TY - JOUR
T1 - Nebulization of Antiinfective Agents in Invasively Mechanically Ventilated Adults
T2 - A Systematic Review and Meta-analysis
AU - Solé-Lleonart, Candela
AU - Rouby, Jean Jacques
AU - Blot, Stijn
AU - Poulakou, Garyfallia
AU - Chastre, Jean
AU - Palmer, Lucy B.
AU - Bassetti, Matteo
AU - Luyt, Charles Edouard
AU - Pereira, Jose M.
AU - Riera, Jordi
AU - Felton, Tim
AU - Dhanani, Jayesh
AU - Welte, Tobias
AU - Garcia-Alamino, Jose M.
AU - Roberts, Jason A.
AU - Rello, Jordi
N1 - Publisher Copyright:
Copyright © 2017, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Background: Nebulization of antiinfective agents is a common but unstandardized practice in critically ill patients. Methods: A systematic review of 1,435 studies was performed in adults receiving invasive mechanical ventilation. Two different administration strategies (adjunctive and substitute) were considered clinically relevant. Inclusion was restricted to studies using jet, ultrasonic, and vibrating-mesh nebulizers. Studies involving children, colonized-but-not-infected adults, and cystic fibrosis patients were excluded. Results: Five of the 11 studies included had a small sample size (fewer than 50 patients), and only 6 were randomized. Diversity of case-mix, dosage, and devices are sources of bias. Only a few patients had severe hypoxemia. Aminoglycosides and colistin were the most common antibiotics, being safe regarding nephrotoxicity and neurotoxicity, but increased respiratory complications in 9% (95% CI, 0.01 to 0.18; I2 = 52%), particularly when administered to hypoxemic patients. For tracheobronchitis, a significant decrease in emergence of resistance was evidenced (risk ratio, 0.18; 95% CI, 0.05 to 0.64; I2 = 0%). Similar findings were observed in pneumonia by susceptible pathogens, without improvement in mortality or ventilation duration. In pneumonia caused by resistant pathogens, higher clinical resolution (odds ratio, 1.96; 95% CI, 1.30 to 2.96; I2 = 0%) was evidenced. These findings were not consistently evidenced in the assessment of efficacy against pneumonia caused by susceptible pathogens. Conclusions: Performance of randomized trials evaluating the impact of nebulized antibiotics with more homogeneous populations, standardized drug delivery, predetermined clinical efficacy, and safety outcomes is urgently required. Infections by resistant pathogens might potentially have higher benefit from nebulized antiinfective agents. Nebulization, without concomitant systemic administration of the drug, may reduce nephrotoxicity but may also be associated with higher risk of respiratory complications.
AB - Background: Nebulization of antiinfective agents is a common but unstandardized practice in critically ill patients. Methods: A systematic review of 1,435 studies was performed in adults receiving invasive mechanical ventilation. Two different administration strategies (adjunctive and substitute) were considered clinically relevant. Inclusion was restricted to studies using jet, ultrasonic, and vibrating-mesh nebulizers. Studies involving children, colonized-but-not-infected adults, and cystic fibrosis patients were excluded. Results: Five of the 11 studies included had a small sample size (fewer than 50 patients), and only 6 were randomized. Diversity of case-mix, dosage, and devices are sources of bias. Only a few patients had severe hypoxemia. Aminoglycosides and colistin were the most common antibiotics, being safe regarding nephrotoxicity and neurotoxicity, but increased respiratory complications in 9% (95% CI, 0.01 to 0.18; I2 = 52%), particularly when administered to hypoxemic patients. For tracheobronchitis, a significant decrease in emergence of resistance was evidenced (risk ratio, 0.18; 95% CI, 0.05 to 0.64; I2 = 0%). Similar findings were observed in pneumonia by susceptible pathogens, without improvement in mortality or ventilation duration. In pneumonia caused by resistant pathogens, higher clinical resolution (odds ratio, 1.96; 95% CI, 1.30 to 2.96; I2 = 0%) was evidenced. These findings were not consistently evidenced in the assessment of efficacy against pneumonia caused by susceptible pathogens. Conclusions: Performance of randomized trials evaluating the impact of nebulized antibiotics with more homogeneous populations, standardized drug delivery, predetermined clinical efficacy, and safety outcomes is urgently required. Infections by resistant pathogens might potentially have higher benefit from nebulized antiinfective agents. Nebulization, without concomitant systemic administration of the drug, may reduce nephrotoxicity but may also be associated with higher risk of respiratory complications.
UR - https://www.scopus.com/pages/publications/85014105461
U2 - 10.1097/ALN.0000000000001570
DO - 10.1097/ALN.0000000000001570
M3 - Review article
C2 - 28248714
AN - SCOPUS:85014105461
SN - 0003-3022
VL - 126
SP - 890
EP - 908
JO - Anesthesiology
JF - Anesthesiology
IS - 5
ER -