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Adrenaline for prevention of morbidity and mortality in preterm infants with cardiovascular compromise

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Authors

Paradisis M, Osborn DA

Background - Methods - Results - Characteristics of Included Studies - References


Dates

Date edited: 25/11/2003
Date of last substantive update: 12/09/2003
Date of last minor update: / /
Date next stage expected 30/05/2005
Protocol first published: Issue 1, 2003
Review first published: Issue 1, 2004

Contact reviewer

Dr Mary Paradisis

Fellow
RPA Newborn Care
Royal Prince Alfred Hospital
Missenden Rd
Camperdown, Sydney
AUSTRALIA
2050
Telephone 1: 61 2 9515 8760
Telephone 2: 61 2 9515 8371
Facsimile: 61 2 9550 4375

E-mail: mary.paradisis@email.cs.nsw.gov.au
Secondary contact person's name: Dr David Osborn

Contribution of reviewers

  • None noted.

Sources of Support

Internal sources of support

RPA Newborn Care, Royal Prince Alfred Hospital, Sydney, AUSTRALIA

External sources of support

Centre for Perinatal Health Services Research, University of Sydney, AUSTRALIA

What's new

Date / Event Description

History

Date / Event Description

Synopsis

  • Synopsis pending

Abstract

Background

Inotropes are widely used in preterm infants to treat cardiovascular compromise, which may result from early adaptive problems of the transitional circulation, perinatal asphyxia or sepsis. Sustained hypotension and poor organ blood flow are associated with brain injury including peri/intraventricular haemorrhage and subsequent poor neurodevelopmental outcomes. Adrenaline (epinephrine) infusions are used in preterm infants with clinical cardiovascular compromise.

Objectives

To determine the effectiveness and safety of adrenaline compared to no treatment or other inotropes in reducing mortality and morbidity in preterm infants with cardiovascular compromise.

Search strategy

Randomised controlled trials were identified by searching MEDLINE (1966-August 2003), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2003) and EMBASE (1980 - 2003), supplemented with searches of reference lists of published trials and abstracts of conference proceedings.

Selection criteria

Randomised controlled trials of preterm newborn infants that compared adrenaline to no treatment or other inotropic agents (including dopamine, dobutamine, noradrenaline or isoprenaline).

Data collection & analysis

Data were extracted and analysed independently by two reviewers. Treatment effects on the following outcomes were to be determined: mortality in the newborn period, long term neurodevelopmental outcomes, radiological evidence of brain injury, short term haemodynamic changes, adverse drug effects and short term neonatal outcomes. Study authors were contacted for additional information. Studies were analysed for methodological quality using the criteria of the Cochrane Neonatal Review Group.

Main results

One ongoing study (Pellicer 2003) was identified. One study comparing adrenaline with dopamine infusion was included but was published in abstract form only (Phillipos 1996). It enrolled hypotensive, predominately preterm infants in the first 24 hours. Only infants >1750g are included in this review (report for infants less than/or equal to1750g appears incomplete). The study was reported as being randomised and double blinded, but methods were not reported. Both adrenaline and dopamine significantly increased heart rate and mean BP, with no statistically significant effect on left or right ventricular outputs. No other clinical outcomes were reported. No studies were identified that compared adrenaline to other inotropes, placebo or no treatment.

Reviewers' conclusions

There are insufficient data on the use of adrenaline infusions in preterm infants with cardiovascular compromise to make recommendations for practice. There is a need for larger trials to determine whether adrenaline is effective in reducing morbidity and mortality in preterm infants with cardiovascular compromise.

