Hypercapnic acidosis attenuates shock and lung injury in early and prolonged systemic sepsis.
OBJECTIVE
To investigate whether acute hypercapnic acidosis--induced by adding CO2 to inspired gas--would protect against severe systemic sepsis-induced lung and systemic organ injury resulting from cecal ligation and puncture. Acute hypercapnic acidosis protects against lung injury after both nonseptic and early pneumonia-induced lung injury. In contrast, prolonged hypercapnia worsens pneumonia-induced lung injury. The effects of hypercapnia and acidosis in the setting of systemic sepsis remain to be determined.


METHODS
Prospective randomized animal study.


METHODS
University research laboratory.


METHODS
Adult male Sprague-Dawley rats.


METHODS
In the early systemic sepsis series, post induction of anesthesia and tracheostomy placement, animals were randomized to normocapnia (Fico2 = 0.00, n = 12) or hypercapnic acidosis (Fico2 = 0.05, n = 12). Cecal ligation and puncture were performed and the animals were ventilated for 3 hrs. In the prolonged systemic sepsis series, rats were anesthetized, cecal ligation and puncture were performed, and the animals were allowed to recover. The animals were then randomized to housing under conditions of environmental normocapnia (Fico2 = 0.00, n = 20) or hypercapnia (Fico2 = 0.08, n = 20). After 96 hrs, the animals were reanesthetized, and the severity of lung and hemodynamic injury was assessed.


RESULTS
In early systemic sepsis, hypercapnic acidosis attenuated the development and severity of hypotension, and reduced lactate accumulation and the decrement in central venous oxyhemoglobin levels, compared with normocapnia. Hypercapnic acidosis reduced bronchoalveolar lavage neutrophil infiltration, and lung wet/dry weight ratios. In prolonged systemic sepsis, hypercapnic acidosis reduced histologic indices of lung injury. There was no evidence that hypercapnia worsened prolonged systemic sepsis-induced lung injury. Hypercapnic acidosis did not alter lung or systemic bacterial loads in early or prolonged systemic sepsis.


CONCLUSIONS
Hypercapnic acidosis exerts beneficial effects in early and prolonged cecal ligation and puncture-induced polymicrobial systemic sepsis.
Costello
Joseph
J
Department of Anaesthesia, Clinical Sciences Institute, National University of Ireland, Galway, Ireland.
Higgins
Brendan
B
Contreras
Maya
M
Chonghaile
Martina Ni
MN
Hassett
Patrick
P
O'Toole
Daniel
D
Laffey
John G
JG
D000142:Acidosis, Respiratory; D055371:Acute Lung Injury / Q000473:pathology / Q000628:therapy*; D000818:Animals; D006935:Hypercapnia; D008297:Male; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000379:methods*; D018805:Sepsis / Q000473:pathology / Q000628:therapy*; D016019:Survival Analysis