UMEM Educational Pearls - By Hong Kim

Category: Toxicology

Title: Benefit of activated charcoal in large acetaminophen ( >= 40 gm) overdose.

Keywords: activated charcoal, large acetaminophen overdose, NAC dose (PubMed Search)

Posted: 1/11/2018 by Hong Kim, MD, MPH (Updated: 10/25/2021)
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Acetaminophen (APAP) overdose is the leading cause of liver failure in the U.S. and Europe. Large APAP ingestion can result in hepatotoxicity despite the early initiation of n-acetylcysteine (NAC). 

A recently published study from Austrialia investigated the effect of activate charcoal and increasing the NAC dose for large APAP overdose patients (3rd bag: 100 to 200 mg/kg over 16 hours) during first 21 hours of NAC therapy

acetaminophen ratio (first APAP level taken between 4 to 16 hour post ingestion / APAP level on the Rumack nomogram line at that time point) was determined to compare APAP levels at different time points among study sample

e.g.  

first APAP level at 4 hour post ingestion = 400

APAP level on the Rumack APAP nomogram at 4 hour post ingestion = 150

APAP ratio = 400/150 = 2.67

 

Findings:

  1. Activated charcoal (AC): if given within 4 hours, AC significantly decreased the APAP ratio (OR: 1.4 vs. 2.2)
  2. Increased dose of NAC during the first 21 hour significantly decreased the risk of hepatotoxicity (OR: 0.27; 95% CI: 0.08 - 0.94).

 

Conclusion: 

  1. Administration of AC in patients with history of large APAP overdose (>=40 gm) within 4 hour of ingestion can still be beneficial.
  2. Increasing NAC dosing (3rd bag in first 21 hour thearpy) may decrease the risk of hepatotoxicity. 

Note: Any increase in NAC dosing from the standard 21 hour therapy should be performed after consulting your regional poison center.

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Question

 

Different chemical, food or pharmaceutical agent exposure can change the color of the urine.

What could cause this patient's urine to turn green?

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IMG_4194.JPG (2,012 Kb)


Category: Toxicology

Title: Do you have digoxin-like toxins growing in your backyard?

Keywords: cardioactive steroids, cardioactive glycoside (PubMed Search)

Posted: 11/9/2017 by Hong Kim, MD, MPH (Updated: 10/25/2021)
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Many medications are discovered from plants (quinine – cinchona trees) or organisms (penicillin – mold [penicillicum]).

Digoxin was isolated from foxglove (Digitalis lanata), a colorful floral plant often found in many gardens.  There are other sources of cardioactive steroids (aka cardiac glycosides) that have similar effect as digoxin.

  • Oleander (Nerium oleander)
  • Yellow orleaner (Thevetia peruviana) – frequently used for suicide in Southeast Asia
  • Lily of the valley (Convallari majalis) – use in wedding bouquet
  • Dogbane (Apocynum cannabinum)
  • Red squill (Urginea maritima)
  • Bufo toad (Bufo species)  

 

Non-digoxin cardioactive steroid exposure can result in a positive digoxin level due to cross reactivity. This confirms exposure; however, the “digoxin level” does not represent the true extent of the ingested dose or toxicity. 

Non-digoxin cardioactive steroid toxicity

  • Digibind also binds to non-digoxin cardioactive steroids.
  • However, larger doses are often required (initial dose: 10 to 20 vials) than doses required for digoxin toxicity.   

Category: Toxicology

Title: Agatha Christie 2.0 Strychnine

Keywords: strychnine (PubMed Search)

Posted: 10/26/2017 by Hong Kim, MD, MPH (Emailed: 10/27/2017) (Updated: 10/27/2017)
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Her first book “The mysterious affair at Styles,” Agatha Christie introduced her lead detective in her novels, Hercule Poirot - the Belgian detective.  She also described the death of Mrs. Emily Inglethorp by strychnine.

Strychnine is found in a disc-like seed of strychnos nux-vomica, a tree native to tropical Asia and North Australia.

