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Meconium Aspiration Syndrome

Rita M. Ryan, MD
Chief, Division of Neonatology
Professor of Pediatrics, Pathology and Anatomical
Sciences, and Gynecology-Obstetrics

Meconium
first intestinal discharge from newborns is meconium
a viscous, dark green substance composed of intestinal epithelial cells,
lanugo, mucus, and intestinal secretions, such as bile.
Intestinal secretions, mucosal cells, and solid elements of swallowed
amniotic fluid are the 3 major solid constituents of meconium.
Water is the major liquid constituent, making up 85-95% of meconium.

Intrauterine distress can cause passage of meconium into the


amniotic
i i flfluid.
id
Factors that promote the passage in utero include placental
insufficiency, maternal hypertension, preeclampsia, oligohydramnios, and
maternal drug abuse, especially of tobacco and cocaine.

Meconium-stained amniotic fluid may be aspirated during labor and


delivery, causing neonatal respiratory distress.
Because meconium is rarely found in the amniotic fluid prior to 34
weeks' gestation, meconium aspiration chiefly affects infants at term
and postterm.
Dave Clark emedicine 2004

Pediatric Grand Rounds October 3, 2008

Meconium Aspiration Syndrome - More Than Intrapartum Meconium


[Editorial]
Ross, Michael G.
New England Journal of Medicine. 353(9):946353(9):946-8, 2005 Sep 1.
Harbor--UCLA Medical Center
Harbor

Meconium, the fecal material that


accumulates in the fetal colon throughout
gestation, is a term derived from the Greek
mekoni,
k i meaning
i poppy juice
j i or opium.
i
Beginning with Aristotle's observation of the
association between meconium staining of
the amniotic fluid and a sleepy fetal state or
neonatal depression, obstetricians have been
concerned about fetal well-being in the
presence of meconium-stained amniotic
fluid.

MSAF
The passage of mec in utero accompanies 8% to 20%
(average 12-13%) of all deliveries
<37 weeks
2%
>42 weeks
44%
seen predominantly in infants who are SGA and postmature,
cord complications or other factors compromising the in
utero placental circulation

MSAF is usually considered to be indicative of fetal


distress.
Many MSAF babies exhibit no signs of depression, etc.,
but some brief period of asphyxia could have induced
the passage of mec before delivery.
MAS seen in 4% of MSAF deliveries
Fanaroff and Martin 2002, Miller, Fanaroff and Martin
Avery 1991, Hansen and Corbet

Prenatal Management
presence of MSAF is not always an
indication of fetal distress in all infants

MSAF may signal fetal hypoxia, but if FHR, pH


remain normal then outcome usually
favorable

combination of MSAF and ominous FHR


tracing is often associated with significant
fetal and neonatal asphyxia with
accompanying morbidity

Fanaroff and Martin 2002, Miller, Fanaroff and Martin

Pathophysiology
passage of meconium in utero:
we think it is associated with asphyxia but data
actually are weak
? result of transient parasympathetic stimulation from
cord compression in a neurologically mature fetus
? natural phenomenon that reflects the maturity of
the GI tract
most agree that MSAF plus FHR abnormalities are a
marker for fetal distress and associated with
increased perinatal morbidity

Avery 1991, Hansen and Corbet

Pathophysiology
Mec in the AF may stain the umb cord, placenta
and fetus
when fetal distress is present, gasping may be
initiated in utero AF and particulate matter
contained therein may be inhaled into the large
airways
mec aspiration may occur antenatally
mec inhaled by the fetus may be present in the
trachea or larger bronchi at delivery
after air
breathing has commenced
rapid distal
migration of mec within the lung

Pathophysiology
If aspiration of meconium stained
amniotic fluid before, during, and after
birth occurs, there can be 3 major
pulmonaryy effects:
p
airway obstruction
surfactant dysfunction
chemical pneumonitis

