UMEM Educational Pearls - By Fermin Barrueto

Radiocontrast Induced Nephropathy (RCIN)

• Occurs within 24 hrs of administration followed by oliguric phase
• Usually improves within a week and rarely needs dialysis
• Initial injection is an osmotic load, leads to volume expansion and diuresis. Follwed by intense vasoconstriction suggesting possible ischemic role in pathophysiology.
• There is also a direct toxic effect to the kidneys however
• High Risk patients: HTN, DM,  Chronic Renal Insuff, Bence Jones proteinuria and large injections of IV dye
• Possible prophylaxis: There is almost no data studying this effect in the Emerg Dept patient. One trial look at IV acetylcysteine in the Emergent CT (RAPPID trial) did show benefit but has flaws within the study. IV hydration and sodium bicarbonate

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Quinolone Induced Deliurim

Just to give you another reason NOT to give a quinolone - aside from the C. diff. This adverse effect occurs with quinolones unlike many other antibiotics. It can prolong hospital stay, cause falls and further medical work ups. Some risk factors are:

• Elderly
• Renal Insufficiency
• Benzodiazepine dependence (will actually precipitate withdrawal since quinolones displace the BDZ from the receptor - you have probably done this to a patient if you think about it, that may be why they went crazy)
• Epilepsy - can cause seizures especially with NSAIDs

 

A quick christmas one:

The Christmas Rose (Helleborus niger)

Actually containes cardioactive steroids - eating it will help your A fib with RVR as it will act like digoxin, as well as kill like it.

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Here is a table adapted from Goldfrank's Textbook of Toxicologic Emergencies 8th Edition - Drugs that May Induce Parkinsonism. MPTP is the story that everyone hears about and actually has links to Maryland. In 1976, Barry Kidston, a 23-year-old chemistry Maryland graduate student, synthesized MPPP (Meperidine or Demerol) incorrectly and injected the result. It was contaminated with MPTP, and within three days he began exhibiting symptoms of Parkinson's disease. Ooops - permanent.

Reversible

• Chemotherapeutics (several)
• Cyclosporine
• Calcium Channel Blockers
• Dopaminergic withdrawal
• Kava Kava (with manganese)
• Progesterone
• Sertraline
• Valproic Acid
• Trazodone

Irreversible

• Carbon Monoxide
• Cyanide
• Heroin
• Manganese
• MPTP

 Toxicology Expert: Poisoning Of Harvard University Scientists "No Accident"

• 6 scientists in a Boston area lab drank coffee that was laced with sodium azide
• Presented with hypotension, nausea and vomiting - one had a syncopal episode
• Sodium Azide is a chemical compound (NaN3) that is used as a preservative at very low concentrations but in higher concentrations can be lethal. It is even found in the propellant that is found in automobile airbag mechanisms
• It acts similiar to cyanide where it inhibits cytochrome oxidase and presents like a cyanide poisoning.
• No antidote, cyanide antidote kit will not work

This is a semi-synthetic opiate with partial agonist activity at the mu receptor. For an example of what a partial agonist is - see attached illustration. It is used in opioid addiction but is not as regulated as methadone clinics. Take a small course and you are licensed to prescribed it.  Primary caregivers are now able to administer buprenorphine to assist addicts though it is not recommended if the patient is requiring more than 40mg of methadone (rules out everyone in Baltimore).

The tablets (Suboxone) also contain naloxone to prevent intravenous injection which would induce withdrawal. Naloxone is not orally bioavailable and thus can be mixed into the pill.

Overdose is treated like any other opioid and naloxone should work.

Buprenorphine can illicit an opioid withdrawal response if the patient is currently on an opioid and then takes buprenorphine. 

Suppose to be safer than methadone - no QT prolongation and less respiratory depression

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Aripiprazole (Abilify): a new atypical antipsychotic partially agonizes D2 and serotonin receptors though its compelte mechanism is not known. Used in schizophrenia, in overdose you may see the following symptoms (from a retrospective study done over 4 years worth of calls to a PCC):

• Somnolence 89 (56%)
• Tachycardia 32 (20%, heart rate 102-186)
• Nausea/vomiting 29 (18%)
• Dystonic reactions 21 (13%)

The study was with over 255 patients. Though QT prolongation is listed, it is not common with this medication.

