Table 2.

Ibuprofen exposure and sepsis in children

1st Author, Year (Ref)	Population; Country	Study Design	Outcome	Key results	Comments
Bernard, 1997 [45]	455 children with sepsis, defined as fever, tachycardia, tachypnea, and acute failure of at least one organ system.	Randomized, double-blind, placebo-controlled trial	Mortality rate at 30 days from the sepsis	Mortality by day 30 did not differ significantly in the ibuprofen and placebo groups (37% vs 40%). In the ibuprofen group, there were significant declines in urinary levels of prostacyclin and thromboxane, temperature, heart rate, oxygen consumption, and lactic acidosis.	None
Lamagni, 2008 [44]	2607 adults and 318 children with severe Streptococcus pyogenes infection	Prospective, observational, study	STSS development	Patients who used NSAIDs had a 3-fold increased risk for STSS (OR 3.00, 95% CI 1.30–6.93, p = 0.01).	No data collected regarding time, dose, indications, and specific NSAIDs used.
Demirel, 2012 [46]	51 preterm infants with sepsis treated with Ibuprofen for PDA versus 38 preterm infants with sepsis without PDA not treated with Ibuprofen	Prospective, observational, study	Effects on the production of IL-6 and CRP	CRP and IL6 were significantly decreased at day 4th or 5th and 7th or 10th after sepsis diagnosis in the group of children treated with Ibuprofen for PDA (p = 0.02, p = 0.01, p = 0.03, p = 0.01, respectively)	Non-interventional study, with unclear exclusion criteria and relatively small sample size.

CRP C-reactive protein, NSAIDs Non-steroidal anti-inflammatory drugs, PDA Patent ductus arteriosus, STSS Streptococcal toxic shock syndrome