Shock volume: Patient-specific cumulative hypoperfusion predicts organ dysfunction in a prospective cohort of multiply injured patients

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 (aMODSD2–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 (R2 = 0.48 to 0.52) compared to initial BD (R2 = 0.32) and minimum pH (R2 = 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

SHOCK VOLUME: A PRECISION MEDICINE BASED INDEX THAT PREDICTS TRANSFUSION REQUIREMENTS AND ORGAN DYSFUNCTION IN MULTIPLY INJURED PATIENTS

poster abstractIntroduction: 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

Locking Plate Fixation in a Series of Bicondylar Tibial Plateau Fractures Raises Treatment Costs Without Clinical Benefit

Objectives: To compare outcomes and costs between locking and nonlocking constructs in the treatment of bicondylar tibial plateau (BTP) fractures. Design: Retrospective cohort study. Setting: Level 1 academic trauma center. Patients: All patients that presented with complete articular, BTP fractures (AO/OTA 41-C and Schatzker 6) between 2013-2015 were screened (n=112). Patients treated with a mode of fixation other than plate-and-screw were excluded. 56 patients with a minimum follow-up of 12 months were included in the analysis. Intervention: Operative fixation of BTP fractures with locking (n=29) or nonlocking (n=27) implants. Main outcome measurements: Implant cost, patient reported outcomes (PROMIS physical function and pain interference), clinical, and radiographic outcomes. Results: There were no differences between the two groups with respect to demographics, injury characteristics, radiographic outcomes (change in alignment) or clinical outcomes (PROMIS, reoperation, nonunion, infection). Implant costs were significantly greater in the locking group compared to the nonlocking group (mean L $4453; mean NL$2569; p<0.01). Conclusions: This study demonstrated improved value of treatment (less cost with no difference in clinical outcome) with nonlocking implants for bicondylar tibial plateau fractures when dual plate fixation strategies are performed. Level of Evidence: Therapeutic III. See Instructions for Authors for a complete description of levels of evidence

Computational evidence for an early, amplified systemic inflammation program in polytrauma patients with severe extremity injuries

Extremity and soft tissue injuries contribute significantly to inflammation and adverse in-hospital outcomes for trauma survivors; accordingly, we examined the complex association between clinical outcomes inflammatory responses in this setting using in silico tools. Two stringently propensity-matched, moderately/severely injured (Injury Severity Score > 16) patient sub-cohorts of ~30 patients each were derived retrospectively from a cohort of 472 blunt trauma survivors and segregated based on their degree of extremity injury severity (above or below 3 on the Abbreviated Injury Scale). Serial blood samples were analyzed for 31 plasma inflammatory mediators. In addition to standard statistical analyses, Dynamic Network Analysis (DyNA) and Principal Component Analysis (PCA) were used to model systemic inflammation following trauma. Patients in the severe extremity injury sub-cohort experienced longer intensive care unit length of stay (LOS), total LOS, and days on a mechanical ventilator, with higher Marshall Multiple Organ Dysfunction (MOD) Scores over the first 7 days post-injury as compared to the mild/moderate extremity injury sub-cohort. The higher severity cohort had statistically significant elevated lactate, base deficit, and creatine phosphokinase on first blood draw, along with significant changes in multiple circulating inflammatory mediators. DyNA pointed to a sustained role for type 17 immunity in both sub-cohorts, along with IFN-γ in the severe extremity injury group. DyNA network complexity increased over 7 days post-injury in the severe injury group, while generally decreasing over this same time period in the mild/moderate injury group. PCA suggested a more robust activation of multiple pathways in the severe extremity injury group as compared to the mild/moderate injury group. These studies thus point to the possibility of self-sustaining inflammation following severe extremity injury vs. resolving inflammation following less severe extremity injury

Predictors of Improved Early Clinical Outcomes After Elective Implant Removal

Objectives: To determine preoperative factors predictive of improvement in pain and function after elective implant removal. We hypothesized that patients undergoing orthopaedic implant removal to relieve pain would have significant improvements in both pain and function. Design: Prospective cohort study. Setting: Level I Trauma Center. Patients/Participants: One hundred eighty-nine patients were enrolled after consenting for orthopaedic implant removal to address residual pain. One hundred sixty-three were available for 3-month follow-up. Main Outcome Measurement: Preoperative and postoperative outcome measures including Patient Reported Outcomes Measurement Information System (PROMIS) scores were compared. Preoperative scores, surgeon prediction of pain improvement, and palpable implants were analyzed as predictors of outcomes. Results: Median PROMIS physical function and pain interference scores and visual analogue scale significantly improved by 6, 8, and 2 points, respectively (P < 0.001 for all). Worse preinjury scores predicted improvement in respective postoperative outcomes (P < 0.001 for all). Surgeon prediction of improvement was associated with improved PROMIS pain interference (P = 0.005), patient subjective assessment of pain improvement (P = 0.03), and subjective percent of pain remaining at 3 months (P = 0.02). Implant superficial palpability was not predictive for any postoperative outcomes. Conclusions: Although the primary indication for implant removal in this population was pain relief, many patients also had a clinically relevant improvement in physical function. In addition, patients who start with worse global indices of pain and function are more likely to improve after implant removal. This suggests that implant-related pain directly contributes to global dysfunction

Early Dynamic Orchestration of Immunologic Mediators Identifies Multiply Injured Patients who are Tolerant or Sensitive to Hemorrhage