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Background

In the preterm infant cardiovascular compromise may be the result of early adaptive problems of the transitional circulation including high systemic vascular resistance, shunts across the adapting heart and an immature myocardium (Gill 1993; Seri 1995; Kluckow 2000; Osborn 2002a). In addition, sepsis, asphyxia or uncommonly hypovolaemia may also produce cardiovascular compromise (Gill 1993; Seri 1995). Subsequent poor organ blood flow is associated with injury including peri/intraventricular haemorrhage (P/IVH) (Kluckow 2000; Meek 1999; Osborn 2002b) and possibly periventricular leucomalacia (PVL), necrotising enterocolitis (Osborn 2002b) and renal impairment (Kluckow 2001). Clinical features used to detect cardiovascular compromise include hypotension, increased capillary filling time, metabolic acidosis and evidence of impaired organ function (e.g. low urine output). Cardiac output or organ blood flow may be measured directly using Doppler ultrasound or other techniques. Whereas sustained hypotension has been associated with P/IVH (Bada 1990; Miall-Allen 1987) and poor neurodevelopmental outcome (Goldstein 1995; Murphy 1997), studies using Doppler ultrasound have demonstrated that hypotension is imperfectly correlated with systemic blood flow measured using Doppler (Kluckow 1996; Kluckow 2000). Low upper body blood flow has been associated with increased mortality (Osborn 2003) and late P/IVH (Kluckow 2000; Osborn 2003). The association with subsequent poor neurodevelopmental outcome is reported to be stronger for reduced blood flow than for blood pressure (Hunt 2001).

Treatment options for preterm infants with cardiovascular compromise include inotropes, volume expansion and corticosteroids. Inotropes that have the potential for use in preterm infants include adrenaline, dobutamine, dopamine, isoprenaline and noradrenaline. These inotropes have varying pharmacological effects which include increased myocardial contractility and heart rate (via beta receptors), and reduced (via beta receptors) or increased (via alpha receptors) vascular resistance. The mechanism of action is often dose dependent and also depends on which receptors are stimulated.

Adrenaline infusions are most frequently used in neonates for the treatment of hypotension and pulmonary hypertension (Perkin 1982; Zaritsky 1984). Adrenaline has both alpha and beta receptor agonist effects (Seri 1995; Zaritsky 1984). At low dose it is a potent inotrope, chronotrope and systemic and pulmonary vasodilator. At higher doses it has differential effects on the systemic and pulmonary circulations, increasing systemic pressure more than pulmonary pressure (Barrington 1993; Barrington 1995). Animal studies have demonstrated improvement in cardiac output (Barrington 1993; Cheung 1997), myocardial perfusion (Barrington 1995) and increased mesenteric vascular resistance (Cheung 1997). Reported adverse effects of adrenaline infusion in the neonate include increases in peripheral vascular resistance leading to decreased cardiac output and tissue perfusion, hypertension, tachycardia and severe tissue necrosis with extravasation of the infusate (Perkin 1982; Seri 2001). There is a paucity of published studies regarding the circulatory effects of adrenaline infusion in the neonate (Seri 1998a; Campbell 1998) and there is no systematic review of the use of adrenaline in preterm infants with cardiovascular compromise.

Dopamine has been used extensively in neonates for treatment of hypotension and also has dose dependent actions. Low infusion rates (0.5 to 5 microgram/kg/min) are used to improve renal function. Medium ranges (6 to 10 microgram/kg/min) are used for treatment of heart failure. With doses up to 10 microgram/kg/min there is an increase in blood pressure (Osborn 2002b; Padbury 1987) and possibly cardiac output (Lundstrom 2000; Osborn 2002b; Padbury 1987). However, there is concern that higher doses may only increase blood pressure with no improvement in cardiac function or output (Osborn 2002b; Roze 1993). The usual justification of using dopamine in hypotensive preterm infants is to increase cerebral perfusion and avoid ischaemic injury. However, there is no evidence yet that cerebral blood flow is increased by the use of dopamine (Lundstrom 2000; Seri 1998b; Barrington 1995; Osborn 2002b). In the neonate, dopamine has no significant effect on mesenteric blood flow (Seri 1998b; Cheung 1997) or coronary blood flow (Barrington 1995). Reported adverse effects of dopamine in the neonate include severe vasoconstriction, local tissue necrosis if extravasation occurs, tachyarrhythmia (Seri 1995) and hepatic injury after inappropriately placed umbilical venous catheter (Venkataraman 1984).

