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Objectives To quantify the acute immunologic biomarker response in multiply injured patients with axial and lower extremity fractures and to explore associations with adverse short-term outcomes including organ dysfunction and nosocomial infection (NI). Design Prospective cohort study. Setting Level 1 academic trauma center. Patients Consecutive multiply injured patients, 18-55 years of age, with major pelvic and lower extremity orthopaedic injuries (all pelvic/acetabular fractures, operative femur and tibia fractures) that presented as a trauma activation and admitted to the intensive care unit from April 2015 through October 2016. Sixty-one patients met inclusion criteria. Intervention Blood was collected upon presentation to the hospital and at the following time points: 8, 24, 48 hours, and daily during intensive care unit admission. Blood was processed by centrifugation, separation into 1.0-mL plasma aliquots, and cryopreserved within 2 hours of collection. Main outcome measurements Plasma analyses of protein levels of cytokines/chemokines were performed using a Luminex panel Bioassay of 20 immunologic mediators. Organ dysfunction was measured by the Marshall Multiple Organ Dysfunction score (MODScore) and nosocomial infection (NI) was recorded. Patients were stratified into low (MODS ≤ 4; n = 34) and high (MODS > 4; n = 27) organ dysfunction groups. Results The MODS >4 group had higher circulating levels of interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1 (MCP-1), IL-1 receptor antagonist (IL-1RA), and monokine induced by interferon gamma (MIG) compared with the MODS ≤4 group at nearly all time points. MODS >4 exhibited lower levels of IL-21 and IL-22 compared with MODS ≤4. Patients who developed NI (n = 24) had higher circulating concentrations of IL-10, MIG, and high mobility group box 1 (HMGB1) compared with patients who did not develop NI (n = 37). Conclusions Temporal quantification of immune mediators identified 8 biomarkers associated with greater levels of organ dysfunction in polytrauma patients with major orthopaedic injuries. Level of evidence Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Background Multiply injured patients (MIPs) are at risk to develop multiple-organ failure (MOF) and prolonged systemic inflammation response syndrome (SIRS). It is difficult to predict which MIPs are at the highest risk to develop these complications. We have developed a novel method that quantifies the distribution and physical magnitude of all injuries identified on admission computed tomography scanning called the Tissue Damage Volume (TDV) score. We explored how individualized TDV scores corresponded to MOF and SIRS. Materials and methods A retrospective study on 74 MIPs measured mechanical TDV by calculating injury volumes on admission computed tomography scans of all injuries in the head/neck, chest, abdomen, and pelvis. Regional and total TDV scores were compared between patients that did or did not develop MOF or sustained SIRS. The magnitude of organ dysfunction was also stratified by the magnitude of TDV. Results Mean total and pelvic TDV scores were significantly increased in patients who developed MOF. Mean total, chest, and abdominal TDV scores were increased in patients who developed sustained SIRS. The magnitude of organ dysfunction was significantly higher in patients who sustained large volume injuries in the pelvis or abdomen, and in patients who sustained injuries in at least three anatomic regions. Conclusions A novel index that quantifies the magnitude and distribution of mechanical tissue damage volume is a patient-specific index that can be used to identify patients who have sustained injury patterns that predict progression to MOF and SIRS. The preliminary methods will need refinement and prospective validation.

BACKGROUND: Multiply injured patients are at risk of developing hemorrhagic shock and organ dysfunction. We determined how cumulative hypoperfusion predicted organ dysfunction by integrating serial Shock Index measurements. METHODS: In this study, we calculated shock volume (SHVL) which is a patient-specific index that quantifies cumulative hypoperfusion by integrating abnormally elevated Shock Index (heart rate/systolic blood pressure ≥ 0.9) values acutely after injury. Shock volume was calculated at three hours (3 hr), six hours (6 hr), and twenty-four hours (24 hr) after injury. Organ dysfunction was quantified using Marshall Organ Dysfunction Scores averaged from days 2 through 5 after injury (aMODS(D2–D5)). Logistic regression was used to determine correspondence of 3hrSHVL, 6hrSHVL, and 24hrSHVL to organ dysfunction. We compared correspondence of SHVL to organ dysfunction with traditional indices of shock including the initial base deficit (BD) and the lowest pH measurement made in the first 24 hr after injury (minimum pH). RESULTS: SHVL at all three time intervals demonstrated higher correspondence to organ dysfunction (R(2) = 0.48 to 0.52) compared to initial BD (R(2) = 0.32) and minimum pH (R(2) = 0.32). Additionally, we compared predictive capabilities of SHVL, initial BD and minimum pH to identify patients at risk of developing high-magnitude organ dysfunction by constructing receiver operator characteristic curves. SHVL at six hours and 24 hours had higher area under the curve compared to initial BD and minimum pH. CONCLUSION: SHVL is a non-invasive metric that can predict anticipated organ dysfunction and identify patients at risk for high-magnitude organ dysfunction after injury. LEVEL OF EVIDENCE: Prognostic study, level III.

Multiply injured patients (MIPs) in hemorrhagic shock develop oxygen debt which causes organ dysfunction and can lead to death. We developed a noninvasive patient-specific index, Shock Volume (SV), to quantify the magnitude of hypoperfusion. SV integrates the magnitude and duration that incremental shock index values are elevated above known thresholds 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 in a retrospective cohort of 74 MIPs. We measured SV in 6-h increments for 48 h after injury in multiply injured adults (18-65; Injury Severity Score ≥18). Patients who had accumulated 40 units of SV within 6 h of injury and 100 units of SV within 12 h of injury were at high risk for requiring massive transfusion or multiple critical administration transfusions. SV measurements were equally sensitive and specific as compared with base deficit values in predicting transfusions. SV measurements at 6 h after injury stratified patients at risk for multiple organ failure determined by Denver scores. In addition, SV values corresponded to the magnitude of organ failure determined by Sequential Organ Failure Assessment scores. SV is a patient-specific index that can be quantified in real time in critically injured patients. It is a surrogate for cumulative hypoperfusion and it predicts high-volume transfusions and organ dysfunction.