Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared to standard care resuscitation in patients with hemorrhagic shock. SUMMARY BACKGROUND DATA: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at five U.S. trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days vs. standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared to 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P=0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences.

Ideal timing of early cholecystectomy for acute cholecystitis: An ACS-NSQIP review.

BACKGROUND: Current guidelines fail to specify optimal timing of early cholecystectomy for acute cholecystitis. We hypothesized delaying operation past hospital day (HD) 2 would result in increased 30-day morbidity and mortality. METHODS: The ACS-NSQIP database was queried from 2012 to 2015 for all cholecystectomies for acute cholecystitis from HD 1-7. RESULTS: Delay in cholecystectomy to HD 3-7 was observed in 30% of patients with acute cholecystitis. Patients undergoing operation on HD 3-7 were older with higher rates of comorbidities (median 58yrs; 66%) than HD 1 (48yrs; 51%) or HD 2 (51yrs, p < 0.001; 55%, p < 0.001). Operations on HD 3-7 had increased 30-day mortality (1.0%) and morbidity (12%) in comparison to HD 1 (0.3%, 7%) or HD 2 (0.5%, p < 0.001; 8%, p < 0.001). On multivariable analysis, HD was an independent predictor of mortality (OR 1.15, 95% CI [1.04-1.26]). CONCLUSIONS: Acute cholecystitis should be treated with an urgent operation within 2 days of admission due to increased morbidity and mortality when delayed past HD 2.

Population-level outcomes of early versus delayed appendectomy for acute appendicitis using the American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: The optimal timing of appendectomy for acute appendicitis has been analyzed with mixed results. We hypothesized that delayed appendectomy would be associated with increased 30-d morbidity and mortality. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients undergoing nonelective appendectomy from 2012 to 2015 with a postoperative diagnosis of appendicitis. Patients were grouped based on hospital day (HD) of operation. Primary outcomes included 30-d mortality and major complications. Logistic regression was performed to determine predictors of major morbidity and mortality. RESULTS: From 2012 to 2015, 112,122 patients underwent appendectomy for acute appendicitis. Appendectomies performed on HD 3 had significantly worse outcomes as demonstrated by increased 30-d mortality (0.6%) and all major postoperative complications (8%) in comparison with operations taking place on HD 1 (0.1%; 3.4%) or HD 2 (0.1%, P < 0.001; 3.6%, P < 0.001). In subgroup analysis, open operations had significantly higher mortality and major postoperative complications, including organ/space surgical site infections (4.6% open versus 2.1% laparoscopic; P < 0.001). Patients with decreased baseline physical status by the American Society of Anesthesiologists Physical Status class had the worst outcomes (1.5% mortality; 14% major complications) when operation was delayed to HD 3. Logistic regression revealed higher American Society of Anesthesiologists Physical Status class and open operations as predictors of major complications; however, HD was not (P = 0.2). CONCLUSIONS: Data from the American College of Surgeons National Surgical Quality Improvement Program demonstrate similar outcomes of appendectomy for acute appendicitis when the operation is performed on HD 1 or 2; however, outcomes are significantly worse for appendectomies delayed until HD 3. Increased complications in this group are likely not attributable to HD of operation, but rather decreased baseline health status and procedure type.

Surgical rescue: The next pillar of acute care surgery.

BACKGROUND: The evolving field of acute care surgery (ACS) traditionally includes trauma, emergency general surgery, and critical care. However, the critical role of ACS in the rescue of patients with a surgical complication has not been explored. We here describe the role of "surgical rescue" in the practice of ACS. METHODS: A prospective, electronic medical record-based ACS registry spanning January 2013 to May 2014 at a large urban academic medical center was screened by ICD-9 codes for acute surgical complications of an operative or interventional procedure. Long-term outcomes were derived from the Social Security Death Index. RESULTS: Of 2,410 ACS patients, 320 (13%) required "surgical rescue": most commonly, from wound complications (32%), uncontrolled sepsis (19%), and acute obstruction (15%). The majority of complications (85%) were related to an operation; 15% were related to interventional procedures. The most common rescue interventions required were bowel resection (23%), wound debridement (18%), and source control of infection (17%); 63% of patients required operative intervention, and 22% required surgical critical care. Thirty-six percent of complications occurred in ACS primary patients ("local"), whereas 38% were referred from another surgical service ("institutional") and 26% referred from another institution ("regional"). Hospital length of stay was longer, and in-hospital and 1-year mortalities were higher in rescue patients compared with those without a complication. Outcomes were equivalent between "local" and "institutional" patients, but hospital length of stay and discharge to home were significantly worse in "institutional" referrals. CONCLUSION: We here describe the distinct role of the acute care surgeon in the surgical management of complications; this is an additional pillar of ACS. In this vital role, the acute care surgeon provides crucial support to other providers as well as direct patient care in the "surgical rescue" of surgical and procedural complications. LEVEL OF EVIDENCE: Epidemiological study, level III; therapeutic/care management study, level IV.

