UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: Hydrogen Peroxide

Keywords: hydrogen peroxide (PubMed Search)

Posted: 12/22/2011 by Fermin Barrueto, MD (Updated: 5/25/2024)
Click here to contact Fermin Barrueto, MD

Generally H2O2 is available OTC at a concentration of 3-9% and used as an antiseptic. Toxicity is by two methods: local irritation like a caustic and gas formation - both directly correlating with the % concentration. Some interesting findings have occurred with this ingestion including:

1) Portal vein gas seen on CT

2) Arterialization of O2 resulting in CVA

3) Encephalopathy with cortical visual impairment

4) MRI showing b/l hemispheric CVAs

Even use of 3% H2O2 for wound irrgation has caused subcutaneous emphysema and O2 emboli.

Treatment: XR/CT/MRI may detect gas, if present in RV should be placed in Tredelenburg and carefully aspirated through a central venous catheter. Anectdotal case reports have used HBO therapy when patients were critically ill.(1)

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Category: Toxicology

Title: Warfarin management of ED patients

Keywords: warfarin, INR (PubMed Search)

Posted: 11/29/2011 by Bryan Hayes, PharmD (Emailed: 12/8/2011) (Updated: 12/8/2011)
Click here to contact Bryan Hayes, PharmD

A recent study highlighted the challenges we face managing ED patients on warfarin therapy. Some key observations about how we're doing: 

  • Only 71% of patients on warfarin had an INR checked
  • Nontherapeutic INRs were recorded for 49%; ED providers intervened to address these results in 21% of cases
  • 71% of patients with a supratherapeutic INR received an intervention compared with 9% of patients with a subtherapeutic INR
  • 30% of patients received or were prescribed potentially interacting medications
  • Recommendations for specific anticoagulation follow-up were documented for only 19% of all patients

Literature continues to show warfarin is the most dangerous medication for our patients. Meticulous monitoring and follow up will help us potentially avoid serious interactions and adverse events.

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Category: Toxicology

Title: High dose insulin in cardiogenic shock

Keywords: Insulin,beta blockers,calcium channel blockers (PubMed Search)

Posted: 12/1/2011 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

High dose insulin is recommended in treatment of beta-blocker and calcium channel blocker overdose. In a recent observational case series of cardiogenic shock, high dose insulin was evaluated for efficacy and safety.

 
The overdoses were primarily calcium channel and beta blockers, but included other agents
like tricyclic antidepressants.
  • Insulin doses were given at a maximum of 10 units/kg/hour.
  • Seven patients who were on vasopressors when enrolled were tapered off when placed on high dose insulin.
  • 11/12 patients lived and were discharged from the hospital.
  • Adverse effects included hypoglycemia (19 events) and hypokalemia (8).
Bottom line: High dose insulin, when used in doses up to 10 units/kg/hr allows avoidance of vasopressors, and appears to be effective in the treatment of toxin induced shock in this small case series.

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Category: Toxicology

Title: Toxic Epidermal Necrolysis

Keywords: Toxic, epidermal, necrolysis (PubMed Search)

Posted: 11/17/2011 by Fermin Barrueto, MD
Click here to contact Fermin Barrueto, MD

TEN is a rare, life-threatening dermatologic emergency characterized initially by erythema and tenderness. It is followed by a severe exfoliation that resembles a severe burn patient. Classically occurs within days of the exposure of the drug. Nikolsky's sign may be present - not pathognomonic.

The following is a short list of medications that can cause this lethal reaction:

allopurinol, bactrim, nitrofurantoin, NSAIDs, penicillin, phenytoin, lamotrigine, sulfasalazine

Treatment: transfer to a burn center may be needed, steroids are not generally recommended however immunomodulators are beginning to show promise - IVIG, cyclosporine and cyclophosphamide

 

See pic that is attached for example of the sloughing


Attachments

1111172057_TENPic.jpg (95 Kb)



Category: Toxicology

Title: Medication Causes of Idiopathic Intracranial Hypertension

Keywords: idiopathic intracranial hypertension, pseudotumor cerebri, tetracycline, vitamin a (PubMed Search)

Posted: 10/11/2011 by Bryan Hayes, PharmD (Emailed: 11/10/2011) (Updated: 11/10/2011)
Click here to contact Bryan Hayes, PharmD

Several medications have been linked to causing idiopathic intracranial hypertension (pseudotumor cerebri). Be sure to record an accurate medication history in patients you suspect of having this diagnosis.

  • Excessive doses of vitamin A
    • Other retinoids too: retinol, isotretinoin, and tretinoin
  • Tetracyclines (tetracycline, doxycycline, minocycline)
  • Growth hormone

Withdrawal of the offending agent will generally resolve the symptoms.



