Whole Blood and Blood Component Resuscitation in Trauma: Interaction and Association with Mortality.

OBJECTIVE: Evaluate the interaction between whole blood (WB) and blood component resuscitation in relation to mortality following trauma. SUMMARY BACKGROUND DATA: WB is increasingly available in civilian trauma resuscitation, and it is typically transfused concomitantly with blood components. The interaction between WB and blood component transfusions is unclear. METHODS: Adult trauma patients with a shock index >1 who received ≥4 combined units of red blood cells (RBC) or WB within 4 hours across 501 United States trauma centers were included using the American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP) database. The associations between 1)WB resuscitation and mortality, 2)WB to total transfusion volume ratio (WB:TTV) and mortality, 3)balanced blood component transfusion in the setting of combined WB and component resuscitation and mortality were evaluated with multivariable analysis. RESULTS: A total of 12,275 patients were included (WB: 2,884 vs. component-only: 9,391). WB resuscitation was associated with lower odds of 4-hour (adjusted odds ratio [aOR]: 0.81 [0.68-0.97]), 24-hour, and 30-day mortality compared to component-only. Higher WB:TTV ratios were significantly associated with lower 4-hour, 24-hour, and 30-day mortality, with a 13% decrease in odds of 4-hour mortality for each 10% increase in the WB:TTV ratio (0.87 [95%CI:0.80 - 0.94]). Balanced blood component transfusion was associated with significantly lower odds of 4-hour (aOR: 0.45 [95%CI: 0.29 - 0.68]), 24-hour, and 30-day mortality in the setting of combined WB and blood component resuscitation. CONCLUSIONS: WB resuscitation, higher WB:TTV ratios, and balanced blood component transfusion in conjunction with WB were associated with lower mortality in trauma patients presenting in shock requiring 4 units of RBC and/or WB transfusion within 4 hours of arrival.

Consensus Recommendations for RBC Transfusion Practice in Critically Ill Children From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

OBJECTIVES: To date, there are no published guidelines to direct RBC transfusion decision-making specifically for critically ill children. We present the recommendations from the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. DESIGN: Consensus conference series of multidisciplinary, international experts in RBC transfusion management of critically ill children. SETTING: Not applicable. INTERVENTION: None. SUBJECTS: Children with, or children at risk for, critical illness who receive or are at risk for receiving a RBC transfusion. METHODS: A panel of 38 content and four methodology experts met over the course of 2 years to develop evidence-based, and when evidence lacking, expert consensus-based recommendations regarding decision-making for RBC transfusion management and research priorities for transfusion in critically ill children. The experts focused on nine specific populations of critically ill children: general, respiratory failure, nonhemorrhagic shock, nonlife-threatening bleeding or hemorrhagic shock, acute brain injury, acquired/congenital heart disease, sickle cell/oncology/transplant, extracorporeal membrane oxygenation/ventricular assist/ renal replacement support, and alternative processing. Data to formulate evidence-based and expert consensus recommendations were selected based on searches of PubMed, EMBASE, and Cochrane Library from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. MEASUREMENTS AND RESULTS: The Transfusion and Anemia Expertise Initiative consensus conference developed and reached consensus on a total of 102 recommendations (57 clinical [20 evidence based, 37 expert consensus], 45 research recommendations). All final recommendations met agreement, defined a priori as greater than 80%. A decision tree to aid clinicians was created based on the clinical recommendations. CONCLUSIONS: The Transfusion and Anemia Expertise Initiative recommendations provide important clinical guidance and applicable tools to avoid unnecessary RBC transfusions. Research recommendations identify areas of focus for future investigation to improve outcomes and safety for RBC transfusion.

Fluid balance in critically ill children with acute lung injury.

