UMEM Educational Pearls - Toxicology

Category: Toxicology

Title: Unexplained Lactic Acidosis, a clue to poisoning

Keywords: Lactic acidosis (PubMed Search)

Posted: 1/5/2017 by Kathy Prybys, MD (Emailed: 1/6/2017) (Updated: 1/6/2017)
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Lactic acidosis is the most common cause of anion gap metabolic acidosis in all hospitalized patients. An elevated lactate level is an important marker of inadequate tissue perfusion causing subsequent shift to anaerobic metabolism and occuring in a variety of disease states such as sepsis. In patients with unexplained lactic acidosis without systemic hyoperfusion or seizure suspect  the following toxins:

  • Acetaminophen: Early on in massive ingestion usually associated with coma.
  • Cyanide
  • Metformin
  • HIV Drugs: Nucleotide reverse transcriptase inhibitors = Didanosine, stavudine, zidovudine due to mitochondrial toxicity.
  • Ethylene Glycol: Spuriously elevated lactate may occur with ethylene glycol toxicity due to the structural similarity between glycolic acid and lactate.Check for osmolar gap.
  • Kombucha ``mushroom'' tea 
 

 

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Category: Toxicology

Title: Utility of lactic acid level for diagnosis of cyanide poisoning in smoke inhalation victims

Keywords: cyanide toxicity, lactic acid (PubMed Search)

Posted: 12/29/2016 by Hong Kim, MD (Emailed: 12/30/2016) (Updated: 12/30/2016)
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Question

Smoke inhalation victims (house fires) are at risk of carbon monoxide (CO) and cyanide poisoning (CN). CO exposure/poisoning can be readily evaluated by CO - Oximetry but CN level can be obtained in majority of the hospital.

Lactic acid level is often sent to evaluate for CN poisoning.

 

Bottom line:

  1. Lactatic acid levels should be sent in all smoke inhalation victims.
  2. Elevate lactate > 10 mmol/L is highly suggestive of CN poisoning
    .

 

 

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Category: Toxicology

Title: Acetaminophen induced liver failure

Keywords: Acetaminophen, Liver Failure (PubMed Search)

Posted: 12/16/2016 by Kathy Prybys, MD
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Acetaminophen is one of the most common pharmaceutical ingestions in overdose and a leading cause of acute of liver failure in the U.S.  Early recognition and treatment is critical for prevention of morbidity.

  • Vigilance and screening is required for this "silent poison", available in hundreds of OTC products and in combination with numerous prescription medications. Symptoms may not be present early in course (for up to 24 hours) in poisoning.
  • Maximal benefit with antidote treatment, n-acetylcysteine (NAC) is time dependent within 8 hours of ingestion. Fulminant hepatotoxicity is unusual in acute overdoses treated with NAC within 10 hours of ingestion.
  • Early prediction of poor prognosis is essential to identify patients who may require life-saving liver transplantation.  Kings College Criteria: Arterial pH less than 7.30, INR greater than 6.5, Creatinine greater than 3.4, Grade III or IV encephalopathy combined with Lactate greater than 3.5 and Phosphate greater than 3.75 may increase sensitivity.

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Question

Recent study evaluated whether an acetaminophen (APAP) level obtained less than 4-hour post acute ingestion can predict which patient would not require n-acetylcysteine (NAC).  APAP cutoff level of 100 ug/mL was used for analysis. This was a secondary analysis of the Canadian Acetaminophen Overdose Study database (retrospective study). 

 

Bottom line:

  1. If initial APAP level of 100 ug/mL was applied as a cutoff point, it missed 27 patients (N= 1821) who had toxic APAP level at > 4-hour post ingestion that require NAC.  
  2. Only a very low (< 15 ug/mL) or undetectable initial APAP reliably identify (sensitivity 100%) patients who do not require NAC.
  3. Absorption of APAP can be delayed by coingestion of opioids or antimuscarinics.

 

 

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Category: Toxicology

Title: My patient really has all these drug allergies?

