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Published in: Intensive Care Medicine 2/2012

01-02-2012 | Experimental

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

Authors: Elavazhagan Chakkarapani, Marianne Thoresen, Xun Liu, Lars Walloe, John Dingley

Published in: Intensive Care Medicine | Issue 2/2012

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Abstract

Purpose

To assess the effect of 18 hour (h) 50% xenon (Xe) inhalation at normothermia (NT, 38.5°C) or hypothermia (HT, 33.5°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.

Methods

Newborn pigs ventilated under inhalational anaesthesia, following a 45 min HI (inhaled oxygen fraction reduced until amplitude integrated electroencephalogram was less than 7 μV), 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 × 10 mL/kg saline, dopamine, norepinephrine and hydrocortisone if required.

Results

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/°C during cooling and from 10−7 to 4−3 bpm/°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.

Conclusion

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.
Literature
1.
go back to reference Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ (2005) Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365:663–670PubMed Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ (2005) Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365:663–670PubMed
2.
go back to reference Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353:1574–1584PubMedCrossRef Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353:1574–1584PubMedCrossRef
3.
go back to reference Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P (2009) Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 361:1349–1358PubMedCrossRef Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P (2009) Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med 361:1349–1358PubMedCrossRef
4.
go back to reference Thoresen M, Haaland K, Loberg EM, Whitelaw A, Apricena F, Hanko E, Steen PA (1996) A piglet survival model of posthypoxic encephalopathy. Pediatr Res 40:738–748PubMedCrossRef Thoresen M, Haaland K, Loberg EM, Whitelaw A, Apricena F, Hanko E, Steen PA (1996) A piglet survival model of posthypoxic encephalopathy. Pediatr Res 40:738–748PubMedCrossRef
5.
go back to reference Haaland K, Loberg EM, Steen PA, Satas S, Thoresen M (1997) The effect of mild post-hypoxic hypothermia on organ pathology in a piglet survival model of global hypoxia. Prenat Neonat Med 2:329–337 Haaland K, Loberg EM, Steen PA, Satas S, Thoresen M (1997) The effect of mild post-hypoxic hypothermia on organ pathology in a piglet survival model of global hypoxia. Prenat Neonat Med 2:329–337
6.
go back to reference Liu X, Tooley J, Loberg EM, Suleiman MS, Thoresen M (2011) Immediate hypothermia reduces cardiac troponin I after hypoxic-ischemic encephalopathy in newborn pigs. Pediatr Res 70:352–356PubMed Liu X, Tooley J, Loberg EM, Suleiman MS, Thoresen M (2011) Immediate hypothermia reduces cardiac troponin I after hypoxic-ischemic encephalopathy in newborn pigs. Pediatr Res 70:352–356PubMed
7.
go back to reference Battin MR, Thoresen M, Robinson E, Polin RA, Edwards AD, Gunn AJ (2009) Does head cooling with mild systemic hypothermia affect requirement for blood pressure support? Pediatrics 123:1031–1036PubMedCrossRef Battin MR, Thoresen M, Robinson E, Polin RA, Edwards AD, Gunn AJ (2009) Does head cooling with mild systemic hypothermia affect requirement for blood pressure support? Pediatrics 123:1031–1036PubMedCrossRef
8.
