It is not often that a CT will be able to give you a hint to a toxicologic diagnosis. The following are CT findings that are either suggestive and even sometimes almost diagnostic for a given to toxin:

1) Intraparenchymal or Subarachnoid Hemorrhage: sympathomimetics or mycotic anuerysm rupture secondary to IV drug abuse

2) Basal Ganglia bilateral focal necrosis: characteristic of carbon monoxide, cyanide, hydrogen sulfide and even methanol

3) Severe advanced atrophy out of proportion for age: alcoholism, toluene

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As everyone knows by now the New England Compounding Company has been implicated in contaminated steroid vials that were used for epidural injections. Patients that have pleocytosis on CSF after lumber puncture will be admitted and started on liposomal amphotericin B and IV voriconozaole. 

IV Voriconazole Adverse Effects:

Vivid visual hallucinations

Visual Disturbances - 30 min after administration: Blurry, photosensitivity

Hepatotoxitcity

Photoxicity - associated with increased risk of squamous cell CA of the skin

Many who work in urban EDs and have a patient population that has a high rate of methadone use have probably wondered - why don't I see many STEMIs in the ED?

One study has actually attempted to answer the question - is methadone cardioprotective? Comparing 98 decedents with known long-term methadone exposure and compared autopsy coronary artery findings to match controls without, there was significant decrease in incidence of severe CAD:

5/98 Methadone Patients post-mortem had severe CAD vs 16/97 match controls

Better than a baby ASA, who knew?

[I thank Dr. Hoffman for citing this article to me]

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Ever have that alcholic who requires lorazapam doses that start to approach 10mg? 20mg? or even higher. The next step is usually a lorazepam infusion and then send them to the ICU. In the ICU,  the patient develops an unexplained anion gap lactic acidosis.

Check a Lactate - lorazepam has 80% propylene glycol (PG). PG is metabolized to lactate which can accumulate when a lorazepam infusion at an elevated dose is running constantly.  Hypotension, bradycardia and even other EKG changes have been reported. Simply discontinue the infusion and assess your acid-base status. 

Other IV meds that contain PG:

lorazepam - 80% PG

Phenytoin - 40% PG

Phenobarbital - 67.8%

Diazepam - 40% PG

Just when you think buying organic protects you from chemicals and pesticide, along comes the studies detecting arsenic in rice products and specficially in organic foods with brown rice organic sweetener. An organic toddler milk formula reportedly had 6x EPA standards for safe drinking water limit.

The more toxic arsenic is the inorganic arsenic which can cause neuropathy but after chronic exposure can cause a classic arsenic keratosis - see attached pic. The inorganic is seen commonly in seafood and is more easily excreted by the body. Unfortunately, in the study referenced here, inorganic As was the predominant type.

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1209202121_arsenickeratosis.jpg (129 Kb)

I was reading the biography of Steve Jobs looking for incredible insights into leadership and innovation. I have realized that you basically have to be a genuis and it doesn't matter what you do. His favorite drug was LSD which he believed was necessary to improve creativity and innovation. His description of the hallucinations confirm that he was taking this drug.

We describe LSD hallucinations as a crossing of the senses or "synesthesias" - you hear the color blue, you see the smell of roses.

Steve Jobs describes a moment in a wheat field while on LSD and (paraphrasing from the biography) ..." the wheat was playing Bach beautifully"

If you have a patient describing this type of hallucination you can almost be guaranteed that they have taken LSD or some other tryptamine.

Patients that experience altered mental status (specifically lethargy) and are on valproic acid - check a serum ammonia level regardless if it is an overdose or just therapeutically on VPA.

If the ammonia is elevated in combination with the mental status change consider administration of L-carnitine either po or IV. It will lower the ammonia and improve the mental status  within hours.

High risk patients for hyperammonia who therapeutically take VPA are certain pediatric patients that experience malnutrition, have seizure disorder and are on multiple seizure medications.

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CIWA-Ar (Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised)

The use of a scoring system for the disposition of an ethanol withdrawal patient can be helpful. The CIWA-Ar Score can guide both treatment in the ED as well as admission versus discharge. Most studies have verified that a score of <8 can be treated outpatient; 8-15 requires treatment and >15 wil require admission/IV benzodiazepines.