Fanaroff and Martin 2002, Miller, Fanaroff and Martin

Ball--Valve Phenomenon
Ball

Dave Clark emedicine 2004

Pathophysiology
areas of atelectasis, resulting from total airway
obstruction, adjacent to
areas of overexpansion, from gas trapping in regions
with partial obstruction
salt and pepper appearance on CXR
air leaks
pneumomediastinum
pneumothorax

during inspiration, lower


airways open
air can go
into the alveolar air space

however, during expiration, the lower


airways collapse and with the
meconium present air cannot leave
air trapping
hyperinflation, PTX

chemical inflammation
pneumonitis
in vitro: concentration-dependent inhibition of
surfactant
animal models: influx of inflammatory cells and protein,
inactivation of surfactant, decrease in surf proteins

Clinical Findings
postmaturity
mec staining nails, skin, umbilical cord
often perinatal depression
neurologic, resp depression secondary to hypoxia (which
precipitated the passage of mec in the first place)

Severe respiratory distress may be present:

Fanaroff and Martin 2002, Miller, Fanaroff and Martin

Cyanosis
End-expiratory grunting
Alar flaring
Intercostal retractions
Tachypnea
Barrel chest in the presence of air trapping
Rales
Dave Clark emedicine 2004
Fanaroff and Martin 2002, Miller, Fanaroff and Martin

PPHN in MAS

Clinical Manifestations
clinical symptoms progress over 12-24
hours as mec migrates to the periphery
mec ultimately has to be removed by
phagocytosis
p
agocytos s
resp
esp distress
st ess and
a resp
esp
support may be persist for days or even
weeks

can be a major problem in infants with MAS


both prenatal and postnatal maladaptation of the
pulmonary circulation may contribute to the
development of PPHN in infants with MAS
anatomic abnormalities
evidence of injury to the vascular bed of the lung that dates back
several weeks prior to birth.
Vasc smooth muscle extends into the walls of normally nonmuscularized intra-acinar arterioles
bad PPHN

active vasoconstriction
directly or may cause plt aggregation
potent pulm vasoconstrictor

release of thromboxane, a

Avery 1991, Hansen and Corbet


Fanaroff and Martin 2002, Miller, Fanaroff and Martin

Avery 1991, Hansen and Corbet

CXR
coarse, irregular densities with areas of
diminished aeration and consolidation
pneumomediastinum, PTX
hyperinflation
cardiomegaly at times, due to perinatal
asphyxia
salt and pepper
Meconium Aspiration

Air trapping and


yp
p
from
hyperexpansion
airway obstruction

Dave Clark emedicine 2004

Left pneumothorax with


depressed diaphragm
and minimal mediastinal
shift because of
noncompliant lungs

Dave Clark emedicine 2004

Treatment
let them breathe fast in hood oxygen
Diffuse chemical
pneumonitis
from constituents
of meconium

arterial line frequent ABGs


minimal stimulation
try to avoid intubation

if intubate no longer aggressive in hyperventilation /


alkalosis but avoid hypercarbia / acidosis
no consensus on optimal
optimal vent strategy
if a lot of parenchymal disease
HFOV

target normal blood pressure


avoid hypotension

PPHN

not a big fan of nasal CPAP


just makes them mad

if intubate, use sedation generously


may need paralysis (no data)
Dave Clark emedicine 2004

Treatment
r/o sepsis but not automatic commitment
to a full course Abx
steroids are not recommended
textbook
te
tboo recommendation
eco
e at o but this
t s may
ay
be changing.

nothing on this slide has been well-studied

Surfactant
meconium may inhibit surf function
role for exogenous surf
multicenter RCT of term infants with
severee resp
seve
esp failure,
a u e, 50% of
o whom
w o had
a
MAS as primary dx
surf decr need for
ECMO

Fanaroff and Martin 2002, Miller, Fanaroff and Martin

Lotze et al, (J Pediatr 1998;132:401998;132:40-7)

Need for ECMO (%)

A multicenter (n = 44), randomized, doubleblind, placebo-controlled trial was conducted.