Category: Toxicology

Title: Salicylate Toxicity- Mechanism

Keywords: salicylate, aspirin, alkalosis, acidosis (PubMed Search)

Posted: 11/3/2011 by Ellen Lemkin, MD, PharmD (Updated: 5/25/2024)
Click here to contact Ellen Lemkin, MD, PharmD

Salicylates:

  • stimulate the respiratory center in the brainstem, causing respiratory alkalosis
  • interfere with the Krebs cycle, limiting ATP production, leading to an anaerobic metabolism
  • uncouple oxidative phosphorylation, causing accumulation of pyruvic and lactic acid and heat production, resulting in acidosis and hyperthermia
  • increase fatty acid metabolism, generating ketone bodies

Overall, this results in a mixed respiratory alkalosis and metabolic acidosis. 

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Category: Toxicology

Title: Methotrexate

Keywords: overdose, methotrexate (PubMed Search)

Posted: 10/27/2011 by Fermin Barrueto, MD (Updated: 5/25/2024)
Click here to contact Fermin Barrueto, MD

Methotrexate is a chemotherapeutic that is utilized in non-Hodgkin lymphoma and breast CA. It is also used as an immunosuppressant for rheumatoid arthritis and psoriasis. Finally, we see it used in the ED for the treatment of ectopic pregnancy. Overdose, often unintentional, can have a lethal outcome.

Toxicity: LFTs rise, N/V, stomatitis, mucositis, leukopenia, thrombocytopenia, renal failure

Antidote: Leukovorin (Folinic Acid)

Other Tx: Carboxypeptidase G2, Charcoal Hemoperfusion, HD (possible)



Carbon Monoxide Toxicity and Hyperbaric Oxygen Treatment

CO disrupts cellular function by several mechanisms at a
cellular/mitochondrial level.  Ultimately, these disruptions are
manifested as tissue hypoxia and hypoperfusion.
Initial symptoms may be subtle and nonspecific.  Be sure to ask about
CO exposure when evaluating “viral syndrome” or patients that present
with non-specific neurological complaints especially during fall and
winter months, when people first start using their heating, or after
power outages and generator use. Dysrhythmias, cardiomopathy, MI and
sudden cardiac arrest are reported in severe CO poisoning.

Lab studies- COHb, base excess, lactate and any other studies based on
presentation.

Supplemental oxygen is the cornerstone of treatment.   Oxygen
delivered at hyperbaric pressure (as opposed to sea-level) will
increase the rate of CO dissociation from hemoglobin, and mitigate
damage to cellular and mitochondrial function.

Definite Indications for HBOT:  Current evidence supports the use for
HBOT to reduce cognitive sequelae in CO poisoned patients who have:
LOC , seizure, exposure >23 hours, COHb of 25% or more, and age >36.
Relative Indications:  persistent symptoms after 100% O2 or change in
mental status, pregnancy, persistent cardiac ischemia, increased COHb
levels.

 Disposition:  Clinical judgment should guide your decision.  Most
patients with mild symptoms can be discharged after treatment. If
patient has a more concerning presentation with several risk factors
(extremes of age, CAD, unconscious at arrival in the ED, etc…)
consider admission.



Category: Toxicology

Title: ED Pharmacist

Keywords: toxicology, pharmacist (PubMed Search)

Posted: 9/29/2011 by Fermin Barrueto, MD (Updated: 5/25/2024)
Click here to contact Fermin Barrueto, MD

A growing trend in EDs is to have a dedicated ED Pharmacist present to assist with the evaluation of a patient's medication list, appropriate and safe drug administration and to improve drug delivery times. To date, it has been difficult for hospitals to determine if this was a cost-effective measure. There has been increasing research that has shown the proven benefits that physicians feel when they have an ED Pharmacist. With the aging population, increasing polypharmacy, core measure and national patient safety goals all rising to the top of hospital initiatives, the ED pharmacist will be proven to be a valuable cog of the ED - as UofMd already knows

1) Improved safety - this study showed an ED pharmacist caught 2.9 errors/100 medications, very important considering the cost of just one severe reaction can cause a hospitalization or even litigation(1)

2) Improved time to delivery of medication - this study showed improved time of delivery of medications not found in a Pyxis from 61 min with no pharmacist  decreased  to 47 min with ED pharmacist.(2)

Further studies will be needed to determine the true cost:benefit however with core measures like 6hr time to administration of antibiotics and the safe/timely adminstration of tPA combined with patient safety/quality goals - the value of an ED pharmacist will only be accentuated.