N/V: 0-7 (None to Constant N/V)

Tremor: 0-7 (None to Severe even with arms not extended)

Sweats: 0-7 (None to Drenching Sweats)

Anxiety: 0-7 (None to panic attack/delirium)

Agitation: 0-7 (None to pacing/thrashing during interview)

Tactile Disturbance: 0-7 (Mild itching to Continuous Hallucinations)

Auditory Disturbances: 0-7 (None to Continuous Hallucinations)

Visual Disturbances: 0-7 (None to Continuous Hallucinations)

Headache: 1-7 (Miild to Extremely Severe)

Orientation: 0-4

Go to this website to see the actual tool and how it should be administered:

http://www.regionstrauma.org/blogs/ciwa.pdf

Though an uncommon event, Drug-Induced Autoimmune thrombocytopenia occurs in a variety of drugs. Having recently diagnosed a patient that was receiving the "double-dose" bactrim for an MRSA abscess, it is worth mentioning the other drugs that have been reported to do it. Platelet count can go down to lethal levels and result in death due to the coagulopathy. Treatment is effective with platelets and no contraindication like in TTP.

Drugs that have been reported to do it:

abciximab, acetaminophen, amiodarone, amphotericin B

Carbamazepine, danazol, diclofenac, digoxin

Methyldopa, procainamide

Rifampin, trimethoprim-sulfamethoxazole, vancomycin

Transplant patients are the norm now in the ED. Their drug lists are immense and are usually on some form of immunosuppression to prevent rejection of the transplanted organ. Two common medications are cyclosporine and tacrolimus. They share many adverse effects like hepatotoxicity, nephrotoxicity and hypertension. Here is the mechanism of action and some unique adverse effects to these powerful immunosuppressants (there are many more so be wary):

1) Cyclosporine - suppresses T-cell activation and growth. Unique toxicity - painful neuropathy of the fingertips and toes, cortical blindness

2) Tacrolimus - simiar to cyclosporine but actually hampers T-cell communication/signal transduction. Unique toxicity - can also cause cortical blindness but is also known to cause diabetes/hyperglycemiad

Nitrous Oxide(N2O) is a common gas utilized to assist with procedural sedation especially in the pediatric population and dental offices. It has a long track history of safety but also has been abused.

N2O is 35x more solube in blood than N2. This means any air-filled space can have pressure increase thus complications like pneumothorax, TM rupture and bowel distention can occur.

When abused chronically can cause bone marrow suppression, B12 deficiency and resulting in polyneruopathy.

On the street, "whip its" are N2O from whipped cream containers. Balloons filled with N2O are inhaled which combine nitrous oxide and hypoxia effects.

More and more people are going to holistic medicine and "naturopaths". These have been an interesting source of toxicology case reports due to therapeutic misadventures. Vitamins have been an ever increasing adjunct to these health philosophies. The following are the vitamins and their related toxicity in overdose:

Vitamin A: Pseudotumor cerebri, increase ICH, hair thinning, hepatotoxicity

Vitamin D: Hypercalcemia

Vitamin E: can antagonize vitamin K particularly in vitamin K deficient people, could result in coagulopathy

Vitamin K: problem if supplement contains this and patient on coumadin, ask patient

Vitamin C: Association with increased kidney stones though controversial

Dexmedetomidine is an alpha2-agonist that has a similiar mechanism of action to clonidine. Short half-life and no respiratory depression make it possibly more effective than propofol in procedural sedation. Cost/Availability are the biggest barriers. Transient bradycardia is also possible but the actual incidence  of clinically significant bradycardia is not yet elucidated.

I am still awaiting the first emergency department study looking at dexmedetomidine for procedural sedation.

A recent article actually brought up the possibility of utilizing it intranasally which could have some tantalizing pediatric applications.

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Animal studies can pave the way for new clinical treatment modalities. In the setting of lung injury due to smoke inhalation, one of the problems (if you can get the ET tube in) are the elevated ventilatory pressures due to the massive edema. In this sheep model of smoke inhalation, nebulized epinephrine improved ventilatory pressures, PaO2/FiO2 ratio and pulmonary shunting.

