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سورفاکتانت در درمان سندرم آسپیراسیون مکونیوم در نوزادان ترم و پره‌ترم دیرهنگام

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Referencias

Chinese Study Group 2005 {published data only}

Chinese Collaborative Study Group for Neonatal Respiratory Diseases. Treatment of severe meconium aspiration with porcine surfactant: a multicentre, randomized, controlled trial. Acta Paediatrica 2005;94(7):896‐902. CENTRAL

Findlay 1996 {published data only}

Findlay RD, Taeusch HW, Walther FJ. Surfactant replacement therapy for meconium aspiration syndrome. Pediatrics 1996;97(1):48‐52. CENTRAL

Lotze 1998 {published data only}

Lotze A, Mitchell BR, Bulas DI, Zola EM, Shalwitz RA, Gunkel HJ, et al. Multicenter study of surfactant (beractant) use in the treatment of term infants with severe respiratory failure. Journal of Pediatrics 1998;132(1):40‐7. CENTRAL

Maturana 2005 {unpublished data only}

Maturana A, Torres‐Pereyra J, Salinas R, Astudillo P, Moya FR, The Chile Surf Group. A randomized trial of natural surfactant for moderate to severe meconium aspiration syndrome. Pediatric Academic Societies. 2005; Vol. 57:1545. CENTRAL

Auten 1991 {published data only}

Auten RL, Notter RH, Kendig, JW, Davis JM, Shapiro DL. Surfactant treatment of full‐term newborns with respiratory failure. Pediatrics 1991;87(1):101‐7. CENTRAL

Blanke 1993 {published data only}

Blanke JG, Jorch G. Surfactant therapy in severe neonatal respiratory failure ‐ multicenter study ‐ II. Surfactant therapy in 10 newborn infants with meconium aspiration syndrome [Surfactanttherapie bei 10 Neugeborenem mit Mekoniumaspirationssyndrom]. Klinische Padiatrie 1993;205(2):75‐8. CENTRAL

Chang 2003 {published data only}

Chang HY, Hsu CH, Kao HA, Hung HY, Chang JH, Peng CC, Jim WT. Treatment of severe meconium aspiration syndrome with dilute surfactant lavage. Journal of the Formosan Medical Association 2003;102(5):326‐30. CENTRAL

Dargaville 2011 {published data only}

Dargaville PA, Copnell B, Mills JF, Haron I, Lee JK, Tingay DG, et al. lessMAS Trial Study Group. Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome. Journal of Pediatrics 2011;158(3):383‐9. CENTRAL

Diniz 1995 {published data only}

Diniz EMA, Fiori RM. Curosurf therapy in severe meconium aspiration (MAS). Biology of the Neonate 1995;67:86. CENTRAL

Gadzinowski 2008 {published data only}

Gadzinowski J, Kowalska K, Vidyasagar D. Treatment of MAS with PPHN using combined therapy: SLL, bolus surfactant and iNO. Journal of Perinatology 2008;28(Suppl 3):S56‐66. CENTRAL

Halliday 1996 {published data only}

Halliday HL, Speer CP, Robertson B. Treatment of severe meconium aspiration syndrome with porcine surfactant. European Journal of Pediatrics 1996;155(12):1047‐51. CENTRAL

Hung 2006 {published data only}

Hung HY, Jim WT, Hsu CH, Chang JH, Peng CC, Shih SL, et al. Small versus large volume dilute surfactant lavage for meconium aspiration syndrome.. Acta Paediatrica Taiwan 2006;47(4):181‐6. CENTRAL

Ibara 1995 {published data only}

Ibara S, Ikenoue T, Murata Y, Sakamoto H, Saito T, Nakamura Y, et al. Management of meconium aspiration syndrome by tracheobronchial lavage and replacement of surfactant ‐TA. Acta Paediatrica Japonica 1995;37(1):64‐7. CENTRAL

Khammash 1993 {published data only}

Khammash H, Perlman M, Wojtulewicz J, Dunn M. Surfactant therapy in full‐term neonates with severe respiratory failure. Pediatrics 1993;92(1):135‐9. CENTRAL

Lam 1999 {published data only}

Lam BCC, Yeung CY. Surfactant lavage for meconium aspiration syndrome: a pilot study. Pediatrics 1999;103:1014‐8. CENTRAL

Lin 2014 {published data only}

Lin XZ, Lai JD, Lan ZY, Lin YY. [Clinical effect of endotracheal lavage with porcine pulmonary surfactant in term neonates with severe meconium aspiration syndrome]. Zhongguo Dang Dai Er Ke Za Zhi (Chinese Journal of Contemporary Pediatrics) 2014;16(7):709‐13. [PUBMED: 25008878]CENTRAL

Lista 2006 {published data only}

Lista G, Bianchi S, Castoldi F, Fontana P, Cavigioli F. Bronchoalveolar lavage with diluted porcine surfactant in mechanically ventilated term infants with meconium aspiration syndrome. Clinical Drug Investigation 2006;26(1):13‐9. CENTRAL

