What are the cases to avoid Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in pediatric patients?

Cases to Avoid NSAIDs in Pediatrics

NSAIDs should be avoided in pediatric patients with active gastrointestinal bleeding, severe renal impairment, cirrhotic liver disease, coagulopathy or concurrent anticoagulation, neonatal jaundice (when breastfeeding), aspirin-exacerbated respiratory disease, and in neonates/premature infants outside of specific indications like patent ductus arteriosus closure.

Absolute Contraindications

Gastrointestinal Conditions

• Active GI bleeding or peptic ulcer disease represents a clear contraindication, as NSAIDs are known to cause GI bleeding and ulceration even with short-term use 1.
• History of peptic ulcer disease significantly increases complication risk and warrants avoidance 2.

Renal Disease

• Pre-existing renal disease or renal insufficiency is a major contraindication, as NSAIDs can cause acute renal failure particularly in children with compromised kidney function 1, 3.
• Baseline renal function tests (BUN, creatinine, urinalysis) should be obtained before initiating NSAIDs, with monitoring every 6-12 months during chronic use 1.
• Caution is especially critical when NSAIDs are combined with other potentially nephrotoxic drugs 3.

Hepatic Disease

• Cirrhotic liver disease is a contraindication because bleeding problems and renal failure become significantly more likely 4.
• NSAIDs should be avoided in patients with cirrhosis and ascites due to extremely high risk of acute renal failure, hyponatremia, and diuretic resistance 4.

Hematologic Conditions

• Concurrent anticoagulation therapy increases GI bleeding risk 5-6 fold and should be avoided 1, 5.
• Coagulation disorders represent a relative contraindication, though regional anesthesia techniques may be considered as alternatives in specialized centers 1.

Age-Specific Contraindications

Neonates and Premature Infants

• NSAIDs in neonates carry unique risks including disruption of sleep cycles, increased pulmonary hypertension risk, altered cerebral blood flow, decreased renal function, disrupted thermoregulation, and altered hemostasis 6.
• Prostaglandins are critical for normal development of the central nervous, cardiovascular, and renal systems; NSAID exposure may adversely affect organ genesis 6.
• The exception is indomethacin or ibuprofen for patent ductus arteriosus (PDA) closure, where these agents are FDA and EMEA approved 7, 8.
• Ibuprofen has been shown to be as effective as indomethacin for PDA closure without affecting renal function 3.

Breastfeeding Neonates with Jaundice

• NSAIDs are contraindicated when breastfeeding a neonate with jaundice because most NSAIDs displace bilirubin, potentially worsening hyperbilirubinemia 1.
• The American Academy of Pediatrics considers ibuprofen, indomethacin, and naproxen safe in breastfeeding women under normal circumstances, as only trace amounts appear in breast milk 1.

Respiratory Conditions

Aspirin-Exacerbated Respiratory Disease (AERD)

• Children with asthma, particularly those with nasal polyps or recurrent sinusitis, should be evaluated for aspirin-exacerbated respiratory disease before NSAID use 1.
• AERD prevalence reaches up to 21% in adults with asthma, though it is rarely reported in pediatric populations 1.
• This condition results from COX-1 inhibition and shunting of arachidonic acid down the leukotriene pathway, causing bronchoconstriction and rhinitis 1.
• There is high cross-reactivity with other NSAIDs but low cross-reactivity with COX-2 inhibitors and acetaminophen 1.

Perioperative Considerations

Tonsillectomy

• Controversy exists regarding ketorolac use in children undergoing tonsillectomy due to potential increased risk of postoperative hemorrhage 9.
• For most other minor surgeries, NSAIDs used alone or as adjunct to regional anesthesia are well-tolerated and provide opioid-sparing effects 9.

Critical Monitoring Requirements

Dosing Errors

• The main risk to children taking NSAIDs is dosage errors resulting in overdose, which can cause significant morbidity and death 1.
• Parental education on correct dosing intervals, avoidance of combination cold medications containing NSAIDs, and storage in childproof containers is essential 1.

Long-Term Use Monitoring

• For children requiring chronic NSAID therapy, CBC, liver function tests, and renal function tests should be monitored every 6-12 months 1.
• GI distress is common but may not be spontaneously reported; clinicians should actively inquire about and treat GI symptoms 1.

Special Populations

Pregnancy Considerations

• NSAIDs should be discontinued 6-8 weeks before term to avoid maternal effects (prolonged labor, increased peripartum bleeding) and fetal effects (premature ductus arteriosus closure, pulmonary hypertension, renal impairment) 1.
• Women actively trying to conceive should avoid NSAIDs as they can block blastocyst implantation 1.

Cardiovascular Disease

• While less common in pediatrics, congestive heart failure represents a contraindication as NSAIDs can worsen fluid retention and increase blood pressure 2, 5.

Important Clinical Caveats

• Only 31-68% of children with suspected NSAID hypersensitivity have it confirmed on challenge, demonstrating the difficulty of relying on history alone 1.
• In some children, NSAID reaction patterns cannot be adequately explained by current mechanistic understanding 1.
• One large randomized controlled trial showed ibuprofen and acetaminophen were equivalent in adverse event risk, with overall low rates 1.