Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial
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.
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.
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Delić et al., 28 May 2022, Randomized Controlled Trial, Croatia, peer-reviewed, 12 authors, study period October 2020 - June 2021, trial
NCT04755972 (history).
Contact:
ndelic@kbsplit.hr (corresponding author), tkljakgas@kbsplit.hr, lsaric@kbsplit.hr, dilic@kbsplit.hr, sdosenovic@kbsplit.hr, jdomazet@kbsplit.hr, rkovac@kbsplit.hr, sastojanovic@kbsplit.hr, bduplanc@kbsplit.hr, andrija.matetic@gmail.com, frane.runjic@gmail.com, josipa.domjanovic@gmail.com.
Abstract: microorganisms
Article
Effects of Different Inhalation Therapy on Ventilator-Associated
Pneumonia in Ventilated COVID-19 Patients: A Randomized
Controlled Trial
Nikola Delić 1, *, Andrija Matetic 2 , Josipa Domjanović 3 , Toni Kljaković-Gašpić 1 , Lenko Šarić 1 , Darko Ilić 1 ,
Svjetlana Došenović 1 , Josipa Domazet 1 , Ruben Kovač 1 , Frane Runjić 2 , Sanda Stojanović Stipić 1
and Božidar Duplančić 1
1
2
3
*
Citation: Delić, N.; Matetic, A.;
Domjanović, J.; Kljaković-Gašpić, T.;
Šarić, L.; Ilić, D.; Došenović, S.;
Domazet, J.; Kovač, R.; Runjić, F.;
et al. Effects of Different Inhalation
Therapy on Ventilator-Associated
Pneumonia in Ventilated COVID-19
Patients: A Randomized Controlled
Trial. Microorganisms 2022, 10, 1118.
https://doi.org/10.3390/
microorganisms10061118
Academic Editor: Antonella
d’Arminio Monforte
Received: 17 March 2022
Accepted: 25 May 2022
Published: 28 May 2022
Department of Anesthesiology, University Hospital of Split, Spinčićeva 1, 21000 Split, Croatia;
tkljakgas@kbsplit.hr (T.K.-G.); lsaric@kbsplit.hr (L.Š.); dilic@kbsplit.hr (D.I.); sdosenovic@kbsplit.hr (S.D.);
jdomazet@kbsplit.hr (J.D.); rkovac@kbsplit.hr (R.K.); sastojanovic@kbsplit.hr (S.S.S.);
bduplanc@kbsplit.hr (B.D.)
Department of Cardiology, University Hospital of Split, 21000 Split, Croatia; andrija.matetic@gmail.com (A.M.);
frane.runjic@gmail.com (F.R.)
Department of Nephrology, University Hospital of Split, 21000 Split, Croatia; josipa.domjanovic@gmail.com
Correspondence: ndelic@kbsplit.hr; Tel.: +385-9-8900-0150
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.
Publisher’s Note: MDPI stays neutral
with..
Late treatment
is less effective
delic
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