Ogawa 1996 {published data only}

Ogawa Y, Ohara Y, Itakura Y, et al. Bronchial lavage with surfactant solution for the treatment of meconium aspiration syndrome. J Jpn Med Soc Biol Interface 1996;26(Suppl):179‐87. CENTRAL

Wiswell 2002 {published data only}

Wiswell TE, Knight GR, Finer NN, Donn SM, Desai H, Walsh WF, et al. A multicenter, randomized, controlled trial comparing surfaxin (lucinactant) lavage with standard care for treatment of meconium aspiration syndrome. Pediatrics 2002;109(6):1081‐7. CENTRAL

Aaltonen 2007

Aaltonen M, Soukka H, Halkola L, Jalonen J, Kalimo H, Holopainen IE. Inhaled nitric oxide treatment inhibits neuronal injury after meconium aspiration in piglets. Early Human Development 2007;83(2):77‐85.

AAP 2006

American Academy of Pediatrics, American Heart Association. Textbook of neonatal resuscitation. 5th Edition. Elk Grove Village: American Academy of Pediatrics, American Heart Association, 2006.

Abdel‐Latif 2011a

Abdel‐Latif ME, Osborn DA. Laryngeal mask airway surfactant administration for prevention of morbidity and mortality in preterm infants with or at risk of respiratory distress syndrome. Cochrane Database of Systematic Reviews 2011, Issue 7. [DOI: 10.1002/14651858.CD008309.pub2]

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Abdel‐Latif ME, Osborn DA. Pharyngeal instillation of surfactant before the first breath for prevention of morbidity and mortality in preterm infants at risk of respiratory distress syndrome. Cochrane Database of Systematic Reviews 2011, Issue 3. [DOI: 10.1002/14651858.CD008311.pub2]

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Abdel‐Latif ME, Osborn DA. Nebulised surfactant in preterm infants with or at risk of respiratory distress syndrome. Cochrane Database of Systematic Reviews 2012, Issue 10. [DOI: 10.1002/14651858.CD008310.pub2]

Aziz 2012

Aziz A, Ohlsson A. Surfactant for pulmonary haemorrhage in neonates. Cochrane Database of Systematic Reviews 2012, Issue 7. [DOI: 10.1002/14651858.CD005254.pub2]

Bahadue 2012

Bahadue FL, Soll R. Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome. Cochrane Database of Systematic Reviews 2012, Issue 11. [DOI: 10.1002/14651858.CD001456.pub2]

Chen 1985

Chen CT, Toung TJK, Rogers MC. Effect of intra‐alveolar meconium on pulmonary surface tension properties. Critical Care Medicine 1985;13(4):233‐6.

Christou 2000

Christou H, Van Marter LJ, Wessel DL, Allred EN, Kane JW, Thompson JE. Inhaled nitric oxide reduces the need for extracorporeal membrane oxygenation in infants with persistent pulmonary hypertension of the newborn. Critical Care Medicine 2000;28(11):3722‐7.

Clark 1987

Clark DA, Nieman GF, Thompson JE, Paskanik AM, Rokhar JE, Bredenberg CE. Surfactant displacement by meconium free fatty acids: An alternative explanation for atelectasis in meconium aspiration syndrome. Journal of Pediatrics 1987;110(5):765‐70.

Clark 2000

Clark RH, Kueser TJ, Walker MW, Southgate WM, Huckaby JL, Perez JA, et al. Low‐dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. New England Journal of Medicine 2000;342(7):469‐74.

Fakioglu 2005

Fakioglu H, Totapally BR, Torbati D, Raszynski A, Sussmane JB, Wolfsdorf J. Hypoxic respiratory failure in term newborns: clinical indicators for inhaled nitric oxide and extracorporeal membrane oxygenation therapy. Journal of Critical Care 2005;20(3):288‐93.

Finer 2000

Finer NN, Barrington KJ. Nitric oxide therapy for the newborn infant. Seminars in Perinatology 2000;24(1):59‐65.

Hahn 2013

Hahn S, Choi HJ, Soll R, Dargaville PA. Lung lavage for meconium aspiration syndrome in newborn infants. Cochrane Database of Systematic Reviews 2013, Issue 4. [DOI: 10.1002/14651858.CD003486.pub2]

Higgins 2003

Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):556‐60.

Higgins 2011

Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Hofmeyr 2010

Hofmeyr GJ, Xu H. Amnioinfusion for meconium‐stained liquor in labour. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD000014.pub3]

Hsieh 2004

Hsieh TK, Su BH, Chen AC, Lin TW, Tsai CH, Lin HC. Risk factors of meconium aspiration syndrome developing into persistent pulmonary hypertension of newborn. Acta Paediatrica Taiwan 2004;45(4):203‐7.

