UMEM Educational Pearls - By Bryan Hayes

Category: Toxicology

Title: Anion Gap Metabolic Acidosis

Keywords: anion gap, metabolic acidosis (PubMed Search)

Posted: 1/14/2010 by Bryan Hayes, PharmD (Updated: 1/15/2010)
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As we are now into the winter months, exposures to ethylene glycol (antifreeze) and methanol (windshield washer fluid) increase.  Here is a good mnemonic for sorting through an anion gap metabolic acidosis:

C – cyanide, carbon monoxide
A – alcoholic ketoacidosis, acetaminophen (massive OD)
T – toluene (chronic from glue sniffing)
M – methanol, metformin
U – uremia
D – diabetic ketoacidosis
P – propofol infusion syndrome, propylene glycol, paraldehyde
I – iron, isoniazid, ibuprofen (massive OD)
L – lactic acidosis
E – ethylene glycol
S – salicylates, starvation ketoacidosis


Category: Toxicology

Title: Intranasal Naloxone

Keywords: naloxone, intranasal (PubMed Search)

Posted: 12/10/2009 by Bryan Hayes, PharmD (Updated: 10/20/2020)
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When IV access is not immediately available and you don’t want to rely on the erratic absorption of IM administration, naloxone can be given by the intranasal (IN) route.
 
Kinetics are similar to IV: Onset 1-2 minutes, duration 40-50 minutes.
 
Dose is the same as IV: Up to 1 mL (0.4 mg) can be given in each nostril.
 
Advantage of needleless administration.
 
To use: Draw up dose of nalxone and simply add an atomizer to the end of a syringe (see picture).  Administer half of final dose in each nostril.
 
Atomizers are now available in the UMMC ED.


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The newest antidote for cyanide poisoning, hydroxocobalamin, has several advantages over the older Cyanide Antidote Kit (amyl nitrite, sodium nitrite, sodium thiosulfate).  Hydroxocobalamin works rapidly, does not induce methemoglobinemia, and does not cause vasodilation/hypotension.

Two noteworthy adverse effects were noted in human volunteer studies:
  • The first is self-limiting hypertension. However, think about the patient population you are treating.  They are most likely hypotensive from the cyanide/carbon monoxide poisoning.  Increased blood pressure is a welcome adverse effect in these cases.
  • The second is red discoloration of the skin and urine, secondary to the red color of hydroxocobalamin (see attached picture).  This effect can be quite pronounced, especially if you aren’t prepared for it. There is no harm to the patient although it can last up to 8 days.
Bottom line: Adverse effects occur with hydroxocobalamin administration but are not anything to be concerned about, especially considering the toxin you are treating.

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Cyanokit_red_skin.jpg (107 Kb)


Category: Toxicology

Title: Relenza for the treatment of Tamiflu-resistant influenza

Keywords: Relenza, zanamivir, influenza, H1N1 (PubMed Search)

Posted: 10/22/2009 by Bryan Hayes, PharmD (Updated: 10/20/2020)
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Zanamivir (Relenza) is another neuraminidase inhibitor effective against influenza strains A and B. We are currently reserving its use for patients with H1N1 that may develop resistance to oseltamivir (Tamiflu) since it has been effective in these situations with past influenza strains.

  • Zanamivir is given by inhalation only (powder) and can therefore not be given to ventilated patients
  • Treatment dose is 10 mg (two blister packs) BID for 5 days
  • Prophylaxis is 10 mg (two blister packs) once daily for 10 days
  • Most common adverse effects are respiratory related and include bronchospasm and cough
  • Pregnancy category C (same as Tamiflu) and should be used in pregnant patients with suspected/confirmed H1N1 due to the increased risk of morbidity/mortality
    • In fact, zanamivir may be the preferable antiviral for pregnant women because of its limited systemic absorption

Category: Toxicology

Title: Haloperidol use in sympathomimetic poisoning

Keywords: haloperidol, cocaine, amphetamine, sympathomimetic (PubMed Search)

Posted: 10/8/2009 by Bryan Hayes, PharmD (Updated: 10/20/2020)
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A 34 y/o m presents to the ED agitated and combative with the following vitals signs: T 104.6, P 136, BP 198/124. His urine toxicology screen is positive for amphetamines. 

What do you give for sedation? Benzos, benzos, benzos…. On the rare occasion when benzodiazepines fail to achieve an adequate level of sedation, either a rapidly acting barbiturate or propofol should be administered.
 
Why not haloperidol (Haldol)?
  • Controlled animal experience clearly contraindicates the use of phenothiazines (e.g. prochlorperazine, chlorpromazine) and butyrophenones (e.g. haloperidol, droperidol).
  • In animal models, these drugs enhance toxicity (seizures) or lethality, or both.
  • Additional concerns regarding these drugs include their ability to interfere with heat dissipation, exacerbate tachycardia, prolong the QTc interval, and induce torsades de pointes, or precipitate dystonic reactions.
Therefore, although somewhat controversial, haloperidol should be avoided in acute intoxication from cocaine, amphetamines, or other sympathomimetics.

