Usporedba sintetskog surfaktanta s potrebnim proteinima i surfaktanta životinjskog porijekla za prevenciju i liječenje sindroma respiracijskog distresa
Abstract
Background
Respiratory distress syndrome (RDS) is a significant cause of morbidity and mortality in preterm infants. RDS is caused by a deficiency, dysfunction, or inactivation of pulmonary surfactant. Numerous surfactants of either animal extract or synthetic design have been shown to improve outcomes. New surfactant preparations that include peptides or whole proteins that mimic endogenous surfactant protein have recently been developed and tested.
Objectives
To assess the effect of administration of synthetic surfactant containing surfactant protein mimics compared to animal derived surfactant extract on the risk of mortality, chronic lung disease, and other morbidities associated with prematurity in preterm infants at risk for or having RDS.
Search methods
Standard search methods of the Cochrane Neonatal Review Group were used. The search included MEDLINE (1966 ‐ May 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) in all languages. In addition, published abstracts of the Society of Pediatric Research were searched electronically. For abstract books that did not include key words, the search was limited to the relevant sections on pulmonary and neonatology. The bibliography cited in each publication was obtained and searched in order to identify additional relevant articles.
Selection criteria
Randomized and quasi‐randomized controlled clinical trials were considered for this review. Studies that enrolled preterm infants or low birth weight infants at risk for or having RDS who were treated with either a synthetic surfactant containing surfactant protein mimics or an animal‐derived surfactant preparation were included for this review. Studies that either attempted to treat or prevent respiratory distress syndrome were included.
Data collection and analysis
Primary outcome measures, including mortality, chronic lung disease and multiple secondary outcome measures were abstracted by the reviewers. Statistical analysis was performed using Review Manager software. Categorical data was analyzed using relative risk, risk difference, and number needed to treat. 95% confidence intervals reported. A fixed effects model was used for the meta‐analysis. Heterogeneity was assessed using the I‐squared statistic.
Main results
Two studies were identified that compared protein containing synthetic surfactants to animal derived surfactant preparations. In a meta‐analysis of these two studies, infants who received protein containing synthetic surfactant compared to animal derived surfactant extract did not demonstrate significantly different risks of prespecified primary outcomes: mortality at 36 weeks [typical RR 0.81 (95% CI 0.64, 1.03)], chronic lung disease at 36 weeks [typical RR 0.99 (95% CI 0.84, 1.18)], or the combined outcome of mortality or chronic lung disease at 36 weeks [typical RR 0.96 (95% CI 0.82, 1.12)]. There were also no differences in any of the secondary outcomes regarding complications of prematurity between the two surfactant groups with the exception of necrotizing enterocolitis. A decrease in the risk of necrotizing enterocolitis was noted in infants who received protein containing synthetic surfactants compared to animal derived surfactant extract [typical RR 0.60 (95% CI 0.42, 0.86)]. However, this was a secondary outcome in both of the primary studies and there was moderate heterogeneity between the studies.
Authors' conclusions
In two trials of protein containing synthetic surfactants compared to animal derived surfactant extract, no statistically different clinical differences in death and chronic lung disease were noted. In general, clinical outcomes between the two groups were similar. Further well designed studies of adequate size and power will help confirm and refine these findings.
PICO
Plain language summary
Usporedba sintetskog surfaktanta s potrebnim proteinima i surfaktanta životinjskog porijekla za prevenciju i liječenje sindroma respiracijskog distresa
Sindrom respiracijskog distresa (SRD) je značajan uzrok bolesti u nedonoščadi. SRD je uzrokovan manjkom ili poremećenom funkcijom kemijske tvari koja oblaže pluća, zvane plućni surfaktant (površinski aktivna tvar u vodi koja smanjuje površinsku napetost). Brojni preparati koji sadrže surfaktant, bilo životinjskog porijekla bilo sintetske proizvodnje, razvijeni su i testirani za liječenje ili prevenciju sindroma respiracijskog distresa. Ovi preparati surfaktanta smanjili su rupturu pluća (pneumotoraks) i smanjili rizik od smrti te povećali broj preživjelih bez oštećivanja pluća. Iz prethodnih istraživanja je proizišlo da surfaktanti životinjskog porijekla imaju bolji učinak od sintetskih surfaktanata. Razlog bi mogao biti taj što proteine koje sadrži životinjski surfaktant nisu sadržavali sintetski surfaktanti koji su ranije bili dostupni.
Nedavno razvijeni preparati sintetskog surfaktanta uključuju cijele proteine, ili dijelove istih (zvane peptidi), koji se ponašaju kao surfaktantski protein. Ovi preparati su nedavno testirani i uspoređeni s preparatima derivata životinjskog surfaktanta.
Dva nedavna istraživanja, koja uspoređuju sintetski surfaktant koji sadrži protein sa surfaktantima životinjskog porijekla pokazala su napredak u smanjenju smrtnosti i smanjenju učestalosti crijevnih bolesti (nekrotski enterokolitis), dok su ostali klinički ishodi bili slični.
Daljnja istraživanja će pomoći u definiranju preporuke o korištenju sintetskog surfaktanta koji sadrži protein.