Keywords: Drug Allergy, ADR, ADE (PubMed Search)

Posted: 12/1/2016 by Kathy Prybys, MD (Emailed: 12/2/2016) (Updated: 12/2/2016)
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Question

Misclassification of adverse drug effects as allergy is commonly encountered in clinical practice and can lead to use of suboptimal alternate medications which are often less effective.

  • Nomenclature surrounding drug safety needs to be clear and unambiguous to avoid confusion. 
  • Adverse Drug Effect (ADE) = All drug induced disease. Majority are predictable based on drug's known pharmacology. Include harm related to medication errors and drug/food interactions. 
  • Adverse Drug Reaction (ADR) = Noxious or unintended reaction to a drug that is administered at therapeutic doses during normal use. Divided into predictable (majority 75-80%), related to pharmacologic actions of the drug in otherwise normal individuals) and unpredictable reactions (related to individual’s immunological response). 
  • "Drug allergies"  are relatively uncommon with cited incidence of 10%. Immunologically mediated reactions (type I to IV) to a pharmaceutical and/or formulation (excipient) in a sensitized person. They are dose independent and unrelated to pharmacological action of the drug. Most commonly, IgE-mediated type I (immediate) reactions caused by rapid release of vasoactive mediators from mast cells and peripheral basophils causing generalized reaction including urticaria, angioedema, stridor, wheezing, and cardiovascular collapse.
  • The skin is the most frequently and notably affected by drug induced allergic reactions.
  • Antibiotics, particuarly Beta-Lactams, are the most important cause of immediate hypersensitivity reactions. Approximately 10% of patients report a history of penicillin allergy, however after complete evaluation, up to 90% of these individuals are able to tolerate penicillin and are designated as having “penicillin allergy” unnecessarily.
  •  Pseudoallergy can occur with opioids due to histamine release. Codeine and morphine are most commonly associated with pseudoallergy. Coadministration of an antihistamine or use of a semi or synthethic opioid (Fentanyl, hydromorphone) can prevent this reaction.

 

 

 

 

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Category: Toxicology

Title: Management of heroin overdose patients in prehospital and ED setting: How long do they need to be observed?

Keywords: heroin overdose, observation period, bystander naloxone (PubMed Search)

Posted: 11/16/2016 by Hong Kim, MD (Emailed: 11/17/2016) (Updated: 11/17/2016)
Click here to contact Hong Kim, MD

Question

Recently a review paper was published regarding the duration of observation in heroin overdose patients who received naloxone.

It made several conclusions regarding heroin overdose:

  1. Treat (naloxone) and release in a prehospital setting may be safe.
  2. Short observation period (minimum of 1 hour) for heroin OD patients who were treated in the ED may be safe.
  3. Bystander and first responder naloxone administration is effective and safe.

It should be pointed out that this is a review paper of limited number of articles with variable quality. Additionally, the clinical history of “heroin use” may be unreliable as fentanyl and novel synthetic opioids are also sold as “heroin.” Providers should exercise appropriate clinical judgement when caring for these patients. 

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Category: Toxicology

Title: Buprenorphine/naloxone (Suboxone) exposure in pediatric population

Keywords: buprenorphine exposure, pediatrics, retrospective study (PubMed Search)

Posted: 10/26/2016 by Hong Kim, MD (Emailed: 10/27/2016)
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Question

Recently, a retrospective study of unintentional buprenorphine/naloxone exposure among pediatric population was published. All patients were evaluated by toxicologists at the time of initial hospital presentation (or transfer) at the study center.

 

Bottom line

  • 83% and 80% of the patients experienced respiratory and CNS depression, respectively.
  • Majority of the patients became symptomatic within 8 hours of exposure (range not available).
  • Naloxone reversed respiratory depression. Median dose for single naloxone dose: 0.09 mg/kg; median dose for multiple naloxone doses: 0.19 mg/kg.
  • The reported “ceiling effect” on respiratory depression in adult does not exist in pediatric population.
  • The optimal time of observation is unclear but it is prudent to observe pediatric buprenorphine exposure for up to 24 hours.

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Question

US, Canadian and European critical care and toxicology societies recently published a consensus recommendation is the management of CCB poisoning.