Moses 1991

Moses D, Holm BA, Spitale P, Liu M, Enhorning G. Inhibition of pulmonary surfactant function by meconium. American Journal of Obstetrics and Gynecology 1991;164(2):477‐81.

Neonatal iNO 1997

The Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full‐term and nearly full‐term infants with hypoxic respiratory failure. New England Journal of Medicine 1997;336:597‐604.

Pfister 2007

Pfister RH, Soll RF, Wiswell T. Protein containing synthetic surfactant versus animal derived surfactant extract for the prevention and treatment of respiratory distress syndrome. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD006069.pub3]

Pfister 2009

Pfister RH, Soll R, Wiswell TE. Protein‐containing synthetic surfactant versus protein‐free synthetic surfactant for the prevention and treatment of respiratory distress syndrome. Cochrane Database of Systematic Reviews 2009, Issue 4. [DOI: 10.1002/14651858.CD006180.pub2]

RevMan 2014 [Computer program]

The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). Version 5.3. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Rojas‐Reyes 2012

Rojas‐Reyes MX, Morley CJ, Soll R. Prophylactic versus selective use of surfactant in preventing morbidity and mortality in preterm infants. Cochrane Database of Systematic Reviews 2012, Issue 3. [DOI: 10.1002/14651858.CD000510.pub2]

Seger 2009

Seger N, Soll R. Animal derived surfactant extract for treatment of respiratory distress syndrome. Cochrane Database of Systematic Reviews 2009, Issue 2. [DOI: 10.1002/14651858.CD007836]

Sinclair 1992

Sinclair J, Bracken M. Effective Care of the Newborn. Oxford University Press, 1992.

Singh 2011

Singh N, Hawley KL, Viswanathan K. Efficacy of porcine versus bovine surfactants for preterm newborns with respiratory distress syndrome: systematic review and meta‐analysis. Pediatrics2011; Vol. 128, issue 6:e1588‐95.

Soll 1992

Soll RF, McQueen MC. Respiratory Distress Syndrome. In: Sinclair JC, Bracken MB editor(s). Effective Care of the Newborn Infant. Oxford: Oxford University Press, 1992.

Soll 1997

Soll RF, Ozek E. Prophylactic animal derived surfactant extract for preventing morbidity and mortality in preterm infants. Cochrane Database of Systematic Reviews 1997, Issue 4. [DOI: 10.1002/14651858.CD000511]

Soll 1998

Soll RF. Synthetic surfactant for respiratory distress syndrome in preterm infants. Cochrane Database of Systematic Reviews 1998, Issue 3. [DOI: 10.1002/14651858.CD001149]

Soll 2001

Soll RF, Blanco F. Natural surfactant extract versus synthetic surfactant for neonatal respiratory distress syndrome. Cochrane Database of Systematic Reviews 2001, Issue 2. [DOI: 10.1002/14651858.CD000144]

Soll 2009

Soll R, Ozek E. Multiple versus single doses of exogenous surfactant for the prevention or treatment of neonatal respiratory distress syndrome. Cochrane Database of Systematic Reviews 2009, Issue 1. [DOI: 10.1002/14651858.CD000141.pub2]

Soll 2010

Soll R, Ozek E. Prophylactic protein free synthetic surfactant for preventing morbidity and mortality in preterm infants. Cochrane Database of Systematic Reviews 2010, Issue 1. [DOI: 10.1002/14651858.CD001079.pub2]

Soukka 1998

Soukka H, Jalonen J, Kero P, Kaapa P. Endothelin‐1, arterial natriuretic peptide and pathophysiology of pulmonary hypertension in porcine meconium aspiration. Acta Paediatrica 1998;87(4):424‐8.

Stevens 2007

Stevens TP, Harrington EW, Blennow M, Soll RF. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/14651858.CD003063.pub3]

Sun 1993

Sun B, Curstedt T, Song GW, Robertson B. Surfactant improves lung function and morphology in newborn rabbits with meconium aspiration. Biolology of the Neonate 1993;63(2):96‐104.

Tan 2012

Tan K, Lai NM, Sharma A. Surfactant for bacterial pneumonia in late preterm and term infants. Cochrane Database of Systematic Reviews 2012, Issue 2. [DOI: 10.1002/14651858.CD008155.pub2]

Tran 1980

Tran N, Lowe C, Sivieri EM, Shaffer TH. Sequential effects of acute meconium obstruction on pulmonary function. Pediatric Research 1980;14(1):34‐8.

Tyler 1978

Tyler DC, Murphy J, Cheney FW. Mechanical and chemical damage to lung tissue caused by meconium aspiration. Pediatrics 1978;62(4):454‐9.

UK Collab 1996

UK Collaborative ECMO Trial Group. UK collaborative randomized trial of neonatal extracorporeal membrane oxygenation. Lancet 1996;348(9020):75‐82.

