Cochrane Database of Systematic Reviews
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Harish Madhava MS, Settle P
Harish Madhava MS, Settle P. Fluid restriction for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD007800. DOI: 10.1002/14651858.CD007800.
www.cochranelibrary.com
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS HEADER . . . . . . . . . . ABSTRACT . . . . . . . . . BACKGROUND . . . . . . . OBJECTIVES . . . . . . . . METHODS . . . . . . . . . REFERENCES . . . . . . . . HISTORY . . . . . . . . . . CONTRIBUTIONS OF AUTHORS DECLARATIONS OF INTEREST . SOURCES OF SUPPORT . . . .
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Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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1 1 1 2 3 4 5 5 5 5
i
[Intervention Protocol]
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants Murthy Siddanahalli Harish Madhava1 , Paul Settle2 1
Department of Paediatrics, Leeds Teaching Hospitals NHS Trust, Halifax, UK. 2 Neonatal Unit, Hope Hospital, Salford, UK
Contact address: Murthy Siddanahalli Harish Madhava, Department of Paediatrics, Leeds Teaching Hospitals NHS Trust, 45 Hastings way, Halifax, West Yorkshire, HX1 2QB, UK. [email protected]. Editorial group: Cochrane Neonatal Group. Publication status and date: New, published in Issue 2, 2009. Citation: Harish Madhava MS, Settle P. Fluid restriction for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD007800. DOI: 10.1002/14651858.CD007800. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the effects of conservative medical management (fluid restriction with or without diuretics) on ductal closure or reduction of the size of the PDA in preterm infants with symptomatic PDA. Subgroup analysis will evaluate the effectiveness and safety of conservative medical management of symptomatic PDA based on the following criteria: • gestational age (< 28 weeks, 28 - 32 weeks, > 33 - 37 weeks) • birth weight ( 5 days)
• type of intervention (fluid restriction only, fluid restriction with diuretics) Gestational age subgroup analysis will be done preferentially unless only birthweight information is available.
Description of the condition PDA (patent ductus arteriosus) is a common problem among
BACKGROUND Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
1
preterm infants (Duddell 1984; Ellison 1983; Koch 2006). A PDA may occur in up to 65% of infants born at less than 28 weeks’ gestation (EPICure 2000; Mouzinho 1991). The presence of a persistently patent ductus arteriosus may be associated with high morbidity (EPICure 2000; Laughon 2004). Accurate diagnosis, assessment of the significance of the left to right shunt and prompt treatment may be beneficial in improving outcome in these infants (Clyman 1998). However, there is also a school of thought that in preterm infants patency of the ductus arteriosus may represent a normal physiologic adaptation to allow shunting from either systemic-to-pulmonary circulation (e.g. in the first day of life) or from pulmonary-to-systemic circulation (e.g. in the presence of severe lung disease). The medical community is becoming increasingly divided over the pathological significance of a haemodynamically significant PDA (Laughon 2004). Although there is no definite proof that it is beneficial to treat PDA, many clinicians are convinced that there is a link between PDA and adverse outcomes. The general tendency among clinicians is to identify haemodynamically significant ducts and treat them. Infants are often considered to have a “symptomatic PDA” when a combination of clinical signs (Davis 1995) and echocardiographic findings are present (Dani 2000; De Carolis 2000; Lago 2002). These include the presence of a continuous/systolic murmur, the need for ventilator support for at least 48 hours or increased ventilator requirements, hyperactive precordium, increased pulse pressure, tachycardia (heart rate > 170 bpm), tachypnoea (respiratory rate > 70/min), cardiomegaly with pulmonary congestion on chest radiograph and left-to-right shunting through a patent ductus arteriosus on two-dimensional echocardiogram along with Doppler studies (Skinner 2001; Skelton 1994).
is beneficial in treating infants with symptomatic PDA; however, the evidence reviewed by (Bell 2003) does not support this.