Category: Toxicology

Title: Alcohol content of hand sanitizer

Keywords: hand sanitizer, ethanol, alcohol (PubMed Search)

Posted: 9/10/2009 by Bryan Hayes, PharmD (Updated: 10/20/2020)
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     Most hand sanitizers contain ethanol, while some contain isopropyl alcohol. The concentration of alcohol in these products varies from 45% to 95%, with the most commonly used products containing 62%.  How much would a 15 kg child have to ingest to obtain a blood alcohol concentration of 100 mg/dL (or 0.1%)?

     Assuming a volume of distribution of 0.6 L/kg and 100% bioavailability, only 15-20 mL is required to produce this toxic level.  That is equivalent to 3-4 teaspoons or approximately 8-10 “squirts” of hand sanitizer!


Category: Toxicology

Title: Acute Withdrawal of Prostacylcin Analogues for Pulmonary Hypertension

Keywords: treprostinil, epoprostenol, pulmonary hypertension (PubMed Search)

Posted: 8/12/2009 by Bryan Hayes, PharmD (Emailed: 8/13/2009) (Updated: 10/20/2020)
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One of the treatment options for NYHA class III and IV pulmonary hypertension is prostanoids.  All of the prostanoid formulations have the limitations of a short half-life and a heterogeneous response to therapy.  Because the drugs need to be given by continuous infusion, patients may present to the ED due to pump failure.  Sudden cardiopulmonary collapse can occur with infusion interruption.  Here are some important points to remember regarding kinetics:

  • Intravenous epoprostenol (Flolan®) has an extremely short half-life (2–3 min) and lacks stability at room temperature.  Interruption of the pump for even a short period can have drastic consequences.
  • Treprostinil (Remodulin®) has theoretical advantages over epoprostenol because of its stability at room temperature, an elimination half-life of 4-6 hours (subcutaneous), and its ability to be administered by continuous subcutaneous infusion.

Category: Toxicology

Title: Lidocaine toxicity from nebulized solution

Keywords: lidocaine, nebulized (PubMed Search)

Posted: 7/9/2009 by Bryan Hayes, PharmD (Updated: 10/20/2020)
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One of the options in our armamentarium prior to inserting an NG tube or performing a non-emergent nasotracheal intubation is nebulized lidocaine. However, the total dose is always a concern with this anesthetic agent before we have to worry about toxicity such as lightheadedness, tremors, hallucinations, seizures, and cardiac arrest. Here are some points to remember:

  • Maximum IV dose is 3 mg/kg when used as an antiarryhthmic in ACLS.
  • Maximum subcutaneous/intradermal dose is 4.5 mg/kg. When used in combination with epinephrine, this value is increased to 7 mg/kg.
  • One study evaluated lidocaine plasma levels after nebulized administration and found that a dose of 400 mg (5.7 mg/kg in a 70 kg patient) produced a peak of 1.1 mcg/ml, far below the 5 mcg/ml level associated with toxicity.
  • Application to real-life: Using 4% topical lidocaine in a 5-mL nebulizer will give a total dose of 200 mg. This is within the range of safe, studied doses, and will provide the anesthetic effect you (and the patient) desires.

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Category: Toxicology

Title: Reversal of elevated INR due to warfarin

Keywords: vitamin K, phytonadione, warfarin, INR (PubMed Search)

Posted: 6/9/2009 by Bryan Hayes, PharmD (Emailed: 6/11/2009) (Updated: 6/11/2009)
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Patients who present to the ED with an elevated INR due to vitamin K antagonists many times do not need to be reversed.  Simply holding a dose is all that is usually necessary for patients with an INR < 9.  Fortunately, guidelines published in CHEST are available to help guide management.
 

  • INR: >Therapeutic to 5.0 with no bleeding - Lower warfarin dose, or omit a dose and resume warfarin at a lower dose when INR is in therapeutic range
  • INR: >5.0 to 9.0 with no bleeding - Omit the next 1 to 2 doses of warfarin, monitor INR more frequently, and resume treatment at a lower dose when INR is in therapeutic range, or omit a dose and administer 1 to 2.5 mg oral vitamin K.* [*This option is preferred in patients at increased risk for bleeding (eg, history of bleeding, stroke, renal insufficiency, anemia, hypertension.]
  • INR: >9.0 with no bleeding - Hold warfarin and administer 5 to 10 mg oral vitamin K. Monitor INR more frequently and administer more vitamin K as needed.
  • Any INR with serious or life-threatening bleeding - Hold warfarin and administer 10 mg vitamin K by slow IV infusion; supplement with prothrombin complex concentrate, fresh frozen plasma, or recombinant human factor VIIa, depending on clinical urgency. Monitor and repeat as needed.
     