Dobutamine, an inotrope with predominantly beta receptor effects, has been used in asphyxiated hypotensive preterm infants with myocardial dysfunction (Perkin 1982; Seri 2001), and has been compared to dopamine in several randomised trials in preterm infants with hypotension (Subhedar 2002) or low blood flow (Osborn 2002b). The dose range used to increase cardiac output has been up to 20 micrograms/kg/min (Osborn 2002b). Potential adverse effects are similar to the other inotropes and include tachyarrhythmia and hypertension (Seri 2001), although hypertension is unusual (Osborn 2002b). The effects of dopamine versus dobutamine have been examined in a systematic review (Subhedar 2002). Dopamine was more effective than dobutamine for treatment of systemic hypotension in the short term. However, there was insufficient evidence concerning long term benefits and safety to give firm recommendations on the choice of drug to treat neonatal hypotension. Noradrenaline has both alpha and beta activity, producing greater increases in vascular resistance than the other inotropes (Zaritsky 1984). The adverse side effects are similar to adrenaline. There is a paucity of studies with noradrenaline in the preterm population (Derleth 1997). Isoprenaline is a synthetic catecholamine with almost purely beta effects (Zaritsky 1984) with an important adverse effect being tachyarrhythmia.

This review will examine the evidence for the use of adrenaline compared to no treatment or other inotropes for the treatment of preterm infants with cardiovascular compromise. As preterm infants may have different underlying causes of cardiovascular compromise or have different clinical indications for inotrope treatment, subgroup analysis will examine the evidence for use of adrenaline depending on aetiology of compromise or clinical indication for inotrope. This review should be viewed in the context of other Cochrane reviews of cardiovascular interventions in preterm infants including those examining dopamine and dobutamine for hypotension (Subhedar 2002), corticosteroids for hypotension (Whitelaw 2002), and early volume expansion (Osborn 2002c; Osborn 2002d).

Objectives

The aim of this review was to examine the evidence for the effectiveness and safety of adrenaline compared to no treatment or other inotropes in reducing mortality and morbidity in preterm infants with cardiovascular compromise.
Subgroup analysis was prespecified according to:

  • aetiology of cardiovascular compromise
  • indicator used to define cardiovascular compromise (clinical or echocardiography)
  • dose range used for each inotrope

Criteria for considering studies for this review

Types of studies

Randomised controlled trials that compared adrenaline to no treatment or other inotropic agents (including dopamine, dobutamine, noradrenaline or isoprenaline).

Types of participants

Preterm infants < 37 weeks gestation with evidence of cardiovascular compromise. Cardiovascular compromise was defined:

  • Clinically: using indicators of poor perfusion (hypotension: as defined by the individual study investigators, thus the criteria for hypotension may vary between studies), metabolic acidosis, increased capillary refill time or evidence of organ dysfunction (e.g. low urine output).
  • Using direct measures of cardiac output or organ perfusion (e.g. echocardiography or other techniques)

Types of interventions

Adrenaline infusion at any dose compared to no treatment (including placebo) or infusion of other inotrope (including dopamine, dobutamine, noradrenaline or isoprenaline)

Types of outcome measures

Primary:
  1. Mortality in neonatal period (< 28 days) or to discharge from hospital
  2. Long term neurodevelopmental outcome: cerebral palsy and standardised assessment of developmental delay or sensorineural impairment
  3. Periventricular or intraventricular haemorrhage (any grade of severity)
  4. Periventricular leukomalacia
Secondary:
  1. Short term haemodynamic changes:
    • failure to correct systemic hypotension
    • failure to correct low systemic or organ blood flow
    • mean increase in cardiac output or systemic blood flow (defined by Doppler echocardiography)
    • mean increase in blood pressure (hypotension, as defined by individual studies)
  2. Drug side effects:
    • tachyarrhythmias
    • extravasation of infusate
    • hepatic injury
  3. Other short term neonatal outcomes:
    • patent ductus arteriosus
    • gastrointestinal complications (perforation, necrotising enterocolitis)
    • chronic lung disease (respiratory support at 28 days age or >36 weeks postmenstrual age)
    • duration of ventilation and respiratory support
    • duration of hospital stay
    • renal complications (oliguria defined as urine output < 0.5 ml/kg/hr for > 24 hours or creatinine > 120 umol/l)

Search strategy for identification of studies

See: Cochrane Neonatal Group Search Strategy

The standard search method of the Cochrane Neonatal Group as described in the Cochrane Library was used. The following electronic databases were searched: MEDLINE (1966 - August 2003), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2003) and EMBASE (1980 - August 2003). In addition, recent abstracts, conferences and cited references from retrieved articles were hand searched. Unpublished studies were sought by hand searching the conference proceedings of the Society for Pediatric Research (1998-2003). Search strategies were developed using the following keywords/index terms: 'infant, pre term', 'hypotension', 'adrenaline or epinephrine', 'dopamine', 'dobutamine', 'isoproterenol', 'inotrope', 'sepsis', 'asphyxia'. Searches were limited to randomised controlled trials. There was no language restriction.