It is currently used as rodenticide (moles and gophers), in Chinese herbal medicine and a traditional remedy in Cambodia.

Strychnine inhibits binding of glycine (a major inhibitory neurotransmitter in spinal cord) to Cl-channel resulting in identical clinical syndrome – seizure-like generalized muscle contraction with normal mental status – as tetanus toxin. Tetanus toxin inhibits the release of presynaptic glycine in the spinal cord. 

 

Management

Goal: decrease muscle hyperactivity

  • 1st line: benzodiazepine
  • 2nd line: barbiturates or propofol
  • 3rd line: paralysis by non-depolarizing agents

Category: Toxicology

Title: Arsenic and Agatha Christie

Keywords: Arsenic poisoning (PubMed Search)

Posted: 10/19/2017 by Hong Kim, MD, MPH
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Agatha Christie is an English crime novelist who frequently used poisons in her books to murder the victims. In her book, Murder is Easy, Ms. Christie uses arsenic/arsenic trioxide to kill several characters.

 

Primary source of arsenic in general population is contaminated food, water and soil. Arsenic exists in several forms: elemental, gaseous (arsine), organic and inorganic (trivalent or pentavalent).

 

Arsenic trioxide has also been used to treat acute promyelocytic leukemia in China; it’s use in other leukemia, lymphoma, and other solid tumors are currently being investigated.

 

Arsenic primarily inhibits the pyruvate dehydrogenase complex and multiple other enzymes involved in the citric cycle/oxidative phosphorylation, resulting in mitochondrial dysfunction.

 

Acute toxicity of arsenic after ingestion

  1. GI symptoms (minutes to several hours) – nausea, vomiting, abdominal pain and cholera like diarrhea.
  2. Cardiovascular: QT prolongation/torsade de pointes, orthostatic hypotension, ventricular dysrhythmias, myocardial dysfunction and shock.
  3. CNS (days): encephalopathy, delirium, coma, and seizure due to cerebral edema and microhemorrhages.
  4. Respiratory: ARDS, respiratory failure,
  5. Others: AKI, leukemoid reaction, hemolytic anemia, and hepatitis.

 

 Management

  1. Chelation: dimercaptrol (BAL) or succimer
  2. Whole bowel irrigation if radiopaque material is present (abdominal XR)
  3. Electrolyte and fluid management
  4. Cardiac monitoring and pressor support in hypotension

During the past several years, several new classes of diabetic medications were introduced for clinical use, including SGLT2 inhibitors (canagliflozin, dapagliflozin and empagliflozin).

SGLT2 inhibitors prevent reabsorption of glucose in the proximal convoluted tubules in the kidney and does not alter insulin release.

A recent retrospective study (n=88) of 13 poison center data from January 2013 to December 2016 showed

  1. 91% of the patients were asymptomatic.  
  2. 7% developed minor symptoms (tachycardia, nausea/vomiting, abdominal pain, & confusion)
  3. 2% developed moderate symptoms (metabolic acidosis, hypertension [166/101], & hypokalemia)
  4. Hypoglycemia was not reported.

49 patients were evaluated in a health care facility (HCF) with 18 admissions. Referral to HCF was more common in pediatric patients. This was likely due to unfamiliarity with a new mediation and lack of toxicity data.

Other case reports have shown higher incidence of DKA with the therapeutic use of SGLT2 vs. other classes of DM medications.

 

Bottom line:

Limit data is available regarding the toxicologic profile of SGLT2 inhibitors.

Based upon this small retrospective study, hypoglycemia may not occur and majority of the patient experience minimal symptoms.

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There have been reports of “intoxication” or adverse effects among first responders and law enforcement due to exposure to a “powder” suspected to be fentanyl or its analog.