Vain 2004

Vain NE, Szyld EG, Prudent LM, Wiswell TE, Aguilar AM, Vivas NI. Oropharyngeal and nasopharyngeal suctioning of meconium‐stained neonates before delivery of their shoulders: multicentre, randomised controlled trial. Lancet 2004;364(9434):597‐602.

Van Meurs 2003

Van Meurs K, Rhine WD, Benitz WE. Meconium staining and the meconium aspiration syndrome. Fetal and neonatal brain injury. Mechanisms, management and the risks of practice. Cambridge University Press, 2003:636‐62.

Walia 1999

Walia R, Ohlsson A. Differences between information provided in abstracts of randomized controlled trials in neonates submitted to the Annual Meeting of the American Pediatric Society and the Society for Pediatric Research (APS/SPR) and final publications ‐ implications for meta‐analyses. 7th Annual Cochrane Colloquium Abstracts. 1999.

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Ward MC, Sinn JKH. Steroid therapy for meconium aspiration syndrome in newborn infants. Cochrane Database of Systematic Reviews 2003, Issue 4. [DOI: 10.1002/14651858.CD003485]

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El Shahed AI, Dargaville PA, Ohlsson A, Soll R. Surfactant for meconium aspiration syndrome in full term/near term infants. Cochrane Database of Systematic Reviews 2007, Issue 3. [DOI: 10.1002/14651858.CD002054.pub2]

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Soll RF, Dargaville P. Surfactant for meconium aspiration syndrome in full term infants. Cochrane Database of Systematic Reviews 2000, Issue 2. [DOI: 10.1002/14651858.CD002054]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Chinese Study Group 2005

Methods

Multicentre (19 centres) study in China. Study period not stated.
Blinding of randomisation: Yes
Blinding of treatment: No
Complete follow‐up: Yes
Blinding of outcome measure: No

Participants

Term and late preterm neonates with MAS, BW > 2500 gm, postnatal age < 36 hrs, a/A pO₂ ratio < 0.22, OI > 15 and needed mechanical ventilation for 1 to 2 hrs without improvement.
No lethal congenital anomalies, IVH grade II ‐ IV, Apgar score < 3 at 10 minutes or clinically unstable.

Interventions

Sixty‐one term infants with severe MAS were randomly assigned to either a surfactant or a control group within 36 h after birth. The infants in the surfactant group (n=31) received an initial dose of porcine lung‐derived surfactant (Curosurf) at 200 mg/kg, and repeated doses of 200, 100 and 100 mg/kg were given at 6 to 12 h intervals to a maximum of four doses if oxygenation index (OI) deteriorated by > 2 from baseline.

Outcomes

PRIMARY: Reduction of OI to < 10 and an increase of the pretreatment a/A pO₂ ratio of 100% over baseline 24 hrs after surfactant treatment.
SECONDARY: Duration of mechanical ventilation, incidence of complications and survival to discharge from hospital.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information presented

Allocation concealment (selection bias)

Low risk

Surfactant or control therapy was randomly assigned by the randomisation centre staff according to sequentially numbered randomisation cards, provided in sealed randomisation envelopes, based on an expected total enrolment of 64 participants.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Surfactant administration was not conducted in a blind manner because that would have required a separate dosing team for each clinic centre.

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Staff were aware of group assignment.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

66 infants were enrolled and 5 infants (4 in the surfactant group and 1 in the control group were excluded from the final analysis because of violation of the entry criteria).

Selective reporting (reporting bias)

Unclear risk

The protocol for the study was not available to us so we cannot ascertain if there were any deviations from the protocol.

Findlay 1996

Methods

Single‐centre study in the US. Study period not stated.
Blinding of randomisation: Yes
Blinding of treatment: Yes
Complete follow‐up: Yes
Blinding of outcome measure: Yes

Participants

Term infants with MAS, requiring assisted ventilation, supplemental oxygen > 50%, MAP > 7cm H₂0, a/A pO₂ ratio < 0.22, age < 6 hrs and no major congenital anomaly.

Interventions

The treatment group (n = 20) received modified bovine surfactant extract (Survanta 150 mg/kg), repeated at 6‐hr intervals for a maximum of 4 doses, infused intratracheally via a side port adaptor over 20 mins.
The control group (n = 20) received air placebo.

Outcomes

PRIMARY: Improvement in OI, improvement in a/A pO₂ ratio
SECONDARY: Pneumothorax, need for ECMO, duration of assisted ventilation, duration of oxygen therapy, mortality.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information provided

Allocation concealment (selection bias)

Low risk

No specific information provided but the investigators and the physicians and nurses caring for the infants were unaware of the infants' assignment groups.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

The investigators and the physicians and nurses caring for the infants were unaware of the infants' assignment groups.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The investigators and the physicians and nurses caring for the infants were unaware of the infants' assignment groups.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Outcomes reported for all enrolled infants.

Selective reporting (reporting bias)

Unclear risk

The protocol for the study was not available to us so we cannot ascertain if there were any deviations from the protocol.

