What are the assessment findings of a patient has meconium aspiration syndrome?

KEY FACTS

Meconium Aspiration Syndrome

MAS is diagnosed by the presence of meconium below the level of the vocal cords at birth. Infants with MAS are usually post-mature, or have experienced intrauterine stress. The thick, tenacious meconium causes obstruction of small- and medium-sized airways, which leads to areas of both atelectasis and overinflation. The meconium can cause a chemical pneumonitis and also inactivates surfactant within lung alveoli. Chest radiographs in infants with MAS reveal coarsened interstitial densities and bilateral parenchymal opacities interspersed with areas of hyperaeration (Fig. 6-7). MAS is the most common respiratory disease to cause a pleural effusion in the first few days of life.

Meconium Aspiration Syndrome

MAS is associated with inhalation of meconium and amniotic fluid during fetal life or at delivery and is often complicated by significant pulmonary hypertension. It is among the most common causes of hypoxemic respiratory failure in term newborns who require intensive care (Fig. 47.1). The incidence of MAS in babies born after 37 weeks' gestation ranges from 0.4% to 1.8% (Dargaville and Copnell, 2006; Singh et al., 2009), and a study suggests that the rate of MAS may have been declining in recent years (Vivian-Taylor et al., 2011). Among babies born after 39 weeks' gestation with lung disease requiring mechanical ventilation, more than half have MAS (Gouyon et al., 2007). Moreover, MAS is the primary diagnosis for a significant proportion of those newborns who require extracorporeal membrane oxygenation (ECMO) in the United States (26%) and the United Kingdom (51%) (Brown et al., 2010).

Although a significant percentage of term births are complicated by the passage of meconium before or at delivery, less than 10% of those exposed to meconium develop MAS. Among that 10%, fetal acidemia is believed to cause increased intestinal peristaltic activity that results in passage of meconium and fetal gasping, which draws meconium-contaminated amniotic fluid deep into the lungs. Supporting this theory, autopsy studies of babies who died of MAS demonstrate distal muscularization of small pulmonary arterioles, suggesting long-standing hypoxemia (Murphy et al., 1984). Recent work suggests that activation of inflammatory cascades may worsen the severity of MAS (Lindenskov et al., 2015; Lee et al., 2016). Particulate meconium in the distal airways causes check-valve obstruction of air passages and leads to regional hyperinflation and atelectasis. In addition, meconium inactivates surfactant, leading to secondary surfactant deficiency (Moses et al., 1991). Moreover, babies with MAS are at high risk of persistent pulmonary hypertension, which significantly increases their morbidity and complicates their management.

Historically, prevention of MAS has focused on decreasing exposure of the fetal and newborn lung to the noxious effects of intrapulmonary meconium-contaminated amniotic fluid. Infusion of saline into the amniotic cavity (i.e., amnioinfusion) during labor has been studied as a means of both diluting meconium and relieving pressure on the umbilical cord, a potential cause of fetal acidemia. In the largest trial investigating this practice, Fraser et al. (2005) found no reduction in the risk of MAS. An alternative strategy for decreasing lung exposure to meconium is intrapartum oropharyngeal and nasopharyngeal suction of fetuses born through meconium-stained amniotic fluid. Although this practice was widely adopted in the 1970s, more recent studies have failed to demonstrated benefit (Vain et al., 2004), and the practice is no longer endorsed by the American College of Obstetricians and Gynecologists (Committee on Obstetric Practice, American College of Obstetricians and Gynecologists, 2007). Moreover, the current American Academy of Pediatrics/American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care of the neonate no longer recommend intubation and tracheal suctioning for nonvigorous newborns born through meconium-stained amniotic fluid (Wycoff et al., 2015).