Selective roles for toll-like receptors 2, 4, and 9 in systemic inflammation and immune dysfunction following peripheral tissue injury.

BACKGROUND: Toll-like receptors (TLRs) detect endogenous ligands released after trauma and contribute to the proinflammatory response to injury. Posttraumatic mortality correlates with the extent of the immunoinflammatory response to injury that is composed of a complex regulation of innate and adaptive immune responses. Although TLRs are known to modulate innate immune responses, their role in the suppression of lymphocyte responses following traumatic tissue injury is unclear. METHODS: This study used a murine model of severe peripheral tissue injury, involving muscle crush injury and injection of fracture components, to evaluate the roles of TLR2, TLR4, and TLR9 in the early and delayed immunoinflammatory phenotype. Posttraumatic immune dysfunction was measured in our trauma model using the following parameters: ex vivo splenocyte proliferation, TH1 cytokine release, and iNOS (inducible nitric oxide synthase) induction within splenic myeloid-derived suppressor cells. Systemic inflammation and liver damage were determined by circulating interleukin 6 levels and hepatocellular injury. RESULTS: Suppression of splenocyte responses after injury was dependent on TLR4 and TLR9 signaling as was posttraumatic iNOS upregulation in splenic myeloid-derived suppressor cells. TLR2 was found to have only a partial role through contribution to inhibition of splenocyte proliferation. This study also reveals the involvement of TLR2 and TLR4 in the initial systemic inflammatory response to traumatic tissue injury; however, this response was found to be TLR9 independent. CONCLUSION: These findings demonstrate the previously unidentified role of TLR2, TLR4, and TLR9 in the T cell-associated immune dysfunction following traumatic tissue injury. Importantly, this study also illustrates that TLRs play differing and selective roles in both the initial proinflammatory response and adaptive immune response after trauma. Furthermore, results in TLR9-deficient mice establish that the upregulation of early proinflammatory markers do not always correlate with the extent of sustained immune dysfunction. This suggests potential for targeted therapies that could limit immune dysfunction through selective inhibition of receptor function following injury.

Crystalloid to packed red blood cell transfusion ratio in the massively transfused patient: when a little goes a long way.

BACKGROUND: Massive transfusion (MT) protocols have emphasized the importance of ratio-based transfusion of plasma and platelets relative to packed red blood cells (PRBCs); however, the risks attributable to crystalloid resuscitation in patients requiring MT remain largely unexplored. We hypothesized that an increased crystalloid:PRBC (C:PRBC) ratio would be associated with increased morbidity and poor outcome after MT. METHODS: Data were obtained from a multicenter prospective cohort study evaluating outcomes in blunt injured adults with hemorrhagic shock. Patients requiring MT (≥ 10 units PRBCs in first 24 hours) were analyzed. The C:PRBC ratio was computed by the ratio of crystalloid infused in liters (L) to the units of PRBCs transfused in the first 24 hours postinjury. Logistic regression modeling was used to characterize the independent risks associated with the 24-hour C:PRBC ratio, after controlling for important confounders and other blood component transfusion requirements. RESULTS: Logistic regression revealed that the 24-hour C:PRBC ratio was significantly associated with a greater independent risk of multiple organ failure (MOF), acute respiratory distress syndrome (ARDS), and abdominal compartment syndrome (ACS). No association with mortality or nosocomial infection was found. A dose-response analysis revealed that patients with a C:PRBC ratio >1.5:1 had over a 70% higher independent risk of MOF and over a twofold higher risk of ARDS and ACS. CONCLUSION: In patients requiring MT, crystalloid resuscitation in a ratio greater than 1.5:1 per unit of PRBCs transfused was independently associated with a higher risk of MOF, ARDS, and ACS. These results suggest overly aggressive crystalloid resuscitation should be minimized in these severely injured patients. Further research is required to determine whether incorporation of the C:PRBC ratio into MT protocols improves outcome.