Sustained hypercapnic acidosis during pulmonary infection increases bacterial load and worsens lung injury.
OBJECTIVE
Hypercapnic acidosis is commonly permitted in patients with acute respiratory distress syndrome during the use of protective ventilation strategies. Hypercapnic acidosis is also a common complication of multiple lung diseases and is associated with a poor prognosis, although the mechanisms by which it leads to increased mortality is not known. Previous studies using noninfective models of lung injury show that acute (<6 hrs) hypercapnic acidosis reduced lung damage by an anti-inflammatory effect. We hypothesized that this anti-inflammatory effect would be detrimental in vivo in the presence of untreated bacterial infection and sustained hypercapnia (>48 hrs) and, furthermore, that if bacterial reproduction were controlled by antibiotic therapy, then the anti-inflammatory effects of hypercapnic acidosis would no longer prove detrimental.


METHODS
This study was a prospective, randomized animal study.


METHODS
This study was conducted at a university research laboratory.


METHODS
Study subjects were adult male Wistar-Kyoto rats.


METHODS
After intratracheal instillation of Escherichia coli under general anesthesia, rats were housed in normocapnic (21% O2, 0% CO2) or hypercapnic (21% O2, 5% CO2) environments for 2 days. Rats were then reanesthetized for assessment of physiological and quantitative stereologic indices of lung damage, quantitative bacterial counts, and neutrophil phagocytosis.


RESULTS
Hypercapnic acidosis was associated with higher lung bacterial colony counts, more structural damage, and lower static lung compliance than normocapnia. Neutrophils isolated from hypercapnic rats demonstrated impaired phagocytosis. In a further separate series of experiments, in which rats were given antibiotic therapy, lung damage was not different between normocapnic and hypercapnic acidosis groups.


CONCLUSIONS
Prolonged hypercapnic acidosis worsened bacterial infection-induced lung injury. Our findings suggest an immunosuppressive effect of hypercapnic acidosis and have important implications for protective ventilation strategies that permit hypercapnic acidosis in patients with adult respiratory distress syndrome and in the management of hypercapnic acidosis during infective exacerbations of chronic obstructive pulmonary disease and other lung diseases.
O'Croinin
Donall F
DF
School of Medicine and Medical Sciences, Conway Institute, University College Dublin, Ireland.
Nichol
Alistair D
AD
Hopkins
Natalie
N
Boylan
John
J
O'Brien
Sorca
S
O'Connor
Clare
C
Laffey
John G
JG
McLoughlin
Paul
P
D000142:Acidosis, Respiratory / Q000150:complications / Q000503:physiopathology*; D000818:Animals; D004927:Escherichia coli Infections / Q000150:complications*; D006935:Hypercapnia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D010587:Phagocytosis; D051381:Rats; D011921:Rats, Inbred WKY; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000382:microbiology*