Lotze 1998

Methods

Multicentre (44 centres) study in the US. Study period September 1 1992 to October 23 1995.
Blinding of randomisation: Yes (central randomisation)
Blinding of treatment: Yes (dosing investigators)
Complete follow‐up: Yes
Blinding of outcome measurement: Yes

Stratification: primary diagnosis disease severity (oxygenation index)

Participants

Infants > 2000 gm, gestational age > 36 weeks, age < 120 hrs with MAS, PPHN or sepsis and severe respiratory failure but without any major congenital anomalies or IVH > Grade I.

Interventions

The treatment group (n = 87) received modified bovine surfactant extract (Survanta, 100 mg/kg) or air placebo (up to 4 doses prior to ECMO and 4 additional doses if ECMO was required).
The control group (n = 81) received air placebo.

Outcomes

PRIMARY: Need for ECMO, severe complications, mortality.

Notes

Only infants with MAS are included in this review.
Data for this group were obtained by the authors of the first version of this review

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Central randomisation. Computer‐generated random numbers

Stratification: primary diagnosis disease severity (oxygenation index).

Allocation concealment (selection bias)

Low risk

The treatment assignments were made by having the pharmacist or dosing investigator at each site report the primary diagnosis and mean entry oxygen index for each participant to a central randomisation centre, Bio‐Pharm Clinical Services, Inc., which issued a participant number and treatment assignment on the basis of a computer‐generated random number.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Study treatments were administered by dedicated dosing investigators at each site. The dosing investigators shielded the infant with drapes or a screen during treatment, and all other personnel left the immediate bedside area during the dosing procedure. The dosing investigator took the same amount of time to prepare and administer either treatment, and when treatment was complete, all supplies were stored in a locked area. Dosing investigators were prohibited from participating in any other aspect of the infants care and from revealing the treatment assignment.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

With the exception of dosing, the infant's clinical care during the 28 days of the study was provided by clinical investigators who were unaware of the treatment assignment.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All 330 randomised infants accounted for (168 of these infants were enrolled on the basis of MAS, and the remainder on the basis of PPHN or sepsis) . Two infants were later withdrawn from the study when consent was withdrawn. Their limited data were subsequently excluded from analysis. The diagnosis on which their enrolment was based was not stated.

Selective reporting (reporting bias)

Unclear risk

The protocol for the study was not available to us so we cannot ascertain if there were any deviations from the protocol

Maturana 2005

Methods

Multicentre (13 centres) study in Chile between March 2001 and June 2003.
Blinding of randomisation: Yes
Blinding of treatment: Yes
Complete follow‐up: Yes
Blinding of outcome measure: Yes

Participants

Term infants ≥ 37 weeks of gestation with moderate to severe MAS and respiratory insufficiency within the first 12 hrs after birth.

Interventions

The treatment group (n = 28) received 150 mg /kg/dose (6 ml) of Survanta every 6 hours for a total of 3 doses if they remained intubated.
The control group (n = 29) received an equivalent amount of air as placebo.

Outcomes

PRIMARY: Days of mechanical ventilation.
SECONDARY: Days requiring oxygen therapy with a target arterial oxygen saturation > 90%, air leaks, PPHN, OI 2 hrs after the first treatment dose and mortality before discharge.

Notes

We obtained unpublished data from Dr A Maturana. In the unpublished manuscript there were 3 more infants enrolled in the surfactant group and 1 more infant enrolled in the control group. We report the outcomes as per the unpublished report, not the referenced abstract.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation scheme using blocks of 4 (as per unpublished manuscript).

Allocation concealment (selection bias)

Low risk

Sealed envelopes stratified by centre

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

A placebo (air) was used.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Outcomes reported for all randomised (as per unpublished manuscript).

Selective reporting (reporting bias)

Unclear risk

The protocol for the study was not available to us so we cannot ascertain if there were any deviations from the protocol.

a/A pO₂ ratio = arterial/alveolar oxygen tension ratio
BW = birth weight
ECMO = extracorporeal membrane oxygenation
IVH = Intraventricular haemorrhage
MAP = mean airway pressure
MAS = meconium aspiration syndrome
OI = oxygen index
PPHN = persistent pulmonary hypertension of the neonate

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Auten 1991

Sequential case study; no control group

Blanke 1993

Not randomised, no control group.

As a part of a West  German multicentre study (424 participants, 16 hospitals) 10 term neonates ventilated because of severe meconium aspiration syndrome were treated with 1 to 4 doses of 50 mg/kg/BW of a bovine surfactant (Alveofact). Before treatment respiratory distress was severe (median FiO₂: 1.0, median MAD 9.9 mmHg, median OI: 20). Acute improvement ("responders") was shown in 4 participants. All infants survived. Time of mechanical ventilation was 6 to 26 days. High frequency ventilation was applied in 2 non‐responders, ECMO in 1.

