor-containing rubs
3. Opioids/opiates
4. Oil of wintergreen/ aspirin
5. Cyclic antidepressants
6. Topical blood pressure patches (clonidine)
7. Eye drops and nasal sprays (oxymetazoline)
8. Sulfonylureas
9. Antimalarial drugs (cloroquine)

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