 

This has led to a significant concern among first responders and law enforcement when investigating or handling “powder” at the scene of overdose or drug enforcement related raids. (http://www.foxnews.com/health/2017/08/15/police-department-gets-hazmat-like-protective-gear-for-overdose-calls.html)

 

American College of Medical Toxicology and American Association of Clinical Toxicology recently published a position statement to help clarify the potential health risk associated with exposure to fentanyl and its analogs.

 

  1. Opioid toxicity is unlikely from incidental dermal exposure.
  2. Nitrile gloves provide sufficient protection against dermal exposure.
  3. N95 respirator provide sufficient protection against aerosolize fentanyl/opioids.
  4. Naloxone should be administered for patients with objective signs of opioid toxicity - hypoventilation and CNS depression – not for vague or subjective symptoms.

Category: Toxicology

Title: Idarucizumab for Dabigatran reversal 2.0

Keywords: dabigatran reversal, Idarucizumab (PubMed Search)

Posted: 8/25/2017 by Hong Kim, MD, MPH
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Takeaways

Full cohort analysis idarucizumab for dabigatran associated bleeding was recently published in NEJM.

This study evaluated the laboratory correction of elevated ecarin clotting time or diluted thrombin time induced by dabigatran and time to either cessation of bleeding (Group A: patients with GI bleeding, traumatic bleeding, or ICH) or time to surgery (Group B: patients requiring surgical intervention within 8 hours).

Findings

Group A (n=301): Median time to the cessation of bleeding was 2.5 hours in 134 patients.

HOWEVER:

  • Bleeding cessation could not be determined in 67 patients
  • Cessation of bleeding could not be assess in 98 patients with ICH
  • Bleeding stopped spontaneously in 2 patients.

Group B (n=202): Median time to intended surgery after infusion of idarucizumab was 1.6 hours.

  • Normal hemostasis in 184 patients (93.4%), mildly abnormal in 10, and moderately abnormal in 3.
  • Many received PRBC and other blood products during surgery

Laboratory markers:

100% reversal of abnormal ecarin clotting time or diluted thrombin time within 4 hours after the administration

Mortality

  • 5 Day: Group A: 6.3% vs. Group B: 12.6%
  • 30 Day: Group A: 13.5% vs. Group B: 12.6%
  • 90 Day: Group A: 18.8% vs. Group B: 18.9%

 

Conclusion

Authors concluded thate idaurcizumab is an "effective" reversal agent for dabigatran.

Overall, the findings are more promising compared to the interim analysis that was published in 2015.

 

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Category: Toxicology

Title: Importance of hemodialysis in intubated salicylate poisoned patients

Keywords: salicylate poisoning, endotracheal intubation, hemodialysis (PubMed Search)

Posted: 7/27/2017 by Hong Kim, MD, MPH
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Patients with severe salicylate poisoning may require endotracheal intubation due to fatigue from hyperventilation or mental status change.

A previously published study (Stolbach et al. 2008) showed that mechanical ventilation increases the risk of acidemia and clinical deterioration.

A small retrospective study investigated the impact of hemodialysis (HD) in intubated patients with salicylate poisoning.

 

Findings:

53 cases with overall survival rate of 73.2%

In patients with salicylate level > 50 mg/dL

  • No HD: 56% survival (14/25)
  • HD: 83.9% survival (0/9)

If salicylate level > 80 mg/dL

  • No HD: 0% survival (26/31)
  • HD: 83.3% survival (15/18)

Bottom Line:

There is moratality benefit of HD in intubated salicylate-poisoned patient.

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Hydrogen peroxide (H2O2) is a common household liquid that is used for wound irrigation/antiseptic and cosmetic purposes. The concentration of household product is 3% to 5% and is considered to be relatively safe except in large volume ingestion.

High-concentration H2O2 (>10%) is commercially available as “food grade” (35%) that is diluted for household use or for alternative medicine therapy (i.e. hyperoxygenation).

Ingestion of high-concentration of H2O2 can result in caustic injury as well as ischemic injury from gas embolism.

Ingestion of 1 mL of 3% H2O2 produces 10 mL of O2 gas while 1 mL of 35% H2O2 produces 115 mL of O2 gas.

