THAM reduces CO(2)-associated increase in pulmonary vascular resistance – an experimental study in lung-injured piglets

INTRODUCTION: Low tidal volume (V(T)) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO(2)), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR. METHODS: A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with V(T) of 6 ml/kg to maintain normocapnia, V(T) was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment. RESULTS: In the controls, the decrease in V(T) from 6 to 3 ml/kg increased PaCO(2) from 6.0±0.5 to 13.8±1.5 kPa and lowered pH from 7.40±0.01 to 7.12±0.06, whereas base excess (BE) remained stable at 2.7±2.3 mEq/L to 3.4±3.2 mEq/L. In the THAM groups, PaCO(2) decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO(2) increased above the corresponding level of the controls (15.2±1.7 kPa and 22.6±3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8±3.5 and 31.2±2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329±77 dyn∙s/m(5) and 255±43 dyn∙s/m(5) in the 1-h and 3-h groups, respectively, compared with 450±141 dyn∙s/m(5) in the controls), as were pulmonary arterial pressures. CONCLUSIONS: The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO(2) after stopping the THAM infusion, possibly by intracellular release of CO(2). Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.