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

Chakkarapani, Ela; Thoresen, Marianne; Liu, Xun; Walløe, Lars; Dingley, John

doi:10.1007/s00134-011-2442-7

Cited by 25 publications

(15 citation statements)

References 34 publications

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“…The mean HR decreased by 60 bpm during SHC equating to 17 bpm/°C using T deep brain or 40 bpm/°C using T rectal , and we previously reported that HT reduces HR by around 10 bpm/°C. This suggests that brain temperature is a more important determinant for HR than body temperature, consistent with the temperature-sensing area being in the hypothalamus (34).…”

Section: Cardiovascular Effectssupporting

confidence: 52%

Minimal systemic hypothermia combined with selective head cooling evaluated in a pig model of hypoxia-ischemia

et al. 2015

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Background: Selective head cooling (SHC) with moderate hypothermia (HT) and whole-body cooling are beneficial following perinatal asphyxia. SHC with systemic normothermia (NT) or minimal HT is under-investigated, could obviate systemic complications of moderate HT, and be applicable to preterm infants. We hypothesized that minimal systemic HT with SHC following hypoxia-ischemia (HI) would be neuroprotective compared with systemic NT. Methods: Newborn pigs underwent global HI causing permanent brain injury before being randomized to NT (rectal temperature (T rectal ) 38.5 °C) or minimal HT (T rectal 37.0 °C) with SHC (cooling cap and body wrap) for 48 h followed by 24-h NT with 72-h survival. results: SHC did not reduce global or regional neuropathology score when correcting for insult severity or compared with a NT group matched for HI severity but increased mortality by 26%. During 48 h, the SHC mean ± SD T rectal was 37.0 ± 0.2 °C, and T deep brain and T superficial brain were 35.0 ± 1.1 °C and 31.5 ± 1.6 °C, respectively, with stable T brain achieved ≥3 h after starting cooling. conclusion: This is the first study in newborn pigs of minimal systemic HT with SHC for 48 h and a further 24 h of NT following HI. Mortality was increased in the cooled group with no neuroprotection in survivors. t herapeutic hypothermia (HT) using whole-body cooling (WBC) to a rectal temperature (T rectal ) of 33.5 °C or selective head cooling (SHC) with moderate systemic HT to 34.5 °C is the only effective treatment for hypoxic ischemic encephalopathy (HIE) in term infants (1). HIE also occurs in preterm infants and HT trials are planned (e.g., Preemie Hypothermia for Neonatal Encephalopathy, NCT01793129) but concerns remain about systemic adverse effects (2-4). SHC without moderate systemic HT is under-investigated and is suggested to reduce potential systemic complications of whole body-HT. Reducing deep-brain temperature (T deep brain ) using SHC in term infants is difficult but may be easier in preterm infants with their smaller head size, thinner skin, and skull (5). In newborn pigs, T deep brain is within 1 °C of core temperature at normothermia (NT) but during SHC there is a gradient of between 3 and 7 °C (6-9). SHC may offer an advantage over WBC because different brain regions may have different optimum temperatures for neuroprotection (9-11).Short-term SHC with systemic NT is possible experimentally but neuroprotection has not been assessed using an adequate treatment period using clinically available equipments (12-14). We showed previously that SHC combined with moderate systemic HT to 33.5 °C was neuroprotective using a global model of perinatal hypoxia-ischemia (HI) in the newborn pig (8). We hypothesized that minimal systemic HT (1.5 °C below core temperature) combined with SHC for 48 h would be neuroprotective compared with systemic NT using a validated neuropathology score. RESULTSThere were no differences in age, weight, sex distribution or baseline arterial pH, lactate, and blood glucose between groups ( Table 1)...

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Section: Cardiovascular Effectssupporting

confidence: 52%

Minimal systemic hypothermia combined with selective head cooling evaluated in a pig model of hypoxia-ischemia

et al. 2015

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“…22 Xe + TH improved cardiovascular stability and reduced inotropic requirements. 23 There was no increased oxygen requirement, no cuffed tracheal tube complications, and no stridor or extubation delays in either our experimental pig study 12 (n = 120) or this clinical study. There are ongoing concerns regarding neuroapoptosis in the immature brain with inhalation anesthetic agents.…”

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confidence: 64%

Xenon Ventilation During Therapeutic Hypothermia in Neonatal Encephalopathy: A Feasibility Study

et al. 2014

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BACKGROUND AND OBJECTIVES: Therapeutic hypothermia has become standard of care in newborns with moderate and severe neonatal encephalopathy; however, additional interventions are needed. In experimental models, breathing xenon gas during cooling offers long-term additive neuroprotection. This is the first xenon feasibility study in cooled infants. Xenon is expensive, requiring a closed-circuit delivery system. METHODS: Cooled newborns with neonatal encephalopathy were eligible for this single-arm, dose-escalation study if clinically stable, under 18 hours of age and requiring less than 35% oxygen. Xenon duration increased stepwise from 3 to 18 hours in 14 subjects; 1 received 25% xenon and 13 received 50%. Respiratory, cardiovascular, neurologic (ie, amplitude-integrated EEG, seizures), and inflammatory (C-reactive protein) effects were examined. The effects of starting or stopping xenon rapidly or slowly were studied. Three matched control subjects per xenon treated subject were selected from our cooling database. Follow-up was at 18 months using mental developmental and physical developmental indexes of the Bayley Scales of Infant Development II. RESULTS: No adverse respiratory or cardiovascular effects, including post-extubation stridor, were seen. Xenon increased sedation and suppressed seizures and background electroencephalographic activity. Seizures sometimes occurred during rapid weaning of xenon but not during slow weaning. C-reactive protein levels were similar between groups. Hourly xenon consumption was 0.52 L. Three died, and 7 of 11 survivors had mental and physical developmental index scores ≥70 at follow-up. CONCLUSIONS: Breathing 50% xenon for up to 18 hours with 72 hours of cooling was feasible, with no adverse effects seen with 18 months' follow-up.

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“…23,24 The physiological decrease in HR during TH was counteracted by inotropic support in neonates, similar to previous findings in pigs. 25 The mean arterial blood pressure level for infants during TH did not differ between the infants with and without inotropic support, and it seems as clinicians aim for the same blood pressure at the two temperatures. 22 However, the optimal mean arterial blood pressure during TH is yet to be defined.…”

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confidence: 82%

Heart rate response to therapeutic hypothermia in infants with hypoxic–ischaemic encephalopathy

2016

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Elstad, M., Liu, X., & Thoresen, M. (2016). Heart rate response to therapeutic hypothermia in infants with hypoxic-ischaemic encephalopathy. Resuscitation, 106, 53-57. DOI: 10.1016/j.resuscitation.2016 Peer reviewed version Link to publication record in Explore Bristol Research PDF-document This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Elsevier at http://www.sciencedirect.com/science/article/pii/S0300957216301216. Please refer to any applicable terms of use of the publisher. University of Bristol -Explore Bristol Research General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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

Abstract: 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.

Cited by 25 publications

References 34 publications

Minimal systemic hypothermia combined with selective head cooling evaluated in a pig model of hypoxia-ischemia

Minimal systemic hypothermia combined with selective head cooling evaluated in a pig model of hypoxia-ischemia

Xenon Ventilation During Therapeutic Hypothermia in Neonatal Encephalopathy: A Feasibility Study

Heart rate response to therapeutic hypothermia in infants with hypoxic–ischaemic encephalopathy

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