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Methods of the review

The standard search method of the Cochrane Neonatal Review Group (CNRG) as described in the Cochrane Collaboration Handbook was used to conduct this systematic review.

The pre-specified inclusion criteria regarding gestational age were adjusted after review of the studies. Phillipos 1996 included infants that were both term and preterm. It is not stated how many infants were term or preterm; however, as the mean gestational age was 36 weeks, a decision was made to include this study.

The methodological quality of studies was assessed as recommended by the CNRG. Two reviewers independently assessed and selected the studies to be included in the review. Studies were assessed for methodological quality using the following criteria: allocation concealment, blinding of randomisation, completeness of follow up and blinding of the outcome measure. Data were extracted independently by the reviewers. Additional information was requested from the study authors of the studies that were assessed to be eligible. Authors were contacted by e-mail for additional information regarding individual patient data for haemodynamic measures and any other outcomes. The author of one study (Phillipos 1996) provided a copy of conference proceedings but has not yet provided any further information. The authors of an ongoing study (Pellicer 2003) have provided information regarding the progress of the study to date.

Statistical analysis: When available, data will be analysed using the standard methods of the CNRG. Treatment effects will be analysed using relative risk (RR), risk difference (RD) and number needed to treat (NNT) for categorical outcomes, and mean difference (MD) and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals where appropriate. Heterogeneity between studies will be examined. Meta-analysis will be performed for studies where treatments are used for similar patients and similar dosage schedules. A fixed effect model will be used for the meta analysis unless significant heterogeneity exists between studies, in which case the cause of the heterogeneity will be explored and if appropriate, a random effects model used. Sensitivity analysis will be performed including only studies of good methodology (adequate randomisation and allocation concealment and < 10% post randomisation losses).

Subgroup analysis were to be performed according to trials that enrolled infants on the basis of:

  1. Aetiology of cardiovascular compromise
    • transitional circulation (defined as early cardiovascular compromise in preterm infants without obvious cause such as sepsis or asphyxia)
    • sepsis (proven and suspected)
    • perinatal asphyxia: as evidenced by cord pH < 7.0 and/or cord base excess < -16 mEq/L and/or 5 minute Apgar score < 6
  2. Indicator used to define poor cardiovascular function
    • clinical e.g. hypotension; or
    • echocardiography e.g. low systemic or organ blood flow
  3. Dose range of inotrope used:
    • Adrenaline (up to 0.16 microgram/kg/min)
    • Dopamine (0 - 5, 6 -10 and > 10 microgram/kg/min),
  4. Age at initiation of therapy (early < 72 h v late > 72h)

Description of studies

Two studies were identified that compared adrenaline with dopamine in preterm infants with hypotension. One study (Phillipos 1996) published in abstract form has been included and one study (Pellicer 2003) is ongoing. No studies were identified that enrolled infants with low blood flow or compared adrenaline to any other inotrope, a placebo or no treatment.

Infants: Phillipos 1996 enrolled hypotensive newborn infants < 24 hours age with a mean BP one SD below mean for weight (using data from Versmold 1981) and indwelling arterial line. Infants were stratified into three groups of 20 infants: 750-1250g, 1251-1750g and > 1750g. Infants with congenital heart disease were excluded. For infants >1750g, the dopamine group had a mean gestation of 34 (range 30-34) weeks and birth weight 2471g; the adrenaline group had a mean gestation 36 (range 34-41) weeks and mean birthweight 2642g. Seven infants in each group had a patent ductus arteriosus. For infants less than/or equal to1750g, only 16 of the anticipated 40 infants are reported. Clarification as to whether this is an ongoing or completed study has been sought from the author. This review will only report outcomes for infants >1750g. Infants < 1750g were not included in the current review as we are awaiting clarification from the authors regarding the completion status of the study. When these data become available, it is intended that they be included in a future update of this review.