Why it is important to do this review One of the challenges of fluid restriction is maintaining adequate nutrition. In a growing infant, long-term fluid restriction limits the amount of calories and minerals that can be given. Providing adequate calories and minerals with fluid restriction requires highly concentrated formulas or parenteral alimentation, which may increase the risk of feeding intolerance and sepsis. For many clinicians, fluid restriction represents a poor trade-off to control the symptoms of PDA at the expense of adequate nutrition. The use of diuretics carries potential risks and benefits. The effect of diuretics on PDA is difficult to evaluate because of the transient improvement in respiratory function that may occur (Knight 2001; Wyllie 2003). Diuretics, especially loop diuretics, may cause electrolyte disturbances such as hyponatraemia and hypokalaemia that can be detrimental to the growth and development of the fragile preterm infant (Brion 2001). Diuretics also have a theoretical risk of worsening shunting through the PDA because of their anti-prostaglandin activity (Green 1981). Conservative medical management of PDA includes the use of both fluid restriction and diuretics.The timing and duration of “conservative medical management” is not standardised and most units tend to have their own arbitrary policies that are often based on poor evidence. The following review will explore the evidence base behind the concept of conservative medical management of symptomatic PDA.
Description of the intervention Clinically proven treatments for PDA include indomethacin, ibuprofen and surgical ligation (Knight 2001). However, each of these have side effects (EPICure 2000; Knight 2001; Laughon 2004) and the optimum timings for their use have not been established (Knight 2001). Fluid restriction with or without additional diuretics is often recommended to control the symptoms of a PDA. The timing and duration of fluid restriction are often not standardised and end points to the intervention are often not defined.
OBJECTIVES To evaluate the effects of conservative medical management (fluid restriction with or without diuretics) on ductal closure or reduction of the size of the PDA in preterm infants with symptomatic PDA. Subgroup analysis will evaluate the effectiveness and safety of conservative medical management of symptomatic PDA based on the following criteria: • gestational age (< 28 weeks, 28 - 32 weeks, > 33 - 37 weeks) • birth weight ( 5 days) • type of intervention (fluid restriction only, fluid restriction with diuretics) Gestational age subgroup analysis will be done preferentially unless only birthweight information is available.
METHODS
Criteria for considering studies for this review
Types of studies Randomised and quasi-randomised controlled trials
• requirement of surgical closure of PDA • duration of mechanical ventilation (days) • duration of oxygen dependence (days) • chronic lung disease (oxygen therapy at 36 weeks postmenstrual age) • severe intraventricular haemorrhage (grade 3 - 4) • renal dysfunction [oliguria or elevated serum creatinine (>/ = 1.8 gm/dl)] • necrotizing enterocolitis (Bell’s stage 2 or greater) • isolated intestinal perforation (perforation unrelated to NEC) • sepsis - blood culture positive • duration of hospital stay (days) • duration of therapy (days) • hyponatraemia (serum sodium < 125 mmol/L) or hypernatraemia (serum sodium >150 mmol/L) • hypokalaemia (serum sodium < 3.5 mmol/L) or hyperkalaemia (serum potassium > 6.5 mmol/L) • mortality • other adverse effects
Types of participants Preterm infants (< 37 weeks gestational age) with symptomatic patent ductus arteriosus (diagnosis based on clinical criteria or two-dimension echocardiographic and Doppler criteria or both) No limits on the postnatal age will be applied. Studies involving infants previously treated with indomethacin or ibuprofen for a symptomatic PDA will be excluded.