Bottom line:

1. First line therapy remains unchanged: IV calcium, atropin, high-dose insulin (HIE) therapy, vasopressor support (norepinephrine and/or epinephrine).

2. Refractory to first line therapy: increase HIE, lipid-emulsion, transvenous pacemaker

3. Refractory shock, periarrest or cardiac arrest: Above (#1 & #2) plus ECMO if available.

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Category: Toxicology

Title: "Leaves of 3 let them be"

Keywords: Poison Ivy, Toxicodendron, Urushiol (PubMed Search)

Posted: 10/6/2016 by Kathy Prybys, MD (Emailed: 10/7/2016) (Updated: 10/7/2016)
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Question

Fall clean up = Poison Ivy, oak, sumac (Toxicodendron species) which is ubiquitous in North America but it can also be found in British Columbia, Mexico and in parts of Asia. These plants are truly the scourge of outdoor enthusiasts and agricultural workers responsible for up to 40 million cases of miserable often temporarily incapacitating rashes annually.

Fast Facts:

  • Grows as plant, vine, or shrub with leaves ranging in color from light or glossy green to red and yellow in fall.
  • Exposure by direct contact with plant, indirectly from oil resin on objects, clothes, pets, or airborne from burning plant.
  • Urushiol toxin induced type IV hypersensitivity allergic contact dermatitis. This oily resin toxin is excreted from all parts of plant (stems, leaves, flowers, roots, vines). and is extremely stable staying active even after plant dies.
  • Intensely itchy blistering rash starts 12-72 hours after contact and lasts up to 21 days. Characterized by red streaks or linear configuration where skin brushed up against plant sap. Inflammation (redness, swelling, hives, blistering) to thick leathery plagues depending on severity and vulnerability of skin location. Intense inflammation can mimic cellulitis.
  • Rash is Not contagious but spread of oil on clothes, pets, tools, objects is!
  • Delayed reaction accounts for seemingly "spread" of rash. Eruption rate depends on thickness of skin and dose of urushiol oil.

Treatment Tips:

  • Prevention. Avoidance and universal precautions when gardening. Clusters of 3 leaves each trio growing on their own stem, hairy vines, no thorns, white berries.
  • Cover skin to prevent exposure and if known contact immediately wash skin, clothes, objects.
  • Hot water relieves itch as does cool compresses.
  • Domeboro or witch hazel are astringents can reduce inflammation.
  • External analgesics (e.g., benzocaine, lidocaine, benzyl alcohol) can help itching.
  • Highly viscous or granular cream surfactant washes bind urushiol and can reduce exposure. Zanfel, Mean green, Gojo orange, various generic poison ivy removal scrubs now available. (Zanfel works wonders used every few hours and may alleviate need for steroids but is $$$ and several tubes are required).
  • In severe cases, Steriod burst followed by 2-3 week taper to prevent relapse flare.

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Naloxone has been used to reverse opioid-induced respiratory depression for decades. The “standard” dose of opioid intoxication has been 0.4 mg.  However, over the past decade, initial naloxone dose for opioid intoxication has evolved to recommend a lower initial dose (0.04 – 0.05 mg).

 

A recent article by Connors et al. reviewed 25 medical resources (internet, medical texts and study guides) of different medical specialties (internal medicine, medical toxicology, emergency medicine, pediatrics, anesthesiology, pain medicine and general medicine)

 

Findings:

  • 12 medical resources (48%) recommend using 0.05 mg or less IV as an initial dose.
  • 9 medical resources (36%) recommend using 0.4 – 0.5 mg or higher as an initial dose.
  • Maximum dose also ranged widely from 2 to 20 mg.

 

Recent editions of emergency medicine text (Rosen’s and Tinitinalli) recommend using 0.04 – 0.05 mg IV in ED patients with history of opioid dependence. Higher doses of naloxone are recommended for non-opioid dependent/apneic patients.

 

However, history of opioid dependence is difficult to obtain in patients with opioid induced CNS/respiratory depression.

 

Administering 0.4 mg or higher dose may/can acute agitation or opioid withdrawal symptoms that can utilize more ED resources to calm agitated patient/management of withdrawal. Thus it may be prudent to use low-dose strategy (0.04 mg IV with titration) to minimize the risk of precipitating naloxone-induced opioid withdrawal/agitation.

