UMEM Educational Pearls - Toxicology

Strychnine poisoning is still occasionally found in rat poisons and in adulterated street drugs and herbal products. The typical symptoms are involuntary, generalized muscular contractions resulting in neck, back, and limb pain. The contractions are easily triggered by trivial stimuli (such as turning on a light) and each episode usually lasts for 30 seconds to 2 minutes, for 12 to 24 hours. Classic signs include opisthotonus, facial trismus, and risus sardonicus.

Differential diagnosis includes:

• Tetanus: However, the onset of symptoms is more gradual and the duration much longer than in the case of strychnine poisoning.
• Generalized seizures: However, strychnine poisoning presents with a normal sensorium during the period of diffuse convulsions.
• Dystonic reaction: However, dystonic reactions are usually static, whereas strychnine poisoning results in dynamic muscular activity. 
• Serotonin syndrome
• Malignant hyperthermia
• Neuroleptic malignant syndrome
• Stimulant use

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If you are working in a community hospital and have an acetaminophen overdose, one of the criteria to transfer the patient to a tertiary care center is presence of the King's College Criteria.

The below is taken from mdcalc.com -  http://www.mdcalc.com/kings-college-criteria-for-acetaminophen-toxicity/

Each one is assigned points and can be prognostic for severe toxicity and need for transplant. The lactate and phosphorus are new ones and have modified the criteria. Phosphorus is utilized to create glycogen. If the liver is injured and trying to heal, your phosphorus will be low (good). If the liver is injured and unable to repair itself the phosphorus will be high (bad). This single test has an excellent prognostic ability.

With recent events, a few notes about ricin seems appropriate:

1. Easy to make from castor bean though heat labile
2. No antidote, though Fab like digibind is in development
3. Granule size of the grain of sand can kill
4. Inhalation, IM, IV all effective
5. After immediate exposure likely no symptoms
6. Vomiting and diarrhea initially, acute lung injury and death in 3-5 days

CDC website: http://www.bt.cdc.gov/agent/ricin/

Cocaine toxicity is characterized by the sympathomimetic toxidrome: tachycardia, hypertension, hyperpyrexia, diaphoresis as well as sodium channel blocking effects that can cause local anesthesia topically, QRS widening and even seizure.

Usual treatment for a cocaine toxic patient is benzodiazepines and cooling. Be wary of end organ damage, trauma and seizures.

There was a recent study that looked at dexmedetomidine to treat the sympathomimetic effects. Placebo-controlled trial used cocaine-addicted volunteer and applied intranasal cocaine. Measuring skin sympathetic nerve activity and skin vascular resistance, this study, unfortunately, showed as the dose increased  MAP did not fall further and increased paradoxically in 4 of 12 subjects.

This highlights the incredible physiologic mechanism of catecholamine release from the CNS with cocaine. This mechanism overlaps some with the centrally acting alpha agonist - dexmedetomidine and was shown in the study by Kontak et al. 

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In 2013, the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists published a second update to their position statement on gastric lavage for GI decontamination (original 1997, 1st update 2004).

• Gastric lavage should not be performed routinely, if at all, for the treatment of poisoned patients.
• Further, the evidence supporting gastric lavage as a beneficial treatment even in special situations is weak.
• In the rare instances in which gastric lavage is indicated, it should only be performed by individuals with proper training and expertise.

Bottom line: Gastric lavage generally causes more harm than good. It should not be thought of as a viable GI decontamination method.

Bonus: Dr. Leon Gussow (@poisonreview) reviews the position paper on his blog, The Poison Review, here: http://www.thepoisonreview.com/2013/02/23/gastric-lavage-fuggedaboutit/

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Question

A foley is inserted in a fire victim patient. Urine return is in picture. Describe the reason for this colored urine.

Special Thanks to Dr. Doug Sward for the urine picture 

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Attachments

Foley-Sward.jpg (4,224 Kb)

Typical opioid withdrawal include clinical symtpoms of piloerection, nausea, vomiting and diarrhea. If you were to see seizure, another etiology other than opioid withdrawal should be investigated. 

Except in the case of neonates borne to women who have been taking opioids chronically such as a methodone patient. Once the child is born, symptoms of withdrawal may take days to weeks to materialize though seizures typically occur <10 days. The child is at increased risk of SIDS as well.

Most antidotes have not been adequately studied in pregancy and hold a Pregnancy Risk Category 'C' by the FDA. However, there are a few antidotes that hold a category 'D' or 'X' rating (contraindicated).

1. Ethanol (toxic alcohols) - Category C
   • Reproduction studies have not been conducted with alcohol injection. Ethanol crosses the placenta, enters the fetal circulation, and has teratogenic effects in humans. When used as an antidote during the second or third trimester, Fetal Alcohol Syndrome AS is not likely to occur due to the short treatment period; use during the first trimester is controversial.
   • Alternative (preferred) antidote: fomepizole.
2. Methylene blue (methemoglobinemia) - Category X
   • Use during amniocentesis has shown evidence of fetal abnormalities, but it has been used orally without similar adverse events. IV may be ok.
3. Lorazepam and diazepam (seizures, nerve agents) - Category D
   • Teratogenic effects have been observed in some animal studies and in humans. Lorazepam/diazepam and their metabolite cross the human placenta.
4. Potassium iodide (radioactive iodine) - Category D
   • Iodide crosses the placenta (may cause hypothyroidism and goiter in fetus/newborn). Use for protection against thyroid cancer secondary to radioactive iodine exposure is considered acceptable based upon risk:benefit, keeping in mind the dose and duration.
5. Amyl nitrite (cyanide) - Category C (manufacturer contraindicates)
   • Animal reproduction studies have not been conducted. Because amyl nitrate significantly decreases systemic blood pressure and therefore blood flow to the fetus, use is contraindicated in pregnancy (per manufacturer).
   • Other options exist to treat cyanide exposure including sodium nitrite, sodium thiosulfate, and hydroxocobalamin.
6. Penicillamine (chelator) - Category D

In most cases, the benefits of short-term use probably outweigh the risk, especially when accounting for the health and prognosis of the mother.

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• 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