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CLINICAL OVERVIEW

Meconium aspiration syndrome


Elsevier Point of Care (see details)
Updated September 14, 2018. Copyright Elsevier BV. All rights reserved.

Synopsis Urgent Action


Key Points Infants who are depressed at
Meconium aspiration syndrome is respiratory distress in the immediate neonatal period in infants born birth (eg, low heart rate, poor
tone or respiratory effort)
through meconium-stained amniotic fluid whose symptoms cannot be otherwise explained 1
require immediate positive
Infants at highest risk for meconium aspiration syndrome are postterm, have African or Asian pressure ventilation; infants who
ethnicity, are born through thick meconium-stained amniotic fluid, or have evidence of intrapartum remain depressed despite initial
fetal distress or hypoxia resuscitation efforts require
intubation and mechanical
Diagnose meconium aspiration syndrome based on history and physical examination with chest
ventilation 5
radiograph findings suggestive of meconium aspiration syndrome and without alternate cause for
respiratory distress All symptomatic infants at risk
for meconium aspiration
American Academy of Pediatrics/American Heart Association guidelines no longer recommend
syndrome require immediate
suctioning of trachea before positive pressure ventilation in depressed infants (2015 guidelines);
attention by a specialized
immediate delivery room management of depressed infants includes warming, stimulating, drying, and
neonatal ICU team for close
initiation of positive pressure ventilation before intubation, if required 2
monitoring and supportive care 1
Treatment is supportive in a neonatal ICU. Individualized care includes resuscitation for nonvigorous
Manage infants with severe
infants, oxygenation, ventilation, radiant warming, and minimal handling and stimulation 1 meconium aspiration syndrome
at a facility with specialized
Rescue therapies include surfactant replacement, steroid therapy, high-frequency ventilation, and
capabilities to treat persistent
extracorporeal membrane oxygenation in selected infants when other treatments fail
pulmonary hypertension and
Often antibiotics are started pending blood and tracheal aspirate culture results in ill infants, owing to transition to extracorporeal
the difficulty in differentiating infectious etiologies causing respiratory distress and isolated meconium membrane oxygenation if
aspiration syndrome in the immediate neonatal period; discontinue antibiotics if culture results are needed
negative 3 4
Infants with meconium
Infants with comorbid primary or secondary persistent pulmonary hypertension are difficult to aspiration syndrome may
oxygenate and sometimes require additional specialized management (eg, nitric oxide and high- develop life-threatening tension
frequency ventilation, extracorporeal membrane oxygenation) pneumothorax requiring
emergent pleural space
Short-term complications include death, respiratory failure, ventilator-induced barotrauma decompression, especially
(pneumothorax and other pulmonary air leaks), and development of pulmonary hypertension neonates requiring positive
pressure ventilation; anticipate
Long-term complications include pulmonary sequelae (wheezing in infancy and asthma in childhood)
pneumothorax with any sudden
and adverse neurodevelopmental outcomes
clinical deterioration
Mortality rate is less than 5% in newborns with meconium aspiration syndrome in developed countries
5

Preventive induction and delivery of infants at or beyond 41 weeks of gestation reduces the risk of meconium aspiration syndrome 1

Pitfalls
Do not suction oropharynx or nasopharynx at the perineum during delivery; these maneuvers delay proper resuscitation efforts and do not
prevent meconium aspiration syndrome 5

Do not electively intubate and suction trachea of infants at birth, even if infant is born depressed through thick meconium-stained amniotic
fluid 2

Terminology
Clinical Clarification
Meconium aspiration syndrome is respiratory distress in an infant born through meconium-stained amniotic fluid with radiologic changes
suggestive of this syndrome and whose symptoms cannot be otherwise explained 1

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Most common in postmature infants and infants who are small for gestational age; symptoms range from mild respiratory distress to severe
respiratory distress with cardiopulmonary failure 6

Classification
Mild disease 1

Requires less than 40% oxygen for up to 48 hours

Moderate disease 1

Requires more than 40% oxygen for more than 48 hours

Infants with moderate disease have no associated pulmonary air leak

Severe disease

Requires assisted ventilation for more than 48 hours 1

Often associated with concurrent persistent pulmonary hypertension 7

Diagnosis
Clinical Presentation
History
Term or near-term infant 1

Perinatal history 5

Meconium-stained amniotic fluid

Postterm pregnancy

Infants who are large for gestational age or small for gestational age on prenatal ultrasonography

Fetal distress on fetal heart rate and scalp monitoring

Physical examination
Low Apgar score 8

Bradycardia (heart rate fewer than 100 beats per minute)

Poor respiratory effort

Poor tone

Poor color (pale or cyanotic)

Infants present with variable signs of respiratory distress immediately after delivery; 9 respiratory distress may develop up to 12 hours after
birth, but such delay is unusual 8

Tachypnea

Nasal flaring, grunting, and retractions

Pulmonary rales and rhonchi

Paradoxical abdominal breathing

Barrel chest

Inspiratory stridor

Meconium staining on the infant 7

Greenish to yellow staining of vernix, umbilical cord, and nails

Findings such as unilateral diminished breath sounds suggest pneumothorax and crepitus suggests pneumomediastinum

Causes and Risk Factors


Causes
Intrauterine passage of meconium results from fetal hypoxia and stress 1 10

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Meconium aspiration syndrome is caused by fetal aspiration of meconium during intrauterine gasping triggered by fetal distress 1

Meconium causes variable degrees of pneumonitis, pulmonary vasoconstriction, surfactant inactivation, and mechanical obstruction of
airways

Risk factors and/or associations


Age
Rarely occurs in infants born before 34 weeks of gestation 1

Ethnicity/race
Risk is increased in:

Africans 11

African Americans 12

South Asians 5

Pacific Islanders 1 13

Indigenous Australians 13

Other risk factors/associations


Meconium-stained amniotic fluid is present in 4% to 22% of all pregnancies 14

Risk factors for passage of meconium in utero

Increasing gestational age

4% of deliveries before 37 weeks 6

10% to 20% of term deliveries 6

30% to 40% of postterm deliveries 6

Increasing birth weight

Incidence up to 28% with birth weight more than 5 kg 5

Fetal hypoxia and stress

Maternal drug abuse (particularly tobacco and cocaine)

Chorioamnionitis 5

Oligohydramnios

Difficult or lengthy labor

Use of vaginal misoprostol for labor induction 5

Maternal preeclampsia or hypertension

Maternal diabetes 8

Placental insufficiency

Small for gestational age and intrauterine growth restriction 4

Meconium aspiration syndrome occurs in 3% to 12% of infants born through meconium-stained amniotic fluid 14

Risk factors for severe meconium aspiration syndrome

Increased gestational age 5

Thick meconium 1

Thin meconium rarely results in meconium aspiration syndrome 5

Low Apgar score

Neonates with 1-minute Apgar score of 3 or less are at very high risk 5
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Approximately 19% of neonates with 5-minute Apgar score of 8 or less develop meconium aspiration syndrome 15

Birth at a level I or II facility 5

Fetal acidosis 1

Nonreassuring intrapartum fetal heart rate tracing patterns 1 16

Cesarean delivery 1

Aspiration of meconium to a level below the vocal cords 1

Intubation requirement at birth 1

Lack of prenatal care

Diagnostic Procedures
Primary diagnostic tools

Diagnose meconium aspiration syndrome based on the presence of respiratory distress in infants
born through meconium-stained amniotic fluid without alternative cause for respiratory distress 1

Chest radiograph findings consistent with meconium aspiration syndrome support the diagnosis 1
17

Obtain blood and tracheal aspirate bacterial cultures to help exclude infectious causes for
respiratory distress, especially if infant has risk factors for early-onset neonatal sepsis (no guideline Chest radiograph. - Chest radiograph of
or definitive standard of care established) 1 6
a ventilated infant with meconium
aspiration syndrome showing typical
Echocardiogram is sometimes obtained in infants with severe hypoxia to assess for concurrent
appearances of hyperinflation and
persistent pulmonary hypertension 18 patchy interstitial shadowing.

Laboratory

Blood or tracheal aspirate culture for pneumonia or other infections

Negative culture results are consistent with meconium aspiration syndrome without concomitant sepsis or pneumonia

Other laboratory tests are often obtained but do not specifically contribute to the diagnosis of meconium aspiration syndrome

CBC

Not required for diagnosis, but when obtained it often shows elevated WBC count with neutropenia in neonates with meconium
aspiration syndrome 18

Thrombocytopenia is often noted with persistent pulmonary hypertension and severe asphyxia–associated disseminated intravascular
coagulation 18

Neutropenia or neutrophilia with left shift or abnormal immature to total neutrophil ratio may indicate bacterial infection

Low hemoglobin level may indicate intrauterine or intrapartum hemorrhage

Renal panel with electrolyte levels

Not required for diagnosis, but when obtained it may show hyponatremia with inappropriate antidiuretic hormone secretion
secondary to asphyxia 18

Hyperkalemia and elevated BUN and creatinine levels are apparent with concurrent renal damage secondary to acute tubular necrosis
18

Cord blood pH

Abnormally low cord blood pH may reflect degree of asphyxia

Arterial blood gas levels

Umbilical artery blood gas measurements assist with decisions about ventilatory management but are not necessary to diagnose
meconium aspiration syndrome

Imaging

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Chest radiograph

Radiographic findings are nonspecific and differ between individual infants with disease 1

Severity of radiographic findings does not always correlate with clinical disease severity 1

Characteristic radiographic findings consistent with meconium aspiration syndrome include:

Hyperexpansion of lungs with flat diaphragms and widened rib spaces 1 9

Widespread, coarse, asymmetric, patchy infiltrates 1 9

Areas of lung atelectasis (complete obstruction) flanked by irregular areas of overexpansion (partial obstruction) 14

Diffuse homogeneous ground-glass lung density (similar to that seen in respiratory distress syndrome)

Pneumothorax is common 19 20

Pleural effusion is present in 27% of cases

Echocardiogram

Not routine, but indicated in evaluation of infants with severe meconium aspiration syndrome or infants difficult to oxygenate; useful to
assess for persistent pulmonary hypertension and to exclude cyanotic congenital heart disease 4

Extrapulmonary shunting at the level of the ductus arteriosus and/or atria through a patent foramen ovale is evidence of significant
persistent pulmonary hypertension 4

Differential Diagnosis
Most common

Transient tachypnea of newborn


Caused by delayed clearance of fetal lung fluid and presents with tachypnea, respiratory
distress, and occasionally hypoxia, which gradually develop in the first few hours after birth;
symptoms resolve within 1 to 5 days after birth with minimal intervention 10

Most common after cesarean delivery and occurs in near-term, term, or late preterm infants
10

Chest radiography demonstrates perihilar streaking, patchy infiltrates, increased interstitial


markings, fluid in interlobar fissures, and wet silhouette around the heart 9

Can be initially difficult to differentiate from meconium aspiration syndrome or neonatal


pneumonia; absence of meconium-stained amniotic fluid in history and an overall benign
clinical course definitively differentiates from meconium aspiration syndrome

Infant respiratory distress syndrome Respiratory distress syndrome in neonates


(hyaline membrane disease) (Related: ) 10
Caused by surfactant deficiency and almost exclusively a disease of preterm infants; risk of
the disease increases with decreasing gestational age (5% of near-term infants, 30% of
infants at less than 30 weeks of gestation, and 60% of infants at less than 28 weeks of
gestation are affected)

Other risk factors include male sex in white populations, 19 perinatal asphyxia, family
history of the disease in a sibling, and cesarean delivery

Presents with worsening respiratory distress and hypoxia over hours beginning soon after
birth

Chest radiograph typically shows air bronchograms with a reticulogranular appearance or


ground-glass appearance of the lungs because of microatelectasis and poor expansion

Differentiated by history (preterm delivery with absence of meconium-stained amniotic


fluid), absence of hyperinflation on chest radiograph, and clinical course characterized by
significant improvement with surfactant administration

Pneumonia and sepsis (Related: ) Sepsis in neonates

Congenital pneumonia is a serious infection that frequently results in stillbirth or death in


the first 24 hours after birth; presents with signs of respiratory distress mimicking

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meconium aspiration syndrome in the first few hours after birth 10

Chest radiograph findings are variable depending on cause (eg, lobar consolidation or
bilateral consolidation); blood and tracheal aspirate cultures can isolate bacterial, fungal,
and viral causes 10

Congenital infections causing respiratory distress associated with chest radiograph findings
are very difficult to distinguish from meconium aspiration syndrome; as a result, many
infants in whom meconium aspiration syndrome is eventually diagnosed are started on
antibiotics pending culture results in an effort to exclude infectious processes

Early-onset neonatal sepsis with pneumonia (within the first 7 days after birth) most often
presents with systemic disease (eg, temperature instability, respiratory distress, apnea,
jaundice, lethargy) after a relatively benign immediate postnatal course; mothers may have
risk factors for early-onset sepsis 10

Symptoms usually take hours to days to develop and are not immediately apparent (as they
usually would be in meconium aspiration syndrome) 9

Differentiate from meconium aspiration syndrome by history, clinical course (characterized


by absence of symptoms immediately after birth and improvement with antibiotic
treatment), and positive blood culture results or tracheal aspirates

Delayed transition from fetal circulation


Rapid transition from fetal life to neonatal life is a complex adaption process involving rapid
pulmonary changes (eg, clearance of lung fluid, surfactant secretion, decrease in pulmonary
vascular resistance, increase in pulmonary blood flow), cardiovascular changes (transition
from fetal to neonatal cardiovascular circulation), endocrine changes, and central nervous
system changes that support this transition 21

Infants with delayed transition from fetal circulation present with hypoxia, poor respiratory
drive, and low cardiac output

Differentiated clinically from meconium aspiration syndrome predominantly by clinical


course, as symptoms self-resolve within the first few hours of life with supportive measures 9

Persistent pulmonary hypertension of


newborn Persistent unsuccessful transition to extrauterine life characterized by sustained
suprasystemic pulmonary artery pressures (without the normal drop in pulmonary vascular
resistance and increased pulmonary blood flow that normally occurs at birth) and thickened
labile pulmonary vasculature (predisposed to vasoconstriction)

Primary type is more common in neonates born at 34 or more weeks of gestation whose
mothers took NSAIDs or selective serotonin reuptake inhibitors 23 24 in the perinatal
period; secondary type can result from a variety of causes such as meconium aspiration
syndrome, respiratory distress syndrome, pneumonia and sepsis, other primary pulmonary
disorders of infancy, and pulmonary hypoplasia (eg, congenital diaphragmatic hernia,
oligohydramnios resulting from renal anomalies or premature rupture of membranes) 22

Primary type presents with hypoxemia and respiratory distress shortly after birth in the
absence of other recognizable parenchymal lung disease 22

Typically, infants with this condition have episodic labile periods of hypoxemia; tricuspid
regurgitation and a prominent second heart sound may be evident on examination 22

Differentiate from meconium aspiration syndrome with history, physical examination, and
imaging (a normal chest radiograph, and echocardiogram shows right-to-left
extrapulmonary shunting of blood across a patent foramen ovale or patent ductus arteriosus)
22

Cyanotic congenital heart disease


Usually presents with the acute onset of cyanosis around the time of ductal closure in the
neonatal period, usually 2 to 3 days after birth 25

In contrast with meconium aspiration syndrome, most neonates with cyanotic congenital
heart disease present with relatively comfortable tachypnea (without retractions) and cardiac
murmurs

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In contrast with meconium aspiration syndrome, typically infants with cyanotic congenital
heart disease exhibit minimal response to supplemental oxygen administration and do not
have elevated PCO₂ levels; chest radiograph shows an abnormal cardiac silhouette or
cardiomegaly, with relatively normal lung fields

Differentiate from meconium aspiration syndrome by history, physical examination, chest


radiograph, lack of significant improvement in cyanosis with oxygen, and improvement with
alprostadil (prostaglandin E₁) treatment

Definitive diagnosis is made by echocardiography

Treatment
Goals
Immediate delivery room goal is standard neonatal resuscitation 2

Supportive care once meconium aspiration syndrome has developed 1

Maintain adequate oxygenation

Assist and improve ventilation

Monitor for the development of metabolic abnormalities and maintain metabolic homeostasis

Disposition
Admission criteria
For infants born through meconium-stained amniotic fluid who do not exhibit respiratory distress: admit to hospital and monitor for 24 hours to
ensure that infant is healthy 1

Criteria for ICU admission


For all infants at risk for meconium aspiration syndrome who have signs of respiratory distress: admit to neonatal ICU 1

Recommendations for specialist referral


Consult neonatal rapid response team trained in advanced neonatal life support before delivery of any infant at risk for meconium aspiration
syndrome; team helps with preparation and delivery room management 26

Consult neonatologist for all infants with meconium aspiration syndrome; all such infants are managed by a neonatal ICU team

Treatment Options
Avoid intrapartum suctioning of the infant’s airway at the perineum during delivery 27

Potential harm of routine intrapartum suctioning outweighs benefits (eg, delayed resuscitation efforts, trauma to oropharynx, reflux vagal
apnea and bradycardia) 14 28

Immediate delivery room management depends on infant’s status at birth and follows standard neonatal resuscitation guidelines 2

Vigorous infants 29

Place infant under warmer: dry, position, and stimulate 18

Observe infant closely for 12 hours for any signs of respiratory distress 18 (examinations at 1 and 2 hours after delivery, then every 2 hours
8 )

Depressed infants (eg, diminished respiratory effort, poor muscle tone, or heart rate less than 100 beats per minute) 1

2015 American Heart Association/American Academy of Pediatrics guidelines do not recommend routine intubation for direct tracheal
suctioning for depressed infants 2 14 30 31

Immediately place infant under warmer; dry, position, and stimulate infant, then apply positive pressure ventilation with bag-valve mask
if infant is unresponsive to initial maneuvers, with heart rate under 100 beats per minute or lack of respiratory effort

Begin resuscitation with room air and introduce oxygen based on failure to achieve clinical response (eg, increase in heart rate); titrate
oxygen administration with pulse oximetry 30 31 32

If intubation is required because of sustained apnea, bradycardia, or poor respiratory effort despite bag-valve mask resuscitation, then
intubate and suction airway if obstructed using suction catheter fed through endotracheal tube 14 32

Management for meconium aspiration syndrome

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General supportive care to maintain metabolic homeostasis 1

Maintain body temperature

Minimize infant stimulation

Maintain adequate oxygenation and ventilation while minimizing barotrauma

Maintain optimal blood pressure

Treat hypoglycemia

Correct acidosis and other metabolic disorders

Administer oxygen at first sign of respiratory distress or diminishing oxygen saturation 1

Some infants require only oxygen by hood

Endotracheal intubation with conventional assisted ventilation is indicated for neonates who develop moderate to severe meconium aspiration
syndrome 1

Nasal CPAP with a pressure of 5 to 8 cm H₂O is an alternate and controversial treatment for neonates with mild to moderate meconium
aspiration syndrome 6 33

Limited data suggest a reduction in need for mechanical ventilation with use of bubble nasal CPAP 34

No clear evidence for harm; opponents avoid use owing to potential increased risk for air trapping, air leaks, and infant discomfort
exacerbating pulmonary hypertension

Sedation and analgesia are often required to facilitate effective ventilation and optimal gas exchange 1

Pain and discomfort can precipitate worsening hypoxia and right-to-left shunting, especially in infants with concurrent pulmonary
hypertension 1

Transition to high-frequency ventilation for patients with refractory severe disease unresponsive to conventional ventilatory therapy or with
significant complications (eg, persistent pulmonary hypertension, air leak syndromes) 1

Surfactant therapy

Not considered routine standard of care but may be helpful in select neonates with predominantly parenchymal disease and severe
respiratory failure 3 14

Decreases severity of respiratory distress and progressive respiratory failure requiring extracorporeal membrane oxygenation 35

May be indicated for intubated infants requiring 40% to 50% 36 37 or higher oxygen levels

Conventional bolus dosing is typically used; surfactant lavage is an additional delivery method under investigation, but it is technically
demanding and complications are more common than with standard technique 6 38 39

Steroids

Routine administration is not recommended 14 40

May be beneficial for infants with severe meconium aspiration syndrome with lung edema, pulmonary vasoconstriction, and inflammation 1

Optimal dose and timing are not known 1

Antibiotics

Routine antibiotic administration is not recommended for infants who do not have other perinatal risk factors for infection or clear concerns
for pneumonia 1

In practice, however, it is often difficult to differentiate pneumonia from meconium aspiration syndrome given similar presentation and
that no definitive radiographic findings can reliably exclude pneumonia 14

Start antibiotics if infection is suspected or infant has perinatal risk factors for infection 14

Risk factors for early-onset sepsis include maternal chorioamnionitis, inadequate intrapartum group B streptococcus antibiotic prophylaxis,
prolonged rupture of membranes longer than 18 hours, and birth before 37 weeks of gestation 41

Discontinue antibiotics if blood culture and tracheal aspirate culture results are negative 14

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Nitric oxide 1

Inhaled nitric oxide functions as a local, selective pulmonary vasodilator

Use to treat hypoxic respiratory failure with persistent pulmonary hypertension

Use in combination with high-frequency ventilation for best response

Dose is 10 to 20 ppm 33

Extracorporeal membrane oxygenation is a final rescue therapy for neonates with severe refractory hypoxemia in whom other supportive
measures fail 1

For neonates who do not respond to conventional ventilation, consider early transfer to facility capable of extracorporeal membrane
oxygenation 14

Drug therapy
Sedation and analgesia 1

Opioids

Use to optimize gas exchange, facilitate patient-ventilator synchrony, blunt reflex stress catecholamine release, and improve pulmonary
vascular resistance in ventilated neonates

Fentanyl

Morphine

Neuromuscular blocking agents 1

Second line medications used along with opioids to decrease agitation and hypoxic episodes in ventilated neonates; improves
oxygenation, decreases oxygen consumption, and decreases number of accidental extubations

Use with caution, because these medications are associated with paradoxical ventilation-perfusion mismatch and increased risk of death

Pancuronium

Vecuronium

Surfactant

Administer by conventional bolus technique (standard of care) 42 or diluted bronchoalveolar lavage (investigational technique) 43 35 39

Bolus therapy

2 to 4 boluses over 15 to 30 seconds

Instillation into pharynx

Laryngeal mask

Brief tracheal catheterization (via side port adapter or 5F end-hole catheter inserted in proximal end of endotracheal tube)

Agents

Poractant (Curosurf)

Poractant Alfa (Porcine) Endotracheopulmonary instillation, suspension; Premature neonates: 2.5 mL/kg of birth weight
administered intratracheally; divided and administered in 2 aliquots within 15 h of diagnosis of RDS. Up to 2 subsequent doses of
1.25 mL/kg can be administered at 12-hour intervals if needed. The maximum recommended total dose (sum of all aliquots) is 5
mL/kg.

Calfactant (Infasurf)

Calfactant (Bovine) Endotracheopulmonary instillation, suspension; Neonates, including Premature Neonates: 3 mL/kg
(approximately 100 mg of phospholipids/kg of birth weight) intratracheally; divided and administered in 2 aliquots. Between the 2
aliquots, the infant should be repositioned on the alternate side while respiratory status is evaluated. After the initial dose, wait at
least 12 hours before re-dosing. Repeat doses of 3 mL/kg every 12 hours used in clinical trials for intubated neonates. Total dosage
has not exceeded 4 doses.

Beractant (Survanta)

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Beractant (Bovine) Endotracheopulmonary instillation, suspension; Premature Neonates: 4 mL/kg (100 mg phospholipids/kg of
birth weight) intratracheally. Divide dose in 4 equal aliquots; ventilate infant and allow infant to stabilize between aliquots. Give
each aliquot with the infant in a different position to ensure even distribution of the drug throughout the lungs. After initial dose, at
least 6 hours should elapse before repeating. Four 4 mL/kg (100 mg/kg doses) may be given in the first 48 hours of life; given no
more frequently than every 6 hours. When administered as a preventative, subsequent doses are only given if RDS is confirmed by
radiographic examination.

Antibiotics 6 18

Ampicillin

Ampicillin Sodium Solution for injection; Neonates 0 to 7 days weighing 2 kg or less: 50 mg/kg/dose IV/IM every 12 hours recommended
by AAP; 100 mg/kg/dose IV/IM every 12 hours also acceptable for presumed early-onset GBS sepsis. FDA-approved dosage is 50
mg/kg/dose IV/IM every 12 hours for neonates 34 weeks gestation or less and 50 mg/kg/dose IV/IM every 8 hours for neonates more
than 34 weeks gestation.

Ampicillin Sodium Solution for injection; Neonates 0 to 7 days weighing more than 2 kg: 50 mg/kg/dose IV/IM every 8 hours
recommended by AAP; 100 mg/kg/dose IV/IM every 12 hours also acceptable for presumed early-onset GBS sepsis. FDA-approved
dosage is 50 mg/kg/dose IV/IM every 12 hours for neonates 34 weeks gestation or less and 50 mg/kg/dose IV/IM every 8 hours for
neonates more than 34 weeks gestation.

Gentamicin

Gentamicin Sulfate Solution for injection; Neonates 0 to 7 days weighing less than 1.2 kg: 4 to 5 mg/kg/dose IV every 48 hours.

Gentamicin Sulfate Solution for injection; Neonates 0 to 7 days weighing 1.2 to 2 kg: 5 mg/kg/dose IV every 36 to 48 hours.

Gentamicin Sulfate Solution for injection; Neonates 0 to 7 days weighing more than 2 kg: 5 mg/kg/dose IV every 36 hours or 4
mg/kg/dose IV every 24 hours; consider 4 mg/kg/dose IV every 48 hours if also receiving indomethacin; consider 4 to 5 mg/kg/dose IV
every 36 hours for patients with HIE receiving hypothermia.

Nondrug and supportive care


Maintain thermoneutral body temperature between 36°C and 37°C with optimal thermal environment through radiant warming 1

Continuous cardiorespiratory monitoring for any infant with signs of respiratory distress or hypoxia (eg, cardiac monitor, pulse oximeter,
transcutaneous oxygen and carbon dioxide monitor, and/or end-tidal carbon dioxide monitor) 1

Infants with disease can have rapidly deteriorating status or develop acute life-threatening complications (eg, pneumothorax, pulmonary
hypertension)

Tension pneumothorax may require emergent pleural space decompression, especially in neonates requiring positive pressure ventilation

Minimize handling of infant 1

Infants develop right-to-left shunting with minimal agitation, exacerbating hypoxia and acidosis

Start IV hydration and hold enteral feedings until respiratory status is stable

Perform gastric decompression and suctioning if infant shows evidence of gastric distention, requires prolonged bag-valve mask ventilation, or
requires assisted ventilation 5

Place umbilical artery and venous lines in any infant requiring mechanical ventilation or frequent blood gas monitoring 1

Procedures
Endotracheal intubation with mechanical ventilation 44
General explanation

Procedure in which a tube is inserted into the trachea to maintain an open airway, assist with ventilation, and improve oxygenation

Ventilating infants with meconium aspiration syndrome is challenging; infants with severe meconium aspiration syndrome have complicated
pulmonary dynamics (eg, alternating areas of hyperinflation and atelectasis, other ventilation-perfusion imbalances with the presence of
persistent pulmonary hypertension, and varying degrees of airway obstruction and surfactant deficiency)

Goal of ventilation is to improve oxygenation while minimizing barotrauma

Sedatives and paralytics are sometimes required for effective ventilation in neonates, especially those with persistent pulmonary hypertension

Indication

Persistently depressed respiratory effort or heart rate lower than 100 beats per minute 1

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Apnea or recurrent significant apneic events 3

Significant respiratory acidosis with PaCO₂ greater than 60 mm Hg or pH less than 7.25 3

Supplemental oxygen over 0.7 fraction of inspired oxygen is needed to maintain oxygen saturation above 90% 3

Repeated sustained oxygen desaturations secondary to marked pulmonary hypertension 3

Circulatory compromise associated with poor systemic blood pressure and perfusion 33

Development of air leaks 14

Standard initial ventilation parameters 1

Use pulmonary flow graphics to optimize ventilator settings with the variable and changing pulmonary dynamics characteristic of meconium
aspiration syndrome

A balance between atelectasis and overdistension is the goal; persistent pulmonary hypertension of the newborn often complicates
management

Frequent monitoring is necessary to maintain goal oxygenation and ventilation parameters while minimizing barotrauma and risk for
complications (eg, pneumothorax)

Mode of ventilation

Synchronized intermittent mandatory ventilation is preferred initial mode in spontaneously ventilating patients 33

Trial of alternate modes may be required if autocycling occurs due to air leak or gas trapping occurs with resultant hyperinflation

Ventilator rate of 40 to 60 breaths per minute

Lower ventilator rates (30-39 breaths per minute) with longer inspiratory times (0.5-0.7 seconds) may be needed when persistent
meconium is recovered from endotracheal tube, indicating obstruction 3

Ventilator rate of fewer than 50 breaths per minute with longer expiratory time may be required with evidence of limited expiratory flow,
indicating air trapping 33

Peak inspiratory pressure preferably not exceeding 25 to 30 cm H₂O 33

Lower pressures often do not generate sufficient tidal volume (ie, 5-6 mL/kg) to recruit atelectatic alveoli 33

Avoid higher pressures owing to increased risk of air leak 3

Transition to high frequency ventilation is preferred when peak inspiratory pressure requirement is persistently above 30 cm H₂O 33

PEEP of 4 to 6 cm H₂O to avoid atelectasis

Decrease to 3 to 4 cm H₂O if air trapping occurs

High PEEP up to 10 cm H₂O may required to improve oxygenation or overcome atelectasis 33

PEEP requirement of more than 10 cm H₂O is high risk for pneumothorax and transition to high frequency ventilation is preferred 33

Expiratory time of 0.5 to 0.7 seconds

Increase expiratory time and decrease inspiratory time if air trapping occurs

Increase inspiratory time and decrease expiratory time if atelectasis is prominent

High-frequency oscillatory ventilation

Overall, about 20% to 30% of infants requiring intubation and ventilation require high-frequency oscillatory ventilation 33

Indications for high-frequency oscillatory ventilation include: 33

Ongoing hypoxemia and/or high FiO₂ despite optimal conventional ventilator settings

Persistent respiratory acidosis despite optimal conventional ventilator settings

Persistent pulmonary hypertension of the newborn requiring inhaled nitric oxide treatment

Severe complications from barotrauma or air trapping (eg, pneumothorax)

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Mean airway pressure

High initial mean airway pressure (up to 25 cm H₂O) is often required to recruit alveoli in infants with severe atelectasis 33

Wean to stabilize mean airway pressure at about 16 to 20 cm H₂O once oxygenation improves to avoid air trapping 33

Oscillatory frequency

Preferred setting is between 6 and 8 Hz 33

Sustained frequency higher than 10 to 15 Hz leads to worsening of air trapping 33

High-frequency jet ventilation 33

Combination of atelectasis and gas trapping may be better managed with high-frequency jet ventilation

Method can effectively manage some infants with lower overall mean airway pressure

Infants with intractable hypoxemia and/or respiratory acidosis unresponsive to high-frequency oscillatory ventilation may respond to low-
frequency (240-360 beats per minute) with a low conventional ventilator rate 33

Extracorporeal membrane oxygenation 18


General explanation

Cannulas are placed in 2 circulatory circuits (either venoarterial to support the heart and lungs or venovenous to support the lungs only)

Blood is pumped to an external membrane that functions as a lung by exchanging oxygen and carbon dioxide, then blood is returned into the
patient’s circulation

This procedure allows time for the pulmonary vasculature and parenchyma to recover while avoiding the high-pressure effects of mechanical
ventilation

Severe refractory meconium aspiration syndrome has up to 50% improved survival with use of rescue extracorporeal membrane oxygenation
(compared with treatment without extracorporeal membrane oxygenation) 18

Indication

Indicated for treatment of reversible severe respiratory failure and intractable hypoxemia (eg, infant respiratory distress syndrome, meconium
aspiration syndrome, congenital diaphragmatic hernia, persistent pulmonary hypertension of newborn, neonatal sepsis/pneumonia, severe
respiratory syncytial virus pneumonia) when disease is resistant to other conservative management

Oxygenation index (OI = mean airway pressure × FiO₂ × 100/PaO₂) persistently above 40 despite aggressive standard management is
indication for extracorporeal membrane oxygenation 33

Various regional criteria exist for neonatal eligibility for this procedure; in general, patient is eligible with:

Condition that is a reversible lung disease

No coexistent fatal congenital anomalies present

Gestational age older than 34 weeks 18

Weight more than 2 kg 18

Refractory hypoxemia, with 25 to 30 or higher oxygenation index that is unresponsive to other measures 18

Contraindications

Irreversible respiratory failure

Coexistent fatal congenital anomalies

Relative contraindications are gestational age fewer than 34 weeks or weight less than 2 kg 18

Comorbidities
Persistent pulmonary hypertension

Severe meconium aspiration syndrome is often associated with persistent pulmonary hypertension (primary or secondary) 1

Consider persistent pulmonary hypertension with inability to oxygenate; confirm with echocardiography findings of right-to-left
intracardiac shunting

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Concomitant persistent pulmonary hypertension of newborn may require additional management 1

Correct potentiating factors (eg, hypoglycemia, hypocalcemia, hypomagnesemia, polycythemia, hypothermia, pain) 33

Support systemic blood pressure to reduce right-to-left ductal shunt (eg, volume expansion, pressors) 33

Improve right ventricular function (eg, inotropes) 33

Begin selective pulmonary vasodilation (eg, nitric oxide) 33

Optimize ventilator type and settings

Conventional ventilator adjustments

Mild hyperventilation and higher fraction of inspired oxygen

Combination of high-frequency ventilation and nitric oxide therapy provides the greatest improvement in oxygenation in infants with
severe comorbid persistent pulmonary hypertension

Alternate experimental therapies available before rescue extracorporeal membrane oxygenation include:

Phosphodiesterase 5 inhibitors

Prostaglandins, such as epoprostenol (prostacyclin) or alprostadil (prostaglandin E₁)

Magnesium sulfate

Nitric oxide precursor L-arginine

Free radical scavengers, such as superoxide dismutase

Monitoring
Post–delivery room monitoring of infants born through meconium-stained amniotic fluid for the development of meconium aspiration
syndrome 15

Observe all infants clinically for 24 hours

Most infants who develop meconium aspiration syndrome are symptomatic within 15 minutes of birth

Closely observe infants born with low Apgar scores

Risk of developing meconium aspiration syndrome in neonates with 5-minute Apgar score of 9 or more is very low (approximately 0.3%)

Risk of developing meconium aspiration syndrome in neonates with 5-minute Apgar score of 8 or less is approximately 19%

Monitor blood gas levels and glucose level to gauge ventilator setting adjustments and correct metabolic abnormalities in mechanically
ventilated neonates with meconium aspiration syndrome

Oxygenation and ventilation goals

Target PaO₂ is 50 to 90 mm Hg (others recommend 60-100 mm Hg) 14

Acceptable pulse oximetry saturation is 90% to 95% (others recommend 94% to 98%) 6 14

Target PaCO₂ is 40 to 50 mm Hg 1

Metabolic goals

Target pH is 7.3 to 7.4 1

Normoglycemia

Core body temperature target is 36°C to 37°C 1

Monitor gentamicin levels in infants receiving gentamicin therapy for more than 48 hours

Details of monitoring vary by institution; a representative approach is to obtain initial trough and peak levels at steady state, generally
before the third or fourth dose

Monitor for changes in serum creatinine level and urine output for potential risk of toxicity 45

Complications and Prognosis


Complications
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Death

Mortality rate is less than 5% in newborns with meconium aspiration syndrome in developed countries 5

Mortality rate is up to 39% in newborns with meconium aspiration syndrome in developing and newly industrialized countries 46

Most deaths are related to hypoxic-ischemic encephalopathy; one quarter of deaths are attributed to pulmonary disease 33

Factors associated with increased mortality in neonates with meconium aspiration syndrome 47 :

5-minute Apgar score less than 3

Mechanical ventilation requirement during the first 48 hours after birth

Vasopressor requirement

Presence of major congenital anomaly

Use of cefotaxime

Respiratory insufficiency

30% to 50% of newborns with meconium aspiration syndrome require intubation and assisted ventilation; an additional 10% require CPAP
alone 4 5

Neonates requiring extracorporeal membrane oxygenation for meconium aspiration syndrome have high survival rates (93% or better) 4

Persistent pulmonary hypertension of newborn 18

Many infants with severe meconium aspiration syndrome have primary persistent pulmonary hypertension (because of chronic intrauterine
stress leading to thickening of pulmonary vessels) or develop secondary persistent pulmonary hypertension (from hypoxia, acidosis, and
metabolic stress–induced pulmonary vasoconstriction)

Persistent pulmonary hypertension of newborn is characterized by intracardiac right-to-left shunting through patent ductus arteriosus or
foramen ovale owing to pulmonary vasoconstriction; this leads to a vicious circle of worsening hypoxia, acidosis, and further
vasoconstriction

Meconium aspiration syndrome accounts for up to 66% of neonatal cases overall

Pulmonary air leaks (eg, pneumothorax, pneumomediastinum, pneumopericardium, pneumoperitoneum)

Air leaks develop in 15% to 20% of nonventilated neonates and 30% to 50% of neonates requiring intermittent positive pressure ventilation
18

Inhaled nitric oxide and high-frequency ventilation are alternative therapeutic approaches to minimize barotrauma

Infection

Infants with meconium aspiration syndrome are at increased risk of developing infection owing to compromised status 18

Presence of meconium increases the chance of positive culture result from amniotic fluid 3

Other less common complications in infants with severe meconium aspiration syndrome and birth asphyxia:

Disseminated intravascular coagulation 18

Seizures 15

Intracranial hemorrhage 15

Necrotizing enterocolitis 15

Prognosis
Short-term prognosis

Infants with mild to moderate respiratory distress because of meconium aspiration typically recover over a period of several days; infants
with severe meconium aspiration syndrome typically recover more slowly and experience more complications

Approximately 5% of infants with meconium aspiration syndrome experience persistent oxygen requirement at 28 days of life 47

Severity of disease is often closely related to degree of associated pulmonary hypertension 14

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Long-term prognosis

Most infants recover and have no long-term health effects

Pulmonary function

Meconium aspiration rarely results in serious permanent lung damage 1

Increased wheezing in infancy and asthma in childhood (up to 39% increased risk) 48 6

Neurodevelopmental outcome

Infants with severe meconium aspiration syndrome have increased risk of adverse neurodevelopmental outcome, especially given the
close association of perinatal hypoxia-ischemia with reflex passage of meconium in utero, fetal gasping, perinatal asphyxia, and
subsequent development of meconium aspiration syndrome 6

Risk is compounded in infants requiring therapies associated with intermittent hypoxia, hypercarbia, and cardiovascular compromise
leading to additional postnatal neurologic insult 6

Up to 21% of infants with meconium aspiration syndrome have a poor neurologic outcome (eg, cerebral palsy and global
neurodevelopmental delay) 14 49

Screening and Prevention


Screening
Screening tests
Universal screening for fetal distress is recommended; use intrapartum fetal monitoring to assess for early signs of hypoxia (risk factor for
meconium aspiration syndrome) 1

Continuous external electronic fetal heart rate monitoring (cardiotocography) 16

Baseline fetal heart rate less than 110 beats per minute over more than 5 minutes

Baseline variability less than 5 beats per minute over more than 30 minutes

4 or more late decelerations or 2 or more prolonged decelerations in a 1-hour period

Fetal scalp pH determination 1

7.2 or lower scalp pH 37

Fetal pulse oximetry 1 37

Low fetal arterial oxygen saturation data of less than 30% for at least 10 minutes

Prevention
Prevent postterm delivery

Elective induction of labor at 41 weeks reduces the risk of perinatal mortality from meconium aspiration syndrome 50 51

American College of Obstetricians and Gynecologists recommends consideration of elective induction between 41 to 42 weeks and
recommends induction after 42 weeks 14

Minimize exposure to intrauterine stress and hypoxia

Aggressively manage fetal distress with expedient delivery 1

Standard of care despite lack of evidence that electronic fetal heart rate monitoring or fetal blood gas level determination reduces risk of
neonatal morbidity or mortality

Use of transcervical amnioinfusion is controversial

Proposed method to diminish the risk of meconium aspiration syndrome by diluting meconium-stained amniotic fluid (reducing
mechanical obstruction of airways and risk of chemical pneumonitis) and cushioning the umbilical cord (reducing fetal acidemia) 1

Amnioinfusion carries risk (eg, umbilical cord prolapse, 18 umbilical cord infection, 18 prolonged labor, 18 uterine rupture, 8 amniotic
fluid embolus, 8 placental abruption 28 ) 18

American College of Obstetricians and Gynecologists recommends against the routine use of amnioinfusion 1

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Amnioinfusion improves perinatal outcome only in facilities with limited perinatal surveillance 52

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