UMEM Educational Pearls - By Hong Kim

It is believed that administration of beta-blocker administration in patients with cocaine chest pain will produced increased vasoconstriction due to “unopposed alpha effect.”

 

Several retrospective studies on the use of beta-blocker in patients with cocaine-induced chest pain concluded the use of beta-blocker to be safe.

 

So is the unopposed alpha effect just a theory?

 

Lange RA et al. 1990 Ann Internal Med

Design: randomized, double-blind, placebo controlled trial.

 

30 (38- 68 years old) patients undergoing cardiac catherization for chest pain evaluation were studied.

 

Cocaine (intranasal administration) resulted in:

  • Increased myocardial oxygen demand
  • Increased coronary vascular resistance 22%
  • Decreased coronary sinus blood flow: 10%

 

Administration of propranolol (intracoronary infusion) resulted in additional:

  • Increase coronary vascular resistance 19%
  • Decrease coronary sinus blood flow by 15%
  • No additional change in myocardial oxygen demand

 

Complete coronary occlusion observed in 1 patient with ST elevation

Epicardial coronary arterial segment constriction >10% in 5 patients.

 

Bottom Line: Lange RA et al. 1990 demonstrates that the “unopposed alpha effect” does occur in coronary artery when beta-blocker is administered in a setting of acute cocaine exposure.  Overall, the use of beta-blocker in the ED management of cocaine-induce acute chest pain is not a prudent option.  It is unknown if the cocaine dose, last use of cocaine (days), or CAD history influence the “safety” of beta-blocker initiation/use during inpatient hospitalization.

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Category: Toxicology

Title: Identification of cyanide poisoning in smoke inhalation victims.

Keywords: Cyanide, smoke inhalation, lactate (PubMed Search)

Posted: 11/28/2014 by Hong Kim, MD, MPH (Updated: 10/18/2021)
Click here to contact Hong Kim, MD, MPH

Cyanide poisoning is rare but highly lethal. Cyanide exposure can occur during residential fire (most common source of exposure) where combustion of synthetic materials (i.e. plastic and polyurethane) releases cyanide gas as well as other toxic gases, including carbon monoxide. Although carbon monoxide poisoning can be readily identified by CO-Hb level using CO-oximetry, serum/blood cyanide level is not readily available for acute management.

 

However, elevated lactate level (> 10 mmol/L ) has shown to be highly correlated with toxic level of cyanide (40 micromol/L or 1 mg/L) in smoke inhalation victims (Baude FJ et al. N Engl J Med 1991;325:1761-6).

  • Sensitivity: 87%
  • Specificity: 94%
  • Positive predictive value: 95%

 

Bottom line: when managing smoke inhalation victims, think about cyanide poisoning in addition to carbon monoxide poisoning and check the lactate level. Lactate > 10 mmol/L is suggestive of cyanide poisoning and should be treated with hydroxocobalamin. 

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Category: Toxicology

Title: Valproic acid toxicity

Keywords: valproic acid (PubMed Search)

Posted: 10/16/2014 by Hong Kim, MD, MPH (Updated: 10/18/2021)
Click here to contact Hong Kim, MD, MPH

Valproic acid (VPA) is often used to treat seizure disorder and mania as a mood stabilizer. The mechanism of action involves enhancing GABA effect by preventing its degradation and slows the recovery from inactivation of neuronal Na+ channels (blockade effect).

 

VPA normally undergoes beta-oxidation (same as fatty acid metabolism) in the liver mitochondria, where VPA is transported into the mitochondria by carnitine shuttle pathway.

 

In setting of an overdose, carnitine is depleted and VPA undergoes omega-oxidation in the cytosol, resulting in a toxic metabolite.

 

Elevation NH3 occurs as the toxic metabolite inhibits the carbomyl phosphate synthase I, preventing the incorporation of NH3 into the urea cycle.

