MECONIUM ASPIRATION SYNDROME

Ismail HaronConsultant Paediatrician & Neonatologist

Hospital Sungai Buloh

Symposium 4: Challenges in neonatal care

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Introduction

Epidemiology

Pathogenesis of MAS

Clinical features

ManagementGeneralSpecific

Conclusion

Challenges in neonatal care: Meconium Aspiration Syndrome

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IntroductionMeconium 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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Yoder BA et al. Obstet Gynecol 2002;99:731-9Dargaville PA, Copnell B. Pediatrics 2006;117:1712-1721

Incidence of MAS according to gestation

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Yoder BA et al. Obstet Gynecol 2002;99:731-9Dargaville PA, Copnell B. Pediatrics 2006;117:1712-1721

Incidence of MAS

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Pathogenesis of MAS

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Causes of MSAFUnder 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 sphincterTerminal 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 sphincterPresence of meconium in the amniotic fluid may increase the risk of intraamniotic infection.

Piper HM et al. Obstet Gynecol 1998;91:741-5

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Risk factorsMaternal hypertensionMaternal diabetes mellitusMaternal heavy cigarette smoking.Maternal chronic respiratory or CVS disease.Post-term pregnancy.Pre-eclampsia / eclampsiaOligohydramniosIntrauterine growth retardationPoor biophysical profileAbnormal fetal heart rate patterns

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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;184:1422-6Ghidini A, Spong CY. Am J Obstet Gynecol 2001;185:931-8

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Mechanisms of injury

Mechanical obstruction of airways.

Chemical pneumonitis.

Vasoconstriction of pulmonary vessels.

Inactivation of surfactant.

Activation of complement.

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Mechanical obstruction of airwaysMechanism of injury – cont’

Thick and viscous.Complete or partial airway obstruction.With onset of respiration – meconium migrates from central to peripheral airways.Complete obstruction – atelectasisPartial obstruction –

Ball-valve – air trapping.Risk of pneumothorax - 15 – 33%

Cleary GM, Wiswell TE. Pediatr Clin North Am. 1998;45:511-29

V/Q mismatch

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PneumonitisMechanism of injury – cont’

Neutrophils & Macrophages (alveoli, airway & parenchyma)

Cytokines(TNFα, IL-1β, IL-8)

Pneumonitis

Vascular leakage

Haemorrhagic pulmonary oedema

Bodil S et al. Pediatrics 2008;121:e496-e505Kaoru O et al. Pediatrics 2008;121:e748-e753

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Vasoconstriction of pulmonary vesselsMechanism of injury – cont’

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-1Prostaglandin E2

Hageman JR, Caplan MS. Clin Perinatol 1995;22:251-261

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Inactivation of surfactantMechanism of injury – cont’

In the early 1990s – meconium inactivates surfactant.

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.

Surfactant deficiency due to inactivation leads to increased surface tension;

AtelectasisDecreased lung complianceDecreased lung volumes

Findlay RD et al. Pediatrics 1996;97:48-52

Greenough A. Eur J Pediatr 1995;154:S2-4

Cleary GM et al. Pediatrics 1997;100:998-1003 Higgins ST et al. Pediatr Res 1996;39:443-7

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Activation of complementMechanism of injury – cont’

Meconium is a potent activator of the complement system.

Activation of complement system was correlated with lung dysfunction and mortality.

Meconium-induced cytokines production is mediated by complement and CD14.

Castellheim A et al. Pediatr Res 2004;55(2):310-318Castellheim A et al. Scand J Immunol 2005;61(3):217-225

Lindenskov PH et al. Pediatr Res 2004;56(5):810-817

Bodil S et al. Pediatrics 2008;121:e496-e505

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Physiologic meconium passage(particularly if postdates)

Fetal compromise (hypoxia, cord compression, etc) – meconium passage

Meconium-stained amniotic fluid Umbilical cord spasm

Continued compromiseInutero gaspingPostpartum aspiration

Meconium aspiration

Peripheral airway obstruction

Proximal airway obstruction Cytokines activation Inactivation of surfactant

Pneumonitis

AcidosisHypoxemia

Hypercapnea

AcidosisHypoxemia

Hypercapnea

Remodeling of pulmonary vasculature

(muscular hyperplasia)

PPHN

Decreased lung compliance

Complete

Atelectasis

Vasoactive mediators

Partial

V/Q mismatch

Ball-valve effect

Air trapping

Air leaks

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Clinical features

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Diagnosis

MAS must be considered in any infant born through MSAF who develops symptoms of respiratory distress.

Various radiographic findings may be present.

Diffuse asymmetric patchy infiltrates

Areas of atelectasis

Hyperinflated areas

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Diagnosis

MildRequires < 40% oxygen for less than 48 hours

Moderate.Requires > 40% oxygen for more than 48 hours No air leak

SevereRequires assisted ventilation for more than 48 hoursOften associated with PPHN

Severity of MAS

Cleary GM, Wiswell TE. Pediatr Clin North Am 1998;45:511-29

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Management

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Prevention

Prevention

Prevention

Prevention

Prevention

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Antepartum

Intrapartum

Postnatal

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TreatmentGeneral

Temperature regulation

Haemodynamic status

Biochemistry

Haematology

Possible infection

Associated asphyxia

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TreatmentRespiratory 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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TreatmentMode 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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TreatmentSurfactant 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.

Cochrane meta-analysis – 4 randomised trials;Reduce the use of ECMO (RR 0.64)No effect on mortality

Findlay RD et al. Pediatrics 1996;97:48-52Lotze A et al. J Pediatr 1998;132:40-7

El Shahed A et al. Cochrane Database Syst Rev 2007

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TreatmentSurfactant Therapy

Surfactant inactivation property of meconium.

Search for new synthetic surfactant preparations; highly resistant to inactivation by meconium.

Herting E et a. Pediatr Res 2001;50:44-9

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TreatmentSurfactant Lavage

Removal of noxious material from the lungs.Minimised obstruction.Offset the inactivation of surfactant by meconiumIncrease oxygenation & reduction in duration of mechanical ventilation

LessMAS Trial.

Lam BCC, Yeung CY. Pediatrics 1999;103:1014-8Wiswell TE et al. Pediatrics 2002;109:1081-7

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Aetiology of PPHN

Clark RH et al. N Engl J Med. 2000;342:469-74

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TreatmentInhaled 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.

Finer NN, Barringtan KJ. Cochrane Database Syst Rev 2006

Rais-Bahrami KRO et al. Crit Care Med 1997;25(10):1744-7

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TreatmentInhaled 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)

Clark RH et al. N Engl J Med. 2000;342:469-74

(RR:0.6)(RR:0.6)(RR:0.6)

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TreatmentSteroid

Insufficient evidence to assess the effects of steroid therapy in the management of MAS.

Ward M, Sinn J. Cochrane Database Syst Rev 2003

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Thank you for your kind attention