Types of interventions • fluid restriction without diuretics vs. no fluid restriction and no diuretics for symptomatic PDA • fluid restriction with diuretics vs. no fluid restriction and no diuretics/placebo for symptomatic PDA (Diuretics that will be included are loop diuretics, thiazides and potassium sparing diuretics used in isolation or in combination. No restriction will be applied with regards to choice of drugs, dosage and duration of usage. No restrictions will be applied with regards to time of onset, duration and degree of fluid restriction) Types of outcome measures Primary outcomes: • failure of closure/reduction in degree of shunt of PDA after completion of allocated treatment (outcome determined on clinical criteria or two-dimension Echocardiographic and doppler criteria or both) Secondary outcomes: • requirement of cyclooxygenase inhibitor (ibuprofen, indomethacin or mefenamic acid) for closure of PDA
Search methods for identification of studies The standard search strategy of the Cochrane Neonatal Review Group, including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, most recent issue) and MEDLINE (1966 - to present) will be used. The search will be limited to clinical trials and an age restriction to newborn and infant will be applied. No language restriction will be applied. The following MeSH headings will be used (combined in various permutations to obtain optimal performance): • patent ductus arteriosus • fluid therapy • fluid restriction • diuretics - Furosemide, Spironolactone,Thiazides, Ethacrynic Acid Other databases will be searched including EMBASE (1980 date); CINAHL (1982 - date); and the reference list of identified trials and abstracts published in Pediatric Research (1991 - date ) from conference proceedings of the Academic Pediatric Societies (American Pediatric Society, Society of Pediatric Research) and the European Society of Pediatric Research. References lists of published narrative and systematic reviews will be reviewed. Trial registries - www.clinicaltrials.gov and www.controlled-trials.com will be searched for recently completed and ongoing trials.
Data collection and analysis The standard methods of the Cochrane Collaboration will be used. Review authors will work independently to search and assess trials
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
3
for inclusion and methodological quality. Differences will be resolved by discussion. Study authors will be contacted if additional information is needed. The methodological quality of each trial will be assessed by the review authors following the guidelines described by the Cochrane Collaboration in the Cochrane Reviewer’s Handbook The following will be used as assessment criteria: (1) masking of randomization (2) masking of intervention (3) completeness of follow-up (4) masking of outcome measurements Each review author will independently evaluate and rank the quality of each trial, with respect to concealment of allocation, as adequate (A), unclear (B), or inadequate (C). Conflicts in assessment will be resolved through discussion and, if necessary, through eval-
uation by a third party. With respect to data analysis, the standardized methods of the Cochrane Neonatal Review Group will be employed (http:// neonatal.cochrane.org). For categorical outcomes, typical estimates for relative risk, risk difference and numbers needed to treat will be calculated. 95% confidence intervals will be used. Continuous outcomes will be analysed using weighted mean difference. Forest plot will be used to determine heterogeneity. I2 (I-squared) statistic will be used to estimate the proportion of variation that is due to heterogeneity rather than chance. Significant heterogeneity in relation to degree of fluid restriction, duration of fluid restriction, type of diuretics used and age at onset of treatment if present, will be further explored using subgroup analysis or sensitivity analysis.
REFERENCES
Additional references Bell 2003 Bell EF, Acarregui MJ. Restricted versus liberal water intake for preventing mortality and morbidity in preterm infants. Cochrane Database of Systematic Reviews 2001, Issue 3. [DOI: 10.1002/14651858.CD000503.pub2] Brion 2001 Brion LP, Soll RF. Diuretics for respiratory distress syndrome in preterm infants. Cochrane Database of Systematic Reviews 2001, Issue 2. [DOI: 10.1002/ 14651858.CD001454.pub2] Clyman 1998 Clyman RI. Recommendations for postnatal use of indomethacin - an analysis of four separate treatment strategies. Journal of Pediatrics 1998;128:601–7. Dani 2000 Dani C. Prophylaxis of patent ductus arteriosus in preterm infants with ibuprofen. Acta Paediatrica 2000;89:1369–74. Davis 1995 Davis P, Turner - Gomes D. Precision and accuracy of clinical and radiological signs in premature infants at risk of patent ductus arteriosus. Archives of Pediatric Adolescent Medicine 1995;149:1136–41. De Carolis 2000 De carolis MO, Romognoli C. Prophylactic ibuprofen therapy in patent ductus arteriosus in preterm infants. European Journal of Paediatrics 2000;159:364–8. Duddell 1984 Duddell GG, Gersony M. Patent ductus arteriosus in neonates with severe respiratory distress. Journal of Paedaitrics 1984;104:915–20. Ellison 1983 Ellison RC, Peckam GJ. Evaluation of preterm infant for patent ductus arteriosus. Pedaitrics 1983;71:364–72.