 

Bottom line:

In opioid-induced respiratory depression/apneic patients:

  1. Ventilate with bag-valve mask for apnea/hypoxia
  2. Administer naloxone: 0.04 mg IV every 2 – 3 min until reversal of respiratory depression/hypoxia is achieved.

To make 0.04 mg naloxone solution:

  • Dilute 1 mL of 0.4 mg naloxone with 9 mL normal saline in 10 mL syringe. 

 

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Category: Toxicology

Title: Atypical antipsychotics: are they truly safer than typical antipsychotics?

Keywords: atypical antipsychotic toxicity (PubMed Search)

Posted: 9/8/2016 by Hong Kim, MD (Updated: 7/17/2024)
Click here to contact Hong Kim, MD

Antipsychotic as a class has diverse range of toxicity. The atypical (2nd generation) antipsychotics are considered to possess less toxicologic manifestation compared to the typical (1st generation) antipsychotics - lower K channel blockade and minimum Na channel blockade properties. However, select atypical antipsychotics overdose can results in significant morbidity in addition to sedation.

 

Alpha-1 blockade (hypotension)

  • Clozapine
  • Olanzapine
  • Quetiapine
  • Risperidone
  • Ziprasidone

 

Antimuscarinic effect (anticholinergic toxicity)

  • Clozapine
  • Olanzapine
  • Quetiapine

 

Delayed rectifier K channel blockade (QT prolongation)

  • Ertindole
  • Ziprasidone

 

Bottom line:  Although lethal overdose from atypical antipsychotics are rare, they can result in significant clinical toxicity when ingested alone or in combintation with other classes of medications.

 

 



Category: Toxicology

Title: Lethal in small dose or single pill in pediatric population (age < 5 years old)

Keywords: One pill killers, pediatric (PubMed Search)

Posted: 8/17/2016 by Hong Kim, MD (Emailed: 8/18/2016) (Updated: 8/18/2016)
Click here to contact Hong Kim, MD

In pediatric population, small dose or single pill ingestion can potential result in severe or lethal toxicity.

Clinicians should be mindful of potential toxicity following xenobiotic exposure (below) in pediatric population, especially under the age of 5 years old, even if the patient may initially appear asymptomatic.

  • Benzocaine
  • B-adrenergic antagonist (sustained release)
  • Calcium Channel blockers (sustained release) 
  • Camphor
  • Clonidine
  • TCAs
  • Diphenoxylate/atropine (Lomotil)
  • Toxic alcohol (methanol or ethylene glycol)
  • Methylsalicylate
  • MAO-Is
  • Opioids
  • Phenothiazines
  • Quinine or chloroquine
  • Sulfonylureas
  • Theophylline

 

Suspected ingestion of above medications/xenobiotics may warrent observation up to 24 hours in asymptomatic pediatric population.

 

 



Drug-induced hypoglycemia is an often severe and symptomatic. It is a potentially preventable cause of significant morbidity. In one large study, it accounted for 23% for hospital admissions due to adverse drug events and 4.4% of overall admissions. The majority of hypoglycemic events occur with insulin and sulfonylureas. However, multiple drugs can affect glucose homeostasis and have been cited to cause hypoglycemia in therapeutic dose alone or in combination with other medications or illness. Factors that predispose to low blood sugar include reduced food intake, age, hepatic and renal disease, and severe infection. Beware of the possibility of inducing hypoglycemia in patients taking the following:

  • Ethanol
  • Insulin
  • Pentamidine
  • Quinine
  • Quinolones (Gatifloxin others rare)
  • Sulfonylureas

Agents with lesser quality evidence as predisposing medications or illnesses were present:

  • Ace Inhibitors (with diabetic agents)
  • Propanolol ( less likely in other beta blockers)
  • Trimethoprim/sulfamethoxazole (in renal compromise)
  • Salicylates (high dose or intoxication)

Drugs induced hypoglycemia should always be considered in the differential diagnosis of every patient presenting with low blood glucose. Octreotide antagonizes pancreatic insulin secretion and should be considered for first-line therapy in the treatment of sulfonylurea-induced hypoglycemia particularly when glucose levels cannot be maintained by dextrose infusions. Octreotide is administered 50 mcg subcutaneously (1-10 mcg in children) every 12 hours.

