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A single dose of aminophylline administration during therapeutic hypothermia; does it make a difference in glomerular filtration rate?

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Abstract

Aminophylline has been demonstrated to be effective in improving renal functions of the infants suffering from acute kidney injury (AKI) due to perinatal asphyxia. We aimed to evaluate the effect of a single-dose aminophylline on estimated glomerular filtration rate (eGFR), urine output (UO), and incidence and severity of AKI according to the pediatric-modified RIFLE and neonatal RIFLE criteria in newborns with perinatal asphyxia under therapeutic hypothermia. This was a single-center, retrospective cohort study including newborns (gestational age ≥36 weeks) who underwent therapeutic hypothermia due to hypoxic ischemic encephalopathy between 2016 and 2019. Demographic and clinical data were obtained from electronic medical records and patient files. Two patient groups were established: aminophylline group and control group which were only under therapeutic hypothermia. Twenty-one newborns were in the aminophylline group and 13 newborns were in the control group. Our study revealed that on the third day of life (DOL), eGFR was significantly higher in the control group (p=0.025), but UO was significantly higher in the aminophylline group (p=0.021). In the aminophylline group, eGFR on the first DOL was higher than the value on the second DOL (p=0.017) while UO was higher on the second and third DOL compared to the first DOL (1–2 DOL p=0.006, and 1–3 DOL p=0.004). However, in the control group, there was no statistically significant difference in UO over the four DOL. Both groups were similar in the presence, severity, and outcome of AKI.

Conclusion: This study demonstrated that aminophylline increases UO even in the infants under therapeutic hypothermia. However, the eGFR did not significantly increase in the aminophylline group. Understanding how therapeutic hypothermia affects pharmacokinetics may help us improve our results in future studies.

What is known:

• Therapeutic hypothermia (TH) reduces the incidence of acute kidney injury in asphyxiated newborns.

• Aminophylline is effective in improving renal functions in asphyxiated newborns.

What is new:

• This is the first study evaluating the effect of a single dose of aminophylline on renal functions in newborns under TH.

• A single dose of aminophylline administration in newborns under TH was associated with increased urine output especially on the third day of life. However, no significant increase was detected in glomerular filtration rate associated with aminophylline administration.

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Availability of data and material

Data were recorded in SPSS and are available for evaluation.

Code availability

N/A

Abbreviations

aEEG:

Amplitude integrated electroencephalogram

AG:

Aminophylline group

AKI:

Acute kidney injury

BE:

Base excess

BUN:

Blood urea nitrogen

Ca:

Calcium

CG:

Control group

CRRT:

Continuous renal replacement therapy

DOL:

Days of life

GA:

Gestational age

eGFR:

Estimated glomerular filtration rate

HIE:

Hypoxic ischemic encephalopathy

K:

Potassium

MV:

Mechanical ventilation

Na:

Sodium

NCPAP:

Nasal continuous positive airway pressure

NICU:

Neonatal intensive care units

NIRS:

Near-infrared spectroscopy

P:

Phosphorus

SCr:

Serum creatinine

TH:

Therapeutic hypothermia

UO:

Urine output

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Acknowledgements

The authors are grateful to Dr. Asli Kavaz Tufan and Dr. Nuran Cetin for their assistance in patient monitoring and treatment.

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Authors and Affiliations

  1. Division of Neonatology, Department of Pediatrics, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey

    Ozge Surmeli Onay, Damla Gunes, Ozge Aydemir & Neslihan Tekin

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  1. Ozge Surmeli Onay
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  2. Damla Gunes
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  3. Ozge Aydemir
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Contributions

Dr.Surmeli Onay drafted the manuscript and contributed to the design, analysis, and interpretation of data. Dr. Gunes contributed to the analysis and interpretation of data. Dr.Aydemir critically reviewed the manuscript and contributed to interpretation of data. Dr.Tekin critically reviewed the manuscript and contributed to interpretation of data. All the authors were involved in the care of the patients. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Ozge Surmeli Onay.

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Ethics approval

The Institutional Ethics Committee approved the study (No.: E-25403353-050.99-68917).

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Because of retrospective design, individual consent from parents was not received both for participation and publication.

Competing interests

The authors declare no competing interests.

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Communicated by Daniele De Luca

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Surmeli Onay, O., Gunes, D., Aydemir, O. et al. A single dose of aminophylline administration during therapeutic hypothermia; does it make a difference in glomerular filtration rate?. Eur J Pediatr 180, 3367–3377 (2021). https://doi.org/10.1007/s00431-021-04128-6

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