Common symptoms/findings of H2O2 ingestions includes:

  • Nausea/vomiting
  • Abdominal pain due to gas in portal venous system
  • Caustic injury of GI track (ingestion of > 10% H2O2)
  • Arterialization of O2 gas result in end-organ injury (e.g. CVA)

A retrospective review of  >10% H2O2 ingestion from National Poison Data System showed:

  • 13.9% developed gas embolic event
  • 6.8% experienced permanent disability, including 5 deaths.

Management

  • Minor symptoms: primary supportive
  • CT ABD/Pelvis should be considerd if abdominal pain is present
  • If significant gas is present in portal vein or evidence of end-organ injury (i.e. CVA), HBO therapy is recommended (limited evidence).
  • Endoscopy should be considered in concentrated H2O2 ingestion to evaluate for caustic injury.

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Category: Toxicology

Title: Are you up to date on your street names for drugs of abuse?

Keywords: drugs of abuse, street name (PubMed Search)

Posted: 6/5/2017 by Hong Kim, MD, MPH (Emailed: 6/15/2017) (Updated: 6/15/2017)
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Street names for illicit substance are diverse and unique. Knowing what your patient used prior to ED presentation can help with the management of their intoxication. 

 

DEA recently released 7 page list of common street names for drugs of abuse. 

 

https://ndews.umd.edu/sites/ndews.umd.edu/files/dea-drug-slang-code-words-may2017.pdf

 

But keep in mind that what our patients purchase and use may not actually contain the drug that they intended to purchase (e.g. fentanyl being sold as heroin).  

 


Attachments

dea-drug-slang-code-words-may2017.pdf (2,993 Kb)


Takeaways

Botulism is a rare neurologic condition characterized by GI symptoms that progressed to cranial nerve dysfunction and symmetric descending paralysis. Foodborne botulism is due to ingestion of botulinum toxin that is produced by clostridium botulinum, an ubiquitous bacterium in our environment. 

Bottom line:

  • Foodborne botulism presents with GI symptoms that is followed by symmetric descending flaccid paralysis.
  • Botulinum antitoxin prevents further progression of neurologic deficit; it does not reverse the neurologic deficit that is present prior to administration. 
  • Contact your local poison center, and state health department & CDC regarding management and access to botulinum antitoxin.

Maryland Department of Health and Mental Hygiene

  • During business hours: 410-767-6700
  • After hours: 410-795-7365

CDC Emergency Operations Center: 770-488-7100

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Category: Toxicology

Title: Drug induced lactic acidosis.

Keywords: lactic acidosis (PubMed Search)

Posted: 4/20/2017 by Hong Kim, MD, MPH (Updated: 10/25/2021)
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Lactic acids are often elevated in critical care patients (e.g. septic shock). It can be also elevated in setting of drug overdose or less frequently in therapeutic use due to interference of oxidative phosphorylation. Some of the agents include:

 

  • Carbon monoxide
  • Cyanide
  • Propofol
  • Metformin
  • Propylene glycol
  • Salicylates
  • Beta-2 agonists
  • Thiamine deficiency/alcoholic ketoacidosis
  • Ethylene glycol/toxic alcohols
  • Nucleoside reverse-transcriptase inhibitors

 

Bottom line:

  • Although elevated lactic acid levels are often associated with underlying medical conditions, it is important to recognize drug-induced etiologies of lactic acidosis. 

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Category: Toxicology

Title: Sodium bicarbonate shortage Is there an alternate solution?

Keywords: sodium bicarbonate, sodium acetate (PubMed Search)

Posted: 4/6/2017 by Hong Kim, MD, MPH (Updated: 10/25/2021)
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FDA announced a shortage of sodium bicarbonate on 3/01/17.  Sodium bicarbonate is frequently used in acid-base disorder as well as in poisoning (cardiac toxicity from Na-channel blockade, e.g. TCA & bupropion, and salicylate poisoning).

