Associação entre o uso de clorexidina ou cetilpiridínio oral para prevenção de pneumonia associada à ventilação e a ocorrência de lesão pulmonar aguda em pacientes vítimas de traumatismo cranioencefálico: um ensaio clínico randomizado

Abstract

Introduction: Oral hygiene for critically ill patients on mechanical ventilation (MV) is an important strategy for preventing ventilator-associated pneumonia (VAP), and worldwide, the use of chlorhexidine in this procedure has been recommended and disseminated as routine. However, meta-analyses of double-blind randomized clinical trials have reported an association between the use of chlorhexidine in oral hygiene and increased mortality, and no reduction in VAP rates. The mechanism suggested to explain this increase in mortality is the occurrence of acute lung injury, since chlorhexidine is an acidic substance and, when aspirated, could cause direct pulmonary toxicity. Objectives: To evaluate whether there is an association between the use of chlorhexidine (CHX) in the oral hygiene of critically ill patients on mechanical ventilation and the occurrence of ALI, and whether cetylpyridinium chloride (CCP) is a safe option. Methods: This study is a randomized controlled clinical trial, registered under number RBR-7p6568 in the Brazilian Registry of Clinical Trials. The experimental protocols were approved by the local ethics committee and comply with the CONSORT (CONsolidated Standards of Reporting Trials) guidelines. Of the 59 eligible patients, 34 consented and were randomly allocated to three different groups: (A) oral hygiene with 0.12% chlorhexidine digluconate; (B) 0.075% cetylpyridinium chloride; (C) sterile water. The primary outcome was the occurrence of acute lung injury. Secondary outcomes were all-cause mortality, duration of mechanical ventilation, length of stay in the Intensive Care Unit (ICU), ICU-acquired infections, and antimicrobial resistance. The collected data were pooled and compared. Results: The use of chlorhexidine for oral hygiene in critically ill patients on mechanical ventilation showed a non-statistically significant association with an increased occurrence of acute lung injury and ICU-acquired infections. Statistical analysis showed no differences in prevalence percentages between groups for any variable, applying the Z-test of proportions with Bonferroni correction. In addition, the patients’ daily P/F ratio was collected for 14 days, and this data was analyzed using a Mixed Linear Model, in which no statistically significant differences were observed between the three groups in the daily P/F values throughout the follow-up period. Discussion: Considering that international guidelines have modified their recent recommendations and no longer 11

recommend chlorhexidine for oral hygiene in all critically ill patients, it is imperative to evaluate alternatives to chlorhexidine. In this study, the results showed no evidence of harm with the use of CCP, corroborating the fact that, unlike CHX, it is not an acidic substance. Conclusion: In institutions whose protocols guide the use of oral chlorhexidine only when specifically prescribed, CCP remains a possible alternative. Further investigations will be necessary to assess whether cetylpyridinium chloride in oral hygiene is a safe and effective strategy for preventing VAP and could, therefore, be recommended by guidelines for routine use in all critically ill patients on mechanical ventilation.