Presented at the Neonatal Society 2009 Autumn Meeting.

Chakkarapani E¹, Hoque N¹, Liu X¹, Porter H², Dingley J³, Thoresen M¹

¹ CSSB, University of Bristol, Bristol, UK
² Histopathology, Leicester Royal Infirmary, UK
³ Anaesthetics, Morriston Hospital, Swansea, Wales, UK

Background: Perinatal asphyxia in newborn infants result in cardiac impairment manifesting as hypotension and need for inotropes, both in cooled and non-cooled infants(1-3). Xenon (Xe) offer cardioprotection after myocardial reperfusion injury in animal models and exhibit cardiostability in post operative cardiac surgery adults(4,5) Xe’s potential cardiosupportive effect after perinatal asphyxia is not studied. Our newborn global hypoxic ischaemic (HI) pig model expose the whole body to HI and result in cardiac impairment and histological cardiac injury(6).

Aim: To study the effect of Xe on duration of inotropic support and number of inotropic drugs required compared to hypothermia (HT) and normothermia (NT) in our global HI newborn pig model.

Methods: The study was performed in accordance with UK home office regulations. Ninety eight pigs (mean age (17.6 hours (h), weight (1671g)) were randomised after the HI insult to NT (rectal temperature (Trec):38.5°C, n=18), XeNT (n=12), HT (n=35) (Trec: 33.5°C; 12hHT=18; 24hHT=17) and combined Xenon Hypothermia XeHT (n=33) (Xe12hHT=18; Xe24hHT=15). During the 45 min global HI insult, the inspired oxygen was reduced until the aEEG amplitude fell below 7µv. After HI, all animals were ventilated under intravenous anaesthesia, while XeHT and XeNT animals were ventilated with 18h of 50% Xe, 30%O2 and 20%N2 using a closed circuit system, consuming only 0.2l/hr of Xe (7). 12hHT and 24hHT animals underwent 12h and 24h whole body cooling to 33.5°C respectively and rewarmed to 38.5°C over 10h under intravenous anaesthesia. Intraarterial blood pressure was monitored continuously until extubation and thereafter every 6h until perfusion fixation at 72h. Hypotension (< 40 mmHg for >10 min) was treated with 2×10 mls/kg of saline, followed by Dopamine (D), Noradrenaline (N) and Hydrocortisone (H). Mann Whitney U test, multiple linear regression and logistic regression were used.

Results: There was no difference in the insult severity and intravenous anaesthetic dose between the treatment groups. Xe inhalation significantly reduced the duration of inotropic support at both NT (median duration h, NT (20.75) vs XeNT (0)) and HT (median duration h, HT (17.63) vs XeHT (4)). Xe inhalation and pig’s age (h) in XeHT and HT groups, and Xe inhalation in NT and XeNT groups were the independent significant predictors of inotrope duration (Table 1). Xe reduced the need for inotropes at NT (odds ratio (95% CI): 0.34(0.18, 0.66)). None of the Xe animals needed more than two inotropes at NT or HT.

Table 1: Multiple linear regression model with inotrope duration as dependent variable and age, weight, sex, 18hXe, HT duration (12h or 24h), insult severity as covariates.

Conclusion: Xe inhalation at NT or HT significantly reduced the duration of inotropic support and number of inotropes required compared to NT and HT after global HI. Adding Xe with HT is cardiosupportive after HI.

References
1. Gluckman PD, et al. Lancet. 2005;365:663-670
2. Shankaran S, et al. N Engl J Med.2005;353:1574-1584
3. Azzopardi D, et al. N Engl J Med.2009;361:1349-58
4. Dingley J, et al. Anaesthesia. 2001;56:829-835
5. Preckel B, et al. Anesthesia and analgesia. 2000;91:1327-1332
6. Haaland K, et al. Prenat Neonat Med 2. 1997:329-337
7. Chakkarapani E, et al. Anesthesia and analgesia. 2009;109:451-460.