Infants > 2000g and > 36 wks, OI* 15-39,
n=328
stratified:
by diagnosis (MAS, sepsis, or idiopathic PPHN) and
oxygenation index (15 - 22, 23 - 30, 31 - 39)

four doses of surfactant (Survanta) 100 mg/kg


or air placebo, every 6 hours before ECMO
treatment and four additional doses during
ECMO, if ECMO was required.
*OI = FiO2 x MAP
pO2

The need for ECMO therapy was significantly less in the surfactant group than in
the placebo group (p = 0.038)

Need for ECMO (%)

this effect was greatest within the lowest oxygenation index stratum
(15 to 22; p = 0.013).

Steroids in MAS - Cochrane Review - 2003


Steroid therapy for meconium aspiration syndrome in
newborn infants
Cochrane Reviews
Ward, M; Sinn, J
Date of Most Recent Update: 25-August-2003
At present, there is insufficient evidence to assess the effects of steroid
therapy in the management of meconium aspiration syndrome. A further
large randomized controlled trial assessing potential benefits and harm would
be required to determine its role.
role.
(85 patients in 2 trials)

Modes of action to explain efficacy of


steroids
inhibition of prostaglandin and leukotriene
synthesis
removal of excess edema fluid
suppression of cytokine mediated
inflammatory reaction
inhibition of nitric oxide production

Sultantate of Oman
pilot study, case series, not RCT
all ventilated, all OI >25, all PPHN
average age starting dex 80hrs
dex 0.5/kg/day div q12h x3d, 0.3 x3d, 0.125 x3d
steroids started if not weaning on vent or OI worsening over
16h

RCT, 3 arms
placebo
0.5 mg/kg/d Methylprednisilone div q12h
50 ug q12h budesonide

blinded
not sure if ventilated population
2006

Steroids

Results
2 deaths, both in placebo group (one with
massive PTX, one with sepsis/DIC)
no baby in steroids group needed MV

RCT, n=99, 3 arms, not blinded


placebo, methylprednisilone 0.5mg/kg/d q12h x7d,
budesonide 50ug q12h x7d

Steroids for MAS


Need larger studies
Need long term follow up
Effects on brain / neurodevelopment
Need reallyy large
g studies

Could be useful for sickest babies

Inflammation in MAS
11 neonatal patients with MAS, 16 neonates without
MAS, and 9 healthy children.
6 cytokines higher in MAS compared with non-MAS
neonates:
IL-6, IL-8, GM-CSF, G-CSF, interferon, MIP-1, and TNF

IL-10 (anti-inflammatory cytokine) also was higher in


the MAS group

Steroids in MAS
Tripathi et al, Ind J Med Microbiology (2007) 25
(2):103-7
RCT, blinded, 3 groups
Placebo, methylprednisilone, inhaled budesonide
Steroids given for 7 days

Tracheal aspirates on day 1, 3, 4

Decreased TNF in steroid treated groups


TNF levels correlated with LOS

Controversies in the treatment of


meconium aspiration syndrome
Gelfand, J Fanaroff, Walsh, Clinics in Perinat
2004;31,445-452

Amnioinfusion
intrapartum suctioning
tracheal suctioning

Controversies in the treatment of meconium


aspiration syndrome

25,000-30,000 cases per year in US


1000 deaths annually

13% of live births have MSAF


onlyy 5% of these babies have MAS

MAS defined as resp distress in an


infant born through MSAF whose
symptoms cannot be otherwise
explained
Gelfand, J Fanaroff, Walsh, Clinics in Perinat 2004;31,445-452

Amnioinfusion

Fraser WD et al, N Engl J Med 2005;353: 909-17


Average BW 3.4 kg

dilutes meconium
relieves cord compression
relieving
hypoxia
decreasing gasping
does it reduce MAS? meta-analysis of
13 studies suggests that both fetal
distress and MAS are decreased:
Hofmeyr, GJ et al, Cochrane review, 2001, 2004
update

Gelfand, J Fanaroff, Walsh, Clinics in Perinat 2004;31,445-452

Table 3 continued

Amnioinfusion Fraser WD et al
N Engl J Med 2005;353: 909909-17

Conclusions: For women in labor who


have thick MSAF, amnioinfusion did not
reduce the risk of moderate or severe
meconium aspiration
p
syndrome,
y
perinatal
p
death, or other major maternal or
neonatal disorders.

