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. 2007 Jan 24;2007(1):CD005090.
doi: 10.1002/14651858.CD005090.pub2.

The effect of inotropes on morbidity and mortality in preterm infants with low systemic or organ blood flow

D A Osborn  1 , M Paradisis, N Evans
Affiliations

The effect of inotropes on morbidity and mortality in preterm infants with low systemic or organ blood flow

D A Osborn et al. Cochrane Database Syst Rev. .

Abstract

Background: Low systemic blood flow (SBF) is common in extremely premature infants in the first day after birth and has been associated with peri / intraventricular haemorrhage (PIVH), necrotising enterocolitis (NEC), mortality and developmental impairment.

Objectives: To determine the effect of specific inotropes on morbidity and mortality in preterm infants with low systemic blood flow

Search strategy: Searches were made of The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2006 ), MEDLINE (1966 - April 2006), EMBASE (1980 - April 2006) and CINAHL (1982 - April 2006), supplemented by searches of abstracts of conference proceedings, citations of reviews and expert informants.

Selection criteria: Random and quasi-random controlled trials of inotropes enrolling preterm infants with low systemic or organ blood flow in the neonatal period.

Data collection and analysis: Independent assessment of trial eligibility, quality and data extraction by each review author. Synthesis of data using relative risk (RR) and weighted mean difference (WMD) using standard methods of the Cochrane Collaboration.

Main results: No studies that compared an inotrope to no treatment in preterm infants with low SBF were found. One study (Osborn 2002a) was found that compared dobutamine versus dopamine. The study was of adequate methodology. It enrolled 42 infants < 30 weeks gestation and < 12 hours after birth with low SVC flow. The trial compared the effect of dobutamine versus dopamine titrated 10 to 20 mug/kg/min with the goal of increasing and maintaining SVC flow > 40 ml/kg/min. No significant difference was reported in mortality to discharge (RR 1.41, 95% CI 0.79, 2.52), PIVH (RR 1.01, 95% 0.52, 1.97), grade 3 or 4 PIVH (RR 0.39, 95% CI 0.12, 1.31) or NEC. At three years, there was no significant difference in cerebral palsy, deafness, Developmental quotient > 2 sd below norm or combined disability (RR 0.10, 95% CI 0.01, 1.56). Surviving infants treated with dobutamine had a significantly higher development quotient (MD 35.00, 95% CI 17.68, 52.32). There was no significant difference in death or disability at the latest time reported (RR 0.95, 95% CI 0.66, 1.38). For secondary outcomes, there was no significant difference in periventricular leucomalacia, renal impairment, pulmonary haemorrhage, retinopathy of prematurity or CLD at 36 weeks. There was no significant difference in treatment failure. Dobutamine produced a significantly greater increase in SVC flow at the highest dose reached (MD 13.10, 95% CI 2.87, 23.33), whereas dopamine produced a significantly greater increase in mean BP at 10 and 20 mug/kg/min and at the highest dose reached (MD -7.20, 95% CI -11.41, -2.99).

Authors' conclusions: In preterm infants with low systemic blood flow, there is some evidence that dobutamine is better than dopamine at increasing and maintaining systemic blood flow. The only eligible trial did not demonstrate any consistent differences in clinical outcomes. However, this study was not sufficiently powered to prove or disprove effects on clinical outcomes. It is unclear what is the most effective strategy for improving the cardiovascular status of immature infants in the first day. Further trials are needed to determine effective strategies for preventing and improving low systemic and organ blood flow.

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Conflict of interest statement

The reviewer authors conducted the only included trial of inotropes in infants with low SBF. No funding was received from pharmaceutical companies.

Figures

1.1
1.1. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 1 Mortality before discharge.
1.2
1.2. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 2 Mortality before follow up.
1.3
1.3. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 3 Any peri / intraventricular haemorrhage.
1.4
1.4. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 4 Late peri / intraventricular haemorrhage.
1.5
1.5. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 5 Peri / intraventricular haemorrhage grade 3 or 4.
1.6
1.6. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 6 Necrotising enterocolitis.
1.7
1.7. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 7 Cerebral palsy at 3 years in survivors assessed.
1.8
1.8. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 8 Deafness at 3 years in survivors assessed.
1.9
1.9. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 9 Blind at 3 years survivors assessed.
1.10
1.10. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 10 Griffith's general Quotient >2sd below norm at 3 years in survivors assessed.
1.11
1.11. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 11 Disability at 3 years in survivors assessed.
1.12
1.12. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 12 Death or disability at 3 years.
1.13
1.13. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 13 Death or disability at latest follow up.
1.14
1.14. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 14 Griffith's Mental Scales of Development General Quotient at 3 years in survivors assessed.
1.15
1.15. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 15 Periventricular leucomalacia in survivors.
1.16
1.16. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 16 Renal impairment (creatinine >=120 mmol/l).
1.17
1.17. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 17 Pulmonary haemorrhage.
1.18
1.18. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 18 Chronic lung disease (oxygen at 28 days) in survivors.
1.19
1.19. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 19 Chronic lung disease (oxygen or respiratory support at 36 weeks PMA) in survivors.
1.20
1.20. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 20 Retinopathy of prematurity in survivors examined.
1.21
1.21. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 21 Failed treatment (did not maintain SVC flow >=41ml/kg/min in 1st 24 hours).
1.22
1.22. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 22 Change mean BP at 10mcg/kg/min.
1.23
1.23. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 23 Change mean BP at 20mcg/kg/min.
1.24
1.24. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 24 Change mean BP at highest dose reached.
1.25
1.25. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 25 Change SVC flow at 10mcg/kg/min.
1.26
1.26. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 26 Change SVC flow at 20mcg/kg/min.
1.27
1.27. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 27 Change SVC flow at highest reached.
1.28
1.28. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 28 Change RVO at 10mcg/kg/min.
1.29
1.29. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 29 Change RVO at 20mcg/kg/min.
1.30
1.30. Analysis
Comparison 1 Dobutamine versus dopamine in preterm infants with low SVC flow, Outcome 30 Change RVO at highest dose reached.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Osborn 2002a {published and unpublished data}
    1. Osborn DA. Randomized trial of dobutamine versus dopamine in preterm infants with low systemic blood flow ‐ 3 year follow up. Pediatric Research 2005;57:A. - PubMed
    1. Osborn DA, Evans N, Kluckow M. Dopamine but not dobutamine increases left ventricular (LV) stress, but neither improves LV contractility in very preterm infants. Pediatric Research 2002;51:386A.
    1. Osborn DA, Evans N, Kluckow M. Dopamine but not dobutamine increases left ventricular (LV) stress, but neither improves LV contractility in very preterm infants. Proceedings Perinatal Society of Australia and New Zealand 6th Annual Congress. 2002:A145.
    1. Osborn DA, Evans N, Kluckow M. Left ventricular contractility in extremely premature infants in the first day and response to inotropes. Pediatric Research 2007;61:335‐40. - PubMed
    1. Osborn DA, Evans N, Kluckow M. Randomized trial of dobutamine versus dopamine in preterm infants with low systemic blood flow. Journal of Pediatrics 2002;140:183‐91. - PubMed

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References to other published versions of this review

Osborn 2007
    1. Osborn DA, Paradisis M, Evans NJ. The effect of inotropes on morbidity and mortality in preterm infants with low systemic or organ blood flow. Cochrane Database of Systematic Reviews 2007, Issue 1. [DOI: 10.1002/14651858.CD005090.pub2] - DOI - PMC - PubMed

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