OBJECTIVES: In the Fluid and Catheter Treatment Trial (NCT00281268), adults with acute lung injury randomized to a conservative vs. liberal fluid management protocol had increased days alive and free of mechanical ventilator support (ventilator-free days). Recruiting sufficient children with acute lung injury into a pediatric trial is challenging. A Bayesian statistical approach relies on the adult trial for the a priori effect estimate, requiring fewer patients. Preparing for a Bayesian pediatric trial mirroring the Fluid and Catheter Treatment Trial, we aimed to: 1) identify an inverse association between fluid balance and ventilator-free days; and 2) determine if fluid balance over time is more similar to adults in the Fluid and Catheter Treatment Trial liberal or conservative arms. DESIGN: Multicentered retrospective cohort study. SETTING: Five pediatric intensive care units. PATIENTS: Mechanically ventilated children (age≥1 month to <18 yrs) with acute lung injury admitted in 2007-2010. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fluid intake, output, and net fluid balance were collected on days 1-7 in 168 children with acute lung injury (median age 3 yrs, median PaO2/FIO2 138) and weight-adjusted (mL/kg). Using multivariable linear regression to adjust for age, gender, race, admission day illness severity, PaO2/FIO2, and vasopressor use, increasing cumulative fluid balance (mL/kg) on day 3 was associated with fewer ventilator-free days (p=.02). Adjusted for weight, daily fluid balance on days 1-3 and cumulative fluid balance on days 1-7 were higher in these children compared to adults in the Fluid and Catheter Treatment Trial conservative arm (p<.001, each day) and was similar to adults in the liberal arm. CONCLUSIONS: Increasing fluid balance on day 3 in children with acute lung injury at these centers is independently associated with fewer ventilator-free days. Our findings and the similarity of fluid balance patterns in our cohort to adults in the Fluid and Catheter Treatment Trial liberal arm demonstrate the need to determine whether a conservative fluid management strategy improves clinical outcomes in children with acute lung injury and support a Bayesian trial mirroring the Fluid and Catheter Treatment Trial.

Increased platelet:RBC ratios are associated with improved survival after massive transfusion.

BACKGROUND: Several recent military and civilian trauma studies demonstrate that improved outcomes are associated with early and increased use of plasma-based resuscitation strategies. However, outcomes associated with platelet transfusions are poorly characterized. We hypothesized that increased platelet:red blood cells (RBC) ratios would decrease hemorrhagic death and improve survival after massive transfusion (MT). METHODS: A transfusion database of patients transported from the scene to 22 Level I Trauma Centers over 12 months in 2005 to 2006 was reviewed. MT was defined as receiving ≥ 10 RBC units within 24 hours of admission. To mitigate survival bias, 25 patients who died within 60 minutes of arrival were excluded from analysis. Six random donor platelet units were considered equal to a single apheresis platelet unit. Admission and outcome data associated with the low (>1:20), medium (1:2), and high (1:1) platelet:RBC ratios were examined. These groups were based on the median value of the tertiles for the ratio of platelets:RBC units. RESULTS: Two thousand three hundred twelve patients received at least one unit of blood and 643 received an MT. Admission vital signs, INR, temperature, pH, Glasgow Coma Scale, Injury Severity Score, and age were similar between platelet ratio groups. The average admission platelet counts were lower in the patients who received the high platelet:RBC ratio versus the low ratio (192 vs. 216, p = 0.03). Patients who received MT were severely injured, with a mean (± standard deviation) Injury Severity Score of 33 ± 16 and received 22 ± 15 RBCs and 11 ± 14 platelets within 24 hours of injury. Increased platelet ratios were associated with improved survival at 24 hours and 30 days (p < 0.001 for both). Truncal hemorrhage as a cause of death was decreased (low: 67%, medium: 60%, high: 47%, p = 0.04). Multiple organ failure mortality was increased (low: 7%, medium: 16%, high: 27%, p = 0.003), but overall 30-day survival was improved (low: 52%, medium: 57%, high: 70%) in the high ratio group (medium vs. high: p = 0.008; low vs. high: p = 0.007). CONCLUSION: Similar to recently published military data, transfusion of platelet:RBC ratios of 1:1 was associated with improved early and late survival, decreased hemorrhagic death and a concomitant increase in multiple organ failure-related mortality. Based on this large retrospective study, increased and early use of platelets may be justified, pending the results of prospective randomized transfusion data.

Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients.

