Uncontrolled hemorrhagic shock results in a hypercoagulable state modulated by initial fluid resuscitation regimens

Gordon M. Riha, Nicholas R. Kunio, Philbert Van, Igor Kremenevskiy, Ross Anderson, Gregory J. Hamilton, Jerome A. Differding, Martin Schreiber

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    BACKGROUND: Previous studies have shown large-volume resuscitation modulates coagulopathy and inflammation. Our objective was to analyze the effects of initial bolus fluids used in military and civilian settings on coagulation and inflammation in a prospective, randomized, blinded trial of resuscitation of uncontrolled hemorrhage. METHODS: Fifty swinewere anesthetized, intubated, and ventilated and had monitoring lines placed.AGradeVliver injurywas performed followed by 30 minutes of hemorrhage. After 30 minutes, the liver was packed, and randomized fluid resuscitation was initiated during a 12-minute period with 2 L of normal saline, 2 L of lactated Ringer's solution, 250 mL of 7.5% saline with 3% Dextran, 500 mL of Hextend, or no fluid (NF). Animals were monitored for 2 hours after injury. Thrombelastograms (TEGs), prothrombin time (PT), partial thromboplastin time, fibrinogen aswell as serum interleukin 6, interleukin 8, and tumor necrosis factor > levelswere drawn at baseline and after 1 hour and 2 hours. RESULTS: The NF group had less posttreatment blood loss compared with other groups (p <0.01). Blood losswas similar in the other groups. TEG R values in each group decreased from baseline at 1 and 2 hours (p <0.02). The groups receiving 2 L of normal saline, 250 mL of 7.5% saline with 3% Dextran, or 500 mL of Hextend had lower TEG maximum amplitude values compared with NF group (p <0.02). All fluids except lactated Ringer's solution resulted in significant increases in PT compared with NF, whereas all fluids resulted in significant decreases in fibrinogen compared with NF (p <0.02). Fluid resuscitation groups as well as NF group demonstrated significant increases in inflammatory cytokines from baseline to 1 hour and baseline to 2 hours. There were no significant differences in inflammatory cytokines between groups at 2 hours. CONCLUSION: Withholding fluid resulted in the least significant change in PT, fibrinogen, and maximum amplitude and in the lowest posttreatment blood loss. Resuscitation with different initial fluid resuscitation strategies did not result in increased proinflammatory mediators compared with animals that did not receive fluid.

    Original languageEnglish (US)
    Pages (from-to)129-134
    Number of pages6
    JournalJournal of Trauma and Acute Care Surgery
    Volume75
    Issue number1
    DOIs
    StatePublished - Jul 2013

    Fingerprint

    Hemorrhagic Shock
    Resuscitation
    Prothrombin Time
    Fibrinogen
    Dextrans
    Hemorrhage
    Cytokines
    Inflammation
    Partial Thromboplastin Time
    Interleukin-8
    Interleukin-6
    Tumor Necrosis Factor-alpha
    Liver
    Wounds and Injuries
    Serum

    Keywords

    • Coagulation
    • Hemorrhage
    • Inflammation
    • Shock
    • Swine

    ASJC Scopus subject areas

    • Critical Care and Intensive Care Medicine
    • Surgery

    Cite this

    Uncontrolled hemorrhagic shock results in a hypercoagulable state modulated by initial fluid resuscitation regimens. / Riha, Gordon M.; Kunio, Nicholas R.; Van, Philbert; Kremenevskiy, Igor; Anderson, Ross; Hamilton, Gregory J.; Differding, Jerome A.; Schreiber, Martin.

    In: Journal of Trauma and Acute Care Surgery, Vol. 75, No. 1, 07.2013, p. 129-134.

