Neonatal group B streptococcal sepsis: Effects of late treatment with dazmegrel

Abstract

Neonatal group B streptococcal (GBS) sepsis produces arterial hypertension and hypoxemia that are preventable by pretreatment with the selective thromboxane A2 synthase inhibitor, dazmegrel. In the present experiment we administered dazmegrel (8 mg/kg) 2 h after the initiation of a 2 1/2 h infusion of 5 x 108 GBS/kg/h in ten 2- to 3-wk-old piglets. The multiple inert gas elimination technique was used to measure intrapulmonary shunt and alveolar ventilation to pulmonary perfusion mismatching. Thromboxane B2, the stable metabolite of thromboxane A2, and 6-keto-prostaglandin F(1α), the stable metabolite of prostacyclin, were assayed in arterial blood. Pulmonary arterial pressure, increased immediately after initiation of the GBS infusion, rising from 12 ± 2 to 34 ± 4 torr (p < 0.02); pulmonary vascular resistance increased by 400% (p < 0.01). Arterial hypoxemia developed (p < 0.02) in association with an increase in the low ventilation-perfusion ratio index but without a significant increase in intrapulmonary shunt. Thromboxane B2 levels increased 10-fold. Infusion of the carrier substance for dazmegrel after 2 h of GBS infusion produced no change in any variables. In contrast, infusion of the drug resulted in the return to pre-GBS infusion baseline values for both pulmonary arterial pressure and pulmonary vascular resistance. However, no improvement in arterial pO2 or in the low ventilation-perfusion ratio index occurred. Both pulmonary vascular resistance and pulmonary arterial pressure remained normal for 0.5 h after dazmegrel administration despite continued GBS infusion. Thromboxane B2 levels were decreased 30 min after dazmegrel (p < 0.02), but remained greater than pre-GBS levels. Dazmegrel reversed pulmonary hypertension and elevated pulmonary vascular resistance, but did so without concomitant improvement of in pulmonary gas exchange, when administered after 2 h of GBS infusion.