Challenges in neonatal care: Meconium Aspiration Syndrome
Introduction Epidemiology Pathogenesis of MAS Clinical features Management General Specific
Conclusion
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Introduction Meconium aspiration syndrome (MAS) is not an uncommon problem. Important cause of respiratory distress in the term newborn with high morbidity and mortality. The pathophysiology is complex and is not well defined. Despite advances in neonatal intensive care over the last 2 decades, MAS remains one the most vexing clinical conditions to manage.
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Composition of meconium Sterile compound made primary of water (75%), with mucous glycoproteins, lipids and proteases. Small dried amniotic fluid debris, vernix and lanugo. Bile pigments. The residue from intestinal secretions.
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Epidemiology
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Epidemiology Approximately 10 – 15% of all live births are complicated by meconium stained amniotic fluid (MSAF). About 5% of neonates born through MSAF develop MAS. MSAF and MAS related to advanced gestation. Generally incidence of MSAF and MAS are in a declining trend.
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Incidence of MAS according to gestation
Yoder BA et al. Obstet Gynecol 2002;99:731-9 Dargaville PA, Copnell B. Pediatrics 2006;117:1712-1721 SMC/KL/2008
Incidence of MAS
Yoder BA et al. Obstet Gynecol 2002;99:731-9 Dargaville PA, Copnell B. Pediatrics 2006;117:1712-1721 SMC/KL/2008
Pathogenesis of MAS
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Causes of MSAF Under normal circumstances, the passage of meconium from the fetus into the amnion is prevented by; Lack of intestinal peristalsis (low motilin level) Tonic contraction of anal sphincter Terminal cap of viscous meconium
Fetal maturation – post-term. Vagal stimulation produced by head or cord compression in the absence of fetal distress. In-utero stress (hypoxia and acidosis) producing relaxation of anal sphincter Presence of meconium in the amniotic fluid may increase the risk of intraamniotic infection. Piper HM et al. Obstet Gynecol 1998;91:741-5 SMC/KL/2008
Causes of MAS Reason why some infants born through MSAF develop an aspiration syndrome whereas others do not – unclear.
Aspiration of meconium may occur in-utero or after delivery with the first few breaths. Chronic fetal hypoxia and acidosis may lead to fetal gasping and the subsequent in-utero aspiration of meconium. Chronic in-utero insult may be responsible for most cases of severe MAS as opposed to an acute peripartum event. Blackwell SC et al. Am J Obstet Gynecol 2001;184:1422-6 Ghidini A, Spong CY. Am J Obstet Gynecol 2001;185:931-8 SMC/KL/2008
Mechanisms of injury Mechanical obstruction of airways. Chemical pneumonitis. Vasoconstriction of pulmonary vessels. Inactivation of surfactant. Activation of complement. SMC/KL/2008
Mechanism of injury – cont’
Mechanical obstruction of airways Thick and viscous. Complete or partial airway obstruction. With onset of respiration – meconium migrates from central to peripheral airways. Complete obstruction – atelectasis Partial obstruction – Ball-valve – air trapping. Risk of pneumothorax - 15 – 33% Cleary GM, Wiswell TE. Pediatr Clin North Am. 1998;45:511-29
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Mechanism of injury – cont’
Pneumonitis Neutrophils & Macrophages
Cytokines
(alveoli, airway & parenchyma)
(TNFα, IL-1β, IL-8)
Pneumonitis Vascular leakage
Haemorrhagic pulmonary oedema
Bodil S et al. Pediatrics 2008;121:e496-e505 Kaoru O et al. Pediatrics 2008;121:e748-e753 SMC/KL/2008
Mechanism of injury – cont’
Vasoconstriction of pulmonary vessels Severe MAS may be complicated by PPHN. Pulmonary vasoconstriction is in part may be a result of the underlying inutero stress. The release of vasoactive mediators as a result of injury from meconium; Eicosanoids, Endothelin-1 Prostaglandin E2