go back to reference Thoresen M, Hobbs CE, Wood T, Chakkarapani E, Dingley J (2009) Cooling combined with immediate or delayed xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia. J Cereb Blood Flow Metab 29:707–714PubMedCrossRef Thoresen M, Hobbs CE, Wood T, Chakkarapani E, Dingley J (2009) Cooling combined with immediate or delayed xenon inhalation provides equivalent long-term neuroprotection after neonatal hypoxia-ischemia. J Cereb Blood Flow Metab 29:707–714PubMedCrossRef
9.
go back to reference Hobbs C, Thoresen M, Tucker A, Aquilina K, Chakkarapani E, Dingley J (2008) Xenon and hypothermia combine additively, offering long-term functional and histopathologic neuroprotection after neonatal hypoxia/ischemia. Stroke 39:1307–1313PubMedCrossRef Hobbs C, Thoresen M, Tucker A, Aquilina K, Chakkarapani E, Dingley J (2008) Xenon and hypothermia combine additively, offering long-term functional and histopathologic neuroprotection after neonatal hypoxia/ischemia. Stroke 39:1307–1313PubMedCrossRef
10.
go back to reference Chakkarapani E, Dingley J, Liu X, Hoque N, Aquilina K, Porter H, Thoresen M (2010) Xenon enhances hypothermic neuroprotection in asphyxiated newborn pigs. Ann Neurol 68:330–341PubMedCrossRef Chakkarapani E, Dingley J, Liu X, Hoque N, Aquilina K, Porter H, Thoresen M (2010) Xenon enhances hypothermic neuroprotection in asphyxiated newborn pigs. Ann Neurol 68:330–341PubMedCrossRef
11.
go back to reference Boomsma F, Rupreht J, Man in’t Veld AJ, de Jong FH, Dzoljic M, Lachmann B (1990) Haemodynamic and neurohumoral effects of xenon anaesthesia. A comparison with nitrous oxide. Anaesthesia 45:273–278PubMedCrossRef Boomsma F, Rupreht J, Man in’t Veld AJ, de Jong FH, Dzoljic M, Lachmann B (1990) Haemodynamic and neurohumoral effects of xenon anaesthesia. A comparison with nitrous oxide. Anaesthesia 45:273–278PubMedCrossRef
12.
go back to reference Lachmann B, Armbruster S, Schairer W, Landstra M, Trouwborst A, Van Daal GJ, Kusuma A, Erdmann W (1990) Safety and efficacy of xenon in routine use as an inhalational anaesthetic. Lancet 335:1413–1415PubMedCrossRef Lachmann B, Armbruster S, Schairer W, Landstra M, Trouwborst A, Van Daal GJ, Kusuma A, Erdmann W (1990) Safety and efficacy of xenon in routine use as an inhalational anaesthetic. Lancet 335:1413–1415PubMedCrossRef
13.
go back to reference Rossaint R, Reyle-Hahn M, Schulte Am Esch J, Scholz J, Scherpereel P, Vallet B, Giunta F, Del Turco M, Erdmann W, Tenbrinck R, Hammerle AF, Nagele P (2003) Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery. Anesthesiology 98:6–13PubMedCrossRef Rossaint R, Reyle-Hahn M, Schulte Am Esch J, Scholz J, Scherpereel P, Vallet B, Giunta F, Del Turco M, Erdmann W, Tenbrinck R, Hammerle AF, Nagele P (2003) Multicenter randomized comparison of the efficacy and safety of xenon and isoflurane in patients undergoing elective surgery. Anesthesiology 98:6–13PubMedCrossRef
14.
go back to reference Thoresen M, Whitelaw A (2000) Cardiovascular changes during mild therapeutic hypothermia and rewarming in infants with hypoxic-ischemic encephalopathy. Pediatrics 106:92–99PubMedCrossRef Thoresen M, Whitelaw A (2000) Cardiovascular changes during mild therapeutic hypothermia and rewarming in infants with hypoxic-ischemic encephalopathy. Pediatrics 106:92–99PubMedCrossRef
15.
go back to reference Fugelseth D, Satas S, Steen PA, Thoresen M (2003) Cardiac output, pulmonary artery pressure, and patent ductus arteriosus during therapeutic cooling after global hypoxia-ischaemia. Arch Dis Child 88:F223–F228 Fugelseth D, Satas S, Steen PA, Thoresen M (2003) Cardiac output, pulmonary artery pressure, and patent ductus arteriosus during therapeutic cooling after global hypoxia-ischaemia. Arch Dis Child 88:F223–F228
17.
