Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial

Abstract

The effect of routine inhalation therapy on ventilator-associated pneumonia (VAP) in mechanically ventilated patients with the coronavirus disease (COVID-19) has not been well-defined. This randomized controlled trial included 175 eligible adult patients with COVID-19 who were treated with mechanical ventilation at the University Hospital of Split between October 2020 and June 2021. Patients were randomized and allocated to a control group (no routine inhalation) or one of the treatment arms (inhalation of N-acetylcysteine; 5% saline solution; or 8.4% sodium bicarbonate). The primary outcome was the incidence of VAP, while secondary outcomes included all-cause mortality. Routine inhalation therapy had no effect on the incidence of bacterial or fungal VAP nor on all-cause mortality (p > 0.05). Secondary analyses revealed a significant reduction of Gram-positive and methicillin-resistant Staphylococcus aureus (MRSA) VAP in the treatment groups. Specifically, the bicarbonate group had a statistically significantly lower incidence of Gram-positive bacterial VAP (4.8%), followed by the N-acetylcysteine group (10.3%), 5% saline group (19.0%), and control group (34.6%; p = 0.001). This difference was driven by a lower incidence of MRSA VAP in the bicarbonate group (2.4%), followed by the N-acetylcysteine group (7.7%), 5% saline group (14.3%), and control group (34.6%; p < 0.001). Longer duration of ventilator therapy was the only significant, independent predictor of any bacterial or fungal VAP in the multivariate analysis (aOR 1.14, 95% CI 1.01–1.29, p = 0.038 and aOR 1.05, 95% CI 1.01–1.10, p = 0.028, respectively). In conclusion, inhalation therapy had no effect on the overall VAP incidence or all-cause mortality. Further studies should explore the secondary findings of this study such as the reduction of Gram-positive or MRSA-caused VAP in treated patients.

Clinical efficacy of N-acetylcysteine for COVID-19: A systematic review and meta-analysis of randomized controlled trials

“…The 14 remaining articles underwent a full-text review for eligibility assessment. Finally, this study identified a total of five RCTs [ [17] , [18] , [19] , [20] , [21] ] that met the inclusion criteria. The algorithm for study selection is presented in Fig.…”

“…Table 1 summarizes the characteristics of the five included studies [ [17] , [18] , [19] , [20] , [21] ]. One study [ 21 ] was a phase 2 RCT, and the other four were phase 3 studies [ [17] , [18] , [19] , [20] ].…”

“…Table 1 summarizes the characteristics of the five included studies [ [17] , [18] , [19] , [20] , [21] ]. One study [ 21 ] was a phase 2 RCT, and the other four were phase 3 studies [ [17] , [18] , [19] , [20] ]. All were single-center studies conducted in different countries, including Iran (n = 3), Brazil (n = 1), and Croatia (n = 1).…”

“…An in vitro study demonstrated that NAC can reduce the inflammasome activation induced by SARS-CoV-2 [ 13 ], and several cohort studies have indicated that NAC therapy helped improve clinical recovery and oxygenation parameters, reduced the levels of inflammatory markers such as C-reactive protein and ferritin, and decreased the length of hospitalization [ [14] , [15] , [16] ]. Although additional randomized controlled trials (RCTs) have investigated the clinical efficacy of NAC in the treatment of patients with COVID-19, their findings were not consistent [ [17] , [18] , [19] , [20] , [21] ]. An RCT by de Alencar et al reported that the NAC administration did not reduce the need for invasive mechanical ventilation (IMV), the rate of admissions to the intensive care unit (ICU), or the mortality rate in patients with severe COVID-19 [ 17 ].…”

Neglected Effective Early Therapies against COVID-19: Focus on Functional Foods and Related Active Substances. A Review

“…Figure 10. Random effects meta-analysis for all RCTs about alkalinization in COVID-19 [119][120][121][122][123][124][125][126]. This plot shows pooled effects, see the specific outcome analyses for individual outcomes, and the heterogeneity section [21] for discussion.…”