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Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants

  1. Manoj N Malviya1,*,
  2. Arne Ohlsson2,
  3. Sachin S Shah3

Editorial Group: Cochrane Neonatal Group

Published Online: 28 MAR 2013

DOI: 10.1002/14651858.CD003951.pub3


How to Cite

Malviya MN, Ohlsson A, Shah SS. Surgical versus medical treatment with cyclooxygenase inhibitors for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD003951. DOI: 10.1002/14651858.CD003951.pub3.

Author Information

  1. 1

    Nice Hospital for Children and Newborns, Neonatal Intensive Care Unit, Shantinagar, Hyderabad, India

  2. 2

    University of Toronto, Departments of Paediatrics, Obstetrics and Gynaecology and Institute of Health Policy, Management and Evaluation, Toronto, Ontario, Canada

  3. 3

    Aditya Birla Memorial Hospital, Neonatal and Pediatric Intensive Care Services, Pune, India

*Manoj N Malviya, Neonatal Intensive Care Unit, Nice Hospital for Children and Newborns, Shantinagar, Hyderabad, India. manojmalviya07@gmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 28 MAR 2013

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Characteristics of included studies [ordered by study ID]

Methods13 centres, randomised controlled trial
I. Blinding of randomisation - yes
II. Blinding of intervention, trial B - no
III. Blinding of outcome measurement(s) trial B - not mentioned in the report
IV. Complete follow-up - yes


ParticipantsInclusion criteria:
1. Infants with birth weight < 1750 grams with haemodynamically significant PDA
Exclusion criteria
1. Birth weight < 500 grams
2. Congenital anomalies
3. Chromosomal abnormalities
4. Death within the first 24 hours
5. Age more than 14 days on admission to study centre
6. Lack of parental consent for monitoring
7. BUN more than 30 mg/dl
8. Serum creatinine more than 1.8 mg/dl
9. Total urine output less than 0.6 ml/kg/hr
10. Platelet count < 60,000/mm
11. Stool Hematest > or = to 3+ (or moderate to large)
12. Evidence of bleeding diathesis
13. Clinical or noninvasive evidence of intracranial haemorrhage within preceding 7 days
Demographic data: values presented as number or percentage
Total number of infants entered in trial B = 154
Surgery = 79
Indomethacin = 75

Recruitment period: April 1979 to April 1981


Interventions79 infants underwent surgical closure for PDA
75 infants received intravenous indomethacin at 12-hour intervals for a total of 3 doses, unless contraindications developed or there was evidence of complete ductal closure. Infants received 0.2 mg/kg of body weight as initial dose and then a second and third dose depending upon infant age at time of entry, 0.1 mg/kg or 0.2 mg/kg or 0.25 mg/kg if less than 2 days or 2 to 7 days or more than 8 days respectively


OutcomesDuctal closure rates, hospital mortality, duration of respiratory support, length of hospital stay. Incidence of adverse events (CLD, pneumothorax, IVH, NEC, sepsis, other bleeding, creatinine clearance > or = to 1.8, ROP of grade III and IV)
A diagnosis of significant PDA was made by clinical criteria (heart rate > 170 bpm, increased pulse pressure, hyperactive precordium, hepatomegaly > 3 cm) and echocardiographic demonstration of left atrial to aortic root ratio of = or > 1.15


NotesNational collaborative study involving 13 centres in USA
Study period: April 1979 to April 1981

Details about surgical procedure were not mentioned.

Postnatal age at which babies were randomised to surgical ligation or indomethacin was not clear


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number generation at the co-ordinating centre

Allocation concealment (selection bias)Low riskSealed envelopes containing each assignment

Blinding (performance bias and detection bias)
All outcomes
High riskThe intervention (surgery) could not be blinded

Blinding of participants and personnel (performance bias)
All outcomes
High riskAs the participants were neonates, they would be blinded but personnel could not be blinded

Blinding of outcome assessment (detection bias)
All outcomes
High riskCould not be blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskComplete follow-up

Selective reporting (reporting bias)Unclear riskThe study was not registered in a trials registry and we cannot ascertain whether there were deviations between the study protocol and the study report

Other biasLow riskThe study appears free of other bias

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Cotton 1978aThe study compared medical management versus surgical closure as primary treatment for symptomatic PDA in preterm infants, however the study did not use cyclooxygenase inhibitors in the medical management protocol

Levitsky 1976The study compared medical management versus surgical closure as primary treatment for symptomatic PDA in preterm infants, however the study did not use cyclooxygenase inhibitors in the medical management protocol

 
Comparison 1. Surgical versus medical treatment with indomethacin

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Death before discharge1154Risk Ratio (M-H, Fixed, 95% CI)0.67 [0.34, 1.31]

 2 Failure of ductal closure1154Risk Ratio (M-H, Fixed, 95% CI)0.04 [0.01, 0.27]

 3 Chronic lung disease1154Risk Ratio (M-H, Fixed, 95% CI)1.28 [0.83, 1.98]

 4 Intraventricular haemorrhage1154Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.32, 2.18]

 5 NEC1154Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.29, 3.15]

 6 Creatinine level > 1.8 mg/dl1154Risk Ratio (M-H, Fixed, 95% CI)0.57 [0.14, 2.30]

 7 ROP grade III and IV1154Risk Ratio (M-H, Fixed, 95% CI)3.80 [1.12, 12.93]

 8 Pneumothorax1154Risk Ratio (M-H, Fixed, 95% CI)2.68 [1.45, 4.93]

 9 Sepsis1154Risk Ratio (M-H, Fixed, 95% CI)1.14 [0.62, 2.09]

 10 Other bleeding1154Risk Ratio (M-H, Fixed, 95% CI)1.54 [0.68, 3.51]