Reference:

Ansell, J, Hirsh, J, Hylek, E, et al. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; (6 Suppl):160s.

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Category: Toxicology

Title: Screening for Benzodiazepine Use/Abuse

Keywords: benzodiazepine, oxazepam, toxicology, urine, blood (PubMed Search)

Posted: 5/14/2009 by Bryan Hayes, PharmD (Updated: 10/20/2020)
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Your patient presents unresponsive with an empty bottle of alprazolam (Xanax). You order a urine and blood toxicology screen. The blood comes back negative for benzodiazepines but the urine test is positive. How do you interpret this result?

  • The benzodiazepine toxicology screen typically looks for oxazepam. If it is present in sufficient quantity, the test will be positive.
  • Three benzodiazepines are detected by this test: oxazepam (Serax), diazepam (Valium), and chlordiazepoxide (Librium); [diazepam and chlordiazepoxide are metabolized to oxazepam].
  • Other benzodiazepines such as clonazepam, lorazepam, and alprazolam will generally test negative unless there is cross-reactivity or large quantity.
  • The urine and blood immunoassays are exactly the same. For this patient, there was probably a low overall quantity of alprazolam in the blood but a concentrated amount in the urine. Therefore, the positive urine and negative blood.

Category: Toxicology

Title: Overdose of insulin glargine (Lantus)

Keywords: glargine, insulin, lantus (PubMed Search)

Posted: 4/9/2009 by Bryan Hayes, PharmD (Updated: 10/20/2020)
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Overdoses of insulin glargine (Lantus) are rarely reported in the literature.  In fact, there are only 6 case reports.  We recently had a patient in our ED who was hypoglycemic from insulin glargine.  The hypoglycemic episode was quite prolonged (> 24 hours) in the ED before being the patient was transferred to the MICU.  Here are a few points to remember:

  • Insulin glargine does not peak; it was designed to mimic basal islet cell insulin secretion.
  • In the therapeutic setting, its effects can last up to about 24 hours.  In overdose the hypoglycemic effects have been reported to last up to 60-130 hours!
  • Be prepared to give IV dextrose 5% or 10% infusion for the duration of the patient's hypoglycemic effect.  This can be supplemented with food.
  • Octreotide will be ineffective for exogenous insulin poisonings because its effect comes from its ability to suppress insulin secretion from the pancreas.

Category: Toxicology

Title: Black Box Warning for Metoclopramide

Keywords: metoclopramide, black box warning, tardive dyskinesia (PubMed Search)

Posted: 3/12/2009 by Bryan Hayes, PharmD (Updated: 10/20/2020)
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Add metoclopramide (Reglan) to the laundry list of medications with black box warnings from the FDA. Why was a black box warning added?

  • Long-term metoclopramide use has been linked to tardive dyskinesia (involuntary and repetitive body movements) even after the drug is no longer being taken.
  • Risk factors: Long-term or high-dose use, elderly, female gender.
  • Recommended that metoclopramide treatment not exceed 3 months.
What implications does this have for our practice in the ED?
  • None really.
  • Just be aware of the dopamine antagonist effects (EPS - dystonic reactions) that are possible whenever you order metoclopramide in the acute setting.
  • These effects can be treated effectively with an anticholinergic agent, such as diphenhydramine or benztropine.

Category: Toxicology

Title: Phentolamine Use in Hypertensive Crisis

Keywords: phentolamine, tyramine, pheochromocytoma (PubMed Search)

Posted: 2/12/2009 by Bryan Hayes, PharmD (Updated: 10/20/2020)
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You have a 44 y/o female patient with an arterial line monitoring her blood pressure which is reading 302/156 mm Hg.  Her heart rate is 140 bpm.  Her history reveals she is taking a monoamine oxidase inhibitor (MAOI) and has inadvertantly ingested tyramine at her friend's cheese/wine party.   What do you do?

  • Conditions producing hypertensive crisis from catecholamine surges (phenylephrine overdose, cocaine, tyramine interactions, pheochromocytoma) can be treated with phentolamine
  • Phentolamine is a nonspecifc alpha blocking agent which produces peripheral vasodilation with a resultant fall in blood pressure in most patients.
  • Other uses include extravasation of some vasopressors (e.g. norepineprhine)
  • May see an increase in HR after administration (once alpha blockade is established, beta-blocker can be administered)
  • Dose: 5-15 mg IV/IM
  • Duration: 30-45 minutes

Category: Toxicology

Title: Methadone-induced QT prolongation

Keywords: methadone, QT prolongation, torsade de pointes, magnesium (PubMed Search)

Posted: 1/7/2009 by Bryan Hayes, PharmD (Emailed: 1/8/2009) (Updated: 10/20/2020)
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A few previous pearls have touched on identifying drugs that cause QT prolongation.  In our patient population, methadone is one of the more common causes of drug-induced prolonged QT syndrome.  Of 692 physicians surveyed (35% family practitioners, 25% internests, 22% psychiatrists, and 8% self-identified addiction specialists) only 41% were aware of methadone's QT-prolonging properties and just 24% were aware of methadone's association with torsade de pointes.

