1. Hypercapnic acidosis and mortality in acute lung injury Crit Care Med 2006 Vol. 34, 1-7 R2 이윤정 David A. Kregenow, MD; Gordon D. Rubenfeld, MD ; Leonard D. Hudson, MD; Erik R. Swenson, MD

2. Hypercapnic acidosis (HA) has favorable anti-inflammatory and antioxidative effects at the subcellular, cellular, whole organ, and whole organism levels in hypoxic and inflammatory conditions Introduction (A) Peak airway pressure (Paw). (B) Static Inflation compliance (C ) Dynamic expiratory compliance (D) Lung wet:dry ratio. Am. J. Respir. Crit. Care Med., Volume 162, Number 6, December 2000, 2287-2294

3. ARDS Network trial to separate the effect of HA from lung protective ventilation in patients with ALI Trial compared 12 vs. 6 mL/kg predicted body weight tidal volumes  28 day mortality rate Introduction

4. Methods Figure 1. Day 1 pH and PaCO2 values of the study population. Randomized, multiple-center trial (n 861) compared, ALI and ARDS including acute hypoxic respiratory failure requiring mechanical ventilation

5. Results

6. Table 1. Characteristics of the study population

7. Table 2. Characteristics of patients lacking day 1 blood gas data and therefore excluded from the analysis

8. Table 3. Characteristics of model population by tidal volume and hypercapnic acidosis

9. Table 4. Characteristics of model population by tidal volume and hypercapnic acidosis (HA)2

10. Table 5. Characteristics of model population by tidal volume and hypercapnic acidosis (HA)3

11. Figure 2. Adjusted odds ratios for mortality. §Adjusted for Acute Physiology and Chronic Health Evaluation III score, risk factor for acute lung injury, day 1 PaO2/FIO2, and Pplat.

12. HA is associated with reduced mortality in patients receiving 12 mL/kg tidal volumes in the ARDS Network clinical trial Specific mechanisms – Reduced tumor necrosis factor-release by alveolar macrophages – Reduced neutrophil-endothelial cell adhesion – Reduced activity of xanthine oxidase leading to reduced free radical generation –Reduced nuclear factor-B –Reduced interleukin-8 and free radical production from activated neutrophils –Suppression of nitric oxide production by inhibition of inducible nitric oxide synthase Discussion

13. Many common clinical variables our definition of HA – Increased deadspace –CO2 production, –Shunt fraction, and metabolic acidosis Discussion

14. Conclusion Hypercapnic acidosis was associated with reduced 28-day mortality in the 12 mL/kg predicted body weight tidal volume group Protective effect of hypercapnic acidosis against ventilator-associated lung injury that was not found when the further ongoing injury was reduced by 6 mL/kg predicted body weight tidal volumes.