Chang 2003

Retrospective review; treatment with bronchoalveolar lavage with dilute surfactant preparation

Chang 2003 retrospectively reviewed the charts of all term infants with a diagnosis of MAS who had an oxygenation index (OI) > 20 during a 2‐year period. Tracheobronchial lavage was performed with a dilute surfactant suspension (5 mg/mL or 10 mg/mL) to reach a total dose of 60 to 70 mg/kg of phospholipid, administered in aliquots of 2 mL.

 

The records of 22 patients were reviewed, of whom 12 had undergone lavage. These infants were subdivided into low‐concentration (surfactant concentration, 5 mg/mL; n = 6) and high‐concentration (surfactant concentration, 10 mg/mL; n = 6) subgroups. There were no significant differences in demographic characteristics between the 2 subgroups. The lavaged infants had a significantly higher arterial partial pressure of oxygen (PaO₂) 24 hours after lavage than the infants without lavage (178.3 mm Hg vs 80.6 mm Hg, P < 0.05). The incidence of pneumothorax (1/12 vs 7/10, P < 0.05) and requirement for inhaled nitric oxide (5/12 vs 9/10, P < 0.05) were significantly lower in the lavaged group. All infants tolerated the procedure well except for 2 with transient complications. There were no significant differences in duration of lavage, response and complications between subgroups lavaged at low and high surfactant concentration.

Dargaville 2011

Bronchoalveolar lavage with dilute surfactant preparation

Dargaville 2011 evaluated whether lung lavage with surfactant changes the duration of mechanical respiratory support or other outcomes in meconium aspiration syndrome (MAS).

 

Randomised controlled trial that enrolled ventilated infants with MAS. Infants randomised to lavage received two 15‐mL/kg aliquots of dilute bovine surfactant instilled into, and recovered from, the lung. Control subjects received standard care, which in both groups included high frequency ventilation, nitric oxide, and, where available, ECMO.

 

66 infants were randomised, with 1 ineligible infant excluded from analysis. Median duration of respiratory support was similar in infants who underwent lavage and control subjects (5.5 vs. 6.0 days, P = .77). Requirement for high frequency ventilation and nitric oxide did not differ between the groups. Fewer infants who underwent lavage died or required ECMO: 10% (3/30) compared with 31% (11/35) in the control group (odds ratio, 0.24; 95% confidence interval, 0.060 to 0.97). Lavage transiently reduced oxygen saturation without substantial heart rate or blood pressure alterations. Mean airway pressure was more rapidly weaned in the lavage group after randomisation.

Diniz 1995

Not randomised

Gadzinowski 2008

Gadzinowski 2008 compared the effectiveness of surfactant treatment either by bolus or surfactant lung lavage followed by inhaled nitric oxide (iNO) therapy in infants with MAS complicated by persistent pulmonary hypertension (PPHN).

13 infants with diagnosis of MAS and PPHN were first treated with conventional respiratory support. Then between 2 and 22 hrs of life they were randomised either to bolus surfactant treatment (n = 6) or surfactant lung lavage (SLL, n = 7) treatment. Then all infants were treated with iNO therapy. The groups were compared with regard to their clinical course: changes in PaO₂, FiO₂, MAP, OI, A‐a oxygen gradient, duration of iNO therapy, length of ventilation and hospitalisation. Complications and mortality were also compared.

The results showed that infants treated with SLL had significant improvements in oxygenation, decreases in MAP and A‐a gradients. But there were no significant differences in duration of ventilation, iNO treatment, length of hospitalisation or complications. In conclusion these data show no advantage of SLL therapy over bolus surfactant treatment in infants with MAS complicated by PPHN.

Halliday 1996

Retrospective, not randomised

Hung 2006

Historical controls

Hung 2006 assessed the effects of lavage with a small volume of dilute surfactant in neonates with MAS and compared the results with those of historical controls treated with larger volumes. Eleven newborns with MAS were treated using 20 ml of dilute surfactant at a phospholipid concentration of 10 mg/ml (SVL group). Results were compared with those of 9 infants previously treated with large‐volume lavage (LVL group), using 40 ml of dilute surfactant, 5 mg/ml. Measures of oxygenation, including mean PaO₂, oxygenation index, and arterial/alveolar 0₂ ratio, showed no significant difference between the 2 groups.

Ibara 1995

Saline lavage and surfactant replacement, not randomised

Khammash 1993

Sequential case study; no control group

Lam 1999

Not randomised, historical controls, surfactant used as lavage.

Lam 1999 reported a pilot experience on the use of diluted bovine lung surfactant lipid extract solution (Survanta, Ross Laboratories, Ohio, USA) as a tracheobronchial lavage fluid for the treatment of infants with severe MAS.

 

6 consecutively recruited infants with severe MAS necessitating mechanical ventilation with an oxygen index of ≥ 15 within 6 hours of life during a 1½‐year period were treated with tracheobronchial lavage with 15 mL/kg of diluted surfactant solution (Survanta) at a phospholipid concentration of 5 mg/mL administered in 2‐mL aliquots. The outcome of treatment was assessed by comparison with 6 consecutive historic control infants with equally severe MAS of similar inclusion criteria retrospectively.