The clinical signs of MAS differ widely among babies and may relate to the degree of prenatal compromise, the timing, volume, and consistency of aspirated meconium, and the presence of associated problems. Clinical signs of MAS typically present immediately after birth with tachypnea, increased work of breathing, and cyanosis. Other common associated findings include metabolic acidosis, cardiac dysfunction and hypotension, and postductal desaturation indicative of right-to-left shunting of blood at the ductus arteriosus caused by pulmonary hypertension. Because of the potential for ball-valve obstruction of small airways and failure to empty distal lung segments, pneumothorax can complicate the clinical picture. In recent series, the risk of pneumothorax among ventilated babies with MAS ranged between 10% and 24% (Dargaville and Copnell, 2006; Velaphi and Van Kwawegen, 2008). Like the degree of clinical signs, CXR findings differ widely. The classic CXR shows diffuse, fluffy infiltrates. However, some babies have milder initial radiographic findings, and there is often progression of visible parenchymal disease over time, likely related to secondary surfactant dysfunction.

Approximately half of babies with MAS require mechanical ventilation. The ventilator strategy should be individualized to each baby and to the disease evident on the CXR. In general, because of the likelihood of increased airway resistance, a conventional strategy using slower rates with long inspiratory and expiratory times allows better gas dispersion and more adequate emptying during expiration. Gas trapping and regional or generalized hyperinflation can occur, particularly when rapid rates are used with a conventional mode of ventilation. Some babies respond better to ventilation with a high-frequency device, although there is also a high risk of hyperinflation. When severe, hyperinflation causes impaired gas exchange and hypercarbia, limits systemic venous return (adversely affecting cardiac performance), increases the risk of pneumothorax, and may exacerbate pulmonary hypertension. Surfactant lung lavage has demonstrated some promise in improving lung function in animal models of MAS (Dargaville et al., 2003), but a small clinical trial of this practice demonstrated no benefit (Gadzinowski et al., 2008). However, conventional surfactant administration in infants with MAS may reduce the severity of illness and decrease the need for treatment with ECMO (El Shahed, 2014). In addition to management of parenchymal lung disease in MAS, special consideration must be given to other associated problems, particularly pulmonary hypertension. The risk of PPHN is quite high, exceeding 50% in some series. It has been demonstrated that iNO treatment increases oxygenation in MAS and is particularly efficacious when combined with a ventilator strategy that focuses on improving lung recruitment such as high-frequency oscillatory ventilation (Kinsella et al., 1997). Treatment with antibiotics with systemic effect should also be strongly considered in babies with PPHN for a number of reasons. These include the fact that intrauterine infection might be a precipitating factor in the initial passage of meconium and that in vitro studies suggest that the presence of meconium might facilitate the growth of bacteria in the lung.

In spite of the availability of iNO treatment and high-frequency modes of ventilation, some babies do not respond to medical therapy and require treatment with ECMO. Among babies with MAS treated with ECMO, reported survival ranges between 94% and 97%, markedly higher than for newborns treated for other respiratory conditions (Gill et al., 2002; Brown et al., 2010).

Conclusion

MAS follows fetal hypoxic/ischemic stress that leads to intestinal peristalsis, meconium release and contamination of the amniotic fluid, and gasping respirations, which cause aspiration of noxious meconium-stained fluid deep into the fetal lung. MAS occurs most frequently in the setting of fetal distress and postdates delivery. Aspiration of meconium manifests as airway obstruction with trapping of gas in the lung during exhalation, chemical pneumonitis, and surfactant inactivation with decreased lung compliance. Decreased lung compliance leads to atelectasis and gas trapping produces hyperinflation, such that lung disease in MAS is characterized by marked heterogeneity. Patients typically present with respiratory distress shortly after birth with or without evidence of pulmonary hypertension. Extrapulmonary manifestations include cardiac dysfunction, shock, neonatal ischemic encephalopathy, and in rare cases multiorgan failure. Management is supportive and includes mechanical ventilation for respiratory failure, surfactant replacement, antibiotics, hemodynamic support with inotropes, and screening for neonatal ischemic encephalopathy and multiorgan failure. In rare cases ECMO may be needed for pulmonary or hemodynamic support.

