Xenon offers stable haemodynamics independent of induced hypothermia after hypoxia-ischaemia in newborn pigs

To assess the effect of 18 hour (h) 50% xenon (Xe) inhalation at normothermia (NT, 38.5A degrees C) or hypothermia (HT, 33.5A degrees C) on mean arterial blood pressure (MABP), inotropic support and heart rate (HR) following an induced perinatal global hypoxic-ischaemic insult (HI) in newborn pigs. Newborn pigs ventilated under inhalational anaesthesia, following a 45 min HI (inhaled oxygen fraction reduced until amplitude integrated electroencephalogram was less than 7 mu V), were randomised to three Xe (n = 45) (50% Xe 18 h with NT, HT 12 h or HT 24 h) or three non-Xe groups (n = 53) (0% Xe with NT, HT 12 h or HT 24 h) under otherwise identical conditions. We measured MABP and HR every minute. Hypotension (MABP < 40 mmHg) was treated sequentially with 2 x 10 mL/kg saline, dopamine, norepinephrine and hydrocortisone if required. Xe maintained higher MABP during HT (5.1 mmHg, 95% CI 2.34, 7.89), rewarming (10.1 mmHg, 95% CI 6.26, 13.95) and after cessation (4.1 mmHg, 95% CI 0.37, 7.84) independent of HT, inotropic support and acidosis. Xe reduced the duration of inotropic support by 12.6 h (95% CI 5.5, 19.73). Inotropic support decreased the HR reduction induced by HT from 9 to 5 bpm/A degrees C during cooling and from 10-7 to 4-3 bpm/A degrees C during rewarming. There was no interaction between Xe, HT, inotropic support and acidosis. Xe during HT cleared lactate faster; 3 h post-HI median (IQR) values of (Xe HT) 2.8 mmol/L (0.9, 3.1) vs. (HT) 5.9 mmol/L (2.5, 7.9), p = 0.0004. Xe maintained stable blood pressure, thereby reducing the inotropic support requirements during and after administration independently of induced HT-current neonatal encephalopathy treatment. Xe may offer haemodynamic benefits in clinical neuroprotection studies.