 

Signs and symptoms of acute toxicity include:

  • GI: nausea/vomiting, hepatitis
  • CNS: sedation, respiratory depression, ataxia, seizure and coma/encephalopathy (with serum concentration VPA: > 500 mg/mL)

 

Laboratory abnormalities

  • Serum VPA level: signs of symptoms of toxicity does not correlate well with serum level.
  • NH3: elevated
  • Liver function test: elevated AST/ALT
  • Basic metabolic panel: hypernatremia, metabolic acidosis
  • Complete blood count: pancytopenia

 

Treatment: L-carnitine

  • Indication: hyperammonemia or hepatotoxicity
  • Symptomatic patients: 100 mg/kg (max 6 gm) IV (over 30 min) followed by 15 mg/kg IV Q 4 hours until normalization of NH3 or improving LFT
  • Asymptomatic patients: 100 mg/kg/day (max 3 mg) divided Q 6 hours.

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Category: Toxicology

Title: "Food poisoning": How do you like your fish?

Keywords: ciguatera, scromboid, tetrodotoxin (PubMed Search)

Posted: 9/18/2014 by Hong Kim, MD, MPH
Click here to contact Hong Kim, MD, MPH

Food poisoning can occur with many different food groups/items, as well as how the food is prepared, handled or stored.

There are three specific “food poisonings” associated with fish consumption can cause serious toxicity/illness beyond GI symptoms: Ciguatera, Scrombroid, tetrodotoxin (puffer fish)

 

Ciguatera

  • Endemic to warm tropical water and bottom reef dwelling large carnivorous fish: grouper, red snapper, barracuda, amberjack, parrot fish, etc. (> 500 species).
  • Toxin: ciguatoxin: opens voltage gated Na channel
  • Produced by dinoflagellates (gambierdiscus toxicus) and bioaccumulates in large fish through food chain (eating small fish).

Symptoms:

  • GI symptoms: n/v/d and abdominal pain
  • Hot/cold reversal
  • Paresthesia of tongue/lip >> extremities
  • Dental pain: “loose teeth”

May progress to develop…

  • T wave changes, bradycardia, hypotension
  • Respiratory paralysis and pulmonary edema

Treatment: supportive care and mannitol in presence of severe neurologic symptoms (limited evidence).

 

Scrombroid

  • Endemic in (dark meat) fish living in temperate or tropical water: amberjack, skipjack, tuna, mackerel, albacore, mahi mahi, etc.
  • Associated with poor refrigeration/storage after catching fish.
  • Histidine in tissue is converted to histamine by bacteria on the fish skin.

 

Symptoms:

  • GI symptoms: n/v/d and abdominal pain
  • Upper body flushing
  • Puritis, urticarial and perioral swelling can occur
  • Palpitation and mild hypotension

 

Tx: H1/H2 blockers and supportive care

Serious reactions: treat like allergic/anaphylactic reaction

 

Tetrodotoxin

  • Ingestion of improperly prepared puffer fish (fugu) sushi (or bite from blue ring octopus)
  • Toxin: tetrodotoxin: blocks voltage gated Na channel.
  • Highest concentration in liver and ovary.

 

Symptoms:

  • GI: n/v/d
  • Progressive paresthesia and weakness (bulbar-> extremities), ataxia
  • Ascending paralysis and respiratory distress/paralysis
  • Dysrythmia and hypotension
  • Mental status preserved.

 

Treatment: supportive care and intubated if needed.


Metformin is the first line medication for the treatment of type II diabetes. A rare complication of chronic metformin use is MALA.

  • Incidence: 2-9 cases per 100,000 patients
  • Mortality: 30-50%

The association between metformin accumulation and development of lactic acidosis is controversial as patients with suspected MALA experience concurrent illnesses such as sepsis/septic shock, tissue hypoxia, and/or organ dysfunction (especially renal failure).

