UMEM Educational Pearls - Toxicology

• Found as adulterant in street drugs

• Used in bodybuilding and for weight loss

• Long acting beta-2 agonist

• Has specific anabolic activity and increases lipolysis

• Toxicity presents with tachycardia, palpitations, tremor, and myocardial ischemia

There have been many attempts to reduce the incidence of contrast-induced nephropathy. Mechanism usually centers around antioxidant properties or free radical scavengers that prevent the acute kidney injury that may result after intravenous contrast. IV Fluid hydration, sodium bicarbonate and acetycysteine have been studied with only some evidence. There is also some controversial data that is beginning to surface regarding the use of atorvastatin with a recent article in Circulation 2012 that showed high dose atorvastatin (80mg) 24 hrs prior to angiography prevented contrast-induced acute kidney injury in patients with mild to medium risk. Link to article has been provided:

http://circ.ahajournals.org/content/126/25/3008

Cyclophosphamide-induced hemorrhagic cystitis is a well known to oncologists. This unique complication of this chemotherapeutic drug has a defined mechanism and could be seen in your Emergency Department.

- Hemorrhagic cystitis occurs in 46% of patients that receive cyclophosphamide

- Can occur even months after administration

- 5% can actually die from the hemorrhage

- Treatment: Bladder irrigation, hydration, supportive. Oral adminsitration of MESNA (2mercaptoethan sulfonate) and bladder irrigation with prostaglandins and even methylene blue have been attempted.

SSRIs and SNRIs like venlafaxine and sertraline are well known to cause hyponatremia. Usually considered safe, this adverse drug event can lead to weakness, confusion, seizure and even cerebral edema. Elderly are more susceptible to this adverse effect.

ADH is regulated by serotonin and thus the mechanism for the Hyponatremia is SIADH. 

Tolvaptan, a vasopressin receptor antagonist, has been a new treatment that has been used anecdotally in Europe. Waiting for the first US case report. 

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Several medications can produce a false-positive result for methadone on the urine drug screen: diphenhydramine, doxylamine, clomipramine, chlorpromazine, quetiapine, thioridazine, and verapamil.

Add a new one to the list. Tapentadol, a relatively new opioid analgesic similar to tramadol, can also produce a false-positive result for methadone on certain immunoassays.

A separate study concluded that tapentadol does not affect the amphetamine screen.

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Creatine

• is the most popular nutritional supplement, accounting for $400 million in sales annually
• a nonessential amino acid
• has been shown to improve performance in short, high intensity exercises, including weight lifting

Adverse effects: weight gain, edema, GI cramping, fatigue and diarrhea

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Despite a paucity of data, pain management clinics are administering topical gel mixtures that have included ketamine, tricyclics, calcium channel blockers and baclofen. Internet blogs have already identified this gel mixture as a way to "get high".  This is one of those google searches you have to do on your own.

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  1: Lynch ME, Clark AJ, Sawynok J, Sullivan MJ. Topical 2% amitriptyline and 1%  ketamine in neuropathic pain syndromes: a randomized, double-blind,  placebo-controlled trial. Anesthesiology. 2005 Jul;103(1):140-6.     2: Lynch ME, Clark AJ, Sawynok J. A pilot study examining topical amitriptyline, ketamine, and a combination of both in the treatment of neuropathic pain. Clin J Pain. 2003 Sep-Oct;19(5):323-8.    3: Uzaraga I, Gerbis B, Holwerda E, Gillis D, Wai E. Topical amitriptyline,  ketamine, and lidocaine in neuropathic pain caused by radiation skin reaction: a pilot study. Support Care Cancer. 2012 Jul;20(7):1515-24.   

Myth: The ornamental red plant - poinsettia - gained a reputation as a poisonous plant from a case report. In 1919, a 2-year-old child reportedly died from an ingestion and later an 8-month-old developed mucosal burns.  These anectdotal case reports perpetuated the myth that poinsettia plants are poisonous. In the modern literature there is one single case of anaphylaxis(1) due to poinsettia ingestion/exposure, an allergic dermatitis(2) and one case of dermatitis(4). 

Krenzelok et al.(3) showed there were 22,793 cases of poinsettia exposure and there were no fatalities reported to poison centers. 96.1% were kept at home without sequelae.

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  1: Kimata H. Anaphylaxis by poinsettia in infants with atopic eczema. Allergy.  2007 Jan;62(1):91-2.     2: Bala TM, Panda M. No poinsettia this Christmas. South Med J. 2006  Jul;99(7):772-3.    3: Krenzelok EP, Jacobsen TD, Aronis JM. Poinsettia exposures have good  outcomes...just as we thought. Am J Emerg Med. 1996 Nov;14(7):671-4.     4: Edwards N. Local toxicity from a poinsettia plant: a case report. J Pediatr.1983 Mar;102(3):404-5.  

The more well known causes of toxin-induced hyperthermia include sympathomimetics and anticholinergics. In addition, neuroleptic malignant syndrome, serotonin syndrome, and malignant hyperthermia are high on the differential.

