UMEM Educational Pearls - Toxicology

The Alcoholic Patient in the ED

Well, we have all been there....EMS rolls in with "another drunk guy" found down in the street. The nurses tell you, "he is here all the time...he is just drunk." You should be scared any time you hear this phrase uttered. Always be a little nervous about this group of patients and you won't fall victim to many of the pitfalls that some of us have experienced.

Pearls and Pitfalls in Caring for the Intoxicated Patient in the ED:

• Get a glucose early. Many of these patients are hypoglycemic when they arrive.
• Assume the worst and NEVER tell yourself or others,"He's just drunk." That statement is the kiss of death. Always assume there is occult trauma present. Did they fall and sustain a head bleed, splenic injury, hip fracture?
• Reevaluate during your shift. There is nothing worse than placing an intoxicated patient in a room and ignoring them, only to find out that hours (or shifts) later that they won't wake up.
• Consider a head CT. Although you can't scan them all, have a low threshold to image them. They fall all the time, and you will be surprised at how many subdural hematomas you pick up when you scan this group of patients. If you don't image, perform reassessments frequently during your shift.

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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Oseltamivir (Tamiflu)

• Has low protein binding and does not inhibit CYP450 (resulting in a low incidence of drug interactions)
• Requires dosage adjustment with creatinine clearance of < 30 ml/min
• Does not require dosage adjustment in patients with liver failure or the elderly
• Most common adverse effects are nausea and vomiting
• Serious effects include anaphylaxis and skin reactions. Neuropsychiatric effects reported include hallucinations, delerium and abnormal behavior
• It may be administered to infants and children due to the high potential morbidity associated with influenza

 

For complete indications and dosing: www.cdc.gov/h1n1flu/recommendations.htm

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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.

• Recently, a study was published which compared adverse drug events in patients who had received either fomepizole or ethanol for ethylene glycol or methanol poisoning.
• Importantly, this is the first trial which has compared these events head to head.
• Retrospectively, 172 charts over a 9 year period were reviewed. Toxicologists identified at least 1 ADR in 74 of 130 ethanol treated cases (57%) versus 5 of 42 fomepizole treated cases (12%).
• Severe ADRs occurred in 20% of ethanol treated patients vs 5% fomepizole treated patients.
• This adds further data to support the use of choosing fomepizole over alcohol for treatment of toxic alcohol poisonings

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Ondansetron (Zofran) has been off patent and its price has dropped to the point that it has supplanted promethazine (Phenergan) and even metoclopramide (Reglan) as the antiemetic of choice. With its low side-effect profile and known efficacy it is now being utilized in hyperemesis gravidarum and in pediatric gastroenteritis. - A cochrane review showed ondansetron to be both safe and effective in the pediatric population. Consider it prior to attempting oral rehydration therapy to increase effectiveness. - Dose: 0.1 mg/kg - you can give the oral dissolvable tablet (ODT) - ages 4-11 you can give 4mg ODT - Above age 11 the dosing is the same as an adult.

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Colchicine is a drug used for the treatment of acute gout attacks. It inhibits microtubule formation vital for cellular mitosis. It is also a drug with a narrow therapeutic index and lethal toxicity:

- Colchicine can be lethal at 0.5 mg/kg or even lower. Though this would be about 50 tablets and seems alot, remember it is prescribed 2 tablets initially then every hour until diarrhea presents (i.e. preliminary toxicity)

- Toxicity presents in 3 stages:

1. 0-24hrs: Nausea, vomiting, diarrhea
2. 1-7days: Sudden cardiac death, pancytopenia, renal failure, ARDS
3. >7days: Alopecia, myopathy, neuropathy (if they survive)

- No antidote, supportive care only available.

- Presentation is similiar to that of a radiation exposure

 

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.

Classical illicit recreational drugs like cocaine, ecstacy, and marajuana are sometimes difficult for teens to acquire. As a result, many are turning to their parents medicine cabinets as a source for recreational drugs.