EPICure 2000 Costeloe K, Hennessy E, Gibson AT. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability.. Pediatrics 4 October 2000;106: 659–71. Green 1981 Green TP, Thompson TR. Furosamide use in premature infants and appearance of patent ductus arteriosus. American Journal of Diseases in Children 1981;135:239–43. Knight 2001 Knight D. The treatment of patent ductus arteriosus in preterm infants. a review and overview of randomised trials. Seminars in Neonatology 2001;6:67–73. Koch 2006 Koch J, Hensley G. Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics 2006;117:1113–21. Lago 2002 Lago P, Bettiol T. Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. European Journal of Pediatrics 2002;161:202–7. Laughon 2004 M.M. Laughon, M.A. Simmons, C.L. Bose. Patency of the ductus arteriosus in the premature infant: is it pathologic? Should it be treated?. Curr Opin Pediatr 2004;16:146–151. Mouzinho 1991 Mouzinho AL, Rosenfield CR. Symptomatic patent ductus arteriosus in preterm infant. Early Human Development 1991;27:65–77. Skelton 1994 Skelton R. A blinded comparison of clinical and echocardiographic evaluation of the preterm infant for ductus arteriosus. Journal of Paediatric Child Health 1994; 30:406–11.
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
4
Skinner 2001 Skinner J. Diagnosis of patent ductus arteriosus. Seminars in Neonatology 2001;1:49–61. Wyllie 2003 Wyllie J. Treatment of patent ductus arteriosus. Seminars of Neonatology 2003;6:425–32. ∗ Indicates the major publication for the study
HISTORY Protocol first published: Issue 2, 2009
CONTRIBUTIONS OF AUTHORS Dr Harish Madhava has been the main reviewer and has been involved in identifying the topic for review and taking the project forward. Dr Paul Settle has been actively involved in writing the protocol. He has been involved in all stages of writing the protocol, from the draft stage to the final version. Dr Settle and Dr Madhava will continue to be actively involved in the project until the review is completed.
DECLARATIONS OF INTEREST None
SOURCES OF SUPPORT
Internal sources • Leeds Teaching Hospitals NHS Trust, UK.
External sources • No sources of support supplied
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
5
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Harish Madhava MS, Settle P
Harish Madhava MS, Settle P. Fluid restriction for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD007800. DOI: 10.1002/14651858.CD007800.
www.cochranelibrary.com
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
TABLE OF CONTENTS HEADER . . . . . . . . . . ABSTRACT . . . . . . . . . BACKGROUND . . . . . . . OBJECTIVES . . . . . . . . METHODS . . . . . . . . . REFERENCES . . . . . . . . HISTORY . . . . . . . . . . CONTRIBUTIONS OF AUTHORS DECLARATIONS OF INTEREST . SOURCES OF SUPPORT . . . .
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Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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1 1 1 2 3 4 5 5 5 5
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[Intervention Protocol]
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants Murthy Siddanahalli Harish Madhava1 , Paul Settle2 1
Department of Paediatrics, Leeds Teaching Hospitals NHS Trust, Halifax, UK. 2 Neonatal Unit, Hope Hospital, Salford, UK
Contact address: Murthy Siddanahalli Harish Madhava, Department of Paediatrics, Leeds Teaching Hospitals NHS Trust, 45 Hastings way, Halifax, West Yorkshire, HX1 2QB, UK. [email protected]. Editorial group: Cochrane Neonatal Group. Publication status and date: New, published in Issue 2, 2009. Citation: Harish Madhava MS, Settle P. Fluid restriction for symptomatic patent ductus arteriosus in preterm infants. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD007800. DOI: 10.1002/14651858.CD007800. Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the effects of conservative medical management (fluid restriction with or without diuretics) on ductal closure or reduction of the size of the PDA in preterm infants with symptomatic PDA. Subgroup analysis will evaluate the effectiveness and safety of conservative medical management of symptomatic PDA based on the following criteria: • gestational age (< 28 weeks, 28 - 32 weeks, > 33 - 37 weeks) • birth weight ( 5 days)
• type of intervention (fluid restriction only, fluid restriction with diuretics) Gestational age subgroup analysis will be done preferentially unless only birthweight information is available.
