Combination of therapeutic mild hypothermia and delayed fluid resuscitation improved survival after uncontrolled haemorrhagic shock in mechanically ventilated rats

  • Said Hachimi-Idrissi
    Corresponding author. Tel.: +32 2 4775192; fax: +32 2 4775792.
    Department of Critical Care Medicine and Cerebral Resuscitation Research Group, Academic Hospital, Free University of Brussels, Laarbeeklaan 101, B-1090 Brussels, Belgium
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  • Xin Yang
    Department of Critical Care Medicine and Cerebral Resuscitation Research Group, Academic Hospital, Free University of Brussels, Laarbeeklaan 101, B-1090 Brussels, Belgium
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  • Duc Nam Nguyen
    Department of Critical Care Medicine and Cerebral Resuscitation Research Group, Academic Hospital, Free University of Brussels, Laarbeeklaan 101, B-1090 Brussels, Belgium
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  • Luc Huyghens
    Department of Critical Care Medicine and Cerebral Resuscitation Research Group, Academic Hospital, Free University of Brussels, Laarbeeklaan 101, B-1090 Brussels, Belgium
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      We challenged the current management of uncontrolled haemorrhagic shock (UHS) and put forward a hypothesis that therapeutic mild hypothermia combined with delayed fluid resuscitation will improve the survival rate. After an initial blood withdrawal of 3 ml/100 g for 15 min, the rat’s tail was amputated up to 75% to induce UHS phase I. The mean arterial blood pressure (MAP) was maintained at 40 mmHg or 80 mmHg, according to the assigned study group. This was followed by homeostasis of the tail wound and increase of the MAP up to 100 mmHg during resuscitation phase II. Finally, phase III was an observation of phase up to 72 h. Rats were anaesthetised and randomised into four groups. Group 1 received immediate fluid resuscitation and normothermia. Group 2 received immediate fluid resuscitation and therapeutic mild hypothermia. Group 3 received limited fluid solutions to maintain MAP at 40 mmHg and normothermia. Group 4 also received limited fluid solution, but the rats were subjected to therapeutic mild hypothermia. In groups 2 and 4, the body temperature was kept at 34 °C throughout the UHS phase I and resuscitation phase II. At the end of the observation phase III, the brains of the animals were fixed and analysed histologically. The blood loss from the tail during the UHS phase I was significantly higher in groups 1 and 2. The survival rate was 33.3, 83.3, 58.3 and 91.7%, respectively in groups 1–4. In all surviving rats, no histological brain damage was observed. These results indicate that therapeutic mild hypothermia or delayed fluid resuscitation increase the survival rate in this model. However, when mild hypothermia and limited fluid resuscitation were combined, the survival rate was the highest.


      Analisamos a abordagem habitual do choque hemorrágico não controlado (UHS) e formulamos a hipótese de a hipotermia terapêutica ligeira combinada com reanimação retardada com fluidos melhorar a taxa de sobrevivência. Após uma colheita inicial de sangue de 3 ml/100 g durante 15 min, a cauda do rato foi amputada até 75% para induzir a fase I do UHS. A pressão arterial média (MAP) foi mantida em 40 mmHg versus 80 mmHg, de acordo com o grupo de estudo atribuı́do. Seguiu-se a hemostase da ferida da cauda e normalização da MAP até aos 100 mmHg durante a fase II da reanimação. Finalmente, a fase III foi uma fase de observação até ás 72 h. Os ratos foram anestesiados e randomizados em 4 grupos. O grupo 1 recebeu fluidos imediatos e normotermia. O grupo 2 recebeu fluidos imediatos e hipotermia terapêutica ligeira. O grupo 3 recebeu uma quantidade limitada de fluidos para manter a MAP em 40 mmHg e normotermia. O grupo 4 também recebeu quantidades limitadas de fluidos mas os ratos foram sujeitos a hipotermia ligeira terapêutica. Nos grupos 2 e 4 a temperatura foi mantida em 34 °C durante a fase I do UHS e fase II da reanimação. No final da fase III de observação, os cérebros dos ratos foram fixados e analisados histologicamente. A perda de sangue da cauda durante a fase I do UHS foi significativamente maior nos grupos 1 e 2. A taxa de sobrevivência foi de 33.3, 83.3, 58.3 e 91.7% respectivamente nos grupos 1–4. Em todos os ratos que sobreviveram não se verificaram danos cerebrais a nı́vel histológico. Estes resultados indicam que a hipotermia ligeira terapêutica ou a reanimação retardada com fluidos aumentam a taxa de sobrevida neste modelo. No entanto, quando a hipotermia ligeira e a reanimação limitada com fluidos eram combinadas, a taxa de sobrevivência era a mais elevada.


      Desafiamos el actual manejo de shock por hemorragia sin control (UHS) y planteamos la hipótesis que la hipotermia terapéutica leve combinada con resucitación diferida con fluidos mejorarı́a la tasa de sobrevida. Después de una extracción inicial de 3 ml/100 g de sangre en 15 minutos, se amputó la cola de la rata en 75% para inducir UHS fase I. La presión arterial media (MAP) fue mantenida en 40 mmHg versus 80 mmHg, de acuerdo al estudio asignado. Esto fue seguido por la homeostasis de la herida de la cola y la normalización de la MAP hasta 100 mmHg durante la fase II de resucitación. Finalmente, la fase III fue una fase de observación hasta las 72 h. Se anestesiaron las ratas y se randomizaron en 4 grupos. El grupo 1 recibió resucitación con fluidos inmediata y normotermia. El grupo 2 recibió resucitación inmediata con fluidos e hipotermia terapéutica leve. El grupo 3 recibió cantidades limitadas de fluidos para mantener MAP en 40 mmHg y normotermia. El grupo 4 recibió también soluciones limitadas, pero las ratas fueron sometidas a hipotermia terapéutica leve. En los grupos 2 y 4, la temperatura corporal se mantuvo en 34 °C a lo largo de la fase I de UHS y la fase II de resucitación. Al final de la fase III de observación, se fijaron los cerebros de los animales y se realizó su análisis histológico. La pérdida de sangre de la cola durante la fase I de UHS fue significativamente mayor en los grupos 1 y 2. La tasa de sobrevida fue 33.3, 83.3, 58.3 y 91.7% en los grupos 1–4 respectivamente. En todas las ratas sobrevivientes no se encontró daño cerebral histológico. Estos resultados indican que la hipotermia terapéutica leve o la resucitación con fluidos limitados aumentan la tasa de sobrevida en este modelo. Sin embargo, cuando se combinan la hipotermia moderada y la resucitación diferida con fluidos, la tasa de sobrevida fue la mas alta.


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