Background Alprostadil is used to maintain ductus patency in neonates with ductus dependent congenital heart disease (CHD), until corrective surgery. Fever is a common side effect of alprostadil and may also be a sign of infectious disease. We aimed to identify potential parameters that may differentiate infectious from alprostadil fever.
Methods Retrospective case-control study included all neonates with ductus dependent CHD, who were admitted at the Children´s Hospital in Ramat-Gan, Israel, from August 2003 to August 2017 and developed fever on alprostadil. Cases were defined as neonates with a positive bacterial culture and controls were defined as neonates with a negative culture. Multivariate cox-regression was conducted to identify potential parameters that may differentiate alprostadil from infectious fever.
Results Three hundred and four neonates developed fever under alprostadil. Fifty five (18%) had a positive bacterial culture and 249 (82%) had a negative culture. In univariate analysis, the duration of alprostadil infusion was 95 hours (IQR 45–116) in the case group and 72 hours (IQR 49–215) in the control group (p=0.011). The time between alprostadil initiation and fever was longer for the case group: 14.13 hours (IQR 6.5–47.5) versus 12.96 (IQR 5–30.51), (p=0.039). In multivariate cox-regression, a more than 10% increase in neutrophil count before fever was significantly associated with an increased risk for infection (HR 6.14, 95% CI 1.94–19.42). A trend towards an association was observed with CRP ≥ 10 mg/dl before fever (HR 2.5, 95% CI 0.66–9.47) and in an increase ≥ 1000 micromol/L in WBC before fever (HR 1.74, 95% CI 0.58–5.21).
Conclusions In neonates with CHD on alprostadil therapy, an increase in neutrophil count before the appearance of fever is associated with infection. Full sepsis work-up and is still warranted in neonates who develop fever under alprostadil. Further larger studies are needed to fully establish these results.
Disclosure(s) The authors have no conflict of interests to disclose.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.