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Category: Toxicology

Title: Are synthetic opioids next novel designer drugs of abuse in the U.S?

Keywords: novel synthetic opioid, U-47700 (PubMed Search)

Posted: 8/1/2016 by Hong Kim, MD (Emailed: 8/3/2016) (Updated: 7/17/2024)
Click here to contact Hong Kim, MD

Recently, there have been several news reports regarding the emergence of synthetic opioids in the U.S. and Canada. There are multiple synthetic opioids that have been identified as potential agents of abuse including W-18, U-47700, fentanyl derivatives, AH-7921 and MT-45. These compounds share a similar story with synthetic cannabinoid where they were synthesized for research purpose or by pharmaceutical companies but were not marketed. They are often sold as “research chemicals” over the internet.

In July 2016, three case reports have been published regarding several cases of U-47700 intoxication in San Diego, CA and Dallas, TX.

  • Dallas, TX: A couple in their 20’s purchased U-47700 on the internet believing it to be “synthetic cocaine.” They both suffered CNS and respiratory depression after insufflation. Naloxone was not administered in both cases. The man was intubated while the woman was awake at time of presentation to the ED. U-47700 exposure was confirmed by liquid chromatography/tandem mass spectrometry.

 

  • San Diego, CA: a 22 year old man with history of heroin abuse was found unresponsive and apneic (4 breaths per minute and pulse oximetry of 60%). He received naloxone 2 mg IV which completely reversed his CNS and respiratory depression. He admitted to purchasing U-47700 on the internet and its use prior to being found unresponsive. U-47700 exposure was confirmed using liquid chromatography/mass spectrometry.

 

  • Central CA: 41 year old woman presented with CNS depression and pinpoint pupils after ingesting 3 tablets of “Norco” purchased from the street.  Her intoxication was completely reversed with naloxone 0.4 mg IV and discharged after 4 hour observation. Fentanyl and U-47700 was detected in serum blood test.

It is unknown if currently available heroin is cut with above mentioned synthetic opioids. Like other opioid receptor agonists, administration of naloxone will likely reverse the opioid toxidrome. But clinical experience in reversing synthetic opioids intoxication with naloxone is limited.  

 

Bottom line:

Irrespective of whether an ED patient is exposed to synthetic opioids or "traditional" opioids of abuse (prescription opioid pain medication or heroin), the management of opioid intoxication management remains unchanged for respiratory depression. 

  1. Airway management: bag-valve assisted ventilation if needed
  2. Naloxone administration (initial dose: 0.04 to 0.4 mg IV) with titration as needed. 
  • naloxone's clinical duration of effect ranges from 30 to 90 minutes.

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Category: Toxicology

Title: Laundry detergent pods exposure - the hidden danger.

Keywords: Pediatric exposure, laundry detergent pods (PubMed Search)

Posted: 6/23/2016 by Hong Kim, MD
Click here to contact Hong Kim, MD

Laundry detergent pods were introduced in 2012 to make washing clothes more "convenient." Since then, pediatric exposures to laundry detergent pods have increased as the use of these detergent pods have become more common in homes. Like other household chemical exposure, small, colorful candy like appearances of laundry detergent pods can attract the attention of < 3 years old children resulting in unintentional exposure due to curiosity or taste.