 

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 Valproic Acid (Depakote)

• Can cause carnitine deficiency
• In overdose and therapeutic ingestions can cause hepatic enzyme elevation (idiosyncratic) but can also cause hyperammonemia without hepatic enyme elevation
• Have a patient with somnolence or altered mental status and is on valproic acid - check a level but also check an ammonia level
• Elevated ammonia levels can be treated with an antidote - carnitine (IV or PO)
• Very safe antidote (carnitine) since it is a nutritional supplement, consider in patients on valproic acid and decreased responsivness with elevated ammonia

Priapism - prolonged involuntary erection - is an adverse effect with some drugs. Here is a list of the more commonly reported:

• Androgens
• Anticoagulants
• Antihypertensives: Hydralazaine, labetolol, phentolamine, prazosin
• Antipsychotics
• Cantharidin
• Cocaine
• Diazepam
• Marijuana
• Sildenafil
• Trazadone
• Yohimbine

To feed of off Dr. Liferidge's last pearl - a few more points relevant to your Emergency Department practice:

• Lidocaine toxicity ranges between 5-7mg/kg
• Typical vial used for suture repair is 10cc of 1% lidocaine. 
• 1% = (1g/100cc) thus 100mg lidocaine in one vial
• 70 kg x 5mg/kg = 350 mg typical adult toxic dose (3+vials)
• 10 kg x 5mg/kg = 50 mg peds toxic dose (<1vial)
• Case reports of viscous lidocaine (4%) causing seizures. Very classically in pediatric cases. Cause is from oral transmucosal absorption, bypassing the large first pass effect if absorbed from the stomach.
• Classic symptoms are termed "feeling drunk" progressing to seizure. Shortly after CNS effect can have suppression of intrinsic pacemaker leading to sinus arrest, AV block, hypotension and death

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Ciguatera

• Heat resistant toxin found in fish, thus cooking doesn't protect you
• Found in over 400 species of fish but bioaccumulates in fish so predator tropical reef fish have higher concentration: grouper, barrucuda, snapper, parrotfish
• Found in tropical areas (See attached map for hot bed locations - in case you vacation there)
• Clinical Findings: Very neat hot-cold reversal where you place you hand in bucket of ice water and it feels like it is burning and visa versa, GI symptoms, paresthesias, ataxia and even hallucinations (very cool)
• Treatment: attempts with mannitol and gabapentin are reasonable and safe but completely unproven. Supportive care

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The followings is a list of unique clinical findings related to a certain sedative-hypnotic overdose:

1) Hypothermia:Barbiturates, bromides, ethchlorvynol (others but these more pronounced)

2) Unique odors: chloral hydrate, ethchlorvynol (which is Placidyl)

3) Bradycardia: GHB (again others but pronounced in this OD)

4) Tachydysrhythmias: chloral hydrate

5) Muscular twitching: GHB, methaqualone, etomidate

6) Discolored urine: propofol (green/pink)

 

 

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A patient presents to the University of MD ED in generalized convulsive status epilepticus. Continuous seizure activity that is not stopped by any dose of benzodiazepine [This is actually a very rare entity]. What is your next move?

- Check your basics: Fingerstick blood glucose (hypoglycemics can cause SE)

- Phenytoin is not going to work fast enough, the clock is ticking and the patient's brain cannot handle continuous status epilepticus, after 45-60min permanent neurologic sequelae or death will occur. If the cause is toxin induced, it just won't work.

- In an area where HIV is endemic, you have to consider Isoniazid - an antituberculous drug - and administer antidotal therapy: empiric dosing of vitamin B6 (pyridoxine) 5g IV. It is the only thing that will work.

- From the ED perspective, you will also be using a barbituate though there is evidence to support the use of propofol (after intubation for both). This will hopefully stop the seizure

- General anesthesia is the last chance if all else fails.

 

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You have a patient that is on lithium and a serum concentration is checked: 4.3 mmol/l

Therapeutic range is between 0.5 and 1.5 mmol/l

The patient shows no symptoms - is that possible? what do you do?

Answer: highly unlikely that the patient would asymptomatic, at least nystagmus would be present. Remember the symptoms are cerebellar in nature. What may have happened is the blood was drawn in an inappropriate tube. There are green "Lithium Heparinized" tubes in our Emergency Department. They are typically used for cardiac enzymes. This has been a well reported source of error (1)

 

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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

 

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

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