MIST Didn’t Reduce Death in Preemies With Respiratory Distress Syndrome

A randomized trial showed that minimally invasive surfactant therapy (MIST) did not reduce the incidence of death or neurodevelopmental disability among preterm infants with respiratory distress syndrome at 2 years of age, while a retrospective cohort study showed that survivors of acute respiratory distress syndrome (ARDS) were at high risk of readmission in the first 2 months after discharge.

According to a follow-up study of 453 infants who were supported with continuous positive airway pressure (CPAP) in the randomized OPTIMIST-A trial, which was published in JAMA, death or neurodevelopmental disability occurred in 36.3% of infants in the MIST group versus 36.1% in the control group (relative risk [RR] 1.0, 95% CI 0.81-1.24), reported Peter Dargaville, MD, of the Royal Hobart Hospital in Tasmania, Australia, and colleagues.

However, there was a relative reduction of 34% (RR 0.66, 95% CI 0.54-0.81) in the frequency of one or more hospitalizations for respiratory illness in the MIST group compared with the control group, the authors noted.

Hospitalization with respiratory illness occurred in 25.1% of infants in the MIST group versus 38.2% in the control group (RR 0.66, 95% CI 0.54-0.81) and parent-reported wheezing or breathing difficulty occurred in 40.6% versus 53.6%, respectively (RR 0.76, 95% CI 0.63-0.90).

The primary analysis of OPTIMIST-A showed that MIST did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks’ postmenstrual age compared with sham treatment in preterm infants with respiratory distress syndrome supported with CPAP.

“The study was important because the care of preterm infants, particularly the approach to early respiratory management, changed fundamentally in the past decades,” Dargaville told MedPage Today in an email. “Essentially what has happened is that there is a greater emphasis placed on trying to avoid intubation (with a breathing tube) and mechanical ventilation in the first hours and days of life, and instead using less invasive breathing support in the form of CPAP.”

“However this came at a cost for infants needing a dose of a natural substance called surfactant that can be given routinely to overcome lung immaturity if a breathing tube is in place,” he noted. “Hence there was a dilemma for clinicians whenever a baby supported with CPAP showed features of respiratory distress syndrome and was in need of surfactant.”

“The Hobart method (and others like it) sought to resolve this dilemma by administering surfactant through a thin tube or catheter passed briefly into the windpipe whilst CPAP continues,” he continued. “Our trial examined whether using this method with a low treatment threshold would be better than continuing standard care with CPAP unless the respiratory condition worsened. We found that intervening in this way was associated with considerable short- and long-term improvements in respiratory health compared with standard treatment.”

A separate study published in JAMA Network Open showed that the probability of hospital readmission within 1 year among over 13,000 pediatric survivors of ARDS was 30% (95% CI 29.0-30.8), and half of readmissions occurred within 61 days of discharge (95% CI 56-67), reported Garrett Keim, MD, of Children’s Hospital of Philadelphia, and colleagues.

Respiratory complex chronic conditions were associated with 1-year readmission (adjusted HR 2.69, 95% CI 2.42-2.98), as were non-respiratory complex chronic conditions (aHR 1.86, 95% CI 1.71-2.03), a length of stay of 14 days or longer (aHR 1.87, 95% CI 1.62-2.16) and receipt of a new tracheostomy (aHR 1.98, 95% CI 1.69-2.33).

After excluding children with complex chronic conditions, an initial length of stay of 14 days or longer was still associated with readmission (aHR 1.92, 95% CI 1.49-2.47).

“The lasting consequences of critical illness are being increasingly considered, but clinicians traditionally have not counseled families about the potential long-term impact of critical illness on a child’s life,” Keim told MedPage Today in an email. “One reason for this is lack of rigorous evaluation of important outcomes.”

“Hospital readmissions have important consequences for the children that are readmitted, their families, and the healthcare system,” he added. “Understanding the burden of readmission after pediatric ARDS will be informative to clinicians and begin to allow us to better counsel families. Additionally, identifying key risk factors impacting readmission risk can help clinicians begin to develop readmission mitigation care plans.”

In an editorial accompanying this study, Elizabeth Killien, MD, MPH, of the University of Washington and Seattle Children’s Hospital, wrote that the study authors “have added valuable insight into the ongoing burden of morbidity among survivors of ARDS and the patients most at risk for hospital readmission.”

“Informing a family that their child still has a 30% risk of being back in the hospital within the year after surviving ARDS is an uncomfortable reality that demands improved systemwide efforts to address,” she noted.

Future work in this area will need to “determine whether ARDS confers greater risk of hospital readmission and other comorbidities compared with other PICU [pediatric intensive care unit] survivors with similar illness severity and PICU exposures,” and will need to “identify which comorbidities are associated with greatest risk for readmission, including the relative contribution of preexisting versus acquired comorbidities,” she continued.

Furthermore, future research will need to “explore other patient factors associated with readmission risk to develop interventions to reduce hospital readmissions that can be applied across patient populations and facilities in a cost-effective and time-effective manner,” she concluded.

Details of the Studies

The follow-up study to OPTIMIST-A included 453 infants at 25 to 28 weeks’ gestation across 33 tertiary-level neonatal intensive care units in 11 countries, for whom follow-up data were available. The median gestational age was 27.3 weeks, and 50.3% were girls.

Since this was a follow-up study of a randomized trial, it was not specifically designed to detect differences in 2-year outcomes, Dargaville and colleagues noted. Additionally, the study’s sample size was limited by the early stop to recruitment due to the COVID pandemic.

The retrospective cohort study used data from commercial or Medicaid IBM MarketScan databases between 2013 and 2017, with follow-up data through 2018, and included hospitalized children ages ≥28 days through 17 years who received mechanical ventilation and had algorithm-identified ARDS.

One-year readmission occurred in 3,748 of the included 13,505 children with mechanically ventilated ARDS who survived to hospital discharge. Median age was 4 years, and 58.3% were boys.

The study’s primary outcome examined factors associated with first readmission, but did not account for subsequent readmissions or time spent readmitted, which was a limitation to the study, Keim and colleagues noted.