 

Acetate is a conjugate base of acetic acid where acetate anion forms acetyl CoA and enters Kreb cycle after IV administration. Final metabolic products of acetate are CO2 and H2O, which are in equilibrium with bicarbonate via carbonic anhydrase activity.

 

Administration of sodium acetate increases the strong ion difference by net increase in cations, as acetate is metabolize, and leads to alkalemia.

 

Adverse events from sodium acetate infusion have been associated with its use as dialysate buffer: myocardial depression, hypotension, hypopnea leading to hypoxemia and hyperpyrexia. However, such adverse events have not been reported in toxicologic application.

 

 

Bottom line:

Sodium acetate can be administered safely in place of sodium bicarbonate if sodium bicarbonate is not available due to shortage.

Sodium acetate dose:

  • Bolus: 1 mEq/kg over 15 – 20 min
  • Infusion: 150 mEq in 1L D5%W @ twice maintenance rate   

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Category: Toxicology

Title: How often do we encounter the signs and symptoms of clonidine overdose?

Keywords: adult clonidine overdose (PubMed Search)

Posted: 3/16/2017 by Hong Kim, MD, MPH (Emailed: 3/24/2017) (Updated: 10/25/2021)
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Clinical signs and symptoms of clonidine overdose include CNS depression, bradycardia, and miosis. Other effects include early hypertension, followed by hypotension and respiratory depression, especially in children.

 

Although clonidine overdose in children is well described, frequency of clinical signs/symptoms in adults is not well characterized.

 

Recently, a retrospective study was performed in a hospital in Australia looking at clonidine overdose in adults.  

 

Among isolated clonidine overdose, patients experienced:

  • GCS < 15: 55%
  • GSS < 9: 5%
  • Miosis: 25%
  • Bradycardia (HR< 60): 68%
  • Median HR: 48 (IQR: 40-62)
  • Hypotension (SBP < 90 mmHg): 25%
  • Median LOS: 21 hr (IQR: 11 – 27 hr)
  • Intensive care: 23%
  • No deaths

Bottom line:

  1. The most common symtom of clonidicine overdose was bradycardia
  2. Clonidine overdose results in non-life threatening but prolonged clinical effect in adult.

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Takeaways

Methadone overdose produces classic signs and symptoms of opioid intoxication - CNS and respiratory depression with pinpoint pupils. However, methadone overdose has also been associated with hypoglycemia – a relatively uncommon adverse effect.

Bottom line:

  • Methadone-induced hypoglycemia can occur, although rare, in an acute overdose.

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Category: Toxicology

Title: Risk factors of severe outcome in acute salicylate poisoning

Keywords: salicylate poisoning (PubMed Search)

Posted: 1/13/2017 by Hong Kim, MD, MPH (Updated: 10/25/2021)
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A small retrospective study of an acute poisoning cohort attempted to identify risk factors for severe outcome in salicylate poisoning.

Severe outcomes were defined as

  1. Acidemia pH < 7.3 or bicarbonate < 16 mEq/L
  2. Hemodialysis
  3. Death

A multivariate analysis of 48 patients showed that older age and increased respiratory rate were independent predictors of severe outcomes when adjusted for salicylate level.

Initial salicylate acid level was not predictive of severe outcome.  

Elevated lactic acid level was also a good predictor of severe outcome in univariate analysis but not in multivariate analysis.

Limitations

  1. Small sample size with single center study
  2. Retrospective study design
  3. Validation study of these predictors is needed.

 

Bottom line

  1. Older age and increases respiratory rate is associated with severe outcome (acidemia, hemodialysis or/and death) in this study.
  2. Data must be interpreted with caution due to small sample and retrospective study design.

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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, MPH (Emailed: 12/30/2016) (Updated: 12/30/2016)
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Takeaways

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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Takeaways

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: 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, MPH (Emailed: 11/17/2016) (Updated: 11/17/2016)
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Takeaways

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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