Wu Xianren, Kochanek Patrick M, Cochran Kristin, Nozari Ala, Henchir Jeremy, Stezoski S William, Wagner Robert, Wisniewski Stephen, Tisherman Samuel A
Safar Center for Resuscitation Research, Department of Anesthesiology, University of Pittsburgh, PA 15260, USA.
J Trauma. 2005 Aug;59(2):291-9; discussion 299-301. doi: 10.1097/01.ta.0000179445.76729.2c.
Clinical studies have demonstrated improved survival after cardiac arrest with induction of mild hypothermia (34 degrees C). Infusion of ice-cold saline seems beneficial. The American Heart Association recommends therapeutic hypothermia for comatose survivors of cardiac arrest. For hemorrhagic shock (HS), laboratory studies suggest that mild hypothermia prolongs the golden hour for resuscitation. Yet, the effects of hypothermia during HS are unclear since retrospective clinical studies suggest that hypothermia is associated with increased mortality. Using a clinically relevant, large animal model with trauma and intensive care, we tested the hypothesis that mild hypothermia, induced with intravenous cold saline (ice cold or room temperature) and surface cooling, would improve survival after HS in pigs.
Pigs were prepared under isoflurane anesthesia. After laparotomy, venous blood (75 mL/kg) was continuously withdrawn over 3 hours (no systemic heparin). At HS 35 minutes, the spleen was transected. At HS 40 minutes, pigs were divided into three groups (n = 8, each): 1) Normothermia (Norm)(38 degrees C), induced with warmed saline; 2) Mild hypothermia (34 degrees C) induced with i.v. infusion of 2 degrees C saline (Hypo-Ice) and surface cooling; and 3) Mild hypothermia (34 degrees C), induced with room temperature (24 degrees C) i.v. saline (Hypo-Rm) and surface cooling. Fluids were given when mean arterial pressure (MAP) was <30 mmHg. At HS 3 hours, shed blood was returned and splenectomy was performed. Intensive care was continued to 24 hours.
At 24 hours, there were two survivors in the Norm group, four in the Hypo-Ice group and seven in the Hypo-Rm group (p < 0.05 versus the Norm group, Log Rank). Time required to achieve 34 degrees C was 17 +/- 9 minutes in the Hypo-Ice group and 15 +/- 4 minutes in the Hypo-Rm group (NS). Compared with the Hypo-Rm group, the Hypo-Ice group required less saline during early HS (321 +/- 122 versus 571 +/- 184 mL, p < 0.05). The Hypo-Ice group also had higher lactate levels than the Hypo-Rm group (p < 0.05). Hypothermia did not cause any increase in bleeding compared with normothermia.
Mild hypothermia during HS, induced by infusion of room temperature saline and surface cooling, improves survival in a clinically relevant model of HS and trauma. However, the use of iced saline in this model had detrimental effects and did not cool the animal more quickly than room temperature fluids. These findings suggest that optimal methods for induction of hypothermia need to be addressed for each potential indication, e.g. cardiac arrest versus HS.
临床研究表明，心脏骤停后诱导轻度低温（34摄氏度）可提高生存率。输注冰冷盐水似乎有益。美国心脏协会建议对心脏骤停后的昏迷幸存者进行治疗性低温治疗。对于失血性休克（HS），实验室研究表明轻度低温可延长复苏的黄金时间。然而，HS期间低温的影响尚不清楚，因为回顾性临床研究表明低温与死亡率增加有关。我们使用具有创伤和重症监护的临床相关大型动物模型，测试了以下假设：通过静脉输注冷盐水（冰冷或室温）和体表降温诱导的轻度低温可提高猪HS后的生存率。
猪在异氟烷麻醉下制备。剖腹术后，在3小时内持续抽取静脉血（75 mL/kg）（未使用全身肝素）。在HS 35分钟时，横断脾脏。在HS 40分钟时，将猪分为三组（每组n = 8）：1）常温组（Norm）（38摄氏度），用温热盐水诱导；2）轻度低温组（34摄氏度），通过静脉输注2摄氏度盐水（Hypo-Ice）和体表降温诱导；3）轻度低温组（34摄氏度），通过室温（24摄氏度）静脉盐水（Hypo-Rm）和体表降温诱导。当平均动脉压（MAP）<30 mmHg时给予液体。在HS 3小时时，回输 shed blood并进行脾切除术。重症监护持续至24小时。
在24小时时，Norm组有2只存活，Hypo-Ice组有4只存活，Hypo-Rm组有7只存活（与Norm组相比，p < 0.05，对数秩检验）。Hypo-Ice组达到34摄氏度所需时间为17 +/- 9分钟，Hypo-Rm组为15 +/- 4分钟（无显著性差异）。与Hypo-Rm组相比，Hypo-Ice组在早期HS期间所需盐水较少（321 +/- 122对571 +/- 184 mL，p < 0.05）。Hypo-Ice组的乳酸水平也高于Hypo-Rm组（p < 0.05）。与常温相比，低温未导致出血增加。
在HS期间，通过输注室温盐水和体表降温诱导的轻度低温可提高HS和创伤临床相关模型中的生存率。然而，在该模型中使用冰盐水有有害影响，且与室温液体相比，并未更快地使动物降温。这些发现表明，对于每种潜在适应症，如心脏骤停与HS，需要探讨诱导低温的最佳方法。
