Plasma Resuscitation Improved Survival in a Cecal Ligation and Puncture Rat Model of Sepsis

Ronald Chang, John B. Holcomb, Par I. Johansson, Shibani Pati, Martin Schreiber, Charles E. Wade

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    BACKGROUND:: The paradigm shift from crystalloid to plasma resuscitation of traumatic hemorrhagic shock has improved patient outcomes due in part to plasma-mediated reversal of catecholamine and inflammation-induced endothelial injury, decreasing vascular permeability and attenuating organ injury. Since sepsis induces a similar endothelial injury as seen in hemorrhage, we hypothesized that plasma resuscitation would increase 48-hour survival in a rat sepsis model. METHODS:: Adult male Sprague-Dawley rats (375–425?g) were subjected to 35% cecal ligation and puncture (CLP) (t?=?0?h). Twenty-two hours post-CLP and prior to resuscitation (t?=?22?h), animals were randomized to resuscitation with normal saline (NS, 10?cc/kg/hr) or pooled rat fresh frozen plasma (FFP, 3.33?cc/kg/hr). Resuscitation under general anesthesia proceeded for the next six hours (t?=?22?h to t?=?28?h); lactate was checked every 2?hours, and fluid volumes were titrated based on lactate clearance. Blood samples were obtained before (t?=?22?h) and after resuscitation (t?=?28?h), and at death or study conclusion. Lung specimens were obtained for calculation of wet-to-dry weight ratio. Fisherʼs exact test was used to analyze the primary outcome of 48-hour survival. ANOVA with repeated measures was used to analyze the effect of FFP versus NS resuscitation on blood gas, electrolytes, blood urea nitrogen (BUN), creatinine, interleukin (IL)-6, IL-10, catecholamines, and syndecan-1 (marker for endothelial injury). A two-tailed alpha level of <0.05 was used for all statistical tests. RESULTS:: Thirty-three animals were studied: 14 FFP, 14 NS, and 5 sham. Post-CLP but pre-resuscitation (t?=?22?h) variables between FFP and NS animals were similar and significantly deranged compared to sham animals. FFP significantly increased 48-hour survival compared to NS (n?=?8 [57%] vs n?=?2 [14%]), attenuated the post-resuscitation (t?=?28?h) levels of epinephrine (mean 2.2 vs 7.0?ng/ml), norepinephrine, (3.8 vs 8.9?ng/ml), IL-6 (3.8 vs 18.7?ng/ml), and syndecan-1 (21.8 vs 31.0?ng/ml) (all p?<?0.05), improved the post-resuscitation PO2 to FiO2 ratio (353 vs 151), and reduced the pulmonary wet-to-dry weight ratio (5.28 vs 5.94) (all p?<?0.05). CONCLUSION:: Compared to crystalloid, plasma resuscitation increased 48-hour survival in a rat sepsis model, improved pulmonary function and decreased pulmonary edema, and attenuated markers for inflammation, endothelial injury, and catecholamines.

    Original languageEnglish (US)
    JournalShock
    DOIs
    StateAccepted/In press - Jun 6 2017

    Fingerprint

    Punctures
    Resuscitation
    Ligation
    Sepsis
    Survival
    Syndecan-1
    Wounds and Injuries
    Catecholamines
    Lung
    Lactic Acid
    Interleukin-6
    Traumatic Shock
    Inflammation
    Weights and Measures
    Hemorrhagic Shock
    Blood Urea Nitrogen
    Capillary Permeability
    Pulmonary Edema
    Interleukin-10
    General Anesthesia

    ASJC Scopus subject areas

    • Emergency Medicine
    • Critical Care and Intensive Care Medicine

    Cite this

    Plasma Resuscitation Improved Survival in a Cecal Ligation and Puncture Rat Model of Sepsis. / Chang, Ronald; Holcomb, John B.; Johansson, Par I.; Pati, Shibani; Schreiber, Martin; Wade, Charles E.

    In: Shock, 06.06.2017.