Interventions: Phillipos 1996 allocated infants to dopamine or adrenaline. Dopamine was started at 5 and then increased to 10, 15 and 20 micrograms/kg/min every 20 minutes, and adrenaline was started at 0.125 and increased 0.25, 0.375 and 0.5 micrograms/kg/min every 20 minutes till desired mean BP was achieved for at least one hour. If the desired BP was not achieved, the other drug was added.

Measurement: Phillipos 1996 used invasive BP monitoring of all infants and used 2-D echocardiography to determine left and right ventricular output, left and right stroke volume index, and mean pulmonary artery pressure.
No other clinical outcomes were reported.

Methodological quality of included studies

The overall methodological quality of the included trial is unclear. Phillipos 1996 reported the study to be randomised and double blinded. However, the method of randomisation and blinding were not reported. Allocation concealment is unclear. For infants >1750g, in an initial report Phillipos 1996 reported data for heart rate, mean BP and left and right ventricular output for all 20 infants, but did not report standard deviations. In a second report, Phillipos 1996 excluded 2 (10%) infants but reported both means and standard errors. For infants less than/or equal to1750g, as only 16 of the anticipated 40 infants have been reported, these infants are not included in this review. Clarification has been sought from the author.

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Results

One study (Phillipos 1996) enrolling a total of 20 infants > 1750g met eligibility criteria and was included in this systematic review. No outcome data were able to be entered into the analysis tables, so all treatment effects are reported in text.

Primary clinical outcomes

Effects on mortality, neurodevelopmental outcome, periventricular or intraventricular haemorrhage (any grade of severity), and periventricular leukomalacia were not reported.

Secondary outcomes: Short term haemodynamic changes

Failure to correct systemic hypotension or failure to correct low systemic or organ blood flow was not reported. For infants >1750g, Phillipos 1996 reported a significant increase in mean heart rate and mean BP at the highest dose reached, and at the study endpoint, for both adrenaline and dopamine. The significance of the difference between the two inotropes was not reported. Neither inotrope produced a statistically significant change in left or right ventricular outputs. Dopamine produced a significant fall in left ventricular stroke volume compared to baseline. Whether this was statistically different to the effect of adrenaline was not reported.

Secondary outcomes: Drug side effects

Tachyarrhythmias, extravasation of infusate and hepatic injury were not reported.

Secondary outcomes: Short term neonatal outcomes

Patent ductus arteriosus, gastrointestinal complications (perforation, necrotising enterocolitis), chronic lung disease, duration of ventilation and respiratory support, duration of hospital stay and renal complications not reported.

Subgroup analyses

The available trial enrolled predominately preterm infants with hypotension. There is inadequate information in the reported abstracts to determine the aetiology of the cardiovascular compromise although as infants were enrolled in the first day of life it is likely a substantial number had problems with the transitional circulation. The dose ranges used for both adrenaline and dopamine incorporated all prespecified subgroup analyses. No sensitivity analysis was performed as the methodological quality of the included study is unclear.

Discussion

This review found evidence from one small randomised study (Phillipos 1996), reporting outcomes in 20 hypotensive infants >1750g in the first 24 hours after birth, that both dopamine and adrenaline increased heart rate and mean blood pressure but did not have a statistically significant effect on left or right ventricular outputs. Outcomes from this trial for infants born less than/or equal to1750g were excluded from this review as it is unclear whether the reported infants represent a preliminary report of an incomplete study or a study that was stopped early. The available study was of unclear methodological quality as it has been published in abstract form only and methods of randomisation, allocation concealment and blinding were not reported. The study was reported as being randomised and double blinded. No study reported any other clinically important outcomes including mortality and neurodevelopmental outcome. No study enrolled infants with low systemic or organ blood flow or reported incidence of low blood flow.

The limitations of this review include the lack of published reports including methodology and data, and the small numbers of infants enrolled in the included trial. Publication of existing data is important.

Reviewers' conclusions

Implications for practice

There are insufficient data on the use of adrenaline infusions in preterm infants with cardiovascular compromise to make recommendations for practice.

