# APBA Kısa Özet

Probiotics significantly reduced ventilator-associated pneumonia in critically ill children with high certainty evidence (RR 0.47, 95% CI 0.35-0.64), halving pneumonia risk (NNT ~5). No significant effect on all-cause mortality (RR 0.85, 95% CI 0.66-1.11; low certainty) or length of stay/mechanical ventilation duration (nonsignificant). No serious probiotic-associated adverse events were reported. Probiotics may be considered an adjunctive VAP prevention strategy in PICUs pending larger multicenter trials.

# Çalışma neyi araştırdı?

This systematic review and meta-analysis synthesized data from eight randomized controlled trials (RCTs) involving 744 children admitted to pediatric intensive care units (PICUs). The primary objective was to evaluate the efficacy and safety of probiotic supplementation in critically ill children. The research team searched major databases—PubMed, EMBASE, SCOPUS, and Web of Science—up to 10 June 2024. The primary outcome was all-cause mortality; secondary outcomes included ventilator-associated pneumonia (VAP), length of hospital stay (LOS), and duration of mechanical ventilation (MV).

# Yöntem

Eight RCTs met inclusion criteria and were analyzed using random-effects models (DerSimonian-Laird) with Hartung-Knapp adjustment as a sensitivity analysis. Risk ratios (RR) were calculated for dichotomous outcomes (mortality, VAP), and mean differences (MD) for continuous outcomes (LOS, MV duration). Evidence certainty was assessed using the GRADE framework. The review adhered to PRISMA guidelines and focused exclusively on randomized controlled trials published in English.

# Temel bulgular

  • VAP Reduction: Probiotics significantly reduced the incidence of ventilator-associated pneumonia (RR 0.47, 95% CI 0.35–0.64; P < .0001; I² = 0%), indicating a 53% risk reduction. The absolute risk reduction was 21.9%, and the number needed to treat was approximately 5.
  • Mortality: Probiotics did not significantly reduce all-cause mortality (RR 0.85, 95% CI 0.66–1.11; P = .24; I² = 0%). GRADE assessment rated the evidence as low certainty.
  • Length of Stay and Mechanical Ventilation: Reductions in hospital length of stay (MD -2.57 days, 95% CI -7.26 to 2.11; P = .20) and mechanical ventilation duration (MD -1.61 days, 95% CI -4.43 to 1.20; P = .17) were not statistically significant (low certainty).
  • Safety: No serious probiotic-associated adverse events were reported across the included studies.

# Bulgular ne anlama geliyor?

The findings suggest that probiotic supplementation can be an effective intervention for reducing ventilator-associated pneumonia in critically ill children, with high-certainty evidence supporting a roughly 50% risk reduction. However, the lack of significant impact on mortality or length of stay indicates that probiotics may not improve overall clinical trajectories in all domains. The consistent null effect on mortality and the imprecise GRADE assessment for that outcome underscore the need for cautious interpretation. Clinicians may consider probiotics as an adjunctive measure specifically aimed at VAP prevention, particularly in settings where pneumonia rates are high.

# Klinik önem

Probiotics may be considered an adjunctive strategy for VAP prevention in pediatric intensive care units, pending larger multicenter trials. The high-certainty evidence of VAP reduction (NNT ~5) supports a potential role in PICU protocols, especially when the specific probiotic strain, dosage, and timing are standardized. However, the low certainty evidence for mortality benefit and the absence of effect on length of stay suggest that probiotics should not be viewed as a standalone intervention for improving overall survival or resource utilization. Shared decision-making with families, considering the individual clinical context, is recommended.

# Sınırlılıklar

  • Study Design: The review included only randomized controlled trials; other study designs (e.g., observational studies) were excluded, potentially limiting the breadth of evidence.
  • Heterogeneity in Interventions: Significant variability in probiotic strains, dosages, formulation, and intervention timing across the eight included RCTs may have influenced effect sizes and contributed to imprecision in certain outcomes.
  • Mortality Outcome Power: The low number of mortality events across studies limited the statistical power to detect a significant effect, resulting in low-certainty GRADE evidence for all-cause mortality.
  • Generalizability: Most studies were conducted in pediatric intensive care settings; generalizability to other critical care populations (e.g., adult ICUs or mixed-age units) may be limited.
  • Publication Bias: The review did not explicitly test for publication bias, though the small number of included studies may reduce the sensitivity of such analyses.
  • Strain-Specific Effects: The analysis did not perform sub-group analyses by specific probiotic species or strains, leaving open the question of which formulations may be most effective.

Conclusion: Probiotics significantly reduce the risk of ventilator-associated pneumonia in critically ill children with high certainty evidence, halving pneumonia risk (NNT ~5). No significant effect on all-cause mortality or length of stay was observed. No serious adverse events were reported. Probiotics may be considered an adjunctive VAP prevention strategy in PICUs pending larger multicenter trials.