Advertisement

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

  • Said Hachimi-Idrissi
    Correspondence
    Corresponding author. Tel.: +32 2 4775192; fax: +32 2 4775792.
    Affiliations
    Department of Critical Care Medicine and Cerebral Resuscitation Research Group, Academic Hospital, Free University of Brussels, Laarbeeklaan 101, B-1090 Brussels, Belgium
    Search for articles by this author
  • Xin Yang
    Affiliations
    Department of Critical Care Medicine and Cerebral Resuscitation Research Group, Academic Hospital, Free University of Brussels, Laarbeeklaan 101, B-1090 Brussels, Belgium
    Search for articles by this author
  • Duc Nam Nguyen
    Affiliations
    Department of Critical Care Medicine and Cerebral Resuscitation Research Group, Academic Hospital, Free University of Brussels, Laarbeeklaan 101, B-1090 Brussels, Belgium
    Search for articles by this author
  • Luc Huyghens
    Affiliations
    Department of Critical Care Medicine and Cerebral Resuscitation Research Group, Academic Hospital, Free University of Brussels, Laarbeeklaan 101, B-1090 Brussels, Belgium
    Search for articles by this author

      Abstract

      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.

      Sumàrio

      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.

      Resumen

      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.

      Keywords

      Palavras Chave

      Palabras Clave

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Resuscitation
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Committee on trauma. Advanced trauma life support program for physicians. Instructor Manual: American College of Surgeons; 1993.

        • Bourguignon P.R.
        • Shackford S.R.
        • Shiffer C.
        • Nichols P.
        • Nees A.V.
        Delayed fluid resuscitation of head injury and uncontrolled hemorrhagic shock.
        Arch. Surg. 1998; 133: 390-398
        • Glick Y.A.
        • Wilson L.D.
        • Aiello J.
        Hematocrit and metabolic changes caused by varied resuscitation strategies in a canine model of hemorrhagic shock.
        Am. J. Emerg. Med. 2002; 20: 303-309
        • Holmes J.F.
        • Sakles J.C.
        • Lewis G.
        • Wisner D.H.
        Effects of delaying fluid resuscitation on an injury to the systemic arterial vasculature.
        Acad. Emerg. Med. 2002; 9: 267-274
        • Kim S.H.
        • Stezoski S.W.
        • Safar P.
        • Capone A.
        • Tisherman S.
        Hypothermia and minimal fluid resuscitation increase survival after uncontrolled hemorrhagic shock in rats.
        J. Trauma. 1997; 42: 213-222
        • Gross D.
        • Landau E.H.
        • Assalia A.
        • Krausz M.M.
        Is hypertonic saline resuscitation safe in ‘uncontrolled’ hemorrhagic shock?.
        J. Trauma. 1988; 28: 751-756
        • Gross D.
        • Landau E.H.
        • Klin B.
        • Krausz M.M.
        Quantitative measurement of bleeding following hypertonic saline therapy in ‘uncontrolled’ hemorrhagic shock.
        J. Trauma. 1989; 29: 79-83
        • Sindlinger J.F.
        • Soucy D.M.
        • Greene S.P.
        • Barber A.E.
        • Illner H.
        • Shires G.T.
        The effects of isotonic saline volume resuscitation in uncontrolled hemorrhage.
        Surg. Gynecol. Obstet. 1993; 177: 545-550
        • Craig R.L.
        • Poole G.V.
        Resuscitation in uncontrolled hemorrhage.
        Am. Surg. 1994; 60: 59-62
        • Behrman S.W.
        • Fabian T.C.
        • Kudsk K.A.
        • Proctor K.G.
        Microcirculatory flow changes after initial resuscitation of hemorrhagic shock with 7.5% hypertonic saline/6% dextran 70.
        J. Trauma. 1991; 31: 589-598
        • Bickell W.H.
        • Wall Jr., M.J.
        • Pepe P.E.
        • et al.
        Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries.
        N. Engl. J. Med. 1994; 331: 1105-1109
        • Hachimi-Idrissi S.
        • Corne L.
        • Huyghens L.
        The effect of mild hypothermia and induced hypertension on long-term survival rate and neurological outcome after asphyxial cardiac arrest in rats.
        Resuscitation. 2001; 49: 73-82
        • Tisherman S.A.
        • Rodriguez A.
        • Safar P.
        Therapeutic hypothermia in traumatology.
        Surg. Clin. North Am. 1999; 79: 1269-1289
        • Takasu A.
        • Norio H.
        • Sakamoto T.
        • Okada Y.
        Mild hypothermia prolongs the survival time during uncontrolled hemorrhagic shock in rats.
        Resuscitation. 2002; 54: 303-309
        • Prueckner S.
        • Safar P.
        • Kentner R.
        • Stezoski J.
        • Tisherman S.A.
        Mild hypothermia increases survival from severe pressure-controlled hemorrhagic shock in rats.
        J. Trauma. 2001; 50: 253-262
      2. Yang X, Hachimi-Idrissi S, Nguyen DN, Zizi M, Huyghens L. Effect of resuscitative mild hypothermia and oxygen concentration on the survival time during lethal uncontrolled hemorrhagic shock in mechanically ventilated rats. Eur J Emerg Med (in press).