Inactivation of surfactant In the early 1990s – meconium inactivates surfactant. Greenough A. Eur J Pediatr 1995;154:S2-4
Meconium displaces surfactant from the alveolar surface → inhibits surface tension-lowering ability. Direct inhibitory effect of meconium on the function of surfactant in vitro an in in vivo animal models. Cleary GM et al. Pediatrics 1997;100:998-1003 Higgins ST et al. Pediatr Res 1996;39:443-7
Surfactant deficiency due to inactivation leads to increased surface tension; Atelectasis Decreased lung compliance Decreased lung volumes Findlay RD et al. Pediatrics 1996;97:48-52 SMC/KL/2008
Mechanism of injury – cont’
Activation of complement Meconium is a potent activator of the complement Castellheim A et al. Pediatr Res 2004;55(2):310-318 system. Castellheim A et al. Scand J Immunol 2005;61(3):217-225 Activation of complement system was correlated with lung dysfunction and mortality. Lindenskov PH et al. Pediatr Res 2004;56(5):810-817
Meconium-induced cytokines production is mediated by complement and CD14. Bodil S et al. Pediatrics 2008;121:e496-e505
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Physiologic meconium passage (particularly if postdates)
Treatment General Temperature regulation Haemodynamic status Biochemistry Haematology Possible infection Associated asphyxia SMC/KL/2008
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Treatment Respiratory management Depends on the amount of respiratory distress. Increasing oxygenation while minimising barotrauma/volutrauma. Hyperventilation did not proven beneficial. No randomised trials have compared different forms of ventilation in MAS.
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Treatment Mode of ventilation HFV claimed to be gentler. Theoretically, HFV should reduce air leaks. HFV may slow the progression of meconium down the tracheobronchial tree and allow more time for meconium removal. Hachey WE et al. Crit Care Med 1998;26:556-61
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Treatment Surfactant Therapy Two randomised trials – evaluate the efficacy of exogenous surfactant therapy in MAS showed promising results with decrease in the number of infants requiring ECMO and possible reduction of pneumothorax. Findlay RD et al. Pediatrics 1996;97:48-52 Lotze A et al. J Pediatr 1998;132:40-7
Cochrane meta-analysis – 4 randomised trials; Reduce the use of ECMO (RR 0.64) No effect on mortality El Shahed A et al. Cochrane Database Syst Rev 2007
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Treatment Surfactant Therapy Surfactant inactivation property of meconium. Herting E et a. Pediatr Res 2001;50:44-9
Search for new synthetic surfactant preparations; highly resistant to inactivation by meconium.
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Treatment Surfactant Lavage Removal of noxious material from the lungs. Minimised obstruction. Offset the inactivation of surfactant by meconium Increase oxygenation & reduction in duration of mechanical ventilation Lam BCC, Yeung CY. Pediatrics 1999;103:1014-8 Wiswell TE et al. Pediatrics 2002;109:1081-7
LessMAS Trial.
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Aetiology of PPHN
Clark RH et al. N Engl J Med. 2000;342:469-74 SMC/KL/2008
Treatment Inhaled nitric oxide Selective pulmonary vasodilation. Activate guanylate cyclase and increases cyclic GMP and acting directly on the vascular smooth muscle. Decreased need for ECMO (RR 0.61) but no difference in mortality.
Pretreatment with surfactant improves in delivery of iNO to the alveoli. Rais-Bahrami KRO et al. Crit Care Med 1997;25(10):1744-7 SMC/KL/2008
Treatment Inhaled nitric oxide HFOV + iNO seems to work better, likely due to improve lung inflation and better delivery of the drug. Kinsella JP et al. J Pediatr 1997;131:55-62
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(RR:0.6)
(RR:0.6)
(RR:0.6)
(RR:0.6)
Clark RH et al. N Engl J Med. 2000;342:469-74 SMC/KL/2008
Treatment Steroid Insufficient evidence to assess the effects of steroid therapy in the management of MAS. Ward M, Sinn J. Cochrane Database Syst Rev 2003
