Tromethamine Buffer Modifies the Depressant Effect of Permissive Hypercapnia on Myocardial Contractility in Patients with Acute Respiratory Distress Syndrome

Abstract

In patients with acute respiratory distress syndrome (ARDS), permissive hypercapnia is a strategy to decrease airway pressures to prevent ventilator-induced lung damage by lowering tidal volumes and tolerating higher arterial carbon dioxide tension. However, in experimental studies hypercapnia impairs myocardial contractility and hemodynamic function. We investigated the effect of short-term permissive hypercapnia on myocardial contractility and hemodynamics in patients with ARDS. We hypothesized that the administration of tromethamine (THAM), a buffer which does not increase carbon dioxide production, would modify these changes. In 12 patients with ARDS, permissive hypercapnia was implemented for 2 h with a target Pa(CO(2))of 80 mm Hg. Patients were randomized to have respiratory acidosis corrected by THAM (pH-corrected group), or not corrected (pH-uncorrected group). Hemodynamic responses were measured, and transesophageal echocardiography (TEE) was used to determine myocardial contractility. Permissive hypercapnia resulted in significant decreases in systemic vascular resistance (SVR) and increases in cardiac output (Q). Myocardial contractility decreased in both groups but significantly less in the pH-corrected group (approximately 10%) than in the pH-uncorrected group (approximately 18%, p < 0.05). Mean arterial pressure decreased and mean pulmonary arterial pressure increased significantly only in the pH-uncorrected group. All values returned to baseline conditions 1 h after permissive hypercapnia was terminated. Our study demonstrates a reversible depression of myocardial contractility and hemodynamic alterations during rapid permissive hypercapnia which were attenuated by buffering with THAM. This may have applicability to the clinical strategy of permissive hypercapnia and allow the benefit of decreased airway pressures to be realized while minimizing the adverse hemodynamic effects of hypercapnic acidosis.

Hypercapnic acidosis confers antioxidant and anti-apoptosis effects against ventilator-induced lung injury

“…with ARDS. 46 In addition, our previous study (unpublished data) also demonstrated that moderating hypercapnic acidosis (PaCO 2 of 80-100 mm Hg) could result in the improving oxygenation, histologic characteristics, and a lessened inflammatory response, compared with severe hypercapnic acidosis (PaCO 2 of 130-150 mm Hg). A previous study has also shown that the beneficial effects of moderating hypercapnia may be offset by the high level of adverse effects caused by itself.…”

Impact of buffering hypercapnic acidosis on cell wounding in ventilator-injured rat lungs

“…There is strong animal data suggesting the many potential benefits of hypercapnic acidosis (3,11,22,24), recently augmented by secondary analysis of the ARDSNet data (12). On the other hand, skepticism persists among some, with experimental and clinical data touting drawbacks to hypercapnic acidosis (16) and benefits of various buffering strategies (17,23,28), with some compelling clinical arguments for the use of THAM.…”

“…Not all investigators have reported benefit from hypercapnia, which has been implicated in pulmonary (6,16,17) and extrapulmonary (21,28) organ dysfunction, findings that have likely spurred further interest in the use of buffers. Bicarbonate buffers react to liberate carbon dioxide, which, because of high membrane permeability, may raise concern for further intracellular acidosis (9), a potentially operative, although unproven, mechanism in studies demonstrating worsened lung barrier function with buffering of hypercapnic acidosis (13,18).…”

“…Bicarbonate buffers react to liberate carbon dioxide, which, because of high membrane permeability, may raise concern for further intracellular acidosis (9), a potentially operative, although unproven, mechanism in studies demonstrating worsened lung barrier function with buffering of hypercapnic acidosis (13,18). Tris-hydroxymethyl aminomethane (THAM), acting as a proton acceptor independent of carbon dioxide pathways, has been shown in animal and clinical models to reverse cardio-depressant effects attributed to hypercapnic acidosis (21,23,28).…”

Carbon Dioxide in the Critically Ill: Too Much or Too Little of a Good Thing?

“…56 Through more effectively correcting pH, THAM can also mitigate the adverse effects of acidosis on the cardiovascular system and restore hemodynamic stability. 57 …”