IMPORTANCE: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), ...defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. OBJECTIVE: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. INTERVENTIONS: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). MAIN OUTCOMES AND MEASURES: Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. RESULTS: No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, −4.2% 95% CI, −9.6% to 1.1%; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, −3.7% 95% CI, −10.2% to 2.7%; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, −5.4% 95% CI, −10.4% to −0.5%; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. CONCLUSIONS AND RELEVANCE: Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01545232
In this randomized, placebo-controlled trial, the investigators administered epoetin alfa or placebo to 1460 medical, surgical, or trauma patients between 48 and 96 hours after admission to the ...intensive care unit. Treatment with epoetin alfa did not reduce the percentage of patients receiving a red-cell transfusion (the primary outcome) but did appear to reduce mortality in patients with trauma. However, this therapy was also associated with an increase in the incidence of thrombotic events.
Treatment with epoetin alfa did not reduce the percentage of patients in the intensive care unit receiving a red-cell transfusion, but did appear to reduce mortality in patients with trauma.
Anemia is common in the critically ill, often resulting in red-cell transfusions.
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Two observational studies reported that 35 to 45% of patients admitted to intensive care units (ICUs) receive transfusions of almost 5 red-cell units while in the ICU.
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However, the view that red-cell transfusion is beneficial for critically ill patients has been questioned because of data suggesting that red-cell transfusion may decrease the likelihood of survival in critically ill adults.
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Anemia is evident early in the courses of critical illnesses, and hemoglobin concentrations fall throughout stays in the ICU.
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Impaired production of red cells contributes . . .
Background Human polymerized hemoglobin (PolyHeme, Northfield Laboratories) is a universally compatible oxygen carrier developed to treat life-threatening anemia. This multicenter phase III trial was ...the first US study to assess survival of patients resuscitated with a hemoglobin-based oxygen carrier starting at the scene of injury. Study Design Injured patients with a systolic blood pressure ≤ 90 mmHg were randomized to receive field resuscitation with PolyHeme or crystalloid. Study patients continued to receive up to 6 U of PolyHeme during the first 12 hours postinjury before receiving blood. Control patients received blood on arrival in the trauma center. This trial was conducted as a dual superiority/noninferiority primary end point. Results Seven hundred fourteen patients were enrolled at 29 urban Level I trauma centers (79% men; mean age 37.1 years). Injury mechanism was blunt trauma in 48%, and median transport time was 26 minutes. There was no significant difference between day 30 mortality in the as-randomized (13.4% PolyHeme versus 9.6% control) or per-protocol (11.1% PolyHeme versus 9.3% control) cohorts. Allogeneic blood use was lower in the PolyHeme group (68% versus 50% in the first 12 hours). The incidence of multiple organ failure was similar (7.4% PolyHeme versus 5.5% control). Adverse events (93% versus 88%; p = 0.04) and serious adverse events (40% versus 35%; p = 0.12), as anticipated, were frequent in the PolyHeme and control groups, respectively. Although myocardial infarction was reported by the investigators more frequently in the PolyHeme group (3% PolyHeme versus 1% control), a blinded committee of experts reviewed records of all enrolled patients and found no discernable difference between groups. Conclusions Patients resuscitated with PolyHeme, without stored blood for up to 6 U in 12 hours postinjury, had outcomes comparable with those for the standard of care. Although there were more adverse events in the PolyHeme group, the benefit-to-risk ratio of PolyHeme is favorable when blood is needed but not available.
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GEOZS, NUK, OILJ, SBCE, SBJE, UL, UPUK
The unification of the theory of relativity and quantum mechanics is a long-standing challenge in contemporary physics. Experimental techniques in quantum optics have only recently reached the ...maturity required for the investigation of quantum systems under the influence of non-inertial motion, such as being held at rest in gravitational fields, or subjected to uniform accelerations. Here, we report on experiments in which a genuine quantum state of an entangled photon pair is exposed to a series of different accelerations. We measure an entanglement witness for g-values ranging from 30 mg to up to 30 g-under free-fall as well on a spinning centrifuge-and have thus derived an upper bound on the effects of uniform acceleration on photonic entanglement.
The massive transfusion (MT) concept (>10-U packed red blood cells per 24 hours) is retrospective, arbitrary, and prone to survivor bias. Accounting for rate and timing is a more accurate conceptual ...framework. We redefined MT as a critical administration threshold (CAT) of 3 U/h, which is clinically pertinent and reflects hemorrhagic shock. The purpose of this study was to compare the traditional form of MT to a CAT definition in predicting mortality.
Patients receiving transfusion in the first 24 hours were included. Precise transfusion times for each unit, in minutes, were calculated from time of injury. MT and CAT were compared to determine risk of death. Univariate and multivariate analyses were used to examine inpatient mortality.
A total of 169 patients(70%, >10 New Injury Severity Score NISS) were studied; 46% were CAT+; 22% met the MT criteria. With logistic regression, a CAT of 3 U/h (CAT+) was more predictive of death compared with 2, 4, 5, or 6 U/h. CAT was met once (CAT 1), twice (CAT 2) or more than 3 times (CAT 3) in 21%, 14%, and 11%, respectively. Increasing CAT was associated with increased mortality. CAT identified 75% of all deaths; MT only identified 33% and failed to identify 42% of CAT+ deaths. CAT (relative risk RR 3.58; 95% confidence interval CI 1.80-7.15) had a stronger association with mortality compared with MT(RR, 1.82; 95% confidence interval, 1.02-3.26).
The traditional definition of MT is inadequate to reflect illness severity. Using CATs allows prospective identification of critically ill trauma patients and eliminates survivor bias. CAT may serve as an activation trigger for transfusion protocols, allowing early identification of patients with critical transfusion requirements. Clinical trials involving transfusion strategies should consider CAT as an instrument for evaluating outcomes.
Diagnostic/prognostic study, level II.
Definitions of massive transfusion (MT), 10 or more units of packed red blood cells (PRBCs) in 24 hours, focus on static volumes over fixed times. This arbitrary volume definition promotes survivor ...bias and fails to identify the "massively" transfused patient. In previous work, the critical administration threshold (CAT) was created to incorporate both rate and volume of transfusion. CAT proved a superior predictor of mortality compared with traditional MT. The purpose of this study was to prospectively validate CAT in a larger trauma population.
Patients receiving at least 1 U of PRBCs within the first day of admission were identified prospectively. Administration time of each unit of PRBCs was recorded in minutes. CAT status, defined as receipt of at least 3 U of blood in a 60-minute period, was identified for the first 24 hours. CAT+ patients were quantified by the number of times CAT+ was reached, that is, once (CAT1), twice (CAT2), three times (CAT3), or 4 or more times (CAT4). A multivariable Cox proportional hazard model with a time-varying covariate was used to quantify a patient's risk of death with increasing CAT status.
A total of 316 met inclusion criteria, 161 of whom were CAT+. Seventy-six percent were male, mean age was 38 years, and median Injury Severity Score (ISS) was 15. CAT+ was associated with a twofold increased risk of death (hazard ratio, 1.809; 95% confidence interval, 1.020-3.209). Ninety-one patients were CAT+ and received less than 10 U of blood, thereby MT- (CAT+/MT-). CAT+/MT- had significant injury patterns, with a median ISS of 14, 43% penetrating injury, and 10% mortality.
CAT allows early identification of injured patients at greatest risk of death. Encompassing both rate and volume of transfusion, CAT is a tool more sensitive than common MT definitions. