Meconium Aspiration Syndrome (MAS)

What is Meconium Aspiration Syndrome (MAS)

Meconium aspiration syndrome is a lung problem that can occur if meconium is inhaled before it can be removed from the mouth and throat. Meconium is a thick, dark green, sticky substance that is found in the intestines of an unborn baby (fetus).

Meconium is passed during a baby’s first bowel movement. Usually this occurs after birth, but sometimes it occurs before birth or during labor.

Meconium that is passed before birth or during labor goes into the liquid that surrounds the fetus (amniotic fluid), where it may be breathed into the fetus’ lungs.

12 Interesting Facts of Meconium Aspiration Syndrome

1. Meconium aspiration syndrome is respiratory distress in the immediate neonatal period in infants born through meconium-stained amniotic fluid whose symptoms cannot otherwise be explained 
2. Infants at highest risk are postmature, have African or Asian ethnicity, are born through thick meconium-stained amniotic fluid, or have evidence of intrapartum fetal distress or hypoxia
3. Base diagnosis on presence of respiratory distress in infants born through meconium-stained amniotic fluid without alternative cause for respiratory distress but with suggestive chest radiograph findings
4. American Academy of Pediatrics/American Heart Association 2015 guidelines no longer recommend suctioning trachea before providing positive pressure ventilation in depressed infants. Immediate delivery room management of depressed infants includes warming, stimulating, drying, and initiating positive pressure ventilation before intubating, if required 
5. Treatment is supportive in a neonatal ICU. Individualized care includes resuscitation for depressed (nonvigorous) infants, oxygenation, ventilation, radiant warming, and minimal handling and stimulation 
6. Rescue therapies include surfactant replacement, steroid therapy, high-frequency ventilation, and extracorporeal membrane oxygenation in selected infants when other treatments fail
7. Often, antibiotics are started before blood and tracheal aspirate culture results are received in ill neonates, owing to difficulty differentiating infectious causes of respiratory distress and isolated meconium aspiration syndrome in the immediate neonatal period; discontinue antibiotics if culture results are negative 
8. Infants with comorbid primary or secondary persistent pulmonary hypertension are difficult to oxygenate and sometimes require additional specialized management (eg, nitric oxide and high-frequency ventilation, extracorporeal membrane oxygenation)
9. Complications include death, respiratory failure, ventilator-induced barotrauma (pneumothorax and other pulmonary air leaks), and development of pulmonary hypertension
10. Long-term complications include pulmonary sequelae (wheezing in infancy and asthma in childhood) and adverse neurodevelopmental outcomes
11. Mortality rate is less than 5% in developed countries 
12. Preventive induction and delivery of infants at or beyond 41 weeks of gestation reduces the risk of meconium aspiration syndrome

• Meconium aspiration syndrome is respiratory distress in the immediate neonatal period in an infant born through meconium-stained amniotic fluid with radiologic changes suggestive of this syndrome and whose symptoms cannot be otherwise explained 
• 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 

Classification

• Mild disease 
  • Requires less than 40% oxygen for up to 48 hours
• Moderate disease 
  • 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 
  • Often associated with concurrent persistent pulmonary hypertension 

What are the causes of Meconium Aspiration Syndrome

Causes

• Intrauterine passage of meconium results from fetal hypoxia and stress 
• Meconium aspiration syndrome is caused by fetal aspiration of meconium during intrauterine gasping triggered by fetal distress 
• Meconium causes variable degrees of pneumonitis, pulmonary vasoconstriction, surfactant inactivation, and mechanical obstruction of airways

What increases the risk?

A baby is more likely to develop this condition if:

• The baby is born on or after the due date (is term or overdue).
• The baby does not get enough oxygen, especially during labor (fetal distress).
• The mother has diabetes or high blood pressure (hypertension).
• Labor was long or difficult.
• The mother is African-American.

Age

• Rarely occurs in infants born before 34 weeks of gestation 

Ethnicity/race

• Risk is increased in:
  • Africans 
  • Black Americans of African descent 
  • South Asians 
  • Pacific Islanders 
  • Indigenous Australians 

Other risk factors/associations

• Meconium-stained amniotic fluid is present in 4% to 22% of all pregnancies 
  • Risk factors for passing meconium in utero
    • Increasing gestational age
      • 4% of deliveries before 37 weeks of gestation 
      • 10% to 20% of term deliveries 
      • 30% to 40% of post-term deliveries 
    • Increasing birth weight
      • Incidence up to 28% with birth weight more than 5 kg 
• Fetal hypoxia and stress
  • Excessive maternal drug use (particularly tobacco and cocaine)
  • Chorioamnionitis 
  • Oligohydramnios
  • Difficult or lengthy labor
  • Use of vaginal misoprostol to induce labor 
  • Maternal preeclampsia or hypertension
  • Maternal diabetes 
  • Placental insufficiency
  • Small for gestational age and intrauterine growth restriction 
• Meconium aspiration syndrome occurs in 3% to 12% of infants born through meconium-stained amniotic fluid 
  • Risk factors for severe meconium aspiration syndrome
    • Increased gestational age 
    • Thick meconium 
      • Thin meconium rarely results in meconium aspiration syndrome 
    • Low Apgar score
      • Neonates with 1-minute Apgar score of 3 or less are at very high risk 
      • Approximately 19% of neonates with 5-minute Apgar score of 8 or less develop meconium aspiration syndrome 
    • Birth at a level I or II facility 
    • Fetal acidosis 
    • Nonreassuring intrapartum fetal heart rate tracing patterns 
    • Cesarean delivery 
    • Aspiration of meconium to a level below the vocal cords 
    • Intubation requirement at birth 
    • Lack of prenatal care

What are the symptoms?

Symptoms of this condition in a newborn baby may include:

• Difficulty breathing. This usually lasts only a few days.
• Rapid breathing. This may last for several days, even after the baby is better.
• Grunting noise when breathing out.
• Sucking in of the spaces between the ribs when breathing in.
• Nostrils flaring open when breathing in.
• Blue skin color.
• Skin being stained with meconium.
• Limpness.

Clinical Presentation

History

• Term or near-term infant 
• Perinatal history 
  • Meconium-stained amniotic fluid
  • Post-term 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 
  • Bradycardia (heart rate lower 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; respiratory distress may develop up to 12 hours after birth, but such delay is unusual 
  • Tachypnea
  • Nasal flaring, grunting, and retractions
  • Pulmonary rales and rhonchi
  • Paradoxical abdominal breathing
  • Barrel chest
  • Inspiratory stridor
• Meconium staining on the infant 
  • Greenish to yellow staining of vernix, umbilical cord, and nails
• Findings such as unilateral diminished breath sounds suggest pneumothorax and crepitus suggests pneumomediastinum

How is this diagnosed?

This condition may be diagnosed based on:

• The labor and delivery.
• A physical exam.
• A chest X-ray.
• Blood tests.

• Diagnosis is based on presence of respiratory distress in infants born through meconium-stained amniotic fluid without alternative cause for respiratory distress 
• Chest radiograph findings consistent with meconium aspiration syndrome support the diagnosis 
  • Some centers also use bedside thoracic ultrasonography to establish diagnosis 
• 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 or definitive standard of care has been established) 
• In infants with severe hypoxia, echocardiography is sometimes used to assess for concurrent persistent pulmonary hypertension

• 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, CBC often shows elevated WBC count with neutropenia in neonates with meconium aspiration syndrome 
    • Thrombocytopenia is often noted with persistent pulmonary hypertension and severe asphyxia-associated disseminated intravascular coagulation 
    • 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, renal panel with electrolyte levels may show hyponatremia with inappropriate antidiuretic hormone secretion secondary to asphyxia 
    • Hyperkalemia and elevated BUN and creatinine levels are apparent with concurrent renal damage secondary to acute tubular necrosis 
  • 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 for diagnosis

• Chest radiograph
  • Radiographic findings are nonspecific and differ among individual neonates with disease 
  • Severity of radiographic findings does not always correlate with clinical disease severity 
  • Characteristic radiographic findings consistent with meconium aspiration syndrome include:
    • Hyperexpansion of lungs with flat diaphragms and widened rib spaces 
    • Widespread, coarse, asymmetrical, patchy infiltrates 
    • Areas of lung atelectasis (complete obstruction) flanked by irregular areas of overexpansion (partial obstruction) 
    • Diffuse homogeneous ground-glass lung density (similar to that seen in respiratory distress syndrome)
    • Pneumothorax is common 
    • Pleural effusion is present in 27% of cases
• Echocardiography
  • Not routine, but indicated in evaluation of neonates with severe meconium aspiration syndrome or neonates who are difficult to oxygenate; useful to assess for persistent pulmonary hypertension and to exclude cyanotic congenital heart disease 
  • Extrapulmonary shunting at the level of the ductus arteriosus and/or atria through a patent foramen ovale is evidence of significant persistent pulmonary hypertension

How is this treated?

Your baby may be kept in the neonatal intensive care unit (NICU). Treatment may include:

• Maintaining body temperature with a warmer.
• Oxygen therapy and monitoring for oxygen levels.
• Breathing assistance through a tube that goes into the nostrils (nasal cannula), a face mask (CPAP), or breathing machine (ventilator).
• A treatment that uses a machine to add oxygen to the blood outside of the body (extracorporeal membrane oxygenation, ECMO). ECMO is used in very severe cases when a ventilator has not worked.
• IV fluids to provide your baby with nutrition. This is needed because your baby will not be able to eat until breathing problems improve.
• Antibiotic medicines. Early in the care of your baby, it may be hard to know if your baby has an infection, meconium aspiration syndrome, or both. Antibiotics may be given until your baby’s health care provider is sure that your baby does not have an infection.
• A medicine that helps keep the small air sacs in the lungs from collapsing (surfactant).

Follow these instructions at home:

Medicines

• Give over-the-counter and prescription medicines only as told by your baby’s health care provider. This includes medicines for pain, fever, or discomfort.
• If your child was prescribed an antibiotic medicine, give it to him or her as told by the health care provider. Do not stop giving the antibiotic even if he or she starts to feel better.
• Do not give your baby aspirin because of the association with Reye syndrome.

General instructions

• Follow recommendations from your baby’s health care provider about which immunizations your child needs (immunization schedule).
• Feed your baby as directed by your health care provider.
• Ask your baby’s health care provider if your baby should have his or her hearing monitored. Severe meconium aspiration has been associated with hearing loss.
• If your baby is sent home with oxygen or breathing treatments, follow the health care provider’s recommendations for these treatments. Your baby may need these treatments for the first one or two years of life.
• Monitor your baby closely for signs of illness. Even a mild illness can be more difficult for babies who have had meconium aspiration syndrome.
• Keep all follow-up visits as told by your baby’s health care provider. This is important, especially if your baby needs hearing monitoring.

Contact a health care provider if:

• Your baby has a cough.
• Your baby is not feeding well.

Get help right away if:

• Your child who is younger than 3 months has a fever.
• Your child who is older than 3 months has a fever and symptoms that suddenly get worse or do not go away.
• Your baby has trouble breathing. Signs of trouble breathing include:
  • Rapid or noisy breathing.
  • Grunting noise when breathing out.
  • Sucking in of the spaces between the ribs when breathing in.
  • Nostrils flaring open when breathing in.
• Your baby is not easy to wake up.
• Your baby’s lips or fingers and toes appear blue.

Differential Diagnosis

Most common

• Transient tachypnea of newborn
• Infant respiratory distress syndrome
• Pneumonia and sepsis
• Delayed transition from fetal circulation
• Persistent pulmonary hypertension of newborn
• Cyanotic congenital heart disease

Treatment Goals

• Immediate delivery room goal is standard neonatal resuscitation 
• Supportive care once meconium aspiration syndrome has developed 
  • Maintain adequate oxygenation
  • Assist and improve ventilation
  • Monitor for development of metabolic abnormalities and maintain metabolic homeostasis

Admission criteria

For neonates 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 

Criteria for ICU admission

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

Recommendations for specialist referral

• Consult neonatal rapid response team trained in advanced neonatal life support before delivering any infant at risk for meconium aspiration syndrome; team helps with preparation and delivery room management
  • Every birth should be attended by at least 1 person who can perform the initial steps of newborn resuscitation and initiate positive pressure ventilation, and whose only responsibility is the care of the newborn 
• 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 infant’s airway at the perineum during delivery 

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

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

• Vigorous infants 
  • Place infant under warmer: dry, position, and stimulate 
  • Observe infant closely for 12 hours for any signs of respiratory distress (examine at 1 and 2 hours after delivery, then every 2 hours)
• Depressed infants (diminished respiratory effort, poor muscle tone, or heart rate lower than 100 beats per minute) 
  • Routine endotracheal suctioning is not recommended for depressed infants with meconium-stained amniotic fluid because it does not prevent meconium aspiration syndrome and the procedure may be harmful 
  • Immediately place infant under warmer
    • Dry, position, and stimulate infant
    • If infant is unresponsive to initial maneuvers, with heart rate less than 100 beats per minute or lack of respiratory effort: apply positive pressure ventilation with bag-valve mask
  • Initiate resuscitation with 21% oxygen in neonates born at 35 weeks of gestation or later; do not start with 100% oxygen as this is associated with increased mortality 
    • In neonates born at less than 35 weeks of gestation, it is reasonable to initiate resuscitation with 21% to 30% oxygen 
  • Adjust oxygen concentration based on clinical response (eg, increase in heart rate, oxygen saturation) 
  • Consider CPAP trial if breathing remains labored or oxygen saturation cannot be maintained within target range despite 100% free-flow oxygen 
  • Positive pressure ventilation
    • Indicated if neonate is apneic or gasping or if heart rate is lower than 100 beats per minute 
    • Can be considered if oxygen saturation cannot be maintained within target range despite free-flow oxygen or CPAP
  • If intubation is required owing to 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 

Management for meconium aspiration syndrome

• General supportive care to maintain metabolic homeostasis 
  • 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 
  • Some neonates only require oxygen hood for oxygen delivery
• Endotracheal intubation with conventional assisted ventilation is indicated for neonates who develop moderate to severe meconium aspiration syndrome 
  • Nasal CPAP with a pressure of 5 to 8 cm H₂O is an alternative and controversial treatment for neonates with mild to moderate meconium aspiration syndrome 
    • Limited data suggest reduced need for mechanical ventilation with use of bubble CPAP with nasal delivery 
    • No clear evidence for harm; opponents avoid use because there is 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 
    • Pain and discomfort can precipitate worsening hypoxia and right to left shunting, especially in infants with concurrent pulmonary hypertension 
  • Transition to high-frequency ventilation for patients with severe refractory disease unresponsive to conventional ventilatory therapy or with significant complications (eg, persistent pulmonary hypertension, air leak syndromes) 
• Surfactant therapy
  • Not considered routine standard of care but may be helpful in select neonates with predominantly parenchymal disease and severe respiratory failure 
  • Decreases severity of respiratory distress and progressive respiratory failure requiring extracorporeal membrane oxygenation 
  • May be indicated for intubated infants who require 40% to 50% 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 
• Nitric oxide 
  • 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 
• Antibiotics
  • Routine antibiotic administration is not recommended for infants who do not have other perinatal risk factors for infection or clear concerns for pneumonia 
    • In practice it is often difficult to differentiate pneumonia from meconium aspiration syndrome given that they have similar presentation and that no definitive radiographic findings can reliably exclude pneumonia 
  • Start antibiotics if infection is suspected or infant has perinatal risk factors for infection 
  • Risk factors for early-onset sepsis include maternal colonization with group B streptococcus, inadequate intrapartum group B streptococcus antibiotic prophylaxis, prolonged rupture of membranes, birth before 37 weeks of gestation, intra-amniotic infection, young maternal age, and Black maternal race 
  • Discontinue antibiotics if blood culture and tracheal aspirate culture results are negative 
• Steroids
  • Routine administration is not recommended 
  • May be beneficial for infants who have severe meconium aspiration syndrome with lung edema, pulmonary vasoconstriction, and inflammation 
  • Optimal dose and timing are not known 
• Extracorporeal membrane oxygenation is a final rescue therapy for neonates with severe refractory hypoxemia in whom other supportive measures have failed 
  • For neonates who do not respond to conventional ventilation, consider early transfer to a facility capable of extracorporeal membrane oxygenation 

Drug therapy

• Sedation and analgesia 
  • 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 
    • Second line medications used along with opioids to decrease agitation and hypoxic episodes in ventilated neonates; improve oxygenation, decrease oxygen consumption, and decrease 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) or diluted bronchoalveolar lavage (investigational technique) 
    • Bolus therapy
      • 2 to 4 boluses over 15 to 30 seconds
        • Instill 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; Premature and Term 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)
          • 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 prophylaxis, subsequent doses are only given if RDS is confirmed by radiographic examination.
• Antibiotics 
  • Ampicillin
    • Ampicillin Sodium Solution for injection; Neonates 34 weeks gestation and younger and 0 to 7 days: 50 mg/kg/dose IV/IM every 12 hours.
    • Ampicillin Sodium Solution for injection; Neonates older than 34 weeks gestation: 50 mg/kg/dose IV/IM every 8 hours.
  • Gentamicin (conventional dosing)
    • Gentamicin Sulfate Solution for injection; Neonates 0 to 7 days weighing less than 1.2 kg: 2.5 mg/kg/dose IV/IM every 18 to 24 hours. FDA-approved dosage is 2.5 mg/kg/dose IV/IM every 12 hours.
    • Gentamicin Sulfate Solution for injection; Neonates 0 to 7 days weighing 1.2 to 2 kg: 2.5 mg/kg/dose IV/IM every 12 to 18 hours.
    • Gentamicin Sulfate Solution for injection; Neonates 0 to 7 days weighing more than 2 kg: 2.5 mg/kg/dose IV/IM every 12 hours; extend interval to 18 to 24 hours for neonates on ECMO. Individualize subsequent dosing based on serum concentrations. Dosage adjustment needed after decannulation.

Nondrug and supportive care

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

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

• 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 

• 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 

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

Procedures

Endotracheal intubation with mechanical ventilation 

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 who have 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 
• Apnea or recurrent significant apneic events 
• Significant respiratory acidosis with PaCO₂ greater than 60 mm Hg or pH less than 7.25 
• Supplemental oxygen over 0.7 fraction of inspired oxygen is needed to maintain oxygen saturation above 90% 
• Repeated sustained oxygen desaturations secondary to marked pulmonary hypertension 
• Circulatory compromise associated with poor systemic blood pressure and perfusion 
• Development of air leaks 

Standard initial ventilation parameters 

• Use pulmonary flow graphics to optimize ventilator settings with the variable and changing pulmonary dynamics characteristic of meconium aspiration syndrome
  • Goal is to reach a balance between atelectasis and overdistention; persistent pulmonary hypertension of the neonate 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 
  • Trial of alternate modes may be required in case of autocycling due to air leak or gas trapping 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 
  • 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 
• Peak inspiratory pressure preferably not exceeding 25 to 30 cm H₂O 
  • Lower pressures often do not generate sufficient tidal volume (ie, 5-6 mL/kg) to recruit atelectatic alveoli 
  • Avoid higher pressures owing to increased risk of air leak 
  • Transition to high frequency ventilation is preferred when peak inspiratory pressure requirement is persistently above 30 cm H₂O 
• 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 be required to improve oxygenation or overcome atelectasis 
  • PEEP requirement of more than 10 cm H₂O is high risk for pneumothorax and transition to high frequency ventilation is preferred 
• Expiratory time of 0.5 to 0.7 seconds
  • If air trapping occurs: increase expiratory time and decrease inspiratory time
  • If atelectasis is prominent: increase inspiratory time and decrease expiratory time

High-frequency oscillatory ventilation

• Overall, about 20% to 30% of infants who require intubation and ventilation also require high-frequency oscillatory ventilation 
• Indications for high-frequency oscillatory ventilation include: 
  • Ongoing hypoxemia and/or high FiO₂ despite optimal conventional ventilator settings
  • Persistent respiratory acidosis despite optimal conventional ventilator settings
  • Persistent pulmonary hypertension requiring inhaled nitric oxide treatment
  • Severe complications from barotrauma or air trapping (eg, pneumothorax)
• Mean airway pressure
  • High initial mean airway pressure (up to 25 cm H₂O) is often required to recruit alveoli in infants with severe atelectasis 
  • Wean to stabilize mean airway pressure at about 16 to 20 cm H₂O once oxygenation improves to avoid air trapping 
• Oscillatory frequency
  • Preferred setting is between 6 and 8 Hz 
  • Sustained frequency higher than 10 to 15 Hz leads to worsening of air trapping 

High-frequency jet ventilation 

• 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 

Extracorporeal membrane oxygenation 

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 pulmonary vasculature and parenchyma to recover while avoiding 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) 

Indication

• Indicated to treat 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 an indication for extracorporeal membrane oxygenation 
• 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 
  • Weight more than 2 kg 
  • Refractory hypoxemia, with 25 to 30 or higher oxygenation index that is unresponsive to other measures 

Contraindications

• Irreversible respiratory failure
• Coexistent fatal congenital anomalies
• Relative contraindications are gestational age less than 34 weeks or weight less than 2 kg 

Comorbidities

• Persistent pulmonary hypertension
  • Severe meconium aspiration syndrome is often associated with persistent pulmonary hypertension (primary or secondary) 
  • Consider persistent pulmonary hypertension with inability to oxygenate; confirm with echocardiography findings of right to left intracardiac shunting
  • Concomitant persistent pulmonary hypertension of newborn may require additional management 
    • Correct potentiating factors (eg, hypoglycemia, hypocalcemia, hypomagnesemia, polycythemia, hypothermia, pain) 
    • Support systemic blood pressure to reduce right to left ductal shunt (eg, volume expansion, pressors) 
    • Improve right ventricular function (eg, inotropes) 
    • Begin selective pulmonary vasodilation (eg, nitric oxide) 
    • 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 (eg, epoprostenol [prostacyclin], alprostadil [prostaglandin E₁])
      • Magnesium sulfate
      • Nitric oxide precursor L-arginine
      • Free radical scavengers (eg, superoxide dismutase)

Monitoring

• Post–delivery room monitoring of infants born through meconium-stained amniotic fluid for development of meconium aspiration syndrome 
  • 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
    • Neonates with 5-minute Apgar score of 9 or more: risk of developing meconium aspiration syndrome is very low (approximately 0.3%)
    • Neonates with 5-minute Apgar score of 8 or less: risk of developing meconium aspiration syndrome is approximately 19%
• Monitor blood gas and glucose levels 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) 
    • Acceptable pulse oximetry saturation is 90% to 95% (others recommend 94%-98%) 
    • Target PaCO₂ is 40 to 50 mm Hg 
  • Metabolic goals
    • Target pH is 7.3 to 7.4 
    • Normoglycemia
    • Target core body temperature is 36 °C to 37 °C 
• Monitor gentamicin levels in infants receiving gentamicin therapy for more than 48 hours
  • Monitoring details 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 

Complications and Prognosis

Complications

• Death
  • Mortality rate is less than 5% in developed countries 
  • Mortality rate is up to 39% in developing and newly industrialized countries 
  • Most deaths are related to hypoxic-ischemic encephalopathy; a quarter of deaths are attributed to pulmonary disease
  • Factors associated with increased mortality: 
    • 5-minute Apgar score less than 3
    • Mechanical ventilation required during first 48 hours of life
    • 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 
  • Neonates requiring extracorporeal membrane oxygenation for meconium aspiration syndrome have high survival rates (93% or better)
• Persistent pulmonary hypertension of newborn 
  • Many infants with severe meconium aspiration syndrome have primary persistent pulmonary hypertension due to chronic intrauterine stress leading to thickening of pulmonary vessels, or they develop secondary persistent pulmonary hypertension due to 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 due to pulmonary vasoconstriction; this leads to a cycle 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 
  • Inhaled nitric oxide and high-frequency ventilation are alternative therapeutic approaches to minimize barotrauma
• Infection
  • Infants are at increased risk of developing infection owing to compromised status 
  • Presence of meconium increases chance of positive culture result from amniotic fluid 
• Less common complications in infants with severe meconium aspiration syndrome and birth asphyxia:
  • Disseminated intravascular coagulation 
  • Seizures 
  • Intracranial hemorrhage 
  • Necrotizing enterocolitis 

Prognosis

• Short-term prognosis
  • Neonates with mild to moderate respiratory distress from this syndrome typically recover over several days; those 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 age 28 days 
  • Severity of disease is often closely related to degree of associated pulmonary hypertension 
• Long-term prognosis
  • Most infants recover and have no long-term health effects
  • Pulmonary function
    • Meconium aspiration rarely results in serious permanent lung damage 
    • May lead to increased wheezing in infancy and asthma in childhood (up to 39% increased risk) 
  • 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 
    • Risk is compounded in infants requiring therapies associated with intermittent hypoxia, hypercarbia, and cardiovascular compromise leading to additional postnatal neurologic insult 
    • Up to 21% of infants with meconium aspiration syndrome have a poor neurologic outcome (eg, cerebral palsy, global neurodevelopmental delay) 

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) 
  • Continuous external electronic fetal heart rate monitoring (cardiotocography) 
    • 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 
    • 7.2 or lower scalp pH 
  • Fetal pulse oximetry 
    • Low fetal arterial oxygen saturation data of less than 30% for at least 10 minutes

Prevention

• Prevent post-term delivery
  • Elective labor induction at 41 weeks of gestation reduces risk of perinatal mortality from meconium aspiration syndrome 
  • American College of Obstetricians and Gynecologists recommends considering elective induction between 41 to 42 weeks of gestation and recommends induction after 42 weeks 
• Minimize exposure to intrauterine stress and hypoxia
  • Aggressively manage fetal distress with expedient delivery 
    • Standard of care despite absence 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 risk by diluting meconium-stained amniotic fluid (reducing mechanical obstruction of airways and risk of chemical pneumonitis) and cushioning the umbilical cord (reducing fetal acidemia) 
    • Amnioinfusion carries risk (eg, umbilical cord prolapse, umbilical cord infection, prolonged labor, uterine rupture, amniotic fluid embolus, placental abruption ) 
    • American College of Obstetricians and Gynecologists recommends against routine use of amnioinfusion 
    • Amnioinfusion improves perinatal outcome only in facilities with limited perinatal surveillance

Summary

• Meconium is another word for a baby’s first bowel movement. When meconium occurs before birth, the baby can breathe in the meconium, which causes irritation and other problems in the lungs after birth. This is called meconium aspiration syndrome.
• Meconium aspiration syndrome is treated by supporting your baby’s breathing. This may require breathing assistance, as well as oxygen, medicines, or a combination of these.