Basics
Description
- Inhibit cyclooxygenase (COX), thereby blocking the conversion of arachidonic acid to prostaglandin.
- Typically morbidity is low when an NSAID is ingested
- Most literature on nonselective NSAID toxicity involves ibuprofen exposure likely due to its OTC availability.
- Fatalities have been reported with large ingestions.
- Greater potential for toxicity with underlying CHF or renal failure:
- NSAIDs cause sodium and water retention and decrease renal blood flow.
- Little overdose experience with the COX-2 inhibitors (celecoxib); treatment should be the same as for the traditional NSAIDs.
- Patients may ingest rofecoxib and valdecoxib from stored supplies even though both are no longer available in US
Etiology
- Nonsteroidal medications are available by prescription and over-the-counter.
- NSAIDs include:
- Diclofenac
- Diflunisal
- Etodolac
- Fenoprofen
- Ibuprofen
- Indomethacin
- Ketoprofen
- Ketorolac
- Meclofenamate
- Meloxicam
- Nabumetone
- Naproxen
- Oxaprozin
- Piroxicam
- Sulindac
- Tolmetin
Diagnosis
Signs and Symptoms
- GI:
- Nausea
- Vomiting
- Epigastric pain
- CNS:
- Drowsiness
- Dizziness
- Lethargy
- Aseptic meningitis
- Seizures
- Cardiovascular:
- Pulmonary:
- Eosinophilic pneumonia
- Apnea
- Hyperventilation
- Renal:
- Acute renal failure, hyperkalemia
- Acute tubular necrosis
- Acute interstitial nephritis
- Liver:
- Hepatocellular injury
- Cholestatic jaundice
- Metabolic:
- Mild, short-lived metabolic acidosis
- Hypersensitivity:
- Aseptic meningitis
- Asthma exacerbation
- Angioedema, urticaria
Essential Workup
- Generally, NSAID ingestion results in mild toxicity.
- Exact identification of drug helpful:
- Subtle toxicologic differences among the NSAIDs
- Aseptic meningitis more common with ibuprofen exposure
- Liver toxicity more common with diclofenac and sulindac exposure
Diagnosis Tests & Interpretation
Lab
- Electrolytes, BUN/creatinine, glucose:
- Baseline renal function
- Check for metabolic acidosis.
- CBC
- Arterial blood gas for large overdoses
- PT/PTT:
- False-positive bilirubin/ketone dipstick with etodolac ingestion
- Acetaminophen and salicylate level " ”patients often confuse salicylate, acetaminophen, and NSAID products thinking they are all the same.
- NSAID difficult to detect on toxicology screens and is not beneficial in management
Differential Diagnosis
Agents causing metabolic acidosis, altered mental status, and GI irritation: ‚
- Salicylates
- Isoniazid
- Ethylene glycol
- Methanol
- Isopropanol
Treatment
Pre-Hospital
Collect prescription bottles/medications for identification in the ED. ‚
Initial Stabilization/Therapy
- ABCs
- Naloxone, thiamine, dextrose (or Accu-Chek) for altered mental status
Ed Treatment/Procedures
- Supportive care
- Administer activated charcoal.
- Extracorporeal methods to enhance elimination are not beneficial due to high degree of plasma protein binding.
Medication
- Activated charcoal slurry: 1 " “2 g/kg up to 90 g PO
- Dextrose: D50W 1 amp (50 mL or 25 g; peds: D25W 2 " “4 mL/kg) IV
- Naloxone (Narcan): 2 mg (peds: 0.1 mg/kg) IV or IM initial dose
- Thiamine (vitamin B1): 100 mg (peds: 50 mg) IV or IM
Piroxicam, naproxen, ketoprofen, and mefenamic acid have caused seizures in children. ‚
Follow-Up
Disposition
Admission Criteria
- Protracted vomiting, hematemesis
- CNS depression, seizure activity
- Metabolic acidosis
- CHF, hypotension, hypertension
- Renal failure
Discharge Criteria
Nontoxic ingestion in a patient who is asymptomatic 6 " “8 hr after ingestion ‚
Followup Recommendations
Psychiatry follow-up/referral for intentional ingestion. ‚
Pearls and Pitfalls
- Investigate for coingestions for all NSAID overdoses.
- Obtain acetaminophen and salicylate level on all patients who present with suspected NSAID ingestion.
- NSAID poisoning is generally benign, except with massive overdoses; patients with underlying CHF, coronary artery disease may be at higher risk of toxicity
Additional Reading
- Dajani ‚ EZ, Islam ‚ K. Cardiovascular and gastrointes " “tinal toxicity of selective cyclo-oxygenase-2 inhibitors in man. J Physiol Pharmacol. 2008;59(suppl 2):117 " “133.
- Frei ‚ MY, Nielsen ‚ S, Dobbin ‚ MD, et al. Serious morbidity associated with misuse of over-the-counter codeine-ibuprofen analgesics: A series of 27 cases. Med J Aust. 2010;193:294 " “296.
- Halen ‚ PK, Murumkar ‚ PR, Giridhar ‚ R, et al. Prodrug designing of NSAIDs. Mini Rev Med Chem. 2009;9:124 " “139.
Codes
ICD9
976.0 Poisoning by local anti-infectives and anti-inflammatory drugs ‚
ICD10
- T39.391A Poisoning by other nonsteroidal anti-inflammatory drugs, accidental, init?
- T39.392A Poisoning by other nonsteroidal anti-inflammatory drugs, self-harm, init?
- T39.394A Poisoning by other nonsteroidal anti-inflammatory drugs, undet?, init?
SNOMED
- 278023006 Non-steroidal anti-inflammatory poisoning (disorder)