Implications for research

There is a need for larger trials to determine whether adrenaline is effective at reducing morbidity and mortality in preterm infants with cardiovascular compromise. Trials should enrol infants with evidence of cardiovascular compromise, measure the effects of inotrope infusions on systemic and organ blood flow, and report clinically important outcomes including mortality and neurodevelopmental achievements.

Acknowledgements

  • None noted.

Potential conflict of interest

Both the authors are investigators in trials of cardiovascular interventions in preterm infants.

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Characteristics of studies

Characteristics of Included Studies

Study Methods Participants Interventions Outcomes Notes Allocation concealment
Phillipos 1996 Single centre trial, Canada.
Blinding of randomisation: unclear.
Blinding of intervention: yes, but method not reported.
Blinding of outcome assessment: yes, but method not reported.
Follow up: infants >1750g: 2/20 (10%) not included in analysis.
Infants less than/or equal to1750g: 16 infants reported in abstract (?ongoing study).
Newborn infants < 24 hours age, hypotensive with mean BP 1SD below mean for weight and indwelling arterial line. Stratified into 3 groups of 20 infants: 750-1250g, 1251-1750g and > 1750g.
For infants > 1750g, n =20,
Dopamine group: n = 10, mean gestation 34 weeks, mean BW 2471g.
Adrenaline group: n = 10, mean gestation 36 weeks, mean BW 2642g.
Exclusions: congenital heart disease
  1. Dopamine titrated [5, 10, 15, 20 mcg/kg/min] every 20 minutes till desired mean BP achieved for 1 hour.
  2. Adrenaline titrated [0.125, 0.25, 0.375, 0.5 mcg/kg/min] every 20 minutes till desired mean BP achieved for 1 hour.

If the desired BP was not achieved, the other drug was added.

Primary outcomes: effects on mean BP, mean pulmonary artery pressure, left and right ventricular cardiac indices and stroke volumes.
Outcomes: heart rate; invasive mean blood pressure; study endpoint was stable desired mean BP for 1 hour; echocardiographically measured left and right ventricular output, left and right stroke volume index, and mean pulmonary artery pressure.
No other clinical outcomes reported.
The number of infants who received both inotropes or did not achieve primary end point not reported.
Highest infusion rate to obtain desired mean BP not reported.
Randomised, blinded study of dopamine vs adrenaline in hypotensive predominately preterm infants.
For infants less than/or equal to1750g: only 16 of the anticipated 40 infants were reported, possibly incomplete study. Authors contacted, awaiting reply.
B

Characteristics of ongoing studies

Study Trial name or title Participants Interventions Outcomes Starting date Contact information Notes
Pellicer 2003 Randomised blinded controlled trial on the effects on brain haemodynamics of dopamine v epinephrine for inotropic support in preterm infants. Preterm infants < 31 weeks GA or < 1501 gram with systemic hypotension (MBP mmHg < GA) within the first 24h of age Dopamine 2.5, 5, 7.5, 10 mcg/kg/min or epinephrine 0.125, 0.25, 0.375, 0.5 mcg/kg/min increasing every 20 minutes until a desired MAP is achieved and maintained. If this was not achieved the other drug was added. Changes in cerebral blood volume,
cerebral oxyhaemoglobin and deoxyhaemoglobin
Mean arterial pressure
Heart rate
Transcutaneous pCO2
Peripheral oxygen saturations
May 2002 Adelina Pellicer
apellicer.hulp@salud.madrid.org
Sample size required: 60
Currently 51 infants enrolled

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References to studies

Included studies

Phillipos 1996

{published data only}

* Phillipos EZ, Barrington KJ, Robertson MA. Dopamine versus epinephrine for inotropic support in the neonate: A randomized double blinded controlled trial. Pediatr Res 1996;39:238A.

Phillipos EZ, Barrington KJ, Robertson MA. The effects of dopamine vs epinephrine on the pulmonary circulation in the sick newborn: A randomized double blinded controlled trial. Pediatr Res 1996;39:238A.

Phillipos EZ, Robertson MA. A randomized blinded trial of dopamine versus epinephrine for inotropic support in the sick newborn. In: Proceedings of the 2nd World Congress of PCCS. 1997:897-9.

Phillipos EZ, Robertson MA. A randomized double blinded controlled trial of dopamine vs epinephrine on pulmonary artery pressure in premature infants < 1750 grams. Pediatr Res 2000;47:425A.