    Research output: Contribution to journalArticle

    Riha, Gordon M. ; Kunio, Nicholas R. ; Van, Philbert ; Kremenevskiy, Igor ; Anderson, Ross ; Hamilton, Gregory J. ; Differding, Jerome A. ; Schreiber, Martin. / Uncontrolled hemorrhagic shock results in a hypercoagulable state modulated by initial fluid resuscitation regimens. In: Journal of Trauma and Acute Care Surgery. 2013 ; Vol. 75, No. 1. pp. 129-134.
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    abstract = "BACKGROUND: Previous studies have shown large-volume resuscitation modulates coagulopathy and inflammation. Our objective was to analyze the effects of initial bolus fluids used in military and civilian settings on coagulation and inflammation in a prospective, randomized, blinded trial of resuscitation of uncontrolled hemorrhage. METHODS: Fifty swinewere anesthetized, intubated, and ventilated and had monitoring lines placed.AGradeVliver injurywas performed followed by 30 minutes of hemorrhage. After 30 minutes, the liver was packed, and randomized fluid resuscitation was initiated during a 12-minute period with 2 L of normal saline, 2 L of lactated Ringer's solution, 250 mL of 7.5{\%} saline with 3{\%} Dextran, 500 mL of Hextend, or no fluid (NF). Animals were monitored for 2 hours after injury. Thrombelastograms (TEGs), prothrombin time (PT), partial thromboplastin time, fibrinogen aswell as serum interleukin 6, interleukin 8, and tumor necrosis factor > levelswere drawn at baseline and after 1 hour and 2 hours. RESULTS: The NF group had less posttreatment blood loss compared with other groups (p <0.01). Blood losswas similar in the other groups. TEG R values in each group decreased from baseline at 1 and 2 hours (p <0.02). The groups receiving 2 L of normal saline, 250 mL of 7.5{\%} saline with 3{\%} Dextran, or 500 mL of Hextend had lower TEG maximum amplitude values compared with NF group (p <0.02). All fluids except lactated Ringer's solution resulted in significant increases in PT compared with NF, whereas all fluids resulted in significant decreases in fibrinogen compared with NF (p <0.02). Fluid resuscitation groups as well as NF group demonstrated significant increases in inflammatory cytokines from baseline to 1 hour and baseline to 2 hours. There were no significant differences in inflammatory cytokines between groups at 2 hours. CONCLUSION: Withholding fluid resulted in the least significant change in PT, fibrinogen, and maximum amplitude and in the lowest posttreatment blood loss. Resuscitation with different initial fluid resuscitation strategies did not result in increased proinflammatory mediators compared with animals that did not receive fluid.",
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    AU - Riha, Gordon M.

    AU - Kunio, Nicholas R.

    AU - Van, Philbert

    AU - Kremenevskiy, Igor

    AU - Anderson, Ross

    AU - Hamilton, Gregory J.

    AU - Differding, Jerome A.

    AU - Schreiber, Martin

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    N2 - BACKGROUND: Previous studies have shown large-volume resuscitation modulates coagulopathy and inflammation. Our objective was to analyze the effects of initial bolus fluids used in military and civilian settings on coagulation and inflammation in a prospective, randomized, blinded trial of resuscitation of uncontrolled hemorrhage. METHODS: Fifty swinewere anesthetized, intubated, and ventilated and had monitoring lines placed.AGradeVliver injurywas performed followed by 30 minutes of hemorrhage. After 30 minutes, the liver was packed, and randomized fluid resuscitation was initiated during a 12-minute period with 2 L of normal saline, 2 L of lactated Ringer's solution, 250 mL of 7.5% saline with 3% Dextran, 500 mL of Hextend, or no fluid (NF). Animals were monitored for 2 hours after injury. Thrombelastograms (TEGs), prothrombin time (PT), partial thromboplastin time, fibrinogen aswell as serum interleukin 6, interleukin 8, and tumor necrosis factor > levelswere drawn at baseline and after 1 hour and 2 hours. RESULTS: The NF group had less posttreatment blood loss compared with other groups (p <0.01). Blood losswas similar in the other groups. TEG R values in each group decreased from baseline at 1 and 2 hours (p <0.02). The groups receiving 2 L of normal saline, 250 mL of 7.5% saline with 3% Dextran, or 500 mL of Hextend had lower TEG maximum amplitude values compared with NF group (p <0.02). All fluids except lactated Ringer's solution resulted in significant increases in PT compared with NF, whereas all fluids resulted in significant decreases in fibrinogen compared with NF (p <0.02). Fluid resuscitation groups as well as NF group demonstrated significant increases in inflammatory cytokines from baseline to 1 hour and baseline to 2 hours. There were no significant differences in inflammatory cytokines between groups at 2 hours. CONCLUSION: Withholding fluid resulted in the least significant change in PT, fibrinogen, and maximum amplitude and in the lowest posttreatment blood loss. Resuscitation with different initial fluid resuscitation strategies did not result in increased proinflammatory mediators compared with animals that did not receive fluid.

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