    Research output: Contribution to journalArticle

    Chang, Ronald ; Holcomb, John B. ; Johansson, Par I. ; Pati, Shibani ; Schreiber, Martin ; Wade, Charles E. / Plasma Resuscitation Improved Survival in a Cecal Ligation and Puncture Rat Model of Sepsis. In: Shock. 2017.
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    abstract = "BACKGROUND:: The paradigm shift from crystalloid to plasma resuscitation of traumatic hemorrhagic shock has improved patient outcomes due in part to plasma-mediated reversal of catecholamine and inflammation-induced endothelial injury, decreasing vascular permeability and attenuating organ injury. Since sepsis induces a similar endothelial injury as seen in hemorrhage, we hypothesized that plasma resuscitation would increase 48-hour survival in a rat sepsis model. METHODS:: Adult male Sprague-Dawley rats (375–425?g) were subjected to 35{\%} cecal ligation and puncture (CLP) (t?=?0?h). Twenty-two hours post-CLP and prior to resuscitation (t?=?22?h), animals were randomized to resuscitation with normal saline (NS, 10?cc/kg/hr) or pooled rat fresh frozen plasma (FFP, 3.33?cc/kg/hr). Resuscitation under general anesthesia proceeded for the next six hours (t?=?22?h to t?=?28?h); lactate was checked every 2?hours, and fluid volumes were titrated based on lactate clearance. Blood samples were obtained before (t?=?22?h) and after resuscitation (t?=?28?h), and at death or study conclusion. Lung specimens were obtained for calculation of wet-to-dry weight ratio. Fisherʼs exact test was used to analyze the primary outcome of 48-hour survival. ANOVA with repeated measures was used to analyze the effect of FFP versus NS resuscitation on blood gas, electrolytes, blood urea nitrogen (BUN), creatinine, interleukin (IL)-6, IL-10, catecholamines, and syndecan-1 (marker for endothelial injury). A two-tailed alpha level of <0.05 was used for all statistical tests. RESULTS:: Thirty-three animals were studied: 14 FFP, 14 NS, and 5 sham. Post-CLP but pre-resuscitation (t?=?22?h) variables between FFP and NS animals were similar and significantly deranged compared to sham animals. FFP significantly increased 48-hour survival compared to NS (n?=?8 [57{\%}] vs n?=?2 [14{\%}]), attenuated the post-resuscitation (t?=?28?h) levels of epinephrine (mean 2.2 vs 7.0?ng/ml), norepinephrine, (3.8 vs 8.9?ng/ml), IL-6 (3.8 vs 18.7?ng/ml), and syndecan-1 (21.8 vs 31.0?ng/ml) (all p?<?0.05), improved the post-resuscitation PO2 to FiO2 ratio (353 vs 151), and reduced the pulmonary wet-to-dry weight ratio (5.28 vs 5.94) (all p?<?0.05). CONCLUSION:: Compared to crystalloid, plasma resuscitation increased 48-hour survival in a rat sepsis model, improved pulmonary function and decreased pulmonary edema, and attenuated markers for inflammation, endothelial injury, and catecholamines.",
    author = "Ronald Chang and Holcomb, {John B.} and Johansson, {Par I.} and Shibani Pati and Martin Schreiber and Wade, {Charles E.}",
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    T1 - Plasma Resuscitation Improved Survival in a Cecal Ligation and Puncture Rat Model of Sepsis

    AU - Chang, Ronald

    AU - Holcomb, John B.

    AU - Johansson, Par I.

    AU - Pati, Shibani

    AU - Schreiber, Martin

    AU - Wade, Charles E.