Phillipos EZ, Robertson MA. A randomized double blinded controlled trial of dopamine vs epinephrine for inotropic support in premature infants < 1750 grams. Pediatr Res 2000;47:425A.

References to ongoing studies

Pellicer 2003

{published and unpublished data}

Pellicer A, Valverde E, Elorza MD, Madero R, Gaya F, Quero J, Cababnas F. Randomized blinded controlled trial on the effects on brain hemodynamics of dopamine v epinephrine for inotropic support in preterm infants. Pediatric Academic Societies Annual Meeting 2003:2364A.

* indicates the primary reference for the study

Other references

Additional references

Bada 1990

Bada HS, Korones SB, Perry EH, Arheart KL, Ray JD, Pourcyrous M, Magill HL, Runyan W 3rd, Somes GW, Clark FC et al. Mean arterial blood pressure changes in premature infants and those at risk for intraventricular hemorrhage. J Pediatr 1990;117:607-14.

Barrington 1993

Barrington K, Chan W. The circulatory effects of epinephrine infusion in the anesthetized piglet. Pediatr Res 1993;33:190-4.

Barrington 1995

Barrington KJ, Finer NN, Chan WKY. A blind, randomized comparison of the circulatory effects of dopamine and epinephrine infusions in the newborn piglet during normoxia and hypoxia. Crit Care Med 1995;23:740-8.

Campbell 1998

Campbell ME, Byrne PJ. Outcome after intravenous epinephrine infusion in infants < 750g. Pediatr Res 1998;43:209A.

Cheung 1997

Cheung PY, Barrington KJ, Pearson RJ, Bigam DL, Finer NN, Van Aerde J. Systemic, pulmonary, and mesenteric perfusion and oxygenation effects of dopamine and epinephrine. Am J Respir Crit Care Med 1997;155:32-7.

Derleth 1997

Derleth DP. Clinical experience with norepinephrine infusions in critically ill newborns. Pediatr Res 1997;40:145A.

Gill 1993

Gill AB, Weindling AM. Echocardiographic assessment of cardiac function in shocked very low birthweight infants. Arch Dis Child 1993;68:17-21.

Goldstein 1995

Goldstein RF, Thompson RJ Jr, Oehler JM, Brazy JE. Influence of acidosis, hypoxemia and hypotension on neurodevelopmental outcome in very low birth weight infants. Pediatrics 1995;95:238-43.

Hunt 2001

Hunt RW, Evans N, Rieger I, Kluckow M. Low superior vena cava flow in the first 24 hours of life and 3 year neurodevelopmental outcome. Pediatr Res 2001;49:336A.

Kluckow 1996

Kluckow M, Evans N. Relationship between blood pressure and cardiac output in preterm infants requiring mechanical ventilation. J Pediatr 1996;129:506-12.

Kluckow 2000

Kluckow M, Evans N. Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child Fetal Neonatal Ed 2000;82:F188-94.

Kluckow 2001

Kluckow M, Evans N. Low systemic blood flow in the preterm infant. Semin Neonatol 2001;6:75-84.

Lundstrom 2000

Lundstrom K, Pryds O, Greisen G. The haemodynamic effects of dopamine and volume expansion in sick preterm infants. Earl Hum Dev 2000;57:157-63.

Meek 1999

Meek J, Tyszczuk L, Elwell CE, Wyatt JS. Low cerebral blood flow is a risk factor for severe intraventricular haemorrhage. Arch Dis Child Fetal Neonatal Ed 1999;81:F15-F18.

Miall-Allen 1987

Miall-Allen VM, de Vries LS, Whitelaw AG. Mean arterial blood pressure and neonatal cerebral lesions. Arch Dis Child 1987;62:1068-9.

Murphy 1997

Murphy DJ, Hope P, Johnson A. Neonatal risk factors for cerebral palsy in very preterm babies: case-control study. BMJ 1997;314:404-8.

Osborn 2002a

Osborn DA, Evans N, Kluckow M. Left ventricular contractility and wall stress in very preterm infants in the first day of life. Pediatr Res 2002;51:386A.

Osborn 2002b

Osborn D, Evans N, Kluckow M. Randomised trial of dobutamine versus dopamine in preterm infants with low systemic blood flow. J Pediatr 2002;140:183-91.