 

The mean oxygen index, mean airway pressure, fraction of inspired oxygen, and arterial/alveolar oxygen tension ratio improved significantly within the first 48 hours after treatment in the lavage group. The duration of ventilation (mean ± SEM, 55.3 ± 4.6 hours vs 131 ± 60 hours) and oxygen therapy (mean ± SEM, 4.1 ± 0.5 days vs 20.8 ± 8.2 days) were also significantly reduced in the lavage‐treated group compared with the control group. All 6 infants in the lavage group survived without sequelae whereas there were 2 deaths in the control group. The process of administering the surfactant lavage was well tolerated with no air leak complications.

Lin 2014

Bronchoalveolar lavage with dilute surfactant preparation

Lin 2014 evaluated 136 full‐term infants with severe MAS who were admitted to the neonatal intensive care unit. Infants were randomly allocated to pulmonary surfactant (PS) lavage and PS injection groups.

In the PS lavage group, infants were treated with endotracheal lavage using 3 to 5 mL of diluted PS (12 mg/mL) each time, and the PS injection group was given PS by intratracheal injection with an initial dose of 200 mg/kg.

Blood gas, oxygenation index (OI), and PaO2/FiO2 of the two groups were evaluated before and 2, 12, 24, and 48 hours after the treatment, and the duration of mechanical ventilation, complication rate, and cure rate were compared between the two groups.

Lista 2006

Case series

Lista 2006 evaluated the efficacy and safety of bronchoalveolar lavage (BAL) with diluted porcine surfactant in mechanically ventilated term infants with severe acute respiratory distress syndrome (ARDS) due to MAS.

 

Eight consecutive mechanically ventilated term infants with severe ARDS due to MAS underwent BAL with 15 mL/kg of diluted (5.3 mg phospholipid/mL) surfactant saline suspension (porcine surfactant, Curosurf). Treatment was administered slowly in aliquots of 2.5 mL.

The mean age of neonates at treatment was 3.5 (range 1 ‐ 8) hours. Heart rate, systemic blood pressure and oxygen saturation were monitored continuously. Arterial blood gases were measured immediately before treatment, and again at 3 and 6 hours post‐treatment. Chest x‐rays were taken 6 and 24 hours after treatment.

 

Radiological improvement was evident in all 8 infants 6 hours post‐treatment. Compared with pre‐BAL values, significant improvements (P < 0.05) in mean values for partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, pH, arterial/alveolar O₂ ratio and oxygenation index were documented at 3 and 6 hours after BAL. In all participants, tracheal fluids that had been meconium‐stained prior to BAL were clear of meconium after BAL. Only one infant required nitric oxide therapy for transient pulmonary hypertension. No adverse sequelae of treatment occurred during the study.

Ogawa 1996

Bronchoalveolar lavage with dilute surfactant preparation for the treatment of meconium aspiration syndrome

Wiswell 2002

Bronchoalveolar lavage with dilute surfactant preparation

Wiswell 2002 compared treatment with bronchoalveolar lavage using dilute Surfaxin with standard therapy in a population of newborn infants with MAS.

 

Inclusion criteria were 1) gestational age ≥ 35 weeks, 2) enrolment within 72 hours of birth, 3) diagnosis of MAS, 4) need for mechanical ventilation, and 5) an oxygenation index ≥ 8 and ≤ 25. Infants were randomised to either lavage with Surfaxin or standard care (2:1 proportion). In lavaged infants, a volume of 8 mL/kg dilute Surfaxin (2.5 mg/mL) was instilled into each lung over approximately 20 seconds followed by suctioning after 5 ventilator breaths. The procedure was repeated twice. The third and final lavage was with a more concentrated solution (10 mg/mL) of Surfaxin.

ECMO = extracorporeal membrane oxygenation
MAP = mean airway pressure
MAS = meconium aspiration syndrome

Data and analyses

Open in table viewer
Comparison 1. Surfactant therapy vs. placebo or no therapy in term/near‐term infants

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality Show forest plot

4

326

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.41, 2.39]

Analysis 1.1

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 1 Mortality.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 1 Mortality.

2 Treatment with ECMO Show forest plot

2

208

Risk Ratio (M‐H, Fixed, 95% CI)

0.64 [0.46, 0.91]

Analysis 1.2

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 2 Treatment with ECMO.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 2 Treatment with ECMO.

3 Pneumothorax Show forest plot

3

269

Risk Difference (M‐H, Fixed, 95% CI)

‐0.02 [‐0.08, 0.05]

Analysis 1.3

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 3 Pneumothorax.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 3 Pneumothorax.

4 Pulmonary interstitial emphysema Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.4

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 4 Pulmonary interstitial emphysema.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 4 Pulmonary interstitial emphysema.