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

Polytraumatized patient lower extremity nonunion development: Raw data

In this article we report data collected to evaluate the pathomechanistic effect of acute anaerobic metabolism in the polytraumatized patient and its subsequent effect on fracture nonunion; see "Base Deficit ≥6 within 24 Hours of Injury is a Risk Factor for Fracture Nonunion in the Polytraumatized Patient" (Sardesai et al., 2021) [1]. Data was collected on patients age ≥16 with an Injury Severity Score (ISS) >16 that presented between 2013-2018 who sustained a fracture of the tibia or femur distal to the femoral neck. Patients presenting to our institution greater than 24 hours post-injury and those with less than three months follow-up were excluded. Medical charts were reviewed to collect patient demographic information and known nonunion risk-factors, including smoking, alcohol use, and diabetes. In addition, detailed injury characteristics to quantify injury magnitude including ISS, Glasgow Coma Scale (GCS) at admission, and ICU length of stay were recorded. ISS values were obtained from our institutional trauma database where they are entered by individuals trained in ISS calculations. Associated fracture-related features including fracture location, soft-tissue injury (open vs. closed fracture), vascular injury, and compartment syndrome were recorded. Finally, vital signs, base deficit (BD), and blood transfusions over 24 hours from admission were recorded. We routinely measure BD and less consistently measure serum lactate in trauma patients at the time of presentation or during resuscitation. BD values are automatically produced by our laboratory with any arterial blood gas order, and we recorded BD values from the medical record. Clinical notes and radiographs were reviewed to confirm fracture union versus nonunion and assess for deep infection at the fracture site. Patients were categorized as having a deep infection if they were treated operatively for the infection prior to fracture healing or classification as a nonunion. Nonunion was defined by failure of progressive healing on sequential radiographs and/or surgical treatment for nonunion repair at least six months post-injury

Insights into the association between coagulopathy and inflammation: abnormal clot mechanics are a warning of immunologic dysregulation following major injury

Background: Severe injury initiates a complex physiologic response encompassing multiple systems and varies phenotypically between patients. Trauma-induced coagulopathy may be an early warning of a poorly coordinated response at the molecular level, including a deleterious immunologic response and worsening of shock states. The onset of trauma-induced coagulopathy (TIC) may be subtle however. In previous work, we identified an early warning sign of coagulopathy from the admission thromboelastogram, called the MAR ratio. We hypothesized that a low MAR ratio would be associated with specific derangements in the inflammatory response. Methods: In this prospective, observational study, 88 blunt trauma patients admitted to the intensive care unit (ICU) were identified. Concentrations of inflammatory mediators were recorded serially over the course of a week and the MAR ratio was calculated from the admission thromboelastogram. Correlation analysis was used to assess the relationship between MAR and inflammatory mediators. Dynamic network analysis was used to assess coordination of immunologic response. Results: Seventy-nine percent of patients were male and mean age was 37 years (SD 12). The mean ISS was 30.2 (SD 12) and mortality was 7.2%. CRITICAL patients (MAR ratio ≤14.2) had statistically higher shock volumes at three time points in the first day compared to NORMAL patients (MAR ratio >14.2). CRITICAL patients had significant differences in IL-6 (P=0.0065), IL-8 (P=0.0115), IL-10 (P=0.0316) and MCP-1 (P=0.0039) concentrations compared to NORMAL. Differences in degree of expression and discoordination of immune response continued in CRITICAL patients throughout the first day. Conclusions: The admission MAR ratio may be the earliest warning signal of a pathologic inflammatory response associated with hypoperfusion and TIC. A low MAR ratio is an early indication of complicated dysfunction of multiple molecular processes following trauma

Fixation Using Alternative Implants for the Treatment of Hip Fractures

Objectives: To conduct a pilot trial for the Fixation using Alternative Implants for the Treatment of Hip Fractures (FAITH-2) protocol to assess feasibility of a definitive trial. Design: Pilot trial. Setting: Twenty-five clinical sites across North America and Australia were initiated, but enrolment occurred in only 15 North American sites. Patients/participants: Ninety-one randomized adults aged 18 to 60 years with a femoral neck fracture requiring surgical fixation. Intervention: Eligible patients were randomized to receive surgical treatment (sliding hip screw or cancellous screws) AND nutritional supplementation (4000 IU of vitamin D or placebo) for 6 months postfracture. Main outcome measurements: Feasibility outcomes included: clinical site initiation, participant enrolment rate, proportion of participants with complete 12-month follow-up, level of data quality, and rate of protocol adherence (number of randomization errors, crossovers between treatment groups, and daily supplementation adherence). Results: Eighty-six of 91 participants randomized into the pilot trial from 15 North American hospitals were deemed eligible. Four of five primary feasibility criteria were not achieved as we were unable to initiate clinical sites outside of North America and Australia due to feasibility constraints, slow participant enrolment (60 participants recruited over 36 mo), low adherence with daily nutritional supplementation at the 6-week (72.1%), 3-month (60.5%), and 6-month (54.7%) follow-up visits, and a high loss to follow-up rate of 22.1% at 12 months. Conclusions: Despite not meeting key feasibility criteria, we increased our knowledge on the logistics and anticipated barriers when conducting vitamin D supplementation trials in this trauma population, which can be used to inform the design and conduct of future trials on this topic

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article