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Xenon offers stable haemodynamics after global hypoxic-ischaemia in newborn pigs
  1. E Chakkarapani1,
  2. X Liu1,
  3. J Dingley2,
  4. M Thoresen1
  1. 1University of Bristol, Bristol, UK
  2. 2Swansea University, Swansea, UK

Abstract

Background Perinatal hypoxic ischaemic encephalopathy (HIE) causes cardiac dysfunction/hypotension. Xenon (Xe) anaesthesia offers short term stable haemodynamics in human adults/mature animals with cardiovascular risk. We studied long term haemodynamics during 50% xenon inhalation at normothermia (NT 38.5°C) or hypothermia (HT 33.5°C) in a newborn global Hypoxic-Ischaemic (HI) pig model.

Methods 98 newborn pigs were ventilated under inhalational anaesthesia, given a 45 min global HI insult (inhaled oxygen fraction reduced until amplitude integrated electroencephalogram <7 µV), then randomised to three xenon (50%Xe with NT18 h (h), HT12 h or HT24 h) or three non-xenon groups (NT, HT12 h or HT24 h) with intravenous anaesthesia. Mean arterial blood pressure (MABP) was measured every minute. Hypotension (<40 mm Hg for >10 min) was treated sequentially with 2×10 ml/kg saline, dopamine, norepinephrine, hydrocortisone if required.

Results Xenon maintained a higher MABP than in non-xenon groups; 4.5 mm Hg (95% CI 2.4 to 6.7) during Xe-inhalation and 4.1 mm Hg (95% CI 0.37 to 7.8) post-Xe therapy. Duration of inotropic support was reduced by 6.6 h (95%CI 3.5 to 9.8) during Xe-inhalation and by 7.9 h (95%CI 0.5 to 15.3) post-Xe therapy. Xe-inhalation during rewarming maintained higher MABP by 15.4 mm Hg, 95% CI 10.3 to 20.4. Xenon when combined with HT cleared lactate 3 h faster post-HI ((XeHT) 2.86 mmol (0, 14.7) vs (HT) 5.96 mmol/l (1.7, 13.8), p=0.0004). Hypothermia reduced heart rate by 10 beats/min (bpm)/°C; adding dopamine decreased this reduction to 7 bpm/°C.

Conclusion Xenon reduced post-HI inotropic support requirements during and after administration, independent of temperature. Xenon may offer haemodynamic benefits when used in clinical neuroprotection studies by reducing HI induced hypotension.

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