Procedure-related pulmonary hypertension in patients with hepatocellular carcinoma undergoing percutaneous ethanol injection--role of ethanol, hemolysis, asymmetric dimethylarginine, and the nitric oxide system.

Objective: Local percutaneous tumor ablation with ethanol injection (PEI) under general anesthesia is an established therapy for patients with advanced nonresectable hepatocellular carcinoma (HCC). There are reports of sudden hypotension immediately after PEI therapy, which was attributed to an acute increase in pulmonary vascular resistance. The aim of our study was to objectively confirm pulmonary hypertension by right heart catheterization and to evaluate biochemical markers with relevance to the pulmonary circulation. Design: Cross-sectional clinical study. Setting: Interventional Gastroenterology in a tertiary care center. Patients: We studied 40 patients with HCC who underwent percutaneous ethanol injection under general anesthesia for the treatment of nonresectable HCC. Results: In patients with HCC, PEI leads to a significant increase in pulmonary arterial pressure. Concomitantly, free hemoglobin and blood ethanol level significantly increased, whereas the L-arginine/asymmetric dimethylarginine ratio, a parameter of nitric oxide (NO) production capacity, and nitrite, a marker of NO synthesis, significantly decreased. Conclusion: Procedure-related pulmonary hypertension in patients undergoing PEI is multifactorial. Plasma concentrations of the NO precursor L-arginine are reduced by arginase released from lysed erythrocytes, a condition further exacerbated by the increased concentrations of symmetric dimethylarginine, which may compete with the cellular uptake of L-arginine. The result would be reduced synthesis of NO, the concentration of which would be further decreased extracellularly through free hemoglobin. Predictably, the result would be severe endothelial dysfunction and pulmonary hypertension in patients undergoing PEI. These mechanisms might also be relevant in other states of (sudden) hemolysis. (Crit Care Med 2009; 37:000‐000)