Avaliação da segurança e da eficácia de nanocápsulas poliméricas contendo clorexidina na redução da pneumonia associada à ventilação mecânica: um estudo pré-clínico e clínico

Abstract

With the innovative aim of preventing ventilator-associated pneumonia, this study aimed to pre- clinically and clinically evaluate the safety and efficacy of polymeric nanocapsule suspensions

containing 0.48% chlorhexidine prepared using the interfacial deposition method with Eudragit® RS 100 polymer. In the pre-clinical phase, 30 Wistar rats were divided into 5 groups (n=6): group 1: 0.9% saline solution (positive control), group 2: pure chlorhexidine (CLX), group 3: nanocapsules without chlorhexidine (NANO_0), group 4: nanocapsules with chlorhexidine (N_ CLX) and group 5: 5% formalin (F). 0.1 mL of the substance was administered subcutaneously, and the inflammatory response was assessed 3, 6, and 24 hours after application. The ANOVA test with Tukey's post-hoc test was used to compare the groups, with statistical significance p>0.05. In the clinical phase, a double-blind randomized study was conducted, guided by the STROBE tool. The study included 100 patients admitted to an intensive care unit. The sample was calculated using the G * Power 3.1 software. This resulted in 50 patients in the intervention group who used 0.48% chlorhexidine nanocapsules and underwent oral hygiene once a day and 50 patients in the control group who used conventional 0.12% chlorhexidine and underwent oral hygiene four times a day. The inclusion criteria were patients over the age of 18 undergoing orotracheal intubation and using invasive mechanical ventilation for at least 120 hours. In both groups, in the first 24 hours after intubation, samples of pulmonary secretion were collected using a tracheal aspirate and oral microbiota using a swab. A new buccal swab was collected from both groups 72 hours after the start of treatment. During the intubation period, examinations and clinical data were used to define ventilator-associated pneumonia. The results of the pre-clinical phase showed that the nanocapsule with chlorhexidine did not cause a significant inflammatory response when the intervention and control groups were compared. In the clinical phase, greater effectiveness was observed in reducing microorganisms both in the oral cavity and in the tracheal aspirate of patients who used the nanocapsule with chlorhexidine 0.48% once a

day, with a 40% reduction in positive results between the 1st and 2nd oral swabs, including multi- resistant bacteria such as Staphylococcus aureus MRSA, Acinetobacter baumannii MR, Klebsiella

pneumoniae MR, and Klebsiella pneumonia KPC. About the diagnosis of ventilator-associated pneumonia, the intervention group saw a reduction from 25.26% of cases to 20%, while the chlorhexidine 0.12% group saw an increase from 22.22% to 24.28%. As for the clinical outcome, the intervention group had a higher proportion of hospital discharges n=28 (56%) compared to the control group n=19 (38%). As for mortality, the control group had 31 deaths (62%) and the intervention group 22 (44%) with a p-value of 0.07 and OR of 1.41. The results show that nanotechnology has proven to be an effective strategy for preventing respiratory system infections in the hospital environment.