Indian Pediatrics 1998; 35:1059-1062 

The Meconium Aspiration Syndrome: The Saga Continues

Meconium-stained amniotic fluid (MSAF) occurs in 7%-15% of all deliveries(1-5). The meconium aspiration syndrome (MAS) develops in 5%-10% of in- fants born through MSAF(1-3,5). As many as 12% of infants with MAS will die(1,5). The majority of full-term fetuses do not pass the substance for several reasons. At the most distal end of the, gastrointestinal tract, the meconium "cap" is particularly viscous. Moreover, pronounced peristaltic movements are unusual in the fetus and anal sphincter tone is greater than what it is post-partum. MSAF has long been known to be associated with fetal distress, such as hypoxemia, as well as with vagal responses to events such as cord compression. In addition, meconium passage may be a physiologic consequence of increasing levels of the intestinal hormone motilin. It is unusual for MSAF to be noted prior to 36 weeks gestation. Passage in the pre term fetus may be an ominous event associated with a high likelihood of death or neurologic sequelae in survivors.

The respiratory disorder MAS is not purely due to the obstructive nature of the aspirated viscous meconium. A pronounced inflammatory response occurs within hours of aspiration. Protein leak into the airway commonly occurs. Cytokines and eicosanoids are often present and may contribute to pulmonary vasoconstriction, as well as to direct tissue damage. Meconium causes a pronounced dysfunction of endogenous surfactant Associated in-utero hypoxic events, particularly if they are prolonged, may cause pulmonary vascular remodeling and lung parencymal changes. In any given child with MAS, some or all of these mechanisms may be contributing to their respiratory distress. Babies may aspirate meconium in utero or with their initial postpartum breaths. The thicker the consistency of the MSAF, the greater the likelihood the child will develop MAS. The roentgenographic findings of MAS range from the classic, descriptions of diffuse, patchy infiltrates or lobar consolidation, to a relatively clear, virtually normal appearance of the lung fields. Most recent reports have not found any direct relationship between the severity of MAS and the degree of radiographic abnormalities.

Prevention of MAS has been attempted before and after the child's birth; The work of Carson et al.(6) led to widespread oropharyngeal suctioning of the infant prior to delivery of their trunk. Some have suggested administering opiates to the mother antenatally will prevent pronounced fetal gasping and aspiration of MSAF. Others have suggested performing operative delivery of babies who have passed meconium, particularly if there are signs of fetal distress. However, there have been no trials that support either of these conjectures. Over the past decade, amnioinfusion (AI) has been studied extensively. Theoretically, the administration of fluid into the uterus could dilute the MSAF that is present and potentially mitigate its toxicity. The additional fluid could relieve oligohydramnios and prevent cord compression. The initial reports concerning AI were quite promising(7). However, the most recent publications suggest AI is of little benefit and may actually contribute to both neonatal and maternal morbidity(8). Several other manipulations of the neonate have been described: thorax squeeze, epiglottal pressure, and cricoid pressure. There are no scientific data supporting the use of any of these latter three manipulations. Moreover, all three are potentially harmful to the infant. Thorax squeeze is accomplished by encircling the child's chest immediately after birth in order to prevent deep inspirations until their airway is suctioned. Epiglottal pressure consists of placing 1-2 fingers into the baby's oropharynx in an attempt to physically push the epiglottis over the glottal opening to pre- vent aspiration of secretions. Cricoid pressure could be applied external to the child's trachea to prevent aspiration. We do not recommend use of any of these manipulations. Other therapies in the delivery room aimed at preventing MAS or mitigating the course of the disorder include chest physio- therapy, saline lavage, and suctioning of the gastric contents. None of these therapies has been validated with clinical investigations.

Over the past decade, has appeared considerable debate concerning routine versus selective intubation and suctioning of the airway of meconium-stained infants. The work of Greogry et al.(9), as well as Ting and Brady(10), supported the concept of universal intubation and suctioning of all meconium-stained infants. However, the investigation of Linder and colleagues(II), despite major flaws in its methods, suggested that a more selective approach to illtubation may be possible. In the largest investigation of its kind, a recent trial assessed a selective approach(12). In the latter trial 2094 apparently vigorous meconium-stained infants were randomized to either intubation and suctioning or to expectant management. Babies born through any consistency MSAF (from the thinest to the thickest) were included. Apparent vigor was defined as the presence within the first 10-15 seconds after birth of a heart rate >100/minute, some respiratory effort, and reasonable tone. The subsequent occurrence of MAS (approximately 3%) was identical in both groups. We conclude that routine intubation and suctioning of the vigorous meconium-stained neonate will not prevent MAS.