5 Air leaks (pneumothorax, pneumomediastinum, interstitial emphysema) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.5

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 5 Air leaks (pneumothorax, pneumomediastinum, interstitial emphysema).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 5 Air leaks (pneumothorax, pneumomediastinum, interstitial emphysema).

6 Duration of assisted mechanical ventilation (days) Show forest plot

3

158

Mean Difference (IV, Fixed, 95% CI)

0.60 [‐0.41, 1.62]

Analysis 1.6

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 6 Duration of assisted mechanical ventilation (days).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 6 Duration of assisted mechanical ventilation (days).

7 Duration of supplemental oxygen (days) Show forest plot

2

97

Mean Difference (IV, Fixed, 95% CI)

0.40 [‐2.83, 3.64]

Analysis 1.7

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 7 Duration of supplemental oxygen (days).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 7 Duration of supplemental oxygen (days).

8 Need for supplemental oxygen at discharge Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.8

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 8 Need for supplemental oxygen at discharge.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 8 Need for supplemental oxygen at discharge.

9 Chronic lung disease (age at diagnosis not stated) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.9

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 9 Chronic lung disease (age at diagnosis not stated).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 9 Chronic lung disease (age at diagnosis not stated).

10 Intraventricular haemorrhage (any grade) Show forest plot

2

229

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.31, 1.46]

Analysis 1.10

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 10 Intraventricular haemorrhage (any grade).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 10 Intraventricular haemorrhage (any grade).

11 Severe intraventricular haemorrhage Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Analysis 1.11

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 11 Severe intraventricular haemorrhage.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 11 Severe intraventricular haemorrhage.

12 Duration of hospital stay (days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

Analysis 1.12

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 12 Duration of hospital stay (days).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 12 Duration of hospital stay (days).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 1 Mortality.
Figuras y tablas -
Analysis 1.1

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 1 Mortality.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 2 Treatment with ECMO.
Figuras y tablas -
Analysis 1.2

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 2 Treatment with ECMO.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 3 Pneumothorax.
Figuras y tablas -
Analysis 1.3

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 3 Pneumothorax.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 4 Pulmonary interstitial emphysema.
Figuras y tablas -
Analysis 1.4

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 4 Pulmonary interstitial emphysema.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 5 Air leaks (pneumothorax, pneumomediastinum, interstitial emphysema).
Figuras y tablas -
Analysis 1.5

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 5 Air leaks (pneumothorax, pneumomediastinum, interstitial emphysema).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 6 Duration of assisted mechanical ventilation (days).
Figuras y tablas -
Analysis 1.6

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 6 Duration of assisted mechanical ventilation (days).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 7 Duration of supplemental oxygen (days).
Figuras y tablas -
Analysis 1.7

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 7 Duration of supplemental oxygen (days).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 8 Need for supplemental oxygen at discharge.
Figuras y tablas -
Analysis 1.8

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 8 Need for supplemental oxygen at discharge.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 9 Chronic lung disease (age at diagnosis not stated).
Figuras y tablas -
Analysis 1.9

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 9 Chronic lung disease (age at diagnosis not stated).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 10 Intraventricular haemorrhage (any grade).
Figuras y tablas -
Analysis 1.10

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 10 Intraventricular haemorrhage (any grade).

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 11 Severe intraventricular haemorrhage.
Figuras y tablas -
Analysis 1.11

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 11 Severe intraventricular haemorrhage.

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 12 Duration of hospital stay (days).
Figuras y tablas -
Analysis 1.12

Comparison 1 Surfactant therapy vs. placebo or no therapy in term/near‐term infants, Outcome 12 Duration of hospital stay (days).

Comparison 1. Surfactant therapy vs. placebo or no therapy in term/near‐term infants

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality Show forest plot

4

326

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.41, 2.39]

2 Treatment with ECMO Show forest plot

2

208

Risk Ratio (M‐H, Fixed, 95% CI)

0.64 [0.46, 0.91]

3 Pneumothorax Show forest plot

3

269

Risk Difference (M‐H, Fixed, 95% CI)

‐0.02 [‐0.08, 0.05]

4 Pulmonary interstitial emphysema Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5 Air leaks (pneumothorax, pneumomediastinum, interstitial emphysema) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6 Duration of assisted mechanical ventilation (days) Show forest plot

3

158

Mean Difference (IV, Fixed, 95% CI)

0.60 [‐0.41, 1.62]

7 Duration of supplemental oxygen (days) Show forest plot

2

97

Mean Difference (IV, Fixed, 95% CI)

0.40 [‐2.83, 3.64]

8 Need for supplemental oxygen at discharge Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9 Chronic lung disease (age at diagnosis not stated) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10 Intraventricular haemorrhage (any grade) Show forest plot

2

229

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.31, 1.46]

11 Severe intraventricular haemorrhage Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12 Duration of hospital stay (days) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

Figuras y tablas -
Comparison 1. Surfactant therapy vs. placebo or no therapy in term/near‐term infants