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Theophylline and aminophylline for prevention of acute kidney injury in neonates and children: a systematic review
  1. Girish Chandra Bhatt1,
  2. Priya Gogia1,
  3. Martin Bitzan2,
  4. Rashmi Ranjan Das3
  1. 1 Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Bhopal, Madhya Pradesh, India
  2. 2 Department of Pediatrics, Division of Nephrology, Montreal Children’s Hospital and McGill University, Montreal, Quebec, Canada
  3. 3 Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Bhubaneswar, Odisha, India
  1. Correspondence to Dr Girish Chandra Bhatt, Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Bhopal, Madhya Pradesh, India; drgcbhatt{at}gmail.com

Abstract

Objective To compare the efficacy and safety of theophylline or aminophylline for prevention of acute kidney injury (AKI) in neonates and children.

Design Systematic review and meta-analysis with application of Grading of Recommendations, Assessment, Development and Evaluation system.

Data sources PubMed/MEDLINE, Embase, Google Scholar and Cochrane renal group were searched from 1970 to May 2018.

Eligibility criteria Randomised clinical trials and quasi-randomised trials comparing the efficacy and safety of prophylactic theophylline or aminophylline for prevention of AKI in neonates and children were included. The primary outcomes were: incidence of AKI, serum creatinine levels and all-cause mortality.

Results A total of nine trials were included in the qualitative synthesis. Six trials including 436 term neonates with birth asphyxia who received a single dose of theophylline were finally included in the meta-analysis. The pooled estimate showed 60% reduction in the incidence of AKI in neonates with severe birth asphyxia (RR: 0.40; 95% CI 0.3 to 0.54; heterogeneity: I2=0%) (moderate quality evidence), decrease in serum creatinine over days 2–5 (very low to low quality evidence) without significant difference in all-cause mortality (RR: 0.88; 95% CI 0.52 to 1.50; heterogeneity: I2=0%) (very low-quality evidence). A significant difference in the negative fluid balance, increase in GFR and decrease in urinary β2 microglobulin was seen in favour of theophylline.

Conclusion and relevance A single dose of prophylactic theophylline helps in prevention of AKI/severe renal dysfunction in term neonates with severe birth asphyxia (moderate quality evidence) without increasing the risk of complications and without affecting all-cause mortality (very low-quality evidence).

Trial registration number CRD 42017073600.

  • adenosine antagonists
  • neonates
  • birth asphyxia
  • cardiopulmonary bypass
  • acute kidney injury (AKI)
  • meta-analysis
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Footnotes

  • Contributors GCB designed the research; GCB and PG wrote the paper; GCB, RRD and MB performed the research; GCB and RRD analysed the data and MB supervised the paper; all authors read and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

  • Patient consent for publication Not required.

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