Aminophylline for renal protection in neonatal hypoxic-ischemic encephalopathy in the era of therapeutic hypothermia

Valerie Y Chock, Seo-Ho Cho, Adam Frymoyer, Valerie Y Chock, Seo-Ho Cho, Adam Frymoyer

Abstract

Background: Neonates with hypoxic-ischemic encephalopathy (HIE) frequently develop acute kidney injury (AKI). Aminophylline has been shown to reduce severe renal dysfunction in neonates after perinatal asphyxia. However, the effect of aminophylline on renal function in neonates undergoing hypothermia has not been studied.

Methods: A single-center, retrospective chart review of neonates cooled for moderate/severe HIE who received aminophylline for AKI was conducted to assess changes in urine output (UOP) and serum creatinine (SCr). Comparisons were also made to control neonates matched for hours of life who were cooled but unexposed to aminophylline.

Results: Sixteen neonates cooled for HIE received aminophylline starting at 25 ± 14 h of life. Within 12 h of starting aminophylline, UOP increased by 2.6 ± 1.9 mL/kg/h. SCr declined by 0.4 ± 0.2 mg/dL in survivors over the first 4 days. When compared to control neonates, UOP increase was greater in the aminophylline group (p < 0.001). SCr declined in survivors in both groups, although baseline SCr was higher in the aminophylline group.

Conclusions: Aminophylline use in neonates with HIE undergoing hypothermia was associated with an increase in UOP and a decline in SCr. A randomized trial will be needed to establish a potential renal protective role of aminophylline.

Impact: The renal protective effect of aminophylline in neonates with HIE has not yet been studied in the context of therapeutic hypothermia. Aminophylline exposure in neonates cooled for HIE was associated with increased UOP and a similar decline in SCr when compared to control infants unexposed to aminophylline. Improved renal function after receiving aminophylline in this observational cohort study suggests the need for future randomized trials to establish the potential benefit of aminophylline in the HIE population undergoing hypothermia.

Figures

Figure 1:. Changes in Urine Output
Figure 1:. Changes in Urine Output
Neonates receiving aminophylline (n=12 survivors and n=4 non-survivors) had lower urine output (UOP) during the 12 hour period prior to start of aminophylline compared to an age matched time period in control patients (n=16) (* p# p<0.001 vs. ‘pre’ time point) and in control patients at 24 and 72 hours (+p<0.05 vs. ‘pre’ time point). UOP was significantly higher during the first 12 hours after aminophylline start in survivors compared to control patients (* p<0.05 vs. control at time point) but no differences in UOP between these two groups were seen at later time points. UOP in non-survivors who received aminophylline did not increase significantly over the study period.
Figure 2:. Changes in Serum Creatinine
Figure 2:. Changes in Serum Creatinine
Serum creatinine (SCr) significantly decreased from baseline by 48 hours after aminophylline in survivors (n=12) and by 24 hours during an age matched time period of life in control patients (n=16, # p<0.05 vs. ‘pre’ time point within each group). SCr remained significantly higher at 24, 48, and 72 hours in survivors compared to control patients (*p<0.05 vs. control). Non-survivors (n=4) in the aminophylline group had a rising SCr over the study period prior to withdrawal of intensive care support.
Figure 3:. Change in Urine Output Compared…
Figure 3:. Change in Urine Output Compared to Baseline Renal Saturation
Mean renal saturation (Rsat) in the 12-hour baseline period prior to start of aminophylline therapy shows a positive correlation with increase in urine output for the 12-hour period after aminophylline was given.

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Source: PubMed

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