Description of the condition PDA (patent ductus arteriosus) is a common problem among
BACKGROUND Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
1
preterm infants (Duddell 1984; Ellison 1983; Koch 2006). A PDA may occur in up to 65% of infants born at less than 28 weeks’ gestation (EPICure 2000; Mouzinho 1991). The presence of a persistently patent ductus arteriosus may be associated with high morbidity (EPICure 2000; Laughon 2004). Accurate diagnosis, assessment of the significance of the left to right shunt and prompt treatment may be beneficial in improving outcome in these infants (Clyman 1998). However, there is also a school of thought that in preterm infants patency of the ductus arteriosus may represent a normal physiologic adaptation to allow shunting from either systemic-to-pulmonary circulation (e.g. in the first day of life) or from pulmonary-to-systemic circulation (e.g. in the presence of severe lung disease). The medical community is becoming increasingly divided over the pathological significance of a haemodynamically significant PDA (Laughon 2004). Although there is no definite proof that it is beneficial to treat PDA, many clinicians are convinced that there is a link between PDA and adverse outcomes. The general tendency among clinicians is to identify haemodynamically significant ducts and treat them. Infants are often considered to have a “symptomatic PDA” when a combination of clinical signs (Davis 1995) and echocardiographic findings are present (Dani 2000; De Carolis 2000; Lago 2002). These include the presence of a continuous/systolic murmur, the need for ventilator support for at least 48 hours or increased ventilator requirements, hyperactive precordium, increased pulse pressure, tachycardia (heart rate > 170 bpm), tachypnoea (respiratory rate > 70/min), cardiomegaly with pulmonary congestion on chest radiograph and left-to-right shunting through a patent ductus arteriosus on two-dimensional echocardiogram along with Doppler studies (Skinner 2001; Skelton 1994).
is beneficial in treating infants with symptomatic PDA; however, the evidence reviewed by (Bell 2003) does not support this.
Why it is important to do this review One of the challenges of fluid restriction is maintaining adequate nutrition. In a growing infant, long-term fluid restriction limits the amount of calories and minerals that can be given. Providing adequate calories and minerals with fluid restriction requires highly concentrated formulas or parenteral alimentation, which may increase the risk of feeding intolerance and sepsis. For many clinicians, fluid restriction represents a poor trade-off to control the symptoms of PDA at the expense of adequate nutrition. The use of diuretics carries potential risks and benefits. The effect of diuretics on PDA is difficult to evaluate because of the transient improvement in respiratory function that may occur (Knight 2001; Wyllie 2003). Diuretics, especially loop diuretics, may cause electrolyte disturbances such as hyponatraemia and hypokalaemia that can be detrimental to the growth and development of the fragile preterm infant (Brion 2001). Diuretics also have a theoretical risk of worsening shunting through the PDA because of their anti-prostaglandin activity (Green 1981). Conservative medical management of PDA includes the use of both fluid restriction and diuretics.The timing and duration of “conservative medical management” is not standardised and most units tend to have their own arbitrary policies that are often based on poor evidence. The following review will explore the evidence base behind the concept of conservative medical management of symptomatic PDA.
Description of the intervention Clinically proven treatments for PDA include indomethacin, ibuprofen and surgical ligation (Knight 2001). However, each of these have side effects (EPICure 2000; Knight 2001; Laughon 2004) and the optimum timings for their use have not been established (Knight 2001). Fluid restriction with or without additional diuretics is often recommended to control the symptoms of a PDA. The timing and duration of fluid restriction are often not standardised and end points to the intervention are often not defined.
OBJECTIVES To evaluate the effects of conservative medical management (fluid restriction with or without diuretics) on ductal closure or reduction of the size of the PDA in preterm infants with symptomatic PDA. Subgroup analysis will evaluate the effectiveness and safety of conservative medical management of symptomatic PDA based on the following criteria: • gestational age (< 28 weeks, 28 - 32 weeks, > 33 - 37 weeks) • birth weight ( 5 days) • type of intervention (fluid restriction only, fluid restriction with diuretics) Gestational age subgroup analysis will be done preferentially unless only birthweight information is available.