Several other xenobiotics can cause hyperthermia in overdose as well:

• Salicylates and dinitrophenol cause hyperthermia by uncoupling oxidative phosphorylation.
• Thyroid medications cause hyperthermia via thyroid hormone's thermogenic effect and psychomotor agitation. Hyperthermia can be extreme (>106°F, >41°C).
• Caffeine/theophylline, isoniazid, and strychnine cause hyperthermia through refractory seizures and muscle contraction. Highest temp recorded with strychnine is (109.4°F, 43°C).

In general, benzodiazepines should be considered first-line therapy, followed by barbiturates, propofol, or other sedative hypnotics. Phenytoin rarely has a role in the management of toxin-induced seizures. Extrenal cooling measures are also warranted. Specifically for isoniazid, pyridoxine should be administered immediately with a benzodiazepine.

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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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Background

• Patients who are intoxicated with, or emerging from, phencyclidine (PCP) highs present with acute agitation that can be challenging to treat

• Risks of physical restraints for combative patients include injury, hyperthermia, rhabdomyolysis, and increased agitation or excited delirium

• Haloperidol is an option for chemical restraint that is typically safe and rapid acting

• Some concerns related to haloperidol use in PCP-intoxicated patients include worsened PCP-induced hyperthermia, dystonic or anticholinergic reactions, lower seizure threshold, and hypotension

 Data

• A recent retrospective case series assessed the frequency of adverse effects from the combination of PCP and haloperidol

• Of 59 cases, only two patients experienced an adverse reaction, and neither could be conclusively linked to haloperidol administration

• This analysis had several major limitations including retrospective design for identifying adverse reactions, potential for false positive PCP screens, and possible haloperidol administration more than 24 hours after PCP intoxication

​Bottom Line

While haloperidol may be safe for agitated PCP-intoxicated patients, this paper adds nothing to refute or support its use. Benzodiazepines and calm environment are still first-line therapy.

It should be noted that no data exist showing poor outcomes in PCP-intoxicated patients administered haloperidol, which begs the question "Is there even an issue?" Dr. Leon Gussow, author of The Poison Review, provides a nice answer and summary of the article here.

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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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Activated charcoal is most effective if given within 1 hour of overdose.

Prehospital administration of charcoal can be challenging, but may save significant time compared to waiting until arrival to the ED. The patient has to be transported by EMS, registered, seen by a provider, order for charocal placed...

Two studies evaluated the time difference between prehospital and hospital administration of GI decontamination.

• Study 1 found median time to activated charcoal in the ED was 82 minutes.
• Study 2 found mean time to activated charcoal by EMS was 5 minutes, compared to 51 if held until arrival to ED.

Bottom line: Don't underestimate the amount of time that goes by before you evaluate non-crashing patients upon arrival to the ED. If the story supports an overdose and the patient doesn't have contraindications for receiving charcoal, recommend it be given in the prehospital setting for greatest potential benefit.

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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

• Is associated with chronic use of marijuana

• Patients typically present with severe, recurrent nausea, vomiting, and abdominal pain, usually in the morning

• Temporary relief of symptoms is achieved by taking hot showers or baths

• Diagnostic work up is negative

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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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Attachments

• 1209202121_arsenickeratosis.jpg (129 Kb)

Carbon monoxide (CO) and hydrogen cyanide (HCN) are two of the main gases causing injury and death from smoke inhalation in fire victims. During the first phase of a fire, and prior to depletion of oxygen reserves and subsequent production of CO, formation of HCN from the thermal breakdown of nitrogen-containing materials may be the primary cause of lethal poisoning in an enclosed-space fire.

A recent, retrospective, observational study from Poland assessed the prevalence of toxic HCN exposure in victims of enclosed-space fires.

Important findings:

• Of the 285 patients who died, 169 (59%) had detectable cyanide blood levels. 82% also had elevated carboxyhemoglobin (COHb) levels.
• Of the 40 patients who survived, 20 (50%) had detectable cyanide blood levels. All 20 had elevated COHb levels.

Conclusion: The high prevalence of coincident HCN concentrations and COHb levels in victims of enclosed-space fires emphasises the need to suspect HCN as a co-toxin in all persons rescued from fire who show signs and symptoms of respiratory distress.

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• Exposure to organophosphates can lead to “intermediate syndrome.”

• It is a syndrome characterized by weakness of neck flexors and proximal limbs, cranial nerve palsies, and respiratory muscle weakness, which can lead to respiratory paralysis.

• It follows acute cholinergic syndrome and precedes a delayed neuropathy, thus it is an “intermediate syndrome,” typically developing 24-96 hours post exposure.

• The pathophysiology of IMS remains unclear.

• Serum cholinesterase levels and electrophysiological studies are helpful in confirming the diagnosis.

• With supportive therapy, including artificial ventilation, complete recovery occurs within 5-18 days.

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.