We may have these sheep to thank for this new treatment.

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Coumadin Wannabe's - have indication non-valvular atrial fibrillation

1) Dabigatran (Pradaxa) 

2) Rivaroxaban (Xarelto)

Clopidogrel Wannabe's - both are antiplatelets

1) Ticagrelor (Brilinta)

2) Prasugrel (Effient)

If you were looking for the first case reports of lethal hemorrhage due to pradaxa that could not be reversed - look no further. One patient fall from standing dies from ICH and another death in a spine trauma patient on pradaxa. I am waiting for the first epidural hematoma due to pradaxa, xarelto, etc in ED. Watch out! :

  1: Garber ST, Sivakumar W, Schmidt RH. Neurosurgical complications of direct  thrombin inhibitors-catastrophic hemorrhage after mild traumatic brain injury in  a patient receiving dabigatran. J Neurosurg. 2012 Mar 6.       2: Truumees E, Gaudu T, Dieterichs C, Geck M, Stokes J. Epidural Hematoma &  Intra-operative Hemorrhage in a Spine Trauma Patient on Pradaxa® [Dabigatran].  Spine (Phila Pa 1976). 2012 Feb 16. 

You have seen the study comparing diazepam to lorazepam IV for the cessation of seizures. Lorazepam one that one. Now, for prehospital status epilepticus midazolam IM went head to head with IV lorazepam to see which would stop seizure more quickly.

This study was more about the practicality of starting an IV than it was of the pharmacokinetics or onset of action of a particular benzodiazepine. It was a large enough study to warrant publication in New Engl J Med last month and is worth noting.

Subjects whose seizures ceased before ED arrival (median):

Time to active treatment: 1.2 min IM Midazolam group;  4.8 min IV Lorazepam group

Median times active treatment to cessation of SZ:  3.3 min IM Midazolam and 1.6 min IV Lorazepam

Safety was equal in both groups. This study validates EMS initiating therapy with IM midazolam for the cessation of seizures while intravenous access is being attempted. 

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As we go through the problems of national drug shortages it is important to remember the old drugs but to also remember why they became old and seldom used drugs. Prime example is many hospitals are beginning to develop shortages of rocuronium - the nondepolarizing paralytic that has a fast onset. This shortage has caused many to switch back to succinylcholine. The following case report should serve as reminder of how succinylcholine - due to its depolarizing nature and fasciculations - can cause a transient but significant hyperkalemia.

Never be the first or last person to use a drug 

Vioxx was once touted to be the drug that would be the new standard for anti-inflammatories until it was found to increase your chance of MI by 33% and cause hypertension.

Dabigatran was recently pulled from Japan markets and now is dealing with an impressive meta-analysis by Uchino et al. It showed that dabigatran was significantly associated with higher risk of MI or ACS than other agents.

Control arms (included warfarin, enoxaparin or placebo): MI rate 83 per 10,514

Dabigatran arms: MI rate 237 per 20,000

OR 1.33; 95% CI, 1.03-1.71; p=0.03

The rush for what is perceived as a panaceae for all that is wrong with coumadin could actually cause an MI while it tries to prevent a stroke in nonvalvular a-fib.

Look at the study and decide for yourself and remember Vioxx:

http://archinte.ama-assn.org/cgi/content/full/archinternmed.2011.1666v1

Another great example of the generic drug name being so difficult to pronounce you have no choice but to say - Xarelto. The drug touts ease of use and no need for hematologic monitoring like Pradaxa. This drug has the same indication for stroke prevention in nonvalvular atrial fibrillation. It also is being used in DVT prophylaxis in hip and knee surgeries.

Differences:

- Selective Factor Xa inhibitor unlike Pradaxa which is a competetive direct thrombin inhibitor

- Once a day dosing instead of twice a day for Pradaxa

Same concerns:

- No real reversal but can use FFP in a pinch

- Recommend waiting 24 hrs DC med to perform surgical procedure - this includes LP. I am personally waiting for the first case report of LP performed in ED on a patient taking either Xarelto or Pradaxa with subsequent epidural hematoma. Someone is bound to miss this on the med list. Be careful.

Even if your hospital has not added it to its formulary, you will see patients on this drug in the ED.

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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