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2/7/2019 0 Comments

Aspirin (ASA) Toxicity

Aspirin Toxicity and its Management in the Emergency Department

Mechanism and toxicity:

Salicylates irreversible block the COX-1 pathway and modify the COX-2 pathway resulting in a decrease in inflammation and platelet aggregation
Salicylate is conjugated in the liver and then excreted in the kidneys, which will be important in toxicity. 80-90% is protein bound, however, in acute toxicity, this decreases and more of the drug is in the non-ionized form.
This non-ionized form interferes with the Krebs cycle, uncouples oxidative phosphorylation and limits ATP production, increases fatty acid metabolism and causes accumulation of pyruvic and lactic acid

Effects of toxicity:

Direct stimulation of the respiratory center causing hyperventilation
Altered mental status and hypoglycemia in the CSF
Cerebral edema 2/2 leakage of the BBB
Metabolic acidosis and resp alkalosis causes hyperventilation which leads to dehydration, fluid losses and acute kidney injury
Alters platelet function
Affects cochlear blood flow and membrane permeability outer hair cell organ of corti leading to sensorineural alterations
GI isrupts mucosal barrier that protects from acid, ulcers, bleeding

ASA Level and Indications for Dialysis:

100mg/dL for acute ingestion
60mg/dL for chronic ingestion
Tinnitus with levels as low as 30mg/dL
Also, standard to obtain BMP, ABG, UA and CXR

Management in the ED:

Start off with the ABCs like any acutely ill patient that presents to the ED
Activated charcoal is indicated in acute ingestions
Treat hypoglycemia and hypokalemia, quick bedside BMP/glucose testing will be very helpful
Most importantly is combating the acidosis and elimination of the drug which includes aggressive use of NaHCO3 and HD when indicated
Goal is to alkalize the urine and create ion trapping to assist elimination of the drug
Goals for alkalization of urine are usually a pH of 7.5-8.5. The patient will need a foley and constant monitoring of UOP

Managing intubation?:

Intubation should be avoided at all costs
If you intubate, be sure to increase RR, if not, RR will drop causing worsening acidosis likely resulting in cardiac arrhythmias and possible death.

Chronic ASA Toxicity:

Patient history is key and we often misdiagnose these patients with sepsis, delirium, fever of unknown origin
They may present with mixed acid base picture
More common in elderly, which makes the diagnosis even more difficult. Indication for HD 60mg/dL as mentioned before.

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2/3/2019 0 Comments

TOXIDome's Approach to the Agitated Patient

Pharmacologic Interventions for Undifferentiated Agitation

Introduction

Agitated delirium also known as excited delirium syndrome – is a mental state characterized by violent behavior, speech changes, acute disorientation and abnormal thought process.

Differential

Agitated delirium in the ED has many etiologies, must consider a very broad differential
- Psychiatric - Acute psychosis, paranoia
- Neurologic – intracranial pathology, encephalitis, idiopathic malignant catatonia,
- Medical – hypoxia, sepsis, meningoencephalitis, thyroid storm, pheochromocytoma, hypoglycemia, heat stroke
- Trauma – SDH, SAH, epidural hematoma
- And of course…Toxicology –sympathomimetic toxicity, anticholinergic syndrome, alcohol or benzodiazepine withdrawal syndromes, salicylate poisoning, serotonin syndrome, neuromalignant syndrome, hallucinogens, malignant hyperthermia
- Others

Initial Approach

Attempt to elicit history and physical exam, although may not be feasible
Verbal redirection and de-escalation should be attempted first
Physical exam and history can clue you in to potential ingestions/toxidromes

Pharmacologic Interventions

Benzodiazepines and antipsychotics are the drug classes of choice
Must consider onset of action, duration and route when making decision around these medications
Tradition use of 5mg of IM haloperidol and 2mg of IM lorazepam may not always be the best choice as their onset of action may be delayed and as long as 20-40 minutes
Be aware of repeat dosing (stacking of doses), may lead to respiratory depression
Consider 5mg IM midazolam, onset usually 1-3 minutes, shorter acting and 2mg lorazepam
Must consider side effects of antipsychotics, including QTc prolongation

Ketamine for Acute Agitation

Emerging evidence supports ketamine for this indication
Dose: 4-6mg/kg IM
Consider in patients that may have contraindications for other drug classes

Core Concepts

Keep your differential BROAD
Attempt to obtain history and physical exam as this will guide your management
Consider route, onset of action and duration of the various pharmaceutical options
Traditional 5mg IM Haldol and 2mg IM Ativan may not be best option given delayed onset of action
Recommendation for fastest control is 5mg midazolam and 2mg lorazepam or ketamine IM

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2/3/2019 0 Comments

Toxicology 101 Part 2: Toxidromes

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2/2/2019 0 Comments

EMGuideWire

From the J. Lee Garvey Innovation Studio in the
Department of Emergency Medicine
Carolinas Medical Center
Charlotte, NC

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Aspirin (ASA) Toxicity

TOXIDome's Approach to the Agitated Patient

Toxicology 101 Part 2: Toxidromes

Toxicology 101, Part 1

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