Browsing by Subject "hemorrhagic shock"

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    Blood Purification by Non-Selective Hemoadsorption Prevents Death after Traumatic Brain Injury and Hemorrhagic Shock in Rats
    (Wolters Kluwer, 2018-09) McKinley, Todd O.; Lei, Zhigang; Kalbas, Yannik; White, Fletcher A.; Shi, Zhongshang; Wu, Fan; Xu, Zao C.; Rodgers, Richard B.; Anesthesia, School of Medicine
    Background Patients who sustain traumatic brain injury (TBI) and concomitant hemorrhagic shock (HS) are at high risk of high-magnitude inflammation which can lead to poor outcomes and death. Blood purification by hemoadsorption (HA) offers an alternative intervention to reduce inflammation after injury. We tested the hypothesis that HA would reduce mortality in a rat model of TBI and HS. Methods Male Sprague Dawley rats were subjected to a combined injury of a controlled cortical impact (CCI) to their brain and pressure-controlled hemorrhagic shock (HS). Animals were subsequently instrumented with an extracorporeal blood circuit that passed through a cartridge for sham or experimental treatment. In experimental animals, the treatment cartridge was filled with proprietary beads (Cytosorbents; Monmouth Junction, NJ) that removed circulating molecules between 5 KDa and 60 KDa. Sham rats had equivalent circulation but no blood purification. Serial blood samples were analyzed with multiplex technology to quantify changes in a trauma-relevant panel of immunologic mediators. The primary outcome was survival to 96hr post-injury. Results HA improved survival from 47% in sham treated rats to 86% in HA treated rats. There were no treatment-related changes in histologic appearance. HA affected biomarker concentrations both during the treatment and over the ensuing four days after injury. Distinct changes in biomarker concentrations were also measured in survivor and non-survivor rats from the entire cohort of rats indicating biomarker patterns associated with survival and death after injury. Conclusions Blood purification by non-selective HA is an effective intervention to prevent death in a combined TBI/HS rat model. HA changed circulating concentrations of multiple inmmunologically active mediators during the treatment time frame and after treatment. HA has been safely implemented in human patients with sepsis and may be a treatment option after injury.
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    Early Dynamic Orchestration of Immunologic Mediators Identifies Multiply Injured Patients who are Tolerant or Sensitive to Hemorrhage
    (Wolters Kluwer, 2021-03) McKinley, Todd O.; Gaski, Greg E.; Zamora, Ruben; Shen, Li; Sun, Qing; Namas, Rami A.; Billiar, Timothy R.; Vodovotz, Yoram; Orthopaedic Surgery, School of Medicine
    BACKGROUND Multiply injured patients (MIPs) are at risk of complications including infections, and acute and prolonged organ dysfunction. The immunologic response to injury has been shown to affect outcomes. Recent advances in computational capabilities have shown that early dynamic coordination of the immunologic response is associated with improved outcomes after trauma. We hypothesized that patients who were sensitive or tolerant of hemorrhage would demonstrate differences in dynamic immunologic orchestration within hours of injury. METHODS We identified two groups of MIPs who demonstrated distinct clinical tolerance to hemorrhage (n = 10) or distinct clinical sensitivity to hemorrhage (n = 9) from a consecutive cohort of 100 MIPs. Hemorrhage was quantified by integrating elevated shock index values for 24 hours after injury (shock volume). Clinical outcomes were quantified by average Marshall Organ Dysfunction Scores from days 2 to 5 after injury. Shock-sensitive patients had high cumulative organ dysfunction after lower magnitude hemorrhage. Shock-tolerant (ST) patients had low cumulative organ dysfunction after higher magnitude hemorrhage. Computational methods were used to analyze a panel of 20 immunologic mediators collected serially over the initial 72 hours after injury. RESULTS Dynamic network analysis demonstrated the ST patients had increased orchestration of cytokines that are reparative and protective including interleukins 9, 17E/25, 21, 22, 23, and 33 during the initial 0- to 8-hour and 8- to 24-hour intervals after injury. Shock-sensitive patients had delayed immunologic orchestration of a network of largely proinflammatory and anti-inflammatory mediators. Elastic net linear regression demonstrated that a group of five mediators could discriminate between shock-sensitive and ST patients. CONCLUSIONS Preliminary evidence from this study suggests that early immunologic orchestration discriminates between patients who are notably tolerant or sensitive to hemorrhage. Early orchestration of a group of reparative/protective mediators was amplified in shock-tolerant patients.
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    SHOCK VOLUME: A PRECISION MEDICINE BASED INDEX THAT PREDICTS TRANSFUSION REQUIREMENTS AND ORGAN DYSFUNCTION IN MULTIPLY INJURED PATIENTS
    (Office of the Vice Chancellor for Research, 2016-04-08) McCarroll, Tyler; Metzger, Cameron; Bakdash, Kenaz; Gaski, Greg E.; McKinley, Todd O.
    Introduction: Multiply injured patients (MIPs) in hemorrhagic shock develop oxygen debt, which causes organ dysfunction and can lead to death. Clinicians monitor hypoperfusion by interpreting progression of traditional hemodynamic measures along with serum markers of hypoperfusion, which reflect current hemodynamic and metabolic status. However, these indices are sampled at discrete time points and poorly reflect cumulative hypoperfusion. Shock Volume (SV) is a novel, non-invasive, patient-specific index developed to quantify cumulative hypoperfusion. SV integrates the time and magnitude of shock index (Heart Rate/Systolic Blood Pressure) values above 0.9 (known threshold of hypoperfusion) using serial individual vital sign data. SV can be monitored in real time to assess ongoing hypoperfusion. The goal of this study was to determine how SV corresponded to transfusion requirements and organ dysfunction. Methods: SV was measured in six hour increments for 48 hours after injury in a retrospective cohort of 74 MIPs (18-65; Injury Severity Score > 18). SV was compared to base deficit (BD) in predicting mass transfusions (MT) and critical administration transfusions (CATs). Presence of multiple organ failure (MOF) was determined using the Denver Organ Failure assessment score, while Sequential Organ Failure Assessment scores were used to determine magnitude of organ dysfunction. Results: Patients who had accumulated 40 units of SV within six hours of injury and 100 units of SV within twelve hours of injury were at high risk for requiring MT or multiple CATs. SV measurements were equally sensitive and specific as compared to BD values in predicting transfusions. SV measurements at six hours after injury stratified patients at risk for MOF and corresponded to the magnitude of organ failure. Conclusions: SV is a patient-specific index that can be quantified in real-time in critically injured patients. SV is a non-invasive surrogate for cumulative hypoperfusion and predicts high volume transfusions and organ dysfunction.