    PY - 2017/6/6

    Y1 - 2017/6/6

    N2 - BACKGROUND:: The paradigm shift from crystalloid to plasma resuscitation of traumatic hemorrhagic shock has improved patient outcomes due in part to plasma-mediated reversal of catecholamine and inflammation-induced endothelial injury, decreasing vascular permeability and attenuating organ injury. Since sepsis induces a similar endothelial injury as seen in hemorrhage, we hypothesized that plasma resuscitation would increase 48-hour survival in a rat sepsis model. METHODS:: Adult male Sprague-Dawley rats (375–425?g) were subjected to 35% cecal ligation and puncture (CLP) (t?=?0?h). Twenty-two hours post-CLP and prior to resuscitation (t?=?22?h), animals were randomized to resuscitation with normal saline (NS, 10?cc/kg/hr) or pooled rat fresh frozen plasma (FFP, 3.33?cc/kg/hr). Resuscitation under general anesthesia proceeded for the next six hours (t?=?22?h to t?=?28?h); lactate was checked every 2?hours, and fluid volumes were titrated based on lactate clearance. Blood samples were obtained before (t?=?22?h) and after resuscitation (t?=?28?h), and at death or study conclusion. Lung specimens were obtained for calculation of wet-to-dry weight ratio. Fisherʼs exact test was used to analyze the primary outcome of 48-hour survival. ANOVA with repeated measures was used to analyze the effect of FFP versus NS resuscitation on blood gas, electrolytes, blood urea nitrogen (BUN), creatinine, interleukin (IL)-6, IL-10, catecholamines, and syndecan-1 (marker for endothelial injury). A two-tailed alpha level of <0.05 was used for all statistical tests. RESULTS:: Thirty-three animals were studied: 14 FFP, 14 NS, and 5 sham. Post-CLP but pre-resuscitation (t?=?22?h) variables between FFP and NS animals were similar and significantly deranged compared to sham animals. FFP significantly increased 48-hour survival compared to NS (n?=?8 [57%] vs n?=?2 [14%]), attenuated the post-resuscitation (t?=?28?h) levels of epinephrine (mean 2.2 vs 7.0?ng/ml), norepinephrine, (3.8 vs 8.9?ng/ml), IL-6 (3.8 vs 18.7?ng/ml), and syndecan-1 (21.8 vs 31.0?ng/ml) (all p?<?0.05), improved the post-resuscitation PO2 to FiO2 ratio (353 vs 151), and reduced the pulmonary wet-to-dry weight ratio (5.28 vs 5.94) (all p?<?0.05). CONCLUSION:: Compared to crystalloid, plasma resuscitation increased 48-hour survival in a rat sepsis model, improved pulmonary function and decreased pulmonary edema, and attenuated markers for inflammation, endothelial injury, and catecholamines.

    AB - BACKGROUND:: The paradigm shift from crystalloid to plasma resuscitation of traumatic hemorrhagic shock has improved patient outcomes due in part to plasma-mediated reversal of catecholamine and inflammation-induced endothelial injury, decreasing vascular permeability and attenuating organ injury. Since sepsis induces a similar endothelial injury as seen in hemorrhage, we hypothesized that plasma resuscitation would increase 48-hour survival in a rat sepsis model. METHODS:: Adult male Sprague-Dawley rats (375–425?g) were subjected to 35% cecal ligation and puncture (CLP) (t?=?0?h). Twenty-two hours post-CLP and prior to resuscitation (t?=?22?h), animals were randomized to resuscitation with normal saline (NS, 10?cc/kg/hr) or pooled rat fresh frozen plasma (FFP, 3.33?cc/kg/hr). Resuscitation under general anesthesia proceeded for the next six hours (t?=?22?h to t?=?28?h); lactate was checked every 2?hours, and fluid volumes were titrated based on lactate clearance. Blood samples were obtained before (t?=?22?h) and after resuscitation (t?=?28?h), and at death or study conclusion. Lung specimens were obtained for calculation of wet-to-dry weight ratio. Fisherʼs exact test was used to analyze the primary outcome of 48-hour survival. ANOVA with repeated measures was used to analyze the effect of FFP versus NS resuscitation on blood gas, electrolytes, blood urea nitrogen (BUN), creatinine, interleukin (IL)-6, IL-10, catecholamines, and syndecan-1 (marker for endothelial injury). A two-tailed alpha level of <0.05 was used for all statistical tests. RESULTS:: Thirty-three animals were studied: 14 FFP, 14 NS, and 5 sham. Post-CLP but pre-resuscitation (t?=?22?h) variables between FFP and NS animals were similar and significantly deranged compared to sham animals. FFP significantly increased 48-hour survival compared to NS (n?=?8 [57%] vs n?=?2 [14%]), attenuated the post-resuscitation (t?=?28?h) levels of epinephrine (mean 2.2 vs 7.0?ng/ml), norepinephrine, (3.8 vs 8.9?ng/ml), IL-6 (3.8 vs 18.7?ng/ml), and syndecan-1 (21.8 vs 31.0?ng/ml) (all p?<?0.05), improved the post-resuscitation PO2 to FiO2 ratio (353 vs 151), and reduced the pulmonary wet-to-dry weight ratio (5.28 vs 5.94) (all p?<?0.05). CONCLUSION:: Compared to crystalloid, plasma resuscitation increased 48-hour survival in a rat sepsis model, improved pulmonary function and decreased pulmonary edema, and attenuated markers for inflammation, endothelial injury, and catecholamines.

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