[From the website drugabuse.gov] In 2008, 15.4 percent of 12th-graders reported using a prescription drug nonmedically within the past year. This category includes:

• amphetamines
• sedatives/barbiturates
• tranquilizers
• opiates other than heroin
  • hydrocodone, oxycodone

When adolescent patient presents to the ED, consider the possibility of a poly-pharmacy overdose. Always query parents about the presence of OTC and Rx medications in their home, and what is within reach of their kids.

While sedatives and analgesics are concerning, be alert for overdoses of more mundane medications like beta blockers and calcium-channel blockers which often pose a much more lethal threat. Consider overdose in adolescent patients with:

• GI or respiratory complaints
• Altered mental status (combative or somnolent)
• Abnormal vital signs
• History of depression or psychiatric illness

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Monitoring the Future Study: Trends in Prevalence of Various Drugs for 8th-Graders, 10th-Graders, and 12th-Graders

2005-2008 (in percent)*

	8th-Graders				10th-Graders				12th-Graders
	2005	2006	2007	2008	2005	2006	2007	2008	2005	2006	2007	2008
Any Illicit Drug Use
Lifetime Past Year Past Month	21.4 15.5   8.5	20.9 14.8   8.1	[19.0] [13.2]   7.4	19.6 14.1   7.6	38.2 29.8 17.3	36.1 28.7 16.8	35.6 28.1 16.9	34.1 26.9 15.8	50.4 38.4 23.1	48.2 36.5 21.5	46.8 35.9 21.9	47.4 36.6 22.3

Full chart available by clicking link in references.

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Serotonin is a neurotransmitter that has central and peripheral effects. It regulates the secretion of ADH from the hypothalamus and also controls the chemoreceptive trigger zone (CTZ) which induces emesis. Here are a list of medications categorized by the way they affect serotonin. Remember, any combination of these agonists could precipitate serotonin syndrome:

Enhance 5-HT synthesis: L-tryptophan

Direct HT agonists: Ergots, metoclopramide, sumatriptan, buspirone

Increase 5-HT release: amphetamines, cocaine, dextromethorphan, MDMA, L-dopa

Inhibit 5-HT breakdown: MAOIs, Linezolid

Inhibit 5-HT re-uptake: SSRIs (paxil), amphetamines, carbamazapine, tramadol, TCAs, citalopram, trazodone, lamotrigine, meperidine

 

Goldfrank's sniffing bar: no this is not a pub where toxicologist's hang out but rather a bar that assists with teaching the recognition of odors related to toxicology. Certain drugs and compounds have a distinct aroma.

The following is a list odors, see if you can name a medication or compound that has that odor - scroll down further to see the corresponding answers (if you really got all 5 email me and convince me):

1) Bitter Almond

2) Rotten Eggs

3) Wintergreen

4) Garlic

5) Sweet, Fruity (acetone)

 

Answers:

1) Cyanide; 2) N-acetylcysteine or Hydrogen Sulfide; 3) Methylsalicylate (like bengay); 4) Arsenic, organophosphate insecticides; 5) Chloroform, chloral hydrate

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.

• 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.

Clevidipine

• A new intravenous antihypertensive agent
• Has a very rapid onset (2-4 min) and offset (5-15 min), in contrast to the available IV calcium channel blocker nicardipine, which has a duration of action of 3-6 hours
• Contraindicated in patients with soy or egg allergies, and in those with defective lipid metabolism
• Most common ADR's reported were headache, nausea, and vomiting
• Initiate at 1-2 mg/hr, most respond at doses between 4-6 mg/hr
• Maximum recommended dose is 16 mg/hr
• Costs between $86 to $140 per 50 mg vial

