Effect of low-to-moderate hyperoxia on lung injury in preclinical animal models: a systematic review and meta-analysis

• Published in: Intensive care medicine experimental 2023-04, Vol.11 (1), p.22-22, Article 22
• Main Authors: Minkove, Samuel, Dhamapurkar, Rhea, Cui, Xizhong, Li, Yan, Sun, Junfeng, Cooper, Diane, Eichacker, Peter Q., Torabi-Parizi, Parizad
• Format: Article
• Language: English
• Subjects: Animal models; Clinical medicine; Critical Care Medicine; Inflammatory lung injury; Injuries; Intensive; Intensive care; Laboratory animals; Lungs; Medicine; Medicine & Public Health; Meta-analysis; Oxygen therapy; Oxygen toxicity; Reviews; Systematic review
• ISSN: 2197-425X; 2197-425X
• DOI: 10.1186/s40635-023-00501-x

Background Extensive animal investigation informed clinical practice regarding the harmful effects of high fractional inspired oxygen concentrations (FiO 2 s > 0.60). Since questions persist whether lower but still supraphysiologic FiO 2  ≤ 0.60 and > 0.21 (FiO 2  ≤ 0.60/ > 0.21) are also harmful with inflammatory lung injury in patients, we performed a systematic review examining this question in animal models. Methods Studies retrieved from systematic literature searches of three databases, that compared the effects of exposure to FiO 2  ≤ 0.60/ > 0.21 vs. FiO 2  = 0.21 for ≥ 24 h in adult in vivo animal models including an inflammatory challenge or not were analyzed. Survival, body weight and/or lung injury measures were included in meta-analysis if reported in ≥ 3 studies. Results More than 600 retrieved reports investigated only FiO 2 s > 0.60 and were not analyzed. Ten studies with an inflammatory challenge (6 infectious and 4 noninfectious) and 14 studies without, investigated FiO 2 s ≤ 0.60/ > 0.21 and were analyzed separately. In seven studies with an inflammatory challenge, compared to FiO 2  = 0.21, FiO 2  ≤ 0.60/ > 0.21 had consistent effects across animal types on the overall odds ratio of survival (95%CI) that was on the side of harm but not significant [0.68 (0.38,1.23), p  = 0.21; I 2  = 0%, p  = 0.57]. However, oxygen exposure times were only 1d in 4 studies and 2–4d in another. In a trend approaching significance, FiO 2  ≤ 0.60/ > 0.21 with an inflammatory challenge consistently increased the standardized mean difference (95%CI) (SMD) in lung weights [0.47 (− 0.07,1.00), p  = 0.09; I 2  = 0%, p  = 0.50; n  = 4 studies] but had inconsistent effects on lung lavage protein concentrations ( n  = 3), lung pathology scores ( n  = 4) and/or arterial oxygenation ( n  = 4) ( I 2  ≥ 43%, p  ≤ 0.17). Studies without an inflammatory challenge had consistent effects on lung lavage protein concentration ( n  = 3) SMDs on the side of being increased that was not significant [0.43 (− 0.23,1.09), p  = 0.20; I 2  = 0%, p  = 0.40] but had inconsistent effects on body and lung weights ( n  = 6 and 8 studies, respectively) ( I 2  ≥ 71%, p   0.21 with clinically relevant models and endpoints but suggest even these lower FiO 2 s may be injurious. Given the influence animal studies examining FiO 2  > 0.60 have had on clinical practice, addit