OBJECTIVE: To determine the effect of blood component ratios in massive transfusion (MT), we hypothesized that increased use of plasma and platelet to red blood cell (RBC) ratios would result in decreased early hemorrhagic death and this benefit would be sustained over the ensuing hospitalization. SUMMARY BACKGROUND DATA: Civilian guidelines for massive transfusion (MT > or =10 units of RBC in 24 hours) have typically recommend a 1:3 ratio of plasma:RBC, whereas optimal platelet:RBC ratios are unknown. Conversely, military data shows that a plasma:RBC ratio approaching 1:1 improves long term outcomes in MT combat casualties. There is little consensus on optimal platelet transfusions in either civilian or military practice. At present, the optimal combinations of plasma, platelet, and RBCs for MT in civilian patients is unclear. METHODS: Records of 467 MT trauma patients transported from the scene to 16 level 1 trauma centers between July 2005 and June 2006 were reviewed. One patient who died within 30 minutes of admission was excluded. Based on high and low plasma and platelet to RBC ratios, 4 groups were analyzed. RESULTS: Among 466 MT patients, survival varied by center from 41% to 74%. Mean injury severity score varied by center from 22 to 40; the average of the center means was 33. The plasma:RBC ratio ranged from 0 to 2.89 (mean +/- SD: 0.56 +/- 0.35) and the platelets:RBC ratio ranged from 0 to 2.5 (0.55 +/- 0.50). Plasma and platelet to RBC ratios and injury severity score were predictors of death at 6 hours, 24 hours, and 30 days in multivariate logistic models. Thirty-day survival was increased in patients with high plasma:RBC ratio (> or =1:2) relative to those with low plasma:RBC ratio (<1:2) (low: 40.4% vs. high: 59.6%, P < 0.01). Similarly, 30-day survival was increased in patients with high platelet:RBC ratio (> or =1:2) relative to those with low platelet:RBC ratio (<1:2) (low: 40.1% vs. high: 59.9%, P < 0.01). The combination of high plasma and high platelet to RBC ratios were associated with decreased truncal hemorrhage, increased 6-hour, 24-hour, and 30-day survival, and increased intensive care unit, ventilator, and hospital-free days (P < 0.05), with no change in multiple organ failure deaths. Statistical modeling indicated that a clinical guideline with mean plasma:RBC ratio equal to 1:1 would encompass 98% of patients within the optimal 1:2 ratio. CONCLUSIONS: Current transfusion practices and survival rates of MT patients vary widely among trauma centers. Conventional MT guidelines may underestimate the optimal plasma and platelet to RBC ratios. Survival in civilian MT patients is associated with increased plasma and platelet ratios. Massive transfusion practice guidelines should aim for a 1:1:1 ratio of plasma:platelets:RBCs.

Total intravenous anesthesia including ketamine versus volatile gas anesthesia for combat-related operative traumatic brain injury.

BACKGROUND: Traumatic brain injury is a leading cause of death and severe neurologic disability. The effect of anesthesia techniques on neurologic outcomes in traumatic brain injury and potential benefits of total intravenous anesthesia (TIVA) compared with volatile gas anesthesia (VGA), although proposed, has not been well evaluated. The purpose of this study was to compare TIVA versus VGA in patients with combat-related traumatic brain injury. METHODS: The authors retrospectively reviewed 252 patients who had traumatic brain injury and underwent operative neurosurgical intervention. Statistical analyses, including propensity score and matched analyses, were performed to assess differences between treatment groups (TIVA vs. VGA) and good neurologic outcome. RESULTS: Two hundred fourteen patients met inclusion criteria and were analyzed; 120 received VGA and 94 received TIVA. Good neurologic outcome (Glasgow Outcome Score 4-5) and decreased mortality were associated with TIVA compared with VGA (75% vs. 54%; P = 0.002 and 5% vs. 16%; P = 0.02, respectively). Multivariate logistic regression found admission Glasgow Coma Scale score of 8 or greater (odds ratio, 13.3; P < 0.001) and TIVA use (odds ratio, 2.3; P = 0.05) to be associated with good neurologic outcomes. After controlling for confounding factors using propensity analysis and repeated one-to-one matching of patients receiving TIVA with those receiving VGA with regard to Injury Severity Score, Glasgow Coma Scale score, base deficit, Head Abbreviated Injury Score, and craniectomy or craniotomy, the authors could not find an association between treatment and neurologic outcome. CONCLUSION: Total intravenous anesthesia often including ketamine was not associated with improved neurologic outcome compared with VGA. Multiple confounders limit conclusions that can be drawn from this retrospective study.