DeLee and tracheal suctioning


preventive approach
thorough suctioning of nose and pharynx by
OB after delivery of head but before thorax
is delivered and the infant can take a breath
if infant depressed
tracheal suctioning to
remove residual mec
Amnioinfusion does not prevent meconium aspiration syndrome.
ACOG Committee Opinion No. 346.
American College of Obstetricians and Gynecologists.
Obstet Gynecol 2006;108:10535.

Fanaroff and Martin 2002, Miller, Fanaroff and Martin

Intrapartum suctioning
considered standard for 25 years
Carson et al Am J Ob Gyn 1976;126:712-5

Wiswell et al Peds 2000;105:1-7

Fanaroff
and Martin
2002,
Miller,
Fanaroff
and Martin

RCT studyy to examine tracheal suctioningg 2094 infants


MAS increased in those who did not receive
intrapartum oropharyngeal suctioning before
delivery of the shoulders (8.5% vs. 2.7%, OR
3.35, CI 1.55-7.27)
Gelfand, J Fanaroff, Walsh, Clinics in Perinat 2004;31,445-452

Intrapartum Suctioning NRP


2005
Aspiration of meconium before delivery, during birth, or
during resuscitation can cause severe aspiration pneumonia.
One obstetrical technique to try to decrease aspiration has
been to suction meconium from the infants airway after
delivery of the head but before delivery of the shoulders
(intrapartum suctioning).
Although some studies (LOE 3) suggested that intrapartum
suctioning might be effective for decreasing the risk of
aspiration syndrome, subsequent evidence from a large
multicenter randomized trial (LOE 1) did not show such an
effect.
Therefore, current recommendations no longer advise
routine intrapartum oropharyngeal and nasopharyngeal
suctioning for infants born to mothers with meconium
staining of amniotic fluid (Class I).
Circulation 2005

Circulation 2005

Recommendations were generally labeled Class IIb when the


evidence documented only short-term benefits from the therapy
or when positive results were documented with lower levels of
evidence.
Class IIb recommendations fall into 2 categories:
(1) optional and
(2) recommended by the experts despite the absence of high-level
supporting evidence.
Optional interventions are identified by terms such as can be
considered or may be useful. Interventions that the experts
believe should be carried out are identified with terms such as we
recommend.

Vain et al, Lancet 2004;364;597-602

Intrapartum suctioning
Infants were randomly allocated to either suctioning
of the oropharynx and nasopharynx (including the
hypopharynx) before delivery of the shoulders
(suction group), or no suctioning (no-suction group).
10-Fr to 13-Fr connected to a negative pressure of
150 mm Hg.
Hg
Oropharyngeal suctioning was done first, followed by
bilateral nasopharyngeal suctioning, when possible.
Thereafter, care was given according to NRP
tracheal suctioning for non-vigorous infants

Vain et al, Lancet 2004;364;597-602

Vain et al, Lancet 2004;364;597-602

Intrapartum suctioning
The primary outcome was incidence of MAS.
Diagnosis of the syndrome was defined by
(1) respiratory distress (tachypnea, retractions, or
grunting) in a neonate born through MSAF;
(2) need
d ffor supplemental
l
l oxygen to maintain
i i oxygen
saturation levels at 92% or greater;
(3) oxygen requirements starting during the first 2 h of
life and lasting for 12 h or longer; and
(4) absence of congenital malformation of the airway,
lung, or heart.
Vain et al, Lancet 2004;364;597-602
Vain et al, Lancet 2004;364;597-602

DeLee and tracheal suctioning


preventive approach
thorough suctioning of nose and pharynx by
OB after delivery of head but before thorax is
delivered and the infant can take a breath
if infant depressed
tracheal suctioning to
remove residual mec
Fanaroff
and Martin
2002,
Miller,
Fanaroff
and Martin
Fanaroff and Martin 2002, Miller, Fanaroff and Martin

10

Tracheal Suctioning NRP


2005
Traditional teaching recommended that meconiumstained infants have endotracheal intubation
immediately following birth and that suction be applied
to the endotracheal tube as it is withdrawn.
Randomized controlled trials have shown that this
practice offers no benefit if the infant is vigorous (Class
I). A vigorous infant is defined as one who has strong
respiratory efforts, good muscle tone, and a heart rate
100 beats per minute (bpm).
Endotracheal suctioning for infants who are not
vigorous should be performed immediately after birth
(Class Indeterminate).