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Category: Toxicology

Title: Adenosine in Patients with Only Central Line Access

Keywords: adenosine, central line (PubMed Search)

Posted: 8/29/2011 by Bryan Hayes, PharmD (Emailed: 9/8/2011) (Updated: 9/8/2011)
Click here to contact Bryan Hayes, PharmD

Every so often a patient arrives in PSVT with their only intravenous access being through a hemodialysis port.

Initial dose of adenosine should be reduced to 3 mg if administered through a central line.  Remember a central line delivers the adenosine right where you need it.  This recommendation is supported by the 2010 ACLS guidelines.  Second and third doses should be 6 mg (instead of 12 mg).

Cases of prolonged bradycardia and severe side effects have been reported after full-dose adenosine through a central line.  Other situations to consider lower doses include patients currently receiving carbamazepine or dipyridamole or in those with a transplanted heart.

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End Tidal CO2 continuous capnography is being utilized more in the ED for procedural sedation. One of the best studies is a randomized control trial using propofol that showed you could see signs of hypoventiliation prior to hypoxia by about 60 seconds - which can be plenty of time to get your BVM and airway cart ready.

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Category: Toxicology

Title: Fospropofol - A Water Soluble Propofol

Keywords: propofol, procedural sedation, fospropofol (PubMed Search)

Posted: 8/18/2011 by Fermin Barrueto, MD
Click here to contact Fermin Barrueto, MD

If you think the controversy was just heating up for propofol use in the Emergency Department, just wait until the new agent begins arriving to an ED near you - fospropofol. A new water soluble version of propofol, this agent will remove the problems of pain at the injection site, an easier/wider therapeutic window for sedation and allowing of long-term sedation without the heavy lipid load.

Currently, there is limited FDA approval in the US for monitored anesthesia care. I am waiting for the first paper showing its use in the ED for procedural sedation. Safety data is still growing.

 

     Mini-pearl: Patients allergic to soybean should either avoid propofol or undergo skin testing since the emulsion is made of soybean oil and egg lecithin. There have been reported cases of anaphylaxis after administration of propofol in patients with food allergies, peanut and birch.

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Category: Toxicology

Title: Adenosine in Patients Using Caffeine

Keywords: adenosine, caffeine (PubMed Search)

Posted: 8/9/2011 by Bryan Hayes, PharmD (Emailed: 8/11/2011) (Updated: 8/11/2011)
Click here to contact Bryan Hayes, PharmD

Caffeine can interfere with the successful reversion of paroxysmal supraventricular tachycardia (SVT) by adenosine.

Caffeine is an adenosine receptor blocker.

Ingestion of caffeine less than 4 hours before a 6-mg adenosine bolus significantly reduced its effectiveness in the treatment of SVTTheophylline is similar but not many patients are prescribed it anymore.

An increased initial adenosine dose may be indicated for these patients. A first dose of 12 mg (instead of 6), followed by 2nd and 3rd doses of 18 mg (instead of 12) may be indicated.

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Category: Toxicology

Title: acetaminophen

Keywords: acetaminophen,pain (PubMed Search)

Posted: 8/4/2011 by Ellen Lemkin, MD, PharmD
Click here to contact Ellen Lemkin, MD, PharmD

 

 

o   The FDA is now asking manufacturers to limit the amount of acetaminophen in combination products to 325 mg per dose.

o   The higher dose formulations will be phased out by 2014.

o   The FDA is also considering lowering the maximum total to 3 gm per day, and a maximum dose of 650 mg per dose

o   This does not pertain to OTC, but this is likely to change in the near future; Johnson & Johnson (manufacturer of Tylenol) has already adopted these recommendations.

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Category: Toxicology

Title: Fluoroquinolone-Induced Tendon Rupture

Keywords: fluroquinolone, tendon rupture (PubMed Search)

Posted: 7/28/2011 by Bryan Hayes, PharmD
Click here to contact Bryan Hayes, PharmD

The incidence of tendon rupture related to fluoroquinolone use is reported to be in the range of 1 in 6000.

The risk of tendon rupture associated with FQ use is increased in those older than 60 years of age, those taking steroids, and in patients who have received heart, renal, or pulmonary transplants.

There is no evidence that tendon rupture is more likely for patients taking levofloxacin compared to other FQs.

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Category: Toxicology

Title: Bath Salts on the RIse

Keywords: mephedrone (PubMed Search)

Posted: 7/21/2011 by Fermin Barrueto, MD (Updated: 5/25/2024)
Click here to contact Fermin Barrueto, MD

There are increasing reports of bath salts which are crushed and then either injected, insufflated or taken orally. The actual substance has been found to be mephedrone as well as MDPV.(1)  Both are amphetamine derivatives and the psychosis seen can appear like schizophrenia to the point that some of these patients have been admitted to the psychiatric wards. (2)(3)  For those who have seen methamphetamine patients "tweaking" - where they use the drug for several days in a row without sleep - the presentation is quite similiar.