 

Now that you know, what do you do when a patient on methadone presents with a QTC of 580 msec and intermittent runs of vtach and torsade de pointes?

 

The answer is... the exact same thing you would do with any other patient who presents this way, regardless of the cause.

  • Give magnesium sulfate 2 gm IV for torsade de pointes
  • Check magnesium and potassium levels.  If low (which they often are), replete.
  • Monitor continuous EKG.

Buprenorphine, an alternative to methadone, is not associated with prolonged QT syndrome.

 


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Category: Toxicology

Title: Naloxone for non-opioid overdoses?

Keywords: naloxone, clonidine, valproic acid, captopril (PubMed Search)

Posted: 12/1/2008 by Bryan Hayes, PharmD (Emailed: 12/11/2008) (Updated: 10/20/2020)
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A search of the toxicology literature will reveal that naloxone has been tried in many different overdose situations.  It is thought that the endogenous opioid system mediates several physiologic and pharmacologic pathways.

  • Captopril – naloxone reverses hypotension (Ann Emerg Med 1991;20(10):1125-7)
    • Evidence: One case report.
  • Valproic Acid  naloxone reverses CNS depression possibly through GABA attenuation
    • Evidence: Two case reports demonstrated effectiveness in patients with minimally elevated VPA levels.  Other reports showed no effect in patients with much higher concentrations.
  • Clonidine – naloxone reverses coma, bradycardia, and hypotension
    • Evidence: Several case reports suggest positive response while others demonstrate no benefit.  Anecdotal experience estimates a response in about 50% of cases.

Bottom line: In none of these instances was improvement as dramatic or consistent as in the reversal of the toxic effects of an opioid.  Naloxone can certainly be tried in non-opioid overdoses but should not be considered a first-line antidote.  The most benefit appears to be with clonidine.


Category: Toxicology

Title: Opioid Allergies and Cross-reactivity

Keywords: opioid, opiate, allergy, hypersensitivity (PubMed Search)

Posted: 11/5/2008 by Bryan Hayes, PharmD (Emailed: 11/13/2008) (Updated: 10/20/2020)
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How many times have you had a patient with an allergy to codeine described as stomach upset?  Or how about a rash with morphine (probably secondary to histamine release)?  True anaphylactic reactions to opioids are very rare (< 1%).  But what happens when you have a patient with a true allergy, but still need to give an opioid?  No problem, you just need to choose one that is structurally different.

  • Group 1 (aka opiates) - Naturally occurring agents derived from the opium plant
    • Morphine, codeine, thebaine
  • Group 2 - Semi-synthetics
    • Hydrocodone, oxycodone, hydromorphone, oxymorphone, buprenorphine (heroin is also in this group)
  • Group 3 - Synthetics
    • Fentanyl (alfentanil, sufentanil, etc.), methadone, tramadol, propoxyphene, meperidine

All of the group 1 and 2 agents are structurally very similar to each other and should not be given if a true allergy exists to any other natural or semi-synthetic derivative.  Group 3 agents have structures different enough that they can be given to a patient intolerant to the natural or semi-synthetics without fear of cross reactivity.  They are also very different from others in this same group.

The bottom line is that most of our patients don’t have true opioid allergies.  Just as an example, you will many times see a patient listed as having a percocet or morphine allergy and yet they tolerate hydromorphone without a problem. Go figure…

Category: Toxicology

Title: Octreotide for Pediatric Sulfonylurea Poisoning

Keywords: octreotide, sulfonylurea (PubMed Search)

Posted: 4/12/2013 by Bryan Hayes, PharmD (Emailed: 10/20/2020) (Updated: 4/13/2013)
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Methods: A large retrospective case series evaluated 121 children under 6 years old with hypoglycemia from a sulfonylurea ingestion.

Results:

  • In addition to dextrose, patients who received octreotide had a median of zero hypoglycemic episodes after octreotide (compared to 2 before treatment, p < 0.0001).
  • Median blood glucose concentrations after receiving octreotide were also higher (62 mg/dL vs 44, p < 0.001).
  • Most required only 1 dose of octreotide with no reported adverse effects.


Authors' Conclusion: Octreotide administration decreases the number of hypoglycemic events and increases blood glucose concentrations in children with sulfonylurea ingestion.

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