UMEM Educational Pearls - By Fermin Barrueto

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

Show References

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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Watch out for tradename and generic name's of medications.

They can get the patient and yourself into trouble:

• coumadin: warfarin, jantoven
• diphenhydramine: unisom, benadryl, tylenol PM

Classic example is my own case: Insert a central line in a patient - subclavian - and shortly after completion am alerted the patient's INR is 25. No adverse outcome but when I reviewed the med list, I did not see coumadin or warfarin and assumed I was in the clear. Patient was on jantoven.

Happy Holidays

The FDA has ruled that Long-Acting Beta Agonists (LABAs) are not worth the risk with increased hospitalization and increased mortality. Serevent has largely been replaced by Advair now. Unfortunately, for the children, it took 3 years to look at the data and finally come to this conclusion. Advair (LABA + fluticasone) has escaped the ruling with lack of evidence.

Tryptophan - a precursor to melatonin, it is often blamed for the post prandial coma that many go into after a big turkey dinner. Never mind the 5000 kcals that was consumed during the meal. The supplement really doesn't help with sleeping. Interestingly, turkey isn't even in the top 10 or 20 of foods that contain tryptophan. The top five are:

1) Game meat (Elk): 746 mg of tryptophan

2) Seaweed (Spirulina): 736 mg of tryptophan

3) Spinach: 690 mg of tryptophan

4) Egg White: 673 mg of tryptophan

5) Soy protein: 630 mg of tryptophan

Supplements of L-tryptophan have been contaminated with a compound that has been associated with eosinophilia myalgia syndrome.

 

Local Anesthetic - Bupivacaine (Marcaine) - Sodium channel blocker with duration of action 2-4 hrs (w/epi 3-7 hrs) - Toxic dose is > 2.5 mg/kg or > 175 mg total dose (Infiltrating into SQ) - Bupivacaine 0.25% = 2.5 mg/mL - Inadvertent intravenous injection can result in toxicity - Lethally cardiotoxic with widened QRS, V-tach and neurotoxic with inebriation and seizures - Anesthesia literature reports successful use of Intralipid as an antidote

Methylenedioxymethamphetamine (MDMA) or "Ecstasy"

A designer club drug that has been classified as a "hallucinogenic" amphetamine though it does not cause visual hallucinations like are reported with LSD. It has many of the sympathomimetic effects like other amphetamines but its main mechanism of action which both causes the euphoria and toxicity is serotonin agonism. Since Anti-diuretic hormone is released by the hypothalamus under the direct regulation of serotonin, there is a transient but dangerous episode of Syndrome of Inappropriate ADH (SIADH). Combined with the club culture and fear of dehydration while taking MDMA, patients ingest MDMA concomitantly with free water through the night further exacerbating the hyponatremia. The time sequence of events for these patient is (women appear genetically predisposed to this phenomena):

• Friday Night: Ingestion of MDMA (even one pill is enough) +/- free water
• Saturday Morning: headache, nausea, vomiting
• Saturday Afternoon: (Realizes its not a hangover) patient becomes confused progressing to unresponsive and eventually seizures
• Saturday Evening: Presents to ED with seizures

Treatment: Fluid restriction - this is the one time that the 1L NS Bolus can kill a patient with cerebral edema. If you must give fluid give 3% NaCl if there is symptomatic hyponatremia. Remember the patient has dropped their sodium in about 24 hours so you can replenish in about the same time quite safely and even faster in severe cases. Treated correctly, patients improve rapidly - within 24-48 hours. Read a great case report in the reference below.

Show References

 Olanzapine (Zyprexa)

This is an atypical antipsychotic that gained popularity because it caused less sedation and fewer extrapyramidal effects. However, there are many other adverse effects that need to be emphasized. Some of these may contribute to a patient's condition in the ED:

• Hyperglycemia: has been reported to even cause hyperglycemic hyperosmolar nonketotic coma as well as DKA in patients that were not diabetic prior to initiation of olanzapine.
• Anticholinergic: one of the most anticholinergic antipsychotics, watch for polypharmacy. Perhaps the patients urinary retention and mild confusion is due to the many anticholinergic medications the patient is taking.
• Serotonin Syndrome: again a problem with polypharmacy and in overdose.

Bisphenol A (BPA) is found in epoxy resins that line common food and beverage materials. There has been concern that this compound, like phthalates, may be causing harm through chronic low exposure. An epidemiologic study was performed and published in JAMA that has raised this question. Amazingly, the study did find that:

• Higher urinary BPA levels correlated with an increase incidence of: NIDDM, CAD and elevated liver enzymes
• Mechanism may be an estrogen effect, disruption of Beta-islet cell function and even obesity promoting effects
• Study was strictly epidemiologic but raises a serious public health concern that you will see in the news more

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Clinical Manifestations in relation to lead level in children:

• > 70 - 100 mcg/dL: Encephalopathy, increased ICP, anemia, vomiting
• 50 - 70 mcg/dL: Irritable, difficult child, abdominal pain, anorexia
• >10 mcg/dL: often asymptomatic, may develop impaired cognition, behavior, impaired fine-motor coordination, hearing and growth