Multiple therapies are used to treat neonates who develop MAS. Conventional management consists. of oxygen, mechanical ventilation, and fluid/nutrition support. Although antibiotics are often administered to infants with MAS, there is no evidence that these babies are at any increased risk for bacteremia (13,14). Using conventional mechanical ventilators, the strategies of hyperventilation, as well as "gentle ventilation", have been espoused. No data exist comparing either of these strategies with each other or with standard ventilator strategy. Similarly, routine use of sedation, paralysis, and alkalosis have never been validated as effective treatments.

Non-conventional management of MAS has evolved over the past decade. This indudes use of high frequency ventilation (HFV), exogenous surfactant, inhaled nitric oxide, liquid ventilation, and extracorporeal membrane oxygenation (ECMO). The most commonly used methods of HFV are high frequency oscillatory ventilation and high frequency jet ventilation. To date, no clinical trials have demonstrated benefits of either type of HFV compared to conventional therapy. Because of meconium-associated surfactant dysfunction, it would seem logical that use of exogenous surfactant could benefit babies with MAS. To date, only the small trial of Findlay et al.(15) has assessed such therapy in babies with MAS in randomized, controlled trial. These investigators found exogenous surfactant to be of benefit. However, they used 1^1/2 times the standard surfactant dose which was not administered in a bolus, but via a low infusion over 20 minutes. Moreover, babies in the Findlay trial only responded after a second dose of exogenous surfactant was given 6 hours after the initial one. In order to be considered "standard of care", we believe more trials are needed to assess he potential benefit of exogenous surfacant in the management of MAS. Over the last two years, several large investigations lave assessed the use of inhaled nitric ox- de in the management of respiratory failure in newborn infants(16-18). Approximately half of the infants enrolled in these trials had MAS as their principal respiratory disorder. Among neonates with MAS, n none of these trials has inhaled nitric oxide been shown to be superior to conventional therapy, in preventing death or the need for ECMO. Liquid ventilation has been successfully used in animal models of MAS(19). The sole human trial in term-gestation babies with respiratory failure, including those with MAS, was halted in early 1997, as were all other liquid ventilation trials. At the time we were writing this review, none of the human liquid ventilation trials had been restarted. Extracorporeal membrane oxygenation (ECMO) remains the therapy of last resort for MAS. Since the mid-1980's, more than 11,000 neonates worldwide have been treated with ECMO. Infants with MAS make up the most common diagnostic category of those treated with ECMO (-36%) and have the highest survival rate of all ECMO-treated babies. Nonetheless, there is relatively high associated morbidity with this therapy, which most commonly involves veno-arterial cardiopulmonary bypass, ultimately necessitating ligation of the right carotid artery. Thus, this therapy should not be taken lightly and should still be reserved only for those infants who have a high likelihood of dying without ECMO.

The meconium aspiration syndrome is a complex disorder affecting more than 400,000 neonates worldwide each year. Many of the therapies used to prevent MAS have not been scientifically validated. Similarly, most of the non-conventional therapies used in the treatment of the disorder have not been demonstrated to be superior to current conventional management. There remain many opportunities to investigate methods of preventing MAS and managing the disorder in those children who develop it.
 

Thomas E. Wiswell,
Professor of Pediatrics,
Division of Neonatology,
Thomas Jefferson University,
1025, Walmut Streel, Suite 700.
Philadelphia, PA 19107,
United States of America,
E-mail: [email protected]
Mamta Fuloria,
Wake Forrest University,
Winston-Salem, NC,
United States of America.

 

17. Roberts JD Jr, Fineman JR, Morin FC 3rd, Shoul PW, Rimar S, Schrieber MD, et aI. Inhaled nitric oxide and persistent pulmonary hypertension of the newborn. The Inhaled Nitric Oxide Study Group New Engl J Med 1997; 336: 605-610.

18. Davidson D, Barefield ES, Kattwinkel J, Dudeu G, Dimask M, Straube R, et al. Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: A randomized double- masked, placebo-controlled, dose-response, multicenter study. Pediatrics 1998;101:325-334.

19. Foust R Tran NN, Cox C, Metter TFJ, Greenspon JS, Wolfson MR. An alternative ventilatory strategy for acute meconium aspiration injury. Pediatric Pulmonol1996; 21: 316-321.