METHODS
Criteria for considering studies for this review
Types of studies Randomised and quasi-randomised controlled trials
• requirement of surgical closure of PDA • duration of mechanical ventilation (days) • duration of oxygen dependence (days) • chronic lung disease (oxygen therapy at 36 weeks postmenstrual age) • severe intraventricular haemorrhage (grade 3 - 4) • renal dysfunction [oliguria or elevated serum creatinine (>/ = 1.8 gm/dl)] • necrotizing enterocolitis (Bell’s stage 2 or greater) • isolated intestinal perforation (perforation unrelated to NEC) • sepsis - blood culture positive • duration of hospital stay (days) • duration of therapy (days) • hyponatraemia (serum sodium < 125 mmol/L) or hypernatraemia (serum sodium >150 mmol/L) • hypokalaemia (serum sodium < 3.5 mmol/L) or hyperkalaemia (serum potassium > 6.5 mmol/L) • mortality • other adverse effects
Types of participants Preterm infants (< 37 weeks gestational age) with symptomatic patent ductus arteriosus (diagnosis based on clinical criteria or two-dimension echocardiographic and Doppler criteria or both) No limits on the postnatal age will be applied. Studies involving infants previously treated with indomethacin or ibuprofen for a symptomatic PDA will be excluded.
Types of interventions • fluid restriction without diuretics vs. no fluid restriction and no diuretics for symptomatic PDA • fluid restriction with diuretics vs. no fluid restriction and no diuretics/placebo for symptomatic PDA (Diuretics that will be included are loop diuretics, thiazides and potassium sparing diuretics used in isolation or in combination. No restriction will be applied with regards to choice of drugs, dosage and duration of usage. No restrictions will be applied with regards to time of onset, duration and degree of fluid restriction) Types of outcome measures Primary outcomes: • failure of closure/reduction in degree of shunt of PDA after completion of allocated treatment (outcome determined on clinical criteria or two-dimension Echocardiographic and doppler criteria or both) Secondary outcomes: • requirement of cyclooxygenase inhibitor (ibuprofen, indomethacin or mefenamic acid) for closure of PDA
Search methods for identification of studies The standard search strategy of the Cochrane Neonatal Review Group, including electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, most recent issue) and MEDLINE (1966 - to present) will be used. The search will be limited to clinical trials and an age restriction to newborn and infant will be applied. No language restriction will be applied. The following MeSH headings will be used (combined in various permutations to obtain optimal performance): • patent ductus arteriosus • fluid therapy • fluid restriction • diuretics - Furosemide, Spironolactone,Thiazides, Ethacrynic Acid Other databases will be searched including EMBASE (1980 date); CINAHL (1982 - date); and the reference list of identified trials and abstracts published in Pediatric Research (1991 - date ) from conference proceedings of the Academic Pediatric Societies (American Pediatric Society, Society of Pediatric Research) and the European Society of Pediatric Research. References lists of published narrative and systematic reviews will be reviewed. Trial registries - www.clinicaltrials.gov and www.controlled-trials.com will be searched for recently completed and ongoing trials.
Data collection and analysis The standard methods of the Cochrane Collaboration will be used. Review authors will work independently to search and assess trials
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
3
for inclusion and methodological quality. Differences will be resolved by discussion. Study authors will be contacted if additional information is needed. The methodological quality of each trial will be assessed by the review authors following the guidelines described by the Cochrane Collaboration in the Cochrane Reviewer’s Handbook The following will be used as assessment criteria: (1) masking of randomization (2) masking of intervention (3) completeness of follow-up (4) masking of outcome measurements Each review author will independently evaluate and rank the quality of each trial, with respect to concealment of allocation, as adequate (A), unclear (B), or inadequate (C). Conflicts in assessment will be resolved through discussion and, if necessary, through eval-
uation by a third party. With respect to data analysis, the standardized methods of the Cochrane Neonatal Review Group will be employed (http:// neonatal.cochrane.org). For categorical outcomes, typical estimates for relative risk, risk difference and numbers needed to treat will be calculated. 95% confidence intervals will be used. Continuous outcomes will be analysed using weighted mean difference. Forest plot will be used to determine heterogeneity. I2 (I-squared) statistic will be used to estimate the proportion of variation that is due to heterogeneity rather than chance. Significant heterogeneity in relation to degree of fluid restriction, duration of fluid restriction, type of diuretics used and age at onset of treatment if present, will be further explored using subgroup analysis or sensitivity analysis.
