Lack of association of late onset sepsis with ranitidine use in neonates

Purpose: The primary objective of this study was to determine if an association exists between late onset sepsis (LOS) and ranitidine exposure in critically ill neonates.  Recent literature has suggested that ranitidine use in neonates increases the risk of developing LOS.  

Methods: Medical records of neonates, ≤28 days of life on admission, admitted to a referral, Level IIIC, neonatal intensive care unit between January 1 and December 31, 2010 were reviewed.  Patients' demographics, ranitidine use (received at least one dose), diagnosis of LOS (sepsis after 7 days of life), parenteral nutrition (PN) use, mechanical ventilation, and length of stay were recorded.  T-test, Wilcoxon rank sum, and Fisher's exact test were used for data analysis.  A p-value of <0.05 was considered significant.

Results: Ranitidine was used in 33% of the 276 patients evaluated.  The overall incidence of LOS was 7.6%.  The incidence of LOS in patients exposed to ranitidine and those not exposed to ranitidine was comparable (8.8% vs 7.0%, p=0.6).  Also, birth weight (2.48 kg vs 2.38 kg, p=0.4) and gestational age (35.1 weeks vs 34.5 weeks, p=0.4) were similar in patients exposed to ranitidine and those not exposed to ranitidine, respectively. In patients exposed to ranitidine, LOS was associated with greater duration of ranitidine use (median 26 days vs 9 days, p<0.05).  LOS was associated with lower birth weight (1.43 kg vs 2.49 kg) and gestational age (30.1 weeks vs 35.1 weeks), longer duration of PN (65.8 days vs 13.1 days) and mechanical ventilation (19.0 days vs 5.6 days), and increased length of stay (86.1 days vs 24.6 days); (p<0.001).        

Conclusion: There was no association between LOS and ranitidine exposure. In patients who received any doses of ranitidine, LOS was associated with longer exposure to ranitidine.