 Melamine

• In case you thought the chinese only sent their toxin filled products to the USA, a massive scandal has been occurring with their milk.
• Adding melamine to their milk, companies were able to get falsely elevated readings of protein which is measured by the government to make sure the milk was not watered down.
• 53,000 illnesses, over 12,000 hospitilizations and at least 4 infant deaths have been attributed to their milk supply - 20% of China's milk supply is thought to be contaminated
• Melamine or melamine resin is used to make plastics and involved in other polymeric reactions.
• Toxicity involves the creation of kidney stones - imagine the pain in these poor children
• These children died from renal failure from multiple kidney stones.
• Check the link below to the news article

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 Cheese Heroin: a slang term for the combination of heroin with an over-the-counter antihistamine

• The two are combined and forms a cheesy like powder that is different from pure heroin
• A string of deaths were reported between 2005-2007 in Texas, many adolscents
• This concoction is more often insufflated than smoked or injected
• Combines opioid effect with the anticholinergic confusion and hallucinations
• Scorpion was a heroin that was combined with scopolamine that had similiar effect

Treatment

• Find the anticholinergic toxidrome, place the foley and supportive care are mainstays
• Consider administration of physostigmine 1mg IV slowly over 2-5 minutes (call toxicologist)
• The anticholinergic effects will linger much longer than the heroin effects ( <1hr)

 

 

 Latrodectus sp (Black Widow Spider)

• The only indigenous neurotoxic insect  in the state of Maryland and found through many states in the US
• The "bite" often not visible and does not cause a necrotic lesion like the brown recluse
• Causes Acetycholine release from post-synaptic motor and sensory nerves
• This leads to intense muscle contraction and pain. There have been reports of a black widow spider on the leg and the patient undergoes ex lap surgery for suspected acute abdomen only to find out the abdominal muscles were fasciculating due to envenomation
• Treat with aggresive analgesia and benzodiazepines.
• Not often lethal with approximately 60-70 deaths in the US over 30 years

Take a look at a picture of the black widow on the following attachment

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Buprenorphine (Suboxone)

• Use in opioid maintenance therapy programs, doesn't have QT prolongation and less respiratory depression than methandone
• Patients must been maintained on <40mg of methadone for successful conversion to buprenorphine to take place
• Primary caregivers can prescribe after taking a course
• Partial agonist can actual precipitate withdrawal if patient takes a full opioid (say sneaking a little heroin before appointment)
• Suboxone is buprenorphine+naloxone, since naloxone has poor bioavailability when taken appropriately there is no effect but if the tablet is crushed and injected the patient will go into florid withdrawal.
• Use and abuse has been steadily increasing and death can still occur from overdose.
• Pain is difficult to manage in patient on buprenorphine since opioid effect will be blunted, buprenorphine is potent partial agonist.

 A recent landmark article has cited a connection between non-insulin dependent diabetes and low-level arsenic in our drinking water.

 

• Approximately 13 million in the USA are drinking water that contains Arsenic levels higher than EPA allowable standards
• This study controlled for organic arsenic (found in seafood) and was looking for the effect of inorganic arsenic which is the more toxic compound - don't have to stop eating sushi
• This study essentially found a dose response curve with people with lower arsenic levels having lower incidence of non-insulin dependent diabetes, those with higher levels, higher risk.

 

Show References

• Elemental Mercury is found in manometers, some mercury switches and thermometers.
• Elemental Mercury is also in the CFLs (Compact Fluoroscent Lightbulbs) that are popular now due to rising energy cost (approx 4 mg)
• Organic mercury found in seafood is only toxic in high consistent doses - though has been catastrophic. See attached picture which was the award winning Time magazine cover of the year showing a mother holding her child who had congenital disfigurement due to mercury being dumped into Minamata Bay
• Elemental Mercury is mostly a neurotoxin causing personality changes, nervousness, shyness and depression.
• Acrodynia is pain and pink discoloration of hands and feet due to mercury poisoning in children.

 

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•  Therapeutic concentration considered 10-20 mg/dL
•  Some hospitals report in "mg/L" thus a level of 110 mg/L is therapeutic
•  Symptoms of Toxicity usually > 40 mg/dL
•  Consider Hemodialysis in any patient with a serum concentration >100 mg/dL

First Line Therapy:  Urine Alkalinization (pH >7.5) by administrating NaHCO3

Other Indications for Hemodialysis in Salicylate Poisoned Patient:

1. Renal Failure
2. CHF
3. Acute Lung Injury
4. Persistent CNS disturbances
5. Refractory metabolic acidosis or electrolyte abnormality
6. Hepatic insufficiency with coagulopathy

 

 

• Metformin is the most commonly prescribed oral diabetic mediction in US
• Relative contraindication is in renally impaired patients, they are susceptible to the lactic acidosis
• Lethal adverse effect is the increase production of lactate
• ED patient with an anion gap metabolic acidosis, check for metformin and check the lactate
• The lactic acidosis is often severe (>10 mmol/L) and carries a high mortality rate that has been estimated at >40%
• Correction of pH and emergent hemodialysis are essential

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•  Dapsone has been used to treat leprosy but more commonly to in brown recluse spider bites and to prevent PCP pneumonia and toxoplasmosis in our HIV population
• It can cause methemoglobinemia: a reduced form of iron (ferrous to ferric) in the Hb molecule that decreases your oxygen carrying capacity. 
• Due to its color, cyanosis is a predominant symptom out of proportion to symptoms.
• Treatment: Methylene Blue 1-2 mg/kg IV
• Pitfall: Dapsone's long half-life may cause reoccurrence of MetHb and require retreatment