Synthetic drugs continue to present legal and regulatory problems since the compound is a "designer" synthesized drug that may not be on the DEA Schedule list.  The product is labeled "Not for human consumption". Head shops and the internet remain primary sources of the drug. Bath salts present a serious and dangerous public health risk.

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Category: Toxicology

Title: Levamisole Toxicity from Adulterated Cocaine and Heroin

Keywords: levamisole, cocaine, vasculitis, agranulocytosis, heroin (PubMed Search)

Posted: 6/23/2011 by Bryan Hayes, PharmD (Emailed: 7/14/2011) (Updated: 7/14/2011)
Click here to contact Bryan Hayes, PharmD

Levamisole is an antihelminthic agent used in humans to treat certain parasitic infections and cancers.  It is more commonly used for veterinary purposes.  It has recently seen increasing use as a cutting agent for cocaine and heroin, found in up to 70% of cocaine sample seized by the DEA.  It adds bulk and weight to powdered cocaine and is even theorized to increase the stimulant effects.

Toxicity of levamisole includes agranulocytosis and vasculitis (see attached document for recent image from NEJM).

Trivia: Levamisole was found in DJ AM and Andrew Koppel (Ted Koppel’s son), who both died of drug overdoses.

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Attachments

1106231638_levamisole.doc (526 Kb)



Category: Toxicology

Title: Caffeine and Cardiac Arrhythmias

Keywords: caffeine, arrhythmias, cardiac (PubMed Search)

Posted: 7/7/2011 by Ellen Lemkin, MD, PharmD (Updated: 5/25/2024)
Click here to contact Ellen Lemkin, MD, PharmD

 

Caffeine and Cardiac Arrhythmias

Many physicians will tell patients to avoid caffeine as it is thought to lead to arrhythmias, however evidence does not support this practice.
  • Animal studies show high doses of caffeine produces catecholamine triggered activity

  • Small studies in high risk patients (recent MI, malignant arrhythmias) have shown no increase in frequency or severity of arrhythmia

  • No large scale human studies exist evaluating caffeine's effects on patients with malignant arrhythmias (VF/VT)

  • Overall, the data suggest that caffeine is well tolerated in moderate doses in most patients, even those with known or suspected arrhythmias

  • In patients who claim sensitivity to caffeine, or in those with known arrhythmias where catecholamines are felt to drive the arrhythmia, caffeine may be discouraged by physicians.

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Category: Toxicology

Title: Intralipid

Keywords: lipid emulsion,intralipid,verapamil (PubMed Search)

Posted: 6/30/2011 by Fermin Barrueto, MD
Click here to contact Fermin Barrueto, MD

The mounting evidence on the use of 20% lipid emulsion or intrlipid has been growing for  any patient that is hemodynamically unstable due to a drug exposure. There is now a recent case report of a verapamil overdose patient that received intralipid and did well. They were able to measure verapamil levels before and after administration. They were able to remove the lipid from the serum to appropriately measure the level and found effective removal. This adds to the theory of the "lipid sink" where the lipid actually is binding/surrounding a lipophilic molecule effectively removing it from interaction.

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Category: Toxicology

Title: Risk Factors for Complications of Drug-Induced Seizures

Keywords: hyperglycemia, acidosis, seizures (PubMed Search)

Posted: 6/16/2011 by Fermin Barrueto, MD (Updated: 5/25/2024)
Click here to contact Fermin Barrueto, MD

The true incidence of drug-induced seizure is very difficult to determine, however, a nice poison center study attempted to determine clinical factors associated with complications (potentially life-threatening) of drug-induced seizures. They found 3 predictors that demonstrated statistically significant associations:

  1. Stimulant Exposure (i.e. cocaine, amphetamines etc)
  2. Initial acidosis
  3. Hyperglycemia (limitation they do not give incidence of DM)

They found a 60% complication rate in drug-induced seizures which is much higher than epileptic seizures. Makes sense since these patients are often sedated/altered or vomiting.

Stimulant Exposure is much more prominent in this population and has increased in mortality.

Interesting point with hyperglycemia, may be a novel marker for poor prognosis. Several studies have confirmed an association between hyperglycemia and increased neuronal injury and mortality in other settings like CVA and TBI.

Take home point - Drug-induced Seizure has a high complication rate in the ED. Watch for the 3 predictors as that may clue you in to the increased risk.

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