Osborn 2002c

Osborn DA, Evans N. Early volume expansion for prevention of morbidity and mortality in very preterm infants (Cochrane Review). In: The Cochrane Library, Issue 3, 2002. Oxford: Update Software.

Osborn 2002d

Osborn DA, Evans N. Early volume expansion versus inotrope for prevention of morbidity and mortality in very preterm infants (Cochrane Review). In: The Cochrane Library, Issue 3, 2002. Oxford: Update Software.

Osborn 2003

Osborn DA, Evans N, Kluckow M. Haemodynamic and antecedent risk factors of early and late periventricular/intraventricular hemorrhage in premature infants. Pediatrics 2003;112:33-39.

Padbury 1987

Padbury JF, Agata Y, Baylen BG, Ludlow JK, Polk DH, Goldblatt E, Pescetti J. Dopamine pharmacokinetics in critically ill newborn infants. J Pediatr 1987;110:293-98.

Perkin 1982

Perkin RM, Levin DL. Shock in the pediatric patient. Part II. Therapy. J Pediatr 1982;101:319-32.

Roze 1993

Roze JC, Tohier C, Maingueneau C, Lefevre M, Mouzard A. Response to dobutamine and dopamine in the hypotensive very preterm infant. Arch Dis Child 1993;69:59-63.

Seri 1995

Seri I. Cardiovascular, renal and endocrine actions of dopamine in neonates and children. J Pediatr 1995;126:333-44.

Seri 1998a

Seri I, Evans J. Addition of epinephrine to dopamine increases blood pressure and urine output in critically ill extremely low birth weight neonates with uncompensated shock. Pediatr Res 1998;43:194A.

Seri 1998b

Seri I, Abbasi S, Wood DC, Gerdes JS. Regional hemodynamic effects of dopamine in the sick preterm neonate. J Pediatr 1998;133:728-34.

Seri 2001

Seri I. Circulatory support of the sick preterm infant. Semin Neonatol 2001;6:85-95.

Subhedar 2002

Subhedar NV, Shaw NJ. Dopamine versus dobutamine for hypotensive preterm infants (Cochrane Review). In: The Cochrane Library, Issue 3, 2002. Oxford: Update Software.

Venkataraman 1984

Venkataraman PS, Babcock DS, Tsang RC, Ballard JL. Hepatic injury: a possible complication of dopamine infusion through an inappropriately placed umbilical vein catheter. Am J Perinatol 1984;1:351-54.

Versmold 1981

Versmold HT, Kitterman JA, Phibbs RH, Gregory GA. Tooley WH. Aortic blood pressure during the first 12 hours of life in infants with birth weight 610 to 4, 220 grams. Pediatrics 1981;67:607-13.

Whitelaw 2002

Whitelaw A, Ogbureke K, Subhedar N. Corticosteroids for hypotension in preterm infants (Protocol for a Cochrane Review). In: The Cochrane Library, Issue 3, 2002. Oxford: Update Software.

Zaritsky 1984

Zaritsky A, Chernow B. Use of catecholamines in pediatrics. J Pediatr 1984;105:341-50.

Additional tables

  • None noted.

Amended sections

Cover sheet
Synopsis
Abstract
Background
Objectives
Criteria for considering studies for this review
Search strategy for identification of studies
Methods of the review
Description of studies
Methodological quality of included studies
Results
Discussion
Reviewers' conclusions
Potential conflict of interest
References to studies
Other references
Characteristics of Included Studies
Characteristics of ongoing studies
Comparisons, data or analyses

Contact details for co-reviewers

Dr David A Osborn

Neonatologist
RPA Newborn Care
Royal Prince Alfred Hospital
Missenden Road
Camperdown
New South Wales AUSTRALIA
2050
Telephone 1: +61 2 95158760
Telephone 2: +61 2 95156111
Facsimile: +61 2 95504375

E-mail: david.osborn@email.cs.nsw.gov.au


This review is published as a Cochrane review in The Cochrane Library, Issue 1, 2004 (see http://www.thecochranelibrary.com External Web Site Policy for information). Cochrane reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and The Cochrane Library should be consulted for the most recent version of the Review.