REFERENCES
Additional references Bell 2003 Bell EF, Acarregui MJ. Restricted versus liberal water intake for preventing mortality and morbidity in preterm infants. Cochrane Database of Systematic Reviews 2001, Issue 3. [DOI: 10.1002/14651858.CD000503.pub2] Brion 2001 Brion LP, Soll RF. Diuretics for respiratory distress syndrome in preterm infants. Cochrane Database of Systematic Reviews 2001, Issue 2. [DOI: 10.1002/ 14651858.CD001454.pub2] Clyman 1998 Clyman RI. Recommendations for postnatal use of indomethacin - an analysis of four separate treatment strategies. Journal of Pediatrics 1998;128:601–7. Dani 2000 Dani C. Prophylaxis of patent ductus arteriosus in preterm infants with ibuprofen. Acta Paediatrica 2000;89:1369–74. Davis 1995 Davis P, Turner - Gomes D. Precision and accuracy of clinical and radiological signs in premature infants at risk of patent ductus arteriosus. Archives of Pediatric Adolescent Medicine 1995;149:1136–41. De Carolis 2000 De carolis MO, Romognoli C. Prophylactic ibuprofen therapy in patent ductus arteriosus in preterm infants. European Journal of Paediatrics 2000;159:364–8. Duddell 1984 Duddell GG, Gersony M. Patent ductus arteriosus in neonates with severe respiratory distress. Journal of Paedaitrics 1984;104:915–20. Ellison 1983 Ellison RC, Peckam GJ. Evaluation of preterm infant for patent ductus arteriosus. Pedaitrics 1983;71:364–72.
EPICure 2000 Costeloe K, Hennessy E, Gibson AT. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability.. Pediatrics 4 October 2000;106: 659–71. Green 1981 Green TP, Thompson TR. Furosamide use in premature infants and appearance of patent ductus arteriosus. American Journal of Diseases in Children 1981;135:239–43. Knight 2001 Knight D. The treatment of patent ductus arteriosus in preterm infants. a review and overview of randomised trials. Seminars in Neonatology 2001;6:67–73. Koch 2006 Koch J, Hensley G. Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics 2006;117:1113–21. Lago 2002 Lago P, Bettiol T. Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. European Journal of Pediatrics 2002;161:202–7. Laughon 2004 M.M. Laughon, M.A. Simmons, C.L. Bose. Patency of the ductus arteriosus in the premature infant: is it pathologic? Should it be treated?. Curr Opin Pediatr 2004;16:146–151. Mouzinho 1991 Mouzinho AL, Rosenfield CR. Symptomatic patent ductus arteriosus in preterm infant. Early Human Development 1991;27:65–77. Skelton 1994 Skelton R. A blinded comparison of clinical and echocardiographic evaluation of the preterm infant for ductus arteriosus. Journal of Paediatric Child Health 1994; 30:406–11.
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Skinner 2001 Skinner J. Diagnosis of patent ductus arteriosus. Seminars in Neonatology 2001;1:49–61. Wyllie 2003 Wyllie J. Treatment of patent ductus arteriosus. Seminars of Neonatology 2003;6:425–32. ∗ Indicates the major publication for the study
HISTORY Protocol first published: Issue 2, 2009
CONTRIBUTIONS OF AUTHORS Dr Harish Madhava has been the main reviewer and has been involved in identifying the topic for review and taking the project forward. Dr Paul Settle has been actively involved in writing the protocol. He has been involved in all stages of writing the protocol, from the draft stage to the final version. Dr Settle and Dr Madhava will continue to be actively involved in the project until the review is completed.
DECLARATIONS OF INTEREST None
SOURCES OF SUPPORT
Internal sources • Leeds Teaching Hospitals NHS Trust, UK.
External sources • No sources of support supplied
Fluid restriction for symptomatic patent ductus arteriosus in preterm infants (Protocol) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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