Meconium Aspiration Syndrome

Meconium aspiration syndrome (MAS) is among the most common causes of hypoxemic respiratory failure in term newborns who require intensive care (Figure 47-1). Recent studies estimate that the incidence of MAS in babies greater than 37 weeks’ gestation ranges from 0.4% to 1.8% (Dargaville and Copnell, 2006; Singh et al, 2009). Among babies born after 39 weeks’ gestation with lung disease requiring mechanical ventilation, more than half suffer from MAS (Gouyon et al, 2008).

Moreover, MAS is the primary diagnosis for a significant proportion of those newborns who require extracorporeal membrane oxygenation (ECMO) in the United States (26%) and the United Kingdom (51%) (Brown et al, 2010).

Although a significant percentage of term births are complicated by the passage of meconium before or at delivery, fewer than 10% of those exposed to meconium develop MAS. Among those 10%, fetal acidemia is believed to result in increased intestinal peristaltic activity, passage of meconium, and fetal gasping, which draws particulate meconium deep into the lung. Supporting this theory, autopsy studies of babies who died of MAS demonstrate distal muscularization of small pulmonary arterioles, suggesting long-standing hypoxemia (Murphy et al, 1984). Particulate meconium in the distal lung causes check-valve obstruction of air passages and leads to regional hyperinflation and atelectasis. In addition, meconium inactivates surfactant, leading to secondary surfactant deficiency (Moses et al, 1991). Moreover, babies with MAS are at high risk for persistent pulmonary hypertension, which significantly increases their morbidity and complicates their management.

Historically, prevention of MAS has focused on decreasing exposure of the fetal and newborn lung to the noxious effects of intrapulmonary meconium-contaminated amniotic fluid. Infusion of saline into the amniotic cavity (i.e., amnioinfusion) during labor has been studied as a means for diluting meconium and relieving pressure on the umbilical cord, a potential cause for fetal acidemia. In the largest trial investigating this practice, Fraser et al (2005) found no reduction in the risk of MAS. An alternative strategy to decreasing lung exposure to meconium is intrapartum oro- and nasopharyngeal suction of fetuses born through meconium-stained amniotic fluid. Although this practice was widely adopted in the 1970s, more recent studies have failed to demonstrated benefit (Vain et al, 2004), and the practice is no longer endorsed by the American College of Obstetricians and Gynecologists (ACOG) (Committee on Obstetric Practice, 2007). Whether the routine practice of tracheal suction of depressed, meconium-exposed infants immediately after birth is efficacious has not been adequately studied. In recent reports, surfactant lung lavage has demonstrated some promise in improving lung function in animal models of MAS (Dargaville et al, 2003), but a small clinical trial of this practice demonstrated no benefit (Gadzinowski et al, 2008). The lack of clear efficacy among any of these preventative strategies intended to remove meconium likely speaks to the complex and multifactorial nature of the pathophysiology of MAS.

The clinical signs of MAS vary widely among babies and may relate to the degree of antenatal compromise; the timing, volume, and consistency of aspirated meconium; and the presence of associated problems. Clinical signs of MAS typically present immediately after birth with tachypnea, increased work of breathing, and cyanosis. Other common associated findings are metabolic acidosis, cardiac dysfunction and hypotension, and postductal desaturation indicative of right-to-left shunting of blood at the ductus arteriosus caused by pulmonary hypertension. Because of the potential for ball-valve obstruction of small airways and failure to empty distal lung segments, pneumothorax can complicate the clinical picture. In recent series, the risk of pneumothorax among ventilated babies with MAS ranged between 10% and 24% (Dargaville and Copnell, 2006; Velaphi and Van Kwawegen, 2008). Like the degree of clinical signs, findings on chest radiograph vary widely. The classic chest x-ray shows diffuse, fluffy infiltrates. However, some babies have milder initial radiographic findings, and there is often progression of visible parenchymal disease over time, likely related to secondary surfactant dysfunction.