  • Greater than 90% of metformin (unchanged) is eliminated by the kidney.
  • Metformin accumulation (from renal failure) leads to inhibition of complex I of the electron transport chain.1,2
  • A case series of 66 patients MALA experienced severe lactic acidosis (pH: 6.91+ 0.18; lactate 14.36+ 4.9 mmol/L) and renal failure (Cr 7.24 + 3.29 mg/dL)3
  • Prodromal GI symptoms in 77%
  • Clinical findings at time of admission/presentation:
  • AMS/coma: 57%
  • Dyspnea/hyperventilation: 42%
  • Hemodynamic shock: 39%
  • Hypotension (SBP < 100 mmHg): 23%
  • No correlation between lactate and metformin level.
  • Risk factors
    • Renal failure (metformin accumulation)
    • Elderly population (higher mortality)
    • Cardiac or respiratory insufficiency causing central hypoxia
    • Sepsis/septic shock
    • Liver disease
    • IV contrast use (resulting in renal insufficiency)
  • Treatment: emergent hemodialysis

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NAC is an effective antidote against acetaminophen (APAP) toxicity in preventing acute hepatotoxicity. It provides cysteine that is essential for glutathione synthesis and its availability is rate limiting.

Currently, PO and IV formulation is available in the U.S. Regardless of the route, NAC is equally effective in preventing APAP induced acute hepatotoxicity when administered within 8 hours after single acute ingestion. 1

Adverse effects of NAC

1.     Anaphylactoid reaction

a.     More frequently reported with IV administration and during the first regimen of NAC (150 mg/kg over 60 min) administration. (dose and rate dependent)

b.     Higher risk of anaphylactoid reaction in patients with negative APAP vs. patients with elevated APAP level.2

c.      Management: Benadryl as needed and slow infusion rate.

2.     Hyponatremia in children if inappropriate volume of diluent (D5W) used. Dose calculator: http://acetadote.com/dosecalc.php

3.     Laboratory: increase Prothrombin time (PT).3

4.     Fatality from iatrogenic NAC overdose has been reported.

 

Advantage of IV NAC

1.     Convenience

2.     100% bioavailability

3.     Shorter hospital length of stay

4.     Minimum GI symptoms (nausea & vomiting) compared to PO route

 

Indication of IV NAC

1.     Severe hepatotoxicity or fulminant liver failure

2.     APAP poisoning during pregnancy

3.     Unable to tolerate PO intake (nausea, vomiting, altered mental status)

However many clinicians administer IV NAC for their advantages over PO NAC.

 

 Take home message:

1.     PO and IV NAC are equally effective when administered within 8 hours after single acute ingestion.

2.     Anaphylactoid reaction is frequently encountered AE during the infusion of 1st NAC regimen and patients with negative/low APAP level may be at higher risk.

3.     No emergent need to start NAC in presumed acetaminophen overdose patients prior to obtaining APAP level.

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Currently, no effective reversal agent for new oral anticoagulants (e.g. direct thrombin inhibitor, dabigatran, and factor Xa inhibitors: rivaroxaban and apixaban) exists for emergent management of hemorrhagic complications.

 

Boehringer Ingelheim, the manufacturer of dabigatran, is developing an antibody fragment (Fab) against dabigatran as a reversal agent.1

 

A small ex-vivo porcine study demonstrated partial reversal of anticoagulation effects, measured by PT, aPTT, clotting time, clot formation time and maximum clot firmness, of dabigatran by PCC and activated PCC, while dabigatran-Fab achieved complete reversal. Recombinant fVIIa did not reverse the anticoagulation effect of dabigatran.2

 

Caution should be exercised when interpreting these finding as reversal of laboratory values does not necessarily correlate with clinical effect/outcome. However, dabigatran-Fab holds promise as an effective reversal agent of dabigatran.

 

Dabigatran-Fab is still under development and is not available/approved for clinical use.

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Category: Toxicology

Title: Predictors of esophageal injury in caustic ingestion?

Keywords: caustic ingestion; esophageal injury (PubMed Search)

Posted: 4/17/2014 by Hong Kim, MD, MPH (Updated: 10/18/2021)
Click here to contact Hong Kim, MD, MPH

Caustic ingestion can potentially cause significant esophageal and/or gastric injury that can lead to significant morbidity, including death.

 

Endoscopy is often performed:

·      To determine the presence of caustic injury.

·      To determine the severity of caustic injury (grade: I to III).

