Article Reviews & Commentary
Article Reviews by Thomas J. Mancuso, MD, FAAP
A Multicenter, Randomized,
Controlled Trial Comparing Surfaxin Lavage with Standard Care for the
Treatment of Meconium Aspiration Syndrome.
Wisell TE, Knight GR, Finer NN et al Pediatrics
2002:109;1081-1087
Surfactant Lavage for
Meconium Aspiration Syndrome: A Word of Caution.
Kittiwake J Pediatrics 2002:109;1167-1168
In this open-label controlled phaseI/II study, conventional therapy for MAS is compared to bronchoalveolar lavage with dilute surfactant. Enrollees with a diagnosis of MAS in the study were: > 35 weeks gestation, < 72 hours old, in need of mechanical ventilation and had an oxygenation index (OI) between 8 and 25. Infants who received lavage were given 8 ml/kg of dilute Surfaxin (2.5 mg/ml) into each lung over 20 seconds twice. After each instillation and following 5 ventilator breaths, the surfactant was suctioned out. The third, final treatment was with a more concentrated (5 mg/ml) solution of Surfaxin. Infants received two sets of lavages.
There were 22 newborns enrolled in this study, 15 in the treatment group, 7 who received standard treatment. The groups were similar in weight and gestational age. All infants in the standard treatment group were outborn but 8/15 surfactanttreated infants were outborn. The groups had similar ventilator settings, Oxygenation Indices and Apgar scores. Three patients in the surfactant group did not complete the study. One because of hypoxemia, attributed to concomitant herpes infection. Another because of hypotension, attributed to concomitant gram negative bacteremia. The third developed an OI > 50% above baseline during treatment and was considered a treatment failure. There was no statistically significant difference between the groups in any outcome measure although there was a trend toward fewer days of mechanical ventilation (6.3 vs. 9.9 days) and more rapid decline in OI in the surfactant-treated group compared to the control group. Mean number of days of oxygen therapy and to discharge from NICU was nearly identical, however. The authors conclude that this innovative therapy is relatively well-tolerated, and the results of this investigation justify a large phase III trial as has been approved by the FDA.
Commentary
Newborns with Meconium Aspiration Syndrome (MAS) have marked surfactant dysfunction and clinically often develop progressive respiratory distress, hypoxemia, hypercapnia and acidosis. Intensive respiratory support, even ECMO, may be needed for these infants. MAS infants make up approximately 35% of all cases where ECMO is used as a life saving intervention. Mortality from MAS is in the range of 3%-12%. Although the results did not reach statistical significance in this investigation, therapy with surfactant appears promising. Given the relatively poor prognosis and the much more invasive support of ECMO, this promising line of study holds hope for infants with MAS.
The commentary by Dr. Kattwinkel in the same issue of Pediatrics sounds a note of caution regarding this therapy for MAS. He correctly points out that 3/15 treatment subjects did not complete the full course of lavage, although only one was a treatment failure as a result of worsening OI. The difference in the groups composition regarding inborn vs outborn certainly should not be minimized. Dr. Kattwinkel also notes that even in the case that treatment was effective, surfactant administration alone could be responsible and the lavage procedure unnecessary. One patient with congenital heart disease, had worsening CHF following the lavage procedure, perhaps as a result of fluid overload from the lavage (48 cc/kg total). He concludes remarking that the authors have considered many of his points and that only a larger study will resolve the question. #include ./footer_include.iphtml