Approximately half the babies with MAS require mechanical ventilation. Ventilator strategy should be individualized to each baby and to the pathology evident on the chest radiograph. In general, because of the likelihood of increased airway resistance, a conventional strategy utilizing slower rates with long inspiratory and expiratory times allows for better gas dispersion and more adequate emptying during expiration. Gas trapping and regional or generalized hyperinflation can occur, particularly when rapid rates are used with a conventional mode of ventilation. Some babies respond better to ventilation with a high-frequency device, though there is also a high risk of hyperinflation. When severe, hyperinflation causes impaired gas exchange and hypercarbia, limits systemic venous return (adversely affecting cardiac performance), increases the risk of pneumothorax, and may exacerbate pulmonary hypertension.

In addition to management of parenchymal lung disease in MAS, special consideration must be paid to other problems, particularly pulmonary hypertension. The risk for PPHN is quite high, exceeding 50% in some series. Studies demonstrate that iNO improves oxygenation in MAS and is particularly efficacious when combined with a ventilator strategy that focuses on improving lung recruitment such as high-frequency oscillatory ventilation (HFOV) (Kinsella et al, 1997). Treatment with systemic antibiotics should be strongly considered in babies with PPHN for a number of reasons. These include the fact that intrauterine infection might be a precipitating factor in the initial passage of meconium and that in vitro studies suggest that presence of meconium might facilitate the growth of bacteria in the lung.

In spite of the availability of iNO and high-frequency modes of ventilation, some babies do not respond to medical therapy and require treatment with ECMO. Among babies with MAS treated with ECMO, reported survival ranges between 94% and 97%, markedly higher than for newborns treated for other respiratory conditions (Brown et al, 2010; Gill et al, 2002).

2.2 Meconium Aspiration Syndrome

Meconium aspiration syndrome is a respiratory disorder of the term and near-term newborns. It is defined by inhalation of the meconium present in the amniotic fluid during or before delivery, secondary to anoxic gasping in utero. Meconium aspiration syndrome induces: (1) mechanical obstruction of airways, (2) chemical alveolitis and epithelial damage, (3 and 4) inhibition of surfactant pulmonary artery hypertension (Dargaville and Mills, 2005; Davey et al., 1993; Moses et al., 1991; Park et al., 1996). A variety of animal models of meconium aspiration syndrome have allowed to test various therapeutic options, such as high-frequency ventilation in mongrel puppies (Keszler et al., 1986) or piglets (Wiswell et al., 1994), pulmonary lavage with diluted surfactant in adult rabbits and newborn rhesus monkeys (Cochrane et al., 1998), piglets (Dargaville et al., 2003), newborn rabbits (Lyra et al., 2004) and lambs (Avoine et al., 2011), and liquid ventilation in lambs (Avoine et al., 2011; Foust et al., 1996; Gastiasoro-Cuesta et al., 2001) or piglets (Barrington et al., 1999; Jeng et al., 2006; Kuo et al., 1998; Onasanya et al., 2001).

Meconium Aspiration Syndrome

Meconium aspiration syndrome results from intrapartum or intrauterine aspiration of meconium. It usually occurs secondary to stress, such as hypoxia, and more often occurs in term or postmature neonates. The aspirated meconium causes both obstruction of small airways secondary to its tenacious nature and also chemical pneumonitis. The degree of respiratory failure can be severe. Radiographic findings include hyperinflation (high lung volumes), which may be asymmetric and patchy, and asymmetric lung densities that tend to have a ropy appearance and a perihilar distribution (Fig. 3-1). Commonly there are areas of hyperinflation alternating with areas of atelectasis. Pleural effusions can be present. Because of the small-airway obstruction by the meconium, air-block complications are common, with pneumothorax occurring in 20% to 40% of cases. Meconium aspiration syndrome is relatively common; 25,000 to 30,000 cases occur in the United States annually.