Circulation 2005

Circulation 2005

Tracheal suctioning
Linder et al Israel J Peds 1988 n>500

no morbidity in infants with Apgar scores of 8 or


higher at 1 minute who had been deLee suctioned

Wiswell et al Peds 2000;105:1-7

prospective RCT of vigorous infants with MSAF


2094 iinfants
f t att 12 centers,
t
vigorous
i
bbaby
b
149 (7.1%) of enrolled infants
resp distress
62 (3%) dx with MAS
87 (4.2%) other (TTN, delayed transition, sepsis, PPHN)

no diff whether tracheally suctioned or not


MAS 3.2% intubated vs. 2.7% non-intubated

no diff in other resp disorders

Meconium Aspiration Syndrome


Is Surfactant Lavage the Answer?
John P. Kinsella, AJRCCM, 2003;168:4132003;168:413-4

commentary
method to enhance removal of particulate meconium
from the airway using bronchoalveolar lavage with a
dilute bovine surfactant preparation.
2 week old piglets
They found that a 30-ml/kg lavage volume of dilute
surfactant was associated with increased meconium
removal, improved post-lavage lung function, and less
lung injury as compared with perflourocarbon emulsion
or multiple, smaller aliquots of dilute surfactant.

Endotracheal intubation at birth for preventing


morbidity and mortality in vigorous, meconium
meconium-stained infants born at term
Halliday, HL; Sweet, D; Cochrane review, 2000, 2005
4 RCTs
Meta-analysis of these trials does not support routine
use of endotracheal intubation at birth in vigorous
meconium-stained babies to reduce mortality, MAS,
other resp symptoms / disorders,
disorders PTX,
PTX O2 need,
need stridor,
stridor
HIE and convulsions.
Conclusions: Routine endotracheal intubation at birth in
vigorous term meconium-stained babies has not been
shown to be superior to routine resuscitation including
oro-pharyngeal suction.
This procedure cannot be recommended for vigorous
infants until more research is available.

Dargaville, Morley et al, Melbourne, AJRCCM 2003; 168:456463

controls
perfluorocarbon

dilute surf lavage

11

dilute surf lavage

perfluorocarbon

Therapeutic lung lavage in meconium


aspiration syndrome: A preliminary report
Dargaville, Morley et al (Australia)
Journal of Paediatrics and Child Health 43 (2007) 539545

Infants with severe MAS, HFOV


Lavaged infants typically stablized but not improving, still on high
FiO2 with an alveolar-arterial oxygen difference (AaDO2) of >400
mm Hg
Lavage not performed if arterial pH < 77.20,
20 sat < 75%
75%, or mean bp <35
mm Hg
Lavage performed in sedated muscle-relaxed infants

1/5 dilution of Survanta, mixed gently in sterile NS and warmed to


37C, delivered via catheter protruding approximately 0.5 cm
below ETT
Lavage aliquot volumes were increased through the case series,
aiming to deliver two aliquots of 15 mL/kg 3-5 minutes apart
Dargaville, Morley et al, Melbourne, AJRCCM 2003; 168:456463

Surfactant lavage

8 babies enrolled
median age of 23 h (range 883 h)
88% nitric oxide, 3 on adrenalin infusion
lavage was associated with significant
desaturation but not bradycardia or hypotension

3 in Therapeutic lavage group subgroup


of infants who received at least 25mL/kg
within 24h age
34 babies in non-lavaged group

No lavage
all lavaged infants
Tx lavage

P=0.03 repeated measures ANOVA

Comparable, if anything, lavaged babies sicker

Surfactant lavage

efficacy deserves further investigation in a


randomized controlled trial
About 10 prior human studies
RCT Surfaxin ongoing
lessMAS
Lavage with Exogenous Surf Suspension in MAS

