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. 

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