Beneficial effect of sevoflurane on endotoxin-induced pulmonary hypertension

Introduction

Pulmonary hypertension (PH) is a life-threatening disease commonly seen in ICU septic patients and associated with poor outcome. New and better therapies are required, since the response to various agents such as NO, prostaglandins and phosphodiesterase inhibitors is usually partial and the mortality rate remains high. Inhaled drugs seem to be an attractive treatment option, since they are delivered directly to pulmonary resistance vessels. A new device (anesthetic conserving device-AnaConDa (ACD)) permitting direct administration of volatile anaesthetics - such as sevoflurane - to the breathing circuit of a conventional ICU ventilator in a safe and effective way has recently been introduced. The aim of the present study was to evaluate the efficacy and safety of sevoflurane administration via the ACD on a porcine model of acute PH during sepsis.

Methods

PH was induced in 16 anaesthetized, mechanically ventilated swine (25 kg) by intravenous infusion of 0.5 mg/kg LPS (Escherichia coli, 111:B4) in a period of 30 minutes. After LPS, animals were randomized into two groups. In group A sevoflurane was infused via the ACD, according to the manufacturer's recommendations in order to obtain an end-tidal concentration of 0.5%, whereas group B did not receive sevoflurane and served as control. Haemodynamic parameters (systemic and pulmonary) were recorded before (phase 0) and after the LPS (phase 1) and every 20 minutes for the next 2 hours (phases 2 to 7).

Results

LPS was found to produce PH (phase 1) and to reduce arterial blood pressure in both groups. After sevoflurane infusion, both systolic (PAPs) and diastolic (PAPd) pulmonary pressures exhibited step-by-step reduction, which became statistically significant in phase 3 and thereafter, in relation to phase 1 values. On the contrary, in group B animals, not sevoflurane-treated, pulmonary pressures remained at high levels throughout the study period. Systemic arterial pressure exhibited an endotoxin-related reduction in both groups, which was not found to be affected by sevoflurane treatment.

Conclusions

Sevoflurane administration via the ACD was found to reduce the pulmonary pressure in a porcine model of endotoxin-induced acute PH without any detrimental effects on the systemic circulation. This may represent a significant advance in the treatment of acute PH. However, the potential clinical implications of the method merit further study.