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0 0.5 1 1.5 2+ Mortality 20% Improvement Relative Risk Alkalinization  Delić et al.  INTUBATED PATIENTS  RCT Is very late treatment with alkalinization beneficial for COVID-19? RCT 94 patients in Croatia (October 2020 - June 2021) Lower mortality with alkalinization (not stat. sig., p=0.3) Delić et al., Microorganisms, May 2022 Favors alkalinization Favors control

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

Delić et al., Microorganisms, doi:10.3390/microorganisms10061118, NCT04755972
May 2022  
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31st treatment shown to reduce risk in December 2021
*, now known with p = 0.0000043 from 11 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,900+ studies for 60+ treatments.
RCT mechanically ventilated patients in Croatia, 42 treated with sodium bicarbonate inhalation, and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia.
Targeted administration to the respiratory tract provides treatment directly to the typical source of initial SARS-CoV-2 infection and replication, and allows for rapid onset of action and reduced systemic side effects (early treatment may be more beneficial).
Study covers alkalinization and N-acetylcysteine.
risk of death, 20.1% lower, RR 0.80, p = 0.30, treatment 20 of 42 (47.6%), control 31 of 52 (59.6%), NNT 8.3.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Delić et al., 28 May 2022, Randomized Controlled Trial, Croatia, peer-reviewed, 12 authors, study period October 2020 - June 2021, trial NCT04755972 (history). Contact: (corresponding author),,,,,,,,,,,
This PaperAlkalinizationAll
Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial
Nikola Delić, Andrija Matetic, Josipa Domjanović, Toni Kljaković-Gašpić, Lenko Šarić, Darko Ilić, Svjetlana Došenović, Josipa Domazet, Ruben Kovač, Frane Runjić, Sanda Stojanović Stipić, Božidar Duplančić
Microorganisms, doi:10.3390/microorganisms10061118
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.
Conflicts of Interest: The authors declare no conflict of interest.
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Late treatment
is less effective
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