go back to reference Haaland K, Karlsson B, Skovlund E, Lagercrantz H, Thoresen M (1995) Postnatal development of the cerebral blood flow velocity response to changes in CO2 and mean arterial blood pressure in the piglet. Acta Paediatr 84:1414–1420PubMedCrossRef Haaland K, Karlsson B, Skovlund E, Lagercrantz H, Thoresen M (1995) Postnatal development of the cerebral blood flow velocity response to changes in CO2 and mean arterial blood pressure in the piglet. Acta Paediatr 84:1414–1420PubMedCrossRef
18.
go back to reference Fugelseth D, Satas S, Runde M, Haga P, Thoresen M (1999) Cardiac function and morphology studied by two-dimensional Doppler echocardiography in unsedated newborn pigs. Exp Physiol 84:69–78PubMed Fugelseth D, Satas S, Runde M, Haga P, Thoresen M (1999) Cardiac function and morphology studied by two-dimensional Doppler echocardiography in unsedated newborn pigs. Exp Physiol 84:69–78PubMed
19.
go back to reference Tooley JR, Satas S, Porter H, Silver IA, Thoresen M (2003) Head cooling with mild systemic hypothermia in anesthetized piglets is neuroprotective. Ann Neurol 53:65–72PubMedCrossRef Tooley JR, Satas S, Porter H, Silver IA, Thoresen M (2003) Head cooling with mild systemic hypothermia in anesthetized piglets is neuroprotective. Ann Neurol 53:65–72PubMedCrossRef
20.
go back to reference Haaland K, Loberg EM, Steen PA, Thoresen M (1997) Posthypoxic hypothermia in newborn piglets. Pediatr Res 41:505–512PubMedCrossRef Haaland K, Loberg EM, Steen PA, Thoresen M (1997) Posthypoxic hypothermia in newborn piglets. Pediatr Res 41:505–512PubMedCrossRef
21.
go back to reference Chakkarapani E, Thoresen M, Hobbs CE, Aquilina K, Liu X, Dingley J (2009) A closed-circuit neonatal xenon delivery system: a technical and practical neuroprotection feasibility study in newborn pigs. Anesth Analg 109:451–460PubMedCrossRef Chakkarapani E, Thoresen M, Hobbs CE, Aquilina K, Liu X, Dingley J (2009) A closed-circuit neonatal xenon delivery system: a technical and practical neuroprotection feasibility study in newborn pigs. Anesth Analg 109:451–460PubMedCrossRef
22.
go back to reference Tuchsherer M, Puppe B, Tuchsherer A, Tiemann U (2000) Early identification of neonates at risk: traits of newborn piglets with respect to survival. Thenogenology 54:371–388CrossRef Tuchsherer M, Puppe B, Tuchsherer A, Tiemann U (2000) Early identification of neonates at risk: traits of newborn piglets with respect to survival. Thenogenology 54:371–388CrossRef
25.
go back to reference Marx T, Froeba G, Wagner D, Baeder S, Goertz A, Georgieff M (1997) Effects on haemodynamics and catecholamine release of xenon anaesthesia compared with total iv anaesthesia in the pig. Br J Anaesth 78:326–327PubMed Marx T, Froeba G, Wagner D, Baeder S, Goertz A, Georgieff M (1997) Effects on haemodynamics and catecholamine release of xenon anaesthesia compared with total iv anaesthesia in the pig. Br J Anaesth 78:326–327PubMed
26.
go back to reference Baumert JH, Hein M, Hecker KE, Satlow S, Neef P, Rossaint R (2008) Xenon or propofol anaesthesia for patients at cardiovascular risk in non-cardiac surgery. Br J Anaesth 100:605–611PubMedCrossRef Baumert JH, Hein M, Hecker KE, Satlow S, Neef P, Rossaint R (2008) Xenon or propofol anaesthesia for patients at cardiovascular risk in non-cardiac surgery. Br J Anaesth 100:605–611PubMedCrossRef
27.
go back to reference Goto T, Hanne P, Ishiguro Y, Ichinose F, Niimi Y, Morita S (2004) Cardiovascular effects of xenon and nitrous oxide in patients during fentanyl-midazolam anaesthesia. Anaesthesia 59:1178–1183PubMedCrossRef Goto T, Hanne P, Ishiguro Y, Ichinose F, Niimi Y, Morita S (2004) Cardiovascular effects of xenon and nitrous oxide in patients during fentanyl-midazolam anaesthesia. Anaesthesia 59:1178–1183PubMedCrossRef
28.