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As the economy worsens and our patients pay for more prescriptions out of pocket, here are some tips that may help you better serve your patients: 1) Ondansetron (zofran) is now off patent. Write generic on your script for zofran - for pediatrics the ODT (dissolving tablets) - are all much cheaper ($0.50 to $1.00 per pill or ODT). IV formulation is now cheaper than phenergan. Reglan is probably still the cheapest in most pharmacies. 2) Typical $4 antibiotics are the following: SMP-TMZ (Bactrim), Cephalexin, Amoxicillin, Penicillin, Ciprofloxacin. 3) Albuterol MDIs are now much more expensive because they have to be CFC free. Unfortunately, after this federal regulation, patients will have difficulty getting these inhalers which can be quite expensive. If you write a script and the patient is self-pay, they are going to have difficulty. Hospitals are beginning to discourage "to go" inhalers and even pills due to the fact that insurance companies DO NOT reimburse these costs - only IV meds.

Rocuronium is fast becoming the agent of choice for RSI in the Emergency Department. Here is a head to head comparison of the two drugs to understand why:

	Rocuronium	Succinycholine
Dose	1-1.2mg/kg	1mg/kg
Onset	1-1.5min	1min
Duration	7-12min	30-40min
Histamine Release	No	Minimal Yes
CVS Effect	Tachycardia rare	Severe Brady rare
Other Adverse Effect	No fasciculations, No ICP effect, No Rhabdo	Fasciculations, increase ICP, rhabdo, movement of displaced Fxs

 

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

There have been multiple case reports of patients who have had coronary stents who have been on clopidogrel for > 1 year who have developed coronary thrombosis after clopidogrel cessation. There are also reports of patients who have developed DVTs likewise after clopidogrel cessation. In vivo studies in diabetics have demonstrated increased platelet and inflammatory markers after clopidogrel withdrawal. It appears that abrupt discontinuation of clopidogrel may lead to a thrombotic state in susceptible patients.

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Rodenticides have taken many forms. The following is a list of some of the more interesting ones either due to the mechanism of toxicity or how it is lethal. All of these are also toxic to people.

1) Strychnine - Glycine Antagonist at the post-synaptic spinal cord neurons - patient or rat will have convulsion of the extremeties but will be awake, alert and in extreme pain. Essentially look like generalized seizure except awake. Treatment: Benzodiazepines, Analgesia, Supportive

2) Brodifacoum - Long Acting Coumarin - rat eats, later develops elevated INR then tries to run through thin cracks in the wall or takes a little too high of a jump, then boom - subdural or some other internal hemorrhage. In human, they can stay anticoagulated for weeks after an overdose. Treatment: Vitamin K and large padded room

3) Cholecalciferol - Vitamin D precursor - there are big blocks of this drug in the NY and other subway systems. Rat nibbles, gets hypercalcemic, then gets thirsty because of this. Rat runs out into middle of subway to drink out of puddle then - splatt - the M train to Brooklyn comes along. Treatment: IVF, Loop Diuretics, Bisphosphonates

 

Octreotide

• Somatostatin-analog that supresses insulin secretion but also treats acromegaly, esophageal varices and secretory diarrhea
• Sulfonylurea-induced hypoglycemia requires frequent monitoring and administration of intravenous dextrose
• Octreotide is considered antidotal therapy since it turns off insulin secretion that is caused by sulfonylureas
• Recent article by Fasano et al Ann Emerg Med 2008 showed that octreotide 75 mcg SQ one-time in the ED was superior to "traditional" therapy with fewer recurrent hypoglycemic episodes during the patient's hospitalization.
• Excellent article worth reading, even if its just the abstract

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Tetrodotoxin - Sodium Channel blocker - Extremely toxic causes paresthesias, dysrhythmias and paralysis - Found in the sushi called Fugu (From the Pufferfish) - Eating the sushi is considered a delicacy and goal is to get just enough of the toxin to get perioral paresthesias after eating. - Also found in the blue-ringed octopus, angelfish and parrot fish. Enjoy your seafood and take a look at the attached pic of actual fugu.

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