ECMO usage
iNO
HFOV
surfactant
less post-term pregnancies
less ECMO

Gelfand, J Fanaroff, Walsh, Clinics in Perinat 2004;31,445-452

12

Decreased Use of Neonatal Extracorporeal Membrane


Oxygenation (ECMO): How New Treatment Modalities
Have Affected ECMO Utilization

1993-4

1996-7

Patients were included if:

*OI >15 x 1 within the first 72 hours


of admission
>35 weeks
dx MAS, PPHN or sepsis/pneumonia
<5 days of age on admission

Pre-ECMO surfactant
iNO

3 (6.1%)
0

18 (44.7%)

*OI = FiO2 x MAP


pO2
Hintz S et al, Pediatrics 2000;106:1339 1343

Neonatal Respiratory ECMO

Conrad SA et al, ASAIO Journal 2005;51:4-10

Hintz S et al, Pediatrics 2000;106:1339 1343

Neonatal Respiratory ECMO

Conrad SA et al, ASAIO Journal 2005;51:4-10

From the Departments of Pediatrics and Obstetrics/Gynecology,


Wilford Hall Medical Center, Lackland AFB,Texas

Obstet Gynecol 2002;99:7319

CONCLUSION: Reduction in post-term


delivery was the most important factor in
reducing meconium aspiration syndrome.

Yoder et al, Obstet Gynecol 2002;99:7319

13

Yoder et al, Obstet Gynecol 2002;99:7319

Yoder et al, Obstet Gynecol 2002;99:7319

Yoder et al, Obstet Gynecol 2002;99:7319

Yoder et al, Obstet Gynecol 2002;99:7319

Yoder et al, Obstet Gynecol 2002;99:7319

Yoder et al, Obstet Gynecol 2002;99:7319

14

Results
MASINT
1061of 2,490,862 live births (0.43 of 1000)
decrease in incidence from 1995 to 2002
Pediatrics 2006;117;1712-1721
May 2006

Data were gathered on all of the infants in Australia and New Zealand who
were intubated and mechanically ventilated with a primary diagnosis of
MAS between 1995 and 2002, inclusive. Information on all of the live births
during the same time period was obtained from perinatal data registries.

MASINT = intubated for MAS

MASINT
34% > 40 weeks gestation
6.5% > 41 weeks gestation
g

total birth population


16% > 40 weeks gestation
2.0% > 41 weeks gestation

P < .001 in both cases


Associated with MASINT:
low 5-minute Apgar score
maternal ethnicity Pacific Islander or indigenous Australian
planned home birth

Possible etiology of lower MASINT


Compared with 1995, in 2002, there were
fewer deliveries beyond 41 weeks
gestation (1.6% vs 2.8%; P .001) and
fewer infants with a 5-minute Apgar score
<7
7 (1
(1.4%
4% vs 1.7%;
1 7% P .001).
001)
These factors combined account for 62%
of the reduction in MAS incidence noted
in this time period.

15

Yoder et al, Ob Gyn,


Gyn, March 2008

Is there a trade-off?
Logistic regression
5 factors
independently related
to resp morbidity:
GA, C/S, male, FHR,
low 5 min Apgar

Change in GA distribution from 1990 to 1998


Yoder et al, Ob Gyn March 2008

Summary
MSAF is often associated with in utero fetal distress and
hypoxia.
The pathophysiology of MAS includes airway obstruction,
surfactant inactivation and a chemical pneumonitis leading to
air trapping, atelectasis and PPHN.
Standard therapy for MAS includes supplemental oxygen,
mechanical ventilation, surfactant, nitric oxide and ECMO.
The use of ECMO for MAS-PPHN patients is decreasing due
to the increased use of other therapies such as HFV,
surfactant and iNO.
Preventive measures such as amnioinfusion, intrapartum oroand naso-phayngeal suctioning, and tracheal suctioning are
now controversial and no longer recommended as routine.
The incidence of MAS is decreasing, primarily related to
fewer post-mature infants and less intrapartum fetal distress.

16