Protection of the Neonatal Heart Following Normothermic Ischemia: A Comparison of Oxygenated Saline and Oxygenated versus Nonoxygenated Cardioplegia
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Targeted temperature management
Hospital discharge
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Therapeutic hypothermia after cardiac arrest, in adults and neonates, has been associated with improved survival and neurologic outcome. This approach has its roots in induced hypothermia for cardiopulmonary bypass, though historically, the temperatures targeted during bypass are much lower than in therapeutic hypothermia. Techniques used in therapeutic mild hypothermia range from whole-body cooling to selective head cooling. Overall, this appears to be a relatively low risk and well-tolerated endeavor. Evidence would also support that a slow and methodical rewarming phase is at least as important as the cooling phase. To date there have been no prospective studies in pediatric patients that agree with the benefit of mild hypothermia, as has been seen in adults and neonates. A large, prospective, and multicenter pediatric study is currently in progress.
Targeted temperature management
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Abstract
Hypothermia deaths pose a difficult challenge from the medico-legal point of view because no specific traces are left on the cadaver to be examined post-mortem. The concentrations of urinary catecholamines, adrenaline and noradrenaline increase in various stressful situations including cold stress, and high levels have been considered to be suggestive of lethal hypothermia. There is, however, a need for a better hypothermia indicator. A potential candidate could be thrombomodulin (TM), an endothelially expressed protein whose plasma concentration has been shown to elevate in response to hypothermia.
TM and catecholamine levels were studied in short-term cold exposure (human subjects, n = 7), in mild and severe hypothermia with or without rewarming (rats, n = 96) and in hypothermia deaths compared with deaths from cardiovascular diseases, traumas and other causes (autopsy cases, total n = 552).
Myocardial thrombomodulin transcript expression was increased in severely hypothermic rats, but was lower in hypothermia deaths than in other causes. The circulating TM level was transiently reduced in severe hypothermia. The myocardial and urinary TM protein levels were reduced in lethal hypothermia compared with other causes of death. TM and catecholamine levels correlated significantly in blood and urine both in living subjects and post-mortem examination. In severely hypothermic rats, there was an inverse relationship between plasma adrenaline concentration and myocardial thrombomodulin transcript level.
The results suggest that TM expression and secretion are altered by hypothermia, possibly linked to the actions of catecholamines. Analysing the post-mortem catecholamine and TM levels provides evidence of ante-mortem cold stress in suspected hypothermia deaths. Further studies should be conducted in order to reveal the exact mechanisms behind the regulation of TM on cell level.%%%%Tiivistelma
Paleltumiskuolemat ovat oikeuslaaketieteellisesti haastavia, koska vainajaan ei jaa paleltumiseen viittaavia yksiselitteisia loydoksia. Virtsan katekoliamiinien, adrenaliinin ja noradrenaliinin, pitoisuudet kasvavat stressitilanteissa kuten kylmaaltistuksessa. Korkeita pitoisuuksia on pidetty paleltumiseen viittaavana tekijana. Paremmalle paleltumista osoittavalle merkkiaineelle on kuitenkin selkea tarve. Eras mahdollinen merkkiaine voisi olla trombomoduliini (TM), joka on endoteelisolujen tuottama proteiini. Sen plasmapitoisuuden on aiemmin osoitettu nousevan alilampoisyystilassa.
TM- ja katekoliamiinitasoja tutkittiin lyhyessa kylmaaltistuksessa (koehenkilot, n = 7) seka lievassa ja vaikeassa alilampoisyystilassa joko lammityksen jalkeen tai ilman lammitysta (rotat, n = 96). Lisaksi verrattiin paleltumisen, sydan- ja verisuonitautien, vammojen seka muiden syiden aiheuttamia kuolemia (ruumiinavausaineisto, n = 552).
Sydanlihaksen trombomoduliini-transkriptin taso oli kohonnut vaikeasti alilampoisilla rotilla, mutta se oli matalampi paleltumiskuolemissa kuin muissa kuolemissa. Veren TM-taso oli hetkellisesti alentunut…
Thrombomodulin
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The authors present the first application of therapeutic hypothermia in a newborn in Poland. The female newborn, born with severe asphyxia, was transported to a referral perinatal center where the method of brain cooling was possible. Severe hypoxic ischemic encephalopathy was confirmed by an integrated EEG. During the cooling procedure (which lasted 72 hours), no important side effects were noticed. The neurodevelopmental outcome of the baby assessed during the first 2 years of her life is normal.
Perinatal asphyxia
Hypoxic-Ischemic Encephalopathy
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