FREQUENTIST NETWORK META-ANALYSIS OF THE EFFECTIVENESS OF ANTIOXIDANT THERAPIES USED IN ICUs FOR IMPROVING THE SOFA SCORES OF PATIENTS WITH SEPSIS AND SEPTIC SHOCK

Objectives: This study compared the effectiveness of five antioxidant therapies (melatonin, vitamin C, vitamin E, selenium and N-acetylcysteine) in the treatment of sepsis (SS) or septic shock (ST) in the intensive care unit (ICU) based on the Sequential Organ Failure Assessment (SOFA) scores. Methods: The study involved randomized and multi-arm trials with SS or ST patients using melatonin, vitamin C, vitamin E, selenium, or N-acetylcysteine. Studies with SOFA scores were searched on PubMed, Embase, Cochrane Library, ClinicTrials.gov, and WHO-Clinical Trials Registry Platform. The risk of bias was assessed using the PEDro scale (physiotherapy evidence database). The therapies were compared directly and indirectly using R software. The study protocol was registered with PROSPERO (ID: CRD42024505366). Results: The network meta-analysis included 41 trials with 13 interventional therapies. Bias assessment revealed that 90.2% of the trials were of excellent and good quality. The results of meta-analysis, treatment rankings, and pairwise comparisons indicated that generally, melatonin with proposil effectively improved SOFA scores (MD = –1.32, SUCRA = 93.29%), with a statistically significant difference (z <-1.96, p < 0.05). This result has no publication bias (Egger test: p = 0.73 > 0.05). High-dose vitamin C (SUCRA = 83.97%), vitamin C with vitamin B1 (SUCRA = 78.72%), and melatonin (SUCRA = 67.03%) were potential therapies for organ dysfunction. Vitamin E, selenium, and N-acetylcysteine were ineffective. The inconsistency between studies was high (p < 0.0001). Conclusion: The study offers fresh perspectives on antioxidant therapy treatments for SS or ST in ICUs, highlighting that the combination of melatonin and propolis significantly reduces SOFA scores. Melatonin, high-dose vitamin C, and vitamin C combined with vitamin B1 also have positive effects in preventing complications and addressing multi-organ dysfunction and failure.