go back to reference Francis RC, Reyle-Hahn MS, Hohne C, Klein A, Theruvath I, Donaubauer B, Busch T, Boemke W (2008) The haemodynamic and catecholamine response to xenon/remifentanil anaesthesia in Beagle dogs. Lab Anim 42:338–349PubMedCrossRef Francis RC, Reyle-Hahn MS, Hohne C, Klein A, Theruvath I, Donaubauer B, Busch T, Boemke W (2008) The haemodynamic and catecholamine response to xenon/remifentanil anaesthesia in Beagle dogs. Lab Anim 42:338–349PubMedCrossRef
29.
go back to reference Dingley J, King R, Hughes L, Terblanche C, Mahon S, Hepp M, Youhana A, Watkins A (2001) Exploration of xenon as a potential cardiostable sedative: a comparison with propofol after cardiac surgery. Anaesthesia 56:829–835PubMedCrossRef Dingley J, King R, Hughes L, Terblanche C, Mahon S, Hepp M, Youhana A, Watkins A (2001) Exploration of xenon as a potential cardiostable sedative: a comparison with propofol after cardiac surgery. Anaesthesia 56:829–835PubMedCrossRef
30.
go back to reference Thoresen M (2008) Supportive care during neuroprotective hypothermia in the term newborn: adverse effects and their prevention. Clin Perinatol 35:749−763, vii Thoresen M (2008) Supportive care during neuroprotective hypothermia in the term newborn: adverse effects and their prevention. Clin Perinatol 35:749−763, vii
31.
go back to reference Hettrick DA, Pagel PS, Kersten JR, Tessmer JP, Bosnjak ZJ, Georgieff M, Warltier DC (1998) Cardiovascular effects of xenon in isoflurane-anesthetized dogs with dilated cardiomyopathy. Anesthesiology 89:1166–1173PubMedCrossRef Hettrick DA, Pagel PS, Kersten JR, Tessmer JP, Bosnjak ZJ, Georgieff M, Warltier DC (1998) Cardiovascular effects of xenon in isoflurane-anesthetized dogs with dilated cardiomyopathy. Anesthesiology 89:1166–1173PubMedCrossRef
32.
go back to reference Preckel B, Mullenheim J, Moloschavij A, Thamer V, Schlack W (2000) Xenon administration during early reperfusion reduces infarct size after regional ischemia in the rabbit heart in vivo. Anesth Analg 91:1327–1332PubMedCrossRef Preckel B, Mullenheim J, Moloschavij A, Thamer V, Schlack W (2000) Xenon administration during early reperfusion reduces infarct size after regional ischemia in the rabbit heart in vivo. Anesth Analg 91:1327–1332PubMedCrossRef
33.
go back to reference Seder DB, Fraser GL, Robbins T, Libby L, Riker RR (2010) The bispectral index and suppression ratio are very early predictors of neurological outcome during therapeutic hypothermia after cardiac arrest. Intensive Care Med 36:281–288PubMedCrossRef Seder DB, Fraser GL, Robbins T, Libby L, Riker RR (2010) The bispectral index and suppression ratio are very early predictors of neurological outcome during therapeutic hypothermia after cardiac arrest. Intensive Care Med 36:281–288PubMedCrossRef
34.
go back to reference Goto T, Nakata Y, Saito H, Ishiguro Y, Niimi Y, Suwa K, Morita S (2000) Bispectral analysis of the electroencephalogram does not predict responsiveness to verbal command in patients emerging from xenon anaesthesia. Br J Anaesth 85:359–363PubMedCrossRef Goto T, Nakata Y, Saito H, Ishiguro Y, Niimi Y, Suwa K, Morita S (2000) Bispectral analysis of the electroencephalogram does not predict responsiveness to verbal command in patients emerging from xenon anaesthesia. Br J Anaesth 85:359–363PubMedCrossRef
Metadata
Title
Xenon offers stable haemodynamics independent of induced hypothermia after hypoxia–ischaemia in newborn pigs
Authors
Elavazhagan Chakkarapani
Marianne Thoresen
Xun Liu
Lars Walloe
John Dingley
Publication date
01-02-2012
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 2/2012
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-011-2442-7

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