Surfactant for Meconium Aspiration

Although MAS is becoming less common in the developed world,73 on a worldwide basis it remains an important cause of neonatal morbidity and mortality.74 Meconium aspiration can lead to severe respiratory failure, and some of this may be related to secondary surfactant inactivation.75,76 Almost as soon as surfactant was introduced into neonatal respiratory care, clinicians wanted to determine whether exogenous surfactant might help in MAS. Case series in newborn infants suggested better oxygenation if surfactant was used,77 and this finding was confirmed in randomized trials using piglet models of meconium aspiration.78 Four randomized trials of surfactant therapy in MAS have been included in a Cochrane systematic review that found improved oxygenation and a reduction in need for extracorporeal membrane oxygenation (ECMO) (RR 0.64; 95% CI 0.46-0.91).79 The studies included in this metaanalysis used a 6-hourly dosing regimen of natural bovine surfactant for up to four doses. Later studies have examined dilute surfactant lavage as a means of removing meconium particles from the lungs.80 A randomized controlled trial of 66 babies who underwent either lavage with two aliquots of 15 mL/kg of dilute bovine surfactant in addition to standard supportive therapy or standard therapy without surfactant lavage showed that the lavage-treated babies had a reduced combined outcome of death or requirement for ECMO therapy (10% vs. 31%; OR 0.24; 95% CI 0.06-0.97).81 The lavage resulted in an immediate transient reduction in oxygen saturation, which was followed by a more sustained reduction in mean airway pressure requirements. Future studies may be directed at comparing this method with standard bolus dosing.

Attempts have also been made to formulate surfactant preparations specifically for use in meconium aspiration that are more resistant to inactivation. The addition of polymers such as dextran and polyethylene glycol to surfactants in vitro leads to greater preservation of function in the presence of meconium.82 Polymyxin B, when added to surfactant, also was found to preserve the surface tension–lowering properties of surfactant in the presence of meconium as well as reduce the growth of gram-negative organisms in an in vitro study.83 Animal studies in rats with experimental meconium aspiration have shown better preservation of lung function with mixtures of poractant alfa mixed with 5% dextran than with poractant alfa mixed with 5% polyethylene glycol or poractant alfa on its own.84 A rabbit model of MAS has shown that dilute poractant alfa mixed with dextran was better than dilute poractant alfa alone when used for lung lavage. The surfactant-dextran combination resulted in better recovery of meconium particulate matter in the lavage and improved lung compliance and oxygenation at 60 minutes of age.85 Further work is under way exploring combinations of polymers and synthetic surfactants as potential therapeutic agents for pulmonary disorders with surfactant inactivation.86

PREVENTION

The prevention of MAS must start before birth by taking all the necessary precautions to reduce the risk of fetal distress and avoidance of post-term delivery. Correction of possible cord compression secondary to oligohydramnios and dilution of meconium by the use of intrapartum saline amnioinfusion has been proposed as a means of preventing MAS. Although a meta-analysis of amnioinfusion for prevention of MAS in 2002 noted an overall reduction in MAS and cesarean section, the trials included had small sample sizes and poorly defined outcome measures.159 More recently, a large multicenter trial with 1998 study subjects found that amnioinfusion did not reduce the risk of moderate or severe meconium aspiration syndrome, perinatal death, or other major maternal or neonatal disorders.160 The benefits of amnioinfusion may be restricted to settings where routine intrapartum fetal heart-rate monitoring and neonatal resuscitation are not available.161

Prognosis

The mortality of MAS in a developed setting has been reported to be 2.5%.157 In contrast, mortality can be as high as 32% in developing regions of the world.177 Most deaths are from respiratory failure, pulmonary hypertension, or air leaks. Fifty percent of babies who require mechanical ventilation because of MAS suffer an air leak. Neurodevelopmental delays have been observed even in infants who respond well to conventional ventilation.178 Children with a history of MAS have been found to exhibit long-term lung function abnormalities, increased bronchial hyperreactivity, and higher reported rates of recurrent cough and wheeze.179