 

Grade

Tissue finding

Sequela

I

•  Erythema or edema of mucosa

•  No ulceration

No adverse sequela

IIa

•  Submucosal ulceration and exudates

•  NOT circumferential

No adverse sequela

IIB

•  Submucosal ulceration and exudates

•  Near or circumferential

Stricture > 70%

IIII

•  Deep ulcers/necrosis

•  Periesophageal tissue involvement

Acute

Perforation and death

Chronic

Strictures and increased cancer risk

 

·      Placement of orogastric or nasograstic tube for nutritional support if needed (grade IIb and III)

 

Evidence for predictor of esophageal injury (frequently cited) comes from mostly studies involving pediatric population and unintentional ingestion:

1.     Gaudreault et al. Pediatrics 1983;71:767-770.

o   Studied signs/symptoms: nausea, vomiting, dysphagia, refusal to drink, abdominal pain, drooling or oropharyngeal burn

o   Presence of symptoms: Grade 0/I lesion: 82%; Grade II: 18%

o   Absence of symptoms: Grade 0/I: 88%; Grade II: 12%

2.     Crain et al. Am J Dis Child. 1984;138(9):863-865

o   Presence of 2 or more (vomiting, drooling and stridor) identified all (n=7) grade II and III lesion.

o   Presence of 1 or no symptoms: no grade II/III lesions

o   Stridor alone associated with grade II/III lesions (n=2)

o   10% of patients without oropharyngeal burns had grade II/III lesions.

3.     Gorman et al. Am J Emerge Med 1990;10(3):189-194.

o   Two or more symptoms: vomiting, dysphagia, abdominal pain or oral burns

o   Sensitivity: 94%; specificity 49%

o   Positive predictive value 43% ; negative predictive value: 96%

o   Stridor alone (n=3): grade II or greater lesion

4.     Previtera et al. Pediatric Emerg Care 1990;6(3):176-178.

o   Esopheal injury in 37.5% of patients without oropharyngeal burn

o   Grade II/III injury: 8 patients

 

Available data suggests that there are no “good” or reliable predictors for esophageal injury.

 

However, high suspicion for gastrointestinal injury should be considered with GI consultation for endoscopy in the presence of

·      Stridor alone

·      Two or more sx: vomiting, drooling or stridor (Crain et al)

·      Intentional suicide attempt


Category: Toxicology

Title: Valproic acid toxicity

Keywords: Valproic acid (PubMed Search)

Posted: 10/16/2014 by Hong Kim, MD, MPH (Emailed: 10/18/2021)
Click here to contact Hong Kim, MD, MPH

Valproic acid (VPA) is often used to treat seizure disorder and mania as a mood stabilizer. The mechanism of action involves enhancing GABA effect by preventing its degradation and slows the recovery from inactivation of neuronal Na+ channels (blockade effect).

VPA normally undergoes beta-oxidation (same as fatty acid metabolism) in the liver mitochondria, where VPA is transported into the mitochondria by carnitine shuttle pathway.

In setting of an overdose, carnitine is depleted and VPA undergoes omega-oxidation in the cytosol, resulting in a toxic metabolite.

Elevation NH3 occurs as the toxic metabolite inhibits the carbomyl phosphate synthase I, preventing the incorporation of NH3 into the urea cycle.

Signs and symptoms of acute toxicity include:

  • GI: nausea/vomiting, hepatitis
  • CNS: sedation, respiratory depression, ataxia, seizure and coma/encephalopathy (with serum concentration VPA: > 500 mg/mL)

Laboratory abnormalities

  • Serum VPA level: signs of symptoms of toxicity does not correlate well with serum level.
  • NH3: elevated
  • Liver function test: elevated AST/ALT
  • Basic metabolic panel: hypernatremia, metabolic acidosis
  • Complete blood count: pancytopenia

Treatment: L-carnitine

  • Indication: hyperammonemia or hepatotoxicity
  • Symptomatic patients: 100 mg/kg (max 6 gm) IV (over 30 min) followed by 15 mg/kg IV Q 4 hours until normalization of NH3 or improving LFT
  • Asymptomatic patients: 100 mg/kg/day (max 3 mg) divided Q 6 hours.

Show References