        • Kim S.H.
        • Stezoski S.W.
        • Safar P.
        • Tisherman S.A.
        Hypothermia, but not 100% oxygen breathing, prolongs survival time during lethal uncontrolled hemorrhagic shock in rats.
        J. Trauma. 1998; 44: 485-491
        • Stainsby D.
        • Maclennan S.
        • Hamilton P.J.
        Management of massive blood loss: a template guideline.
        Br. J. Anaesth. 2000; 85: 487-491
        • Greaves I.
        • Porter K.M.
        • Revell M.P.
        Fluid resuscitation in prehospital trauma care: a consensus view.
        J. R. Coll. Surg. Edinb. 2002; 47: 451-457
        • Jurkovish G.J.
        • Greiser W.B.
        • Luterman A.
        • Curreri P.W.
        Hypothermia in trauma victims: an ominous predictor of survival.
        J. Trauma. 1987; 27: 1019-1024
        • Steinmann S.
        • Shackford S.R.
        • Davis J.W.
        Implication of admission hypothermia in trauma patients.
        J. Trauma. 1990; 30: 200-202
        • Gentiletto L.M.
        • Rifley W.J.
        Continuous arteriovenous rewarming: report of a new technique for treating hypothermia.
        J. Trauma. 1991; 31: 1151-1154
        • Mizushima Y.
        • Wang P.
        • Cioffi W.G.
        • Bland K.I.
        • Chaudry I.H.
        Should normothermia be restored and maintained during resuscitation after trauma and haemorrhage?.
        J. Trauma. 2000; 48: 58-65
        • Silbergleit R.
        • Satz W.
        • Lee D.C.
        • McNamara R.M.
        Hypothermia from realistic fluid resuscitation in a model of hemorrhagic shock.
        Ann. Emerg. Med. 1998; 31: 339-343
        • Takasu A.
        • Stezoski S.W.
        • Stezoski J.
        • Safar P.
        • Tisherman S.A.
        Mild or moderate hypothermia, but not increased oxygen breathing, increases long-term survival after uncontrolled hemorrhagic shock in rats.
        Crit. Care Med. 2000; 28: 2465-2474
        • Bauer R.
        • Fritz H.
        • Walter B.
        • et al.
        Effect of mild hypothermia on cerebral oxygen uptake during gradual cerebral perfusion pressure decrease in piglets.
        Crit. Care Med. 2000; 28: 1128-1135
        • Wladis A.
        • Hahn R.G.
        • Brismar B.
        • Kjellstrom B.T.
        Induced hypothermia after high-energy soft-tissue injury and subsequent hemorrhagic shock.
        Shock. 2002; 17: 120-126
        • Lei B.
        • Tan X.
        • Cai H.
        • Xu Q.
        • Guo Q.
        Effect of moderate hypothermia on lipid peroxidation in canine brain tissue after cardiac arrest and resuscitation.
        Stroke. 1994; 25: 147-152
        • Phanithi P.B.
        • Yoshida Y.
        • Santana A.
        • Su M.
        • Kawamura S.
        • Yasui N.
        Mild hypothermia mitigates post-ischemic neuronal death following focal cerebral ischemia in rat brain: immunohistochemical study of Fas, caspase-3 and TUNEL.
        Neuropathology. 2000; 20: 273-282
        • Busto R.
        • Globus M.Y.
        • Dietrich W.D.
        • Martinez E.
        • Valdes I.
        • Ginsberg M.D.
        Effect of mild hypothermia on ischemia-induced release of neurotransmitters and free fatty acids in rat brain.
        Stroke. 1989; 20: 904-910
        • Kentner R.
        • Rollwagen F.M.
        • Prueckner S.
        • et al.
        Effects of mild hypothermia on survival and serum cytokines in uncontrolled hemorrhagic shock in rats.
        Shock. 2002; 17: 521-526
        • Jurkovich G.J.
        • Pitt R.M.
        • Curreri P.W.
        • Granger D.N.
        Hypothermia prevents increased capillary permeability following ischemia-reperfusion injury.
        J. Surg. Res. 1988; 44: 514-521
        • LeBlanc J.
        • Roberge C.
        • Valliere J.
        • Oakson G.
        The sympathetic nervous system in short-term adaptation to cold.
        Can. J. Physiol. Pharmacol. 1971; 49: 96-101
        • Carrillo P.
        • Takasu A.
        • Safar P.
        • et al.
        Prolonged severe hemorrhagic shock and resuscitation in rats does not cause subtle brain damage.
        J. Trauma. 1998; 45: 239-248
        • Soucy D.M.
        • Rude M.
        • Hsia W.C.
        • Hagedorn F.N.
        • Illner H.
        • Shires G.T.
        The effects of varying fluid volume and rate of resuscitation during uncontrolled hemorrhage.
        J. Trauma. 1999; 46: 209-215
        • Shah K.J.
        • Chiu W.C.
        • Scalea T.M.
        • Carlson D.E.
        Detrimental effects of rapid fluid resuscitation on hepatocellular function and survival after hemorrhagic shock.
        Shock. 2002; 18: 242-247