Most frequent clinical effects (2013 - 2014 national poison center data) from exposure to detergents in general (laundry detergent pods and nonpods & dishwasher detergent):

  • GI: nausea & vomiting: 29.1%
  • Cough/choking: 8.3%
  • Ocular irritation/pain: 5.6%
  • Red eye/conjunctivitis: 3.4%
  • Drowsiness/lethargy: 2.8%

Laundry detergent pod vs. nonpods:

  • Higher referral to health care facility: 17.4% vs. 4.7%
  • Higher odds of experiencing > 1 clinical effects (OR: 3.9; 95% CI: 3.7 4.1)
  • Higher odds of hospital admission (OR: 4.8; 95% CI: 4.0 5.8)
  • Higher odd of intubation (OR: 6.9; 95% CI: 3.5 13.6)

Laundry detergent pods (only) also resulted in following:

  • Coma: 17 cases
  • Respiratory arrest: 6 cases
  • Pulmonary edema: 4 cases
  • Cardiac arrest: 2 cases

Cases of caustic exposure-like injuries have also been reported (corneal abrasion and esophageal injury)

Bottom line:

Pediatric laundry detergent (nonpods) exposures usually have self-limited symptoms. However, laundry detergent pod exposure can cause more serious clinical effects that may require hospitalization.

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Category: Toxicology

Title: Loperamide high more than a fix for diarrhea.

Keywords: loperamide, opioid alternative, cardiac toxicity (PubMed Search)

Posted: 6/15/2016 by Hong Kim, MD (Updated: 7/17/2024)
Click here to contact Hong Kim, MD

Loperamide is a peripheral mu-opioid receptor agonist that is found in over the counter anti-diarrheal medication. Following the trend of opioid abuse epidemic, loperamide has been promoted on online drug-use forum as a treatment for opioid withdrawal and as a possible alternative to methadone.  At the same time, recreational use of loperamide has been increasing as an opioid alternative. Unlike therapeutic use of loparamide (2 – 4 mg), loraparmide abusers take supratherapeutic doses (e.g. 50 – 100 mg) to penetrate the CNS to produce opioid effects.  

 

In published case reports, loperamide caused cardiac Na channel blockade (similar to TCA and bupropion) and K channel blockade, resulting in EKG changes including QRS interval > 100 msec with terminal R wave in aVR and QTc prolongation, respectively. Loperamide associated death has also been reported (autopsy finding), although the exact cause of death was not determined.

 

It is unclear if administration of NaHCO3 can reverse the cardiac Na channel blockade as in TCA and bupropion as the clinical experiences have been limited.

 

Bottom line:

  • Clinicians should be aware of potentially lethal cardiac toxicity of loperamide abuse (Na and K channel blockade).

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Category: Toxicology

Title: Ketamine for Prehospital Agitation - Prospective Study Results

Keywords: ketamine, agitation, prehospital, haloperidol (PubMed Search)

Posted: 6/7/2016 by Bryan Hayes, PharmD (Emailed: 6/9/2016) (Updated: 6/27/2016)
Click here to contact Bryan Hayes, PharmD

Ketamine is gaining traction as a prehospital option for managing severe agitation or excited delirium syndrome. Previous reports have mostly been case series, but a new prospective study adds some important information that may help delineate ketamine's role in this setting. [1] The study and an accompanying commentary are both open access. [2]

What They Did

Open-label before-and-after prospective comparison of haloperidol (10 mg IM) versus ketamine (5 mg/kg IM) for the treatment of acute undifferentiated agitation.

What They Found

  • Ketamine demonstrated a statistically and clinically significant difference in median time to sedation compared to haloperidol, 5 min vs. 17 min (p < 0.0001, 95% CI: 9 15)
  • Complications: ketamine, 49%; haloperidol, 5%
    • Ketamine complications: hypersalivation (38%), emergence reaction (10%), vomiting (9%), and laryngospasm (5%)
  • Intubation rate: ketamine, 39%; haloperidol, 4%

Appliation to Clinical Practice

  • Ketamine works for prehospital agitation (and more rapidly)
  • Ketamine has a higher complication and intubation rate
  • Though this study did not find a dose relationship between ketamine and intubations, future studies should evaluate further and potentially use lower ketamine doses
  • At our institution, we start with 2-3 mg/kg IM and repeat if necessary after 5 min. Most patients have not required a second dose and none have been intubated. This allows time to place an IV line and initiate additional treatment.

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Category: Toxicology

Title: Bupropion Toxicity

Keywords: Bupropion, Seizure, Cardivascular instability (PubMed Search)

Posted: 6/2/2016 by Kathy Prybys, MD (Emailed: 6/3/2016) (Updated: 6/3/2016)
Click here to contact Kathy Prybys, MD

Bupropion (Wellbutrin, Zyban) is one of the most frequently prescribed antidepressants and smoking cessation agents. A lesser incidence of undesirable side effects such as weight gain and sexual dysfunction when compared to other antidepressants lends to its popularity. Bupropion's mechanism of action is only partially understood but it is known to be a norepinephine dopamine reuptake inhibitor and anticholinergic receptor blocker at certain nicotinic receptors. Bupropion has a monocyclic structure similar to amphetamines. Seizures are a major concern in overdose. When first released, Bupropion was initially withdrawn from the market due to its narrow therapeutic window with seizures occurring at doses as low as 450 mg.

  • Seizures are dose dependent and all types can occur. Incidence increases dramatically with higher doses. Benzodiazepines are first-line therapy.
  • Most patients experience seizure within 8 hours however, seizures can occur up to 24 hours after ingestion even without preceding symptoms.
  • Longer acting forms: SR, XL, ER cause prolonged toxicity and activated charcoal should be administered in the absence of contraindications (depressed mental status, lack of airway protection, seizure).
  • Myocardial sodium channel blocking properties occur and sodium bicarbonate should be administered when this occurs.
  • Cardiovascular effects including tachycardia, prolonged QT interval, QRS widening, arrhythmia, and cardiovasular collapse.
  • Bupropion is extremely lipid soluble and intravenous lipids should be considered in severe poisonings. Intralipid has been successfully used in several cases of Bupropion poisoning with cardiovascular instability or severe CNS symptom with good outcomes.

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Category: Toxicology

Title: Does Digoxin Immune Fab Work in Chronic Digoxin Poisoning?

Keywords: digoxin, chronic, poisoning, immune Fab (PubMed Search)

Posted: 5/9/2016 by Bryan Hayes, PharmD (Emailed: 5/12/2016) (Updated: 5/12/2016)
Click here to contact Bryan Hayes, PharmD

Patients with chronic digoxin toxicity generally have multiple co-morbidities such as renal failure, dehydration, and cardiac failure. Sick patients with chronically high digoxin levels may have more than just digoxin toxicity as the cause of illness.

A New Study

Prospective observational study with the primary objective to investigate changes in free digoxin concentrations and clinical effects on heart rate and potassium concentrations in chronic digoxin poisoning when digoxin immune Fab are given.

What They Found

One to two vials of digoxin immune Fab initially bound all free digoxin confirming Fab efficacy. However, this was associated with only a moderate improvement in HR (49 to 57 bpm) and potassium (5.3 to 5.0 mmol/L).

Application to Clinical Practice

  • Elevated digoxin concentrations alone may not be solely responsible for bradycardia and hyperkalemia in the chronic setting.
  • Digoxin immune Fab is not a magic bullet in chronic digoxin poisoning.

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Category: Toxicology

Title: ECMO for Severely Poisoned Patients

Keywords: Extracorporeal Membrane Oxygenation, ECMO, toxicology, poison (PubMed Search)

Posted: 4/13/2016 by Bryan Hayes, PharmD (Emailed: 4/14/2016) (Updated: 4/14/2016)
Click here to contact Bryan Hayes, PharmD

The American College of Medical Toxicology's ToxIC Registry is a self-reporting database completed by medical toxicologists across 69 insitutions in the US.

  • Over a 3 year period, just 10 cases in the database received ECMO: 4 pediatric, 2 adolescent, and 4 adults (individual cases presented in the table below)
  • Time of initiation of ECMO ranged from 4 h to 4 days, with duration from 15 h to 12 days
  • Exposures included carbon monoxide/smoke inhalation (2), bitter almonds, methanol, and several medications including antihistamines (2), antipsychotic/antidepressant (2), cardiovascular drugs (2), analgesics (2), sedative/hypnotics (2), and antidiabetics (2)
  • Overall survival rate was 80%

Application to Clinical Practice

In settings where ECMO is available, it may be a potential treatment option in severely poisoned patients. From the limited data, ECMO was generally administered prior to cardiovascular failure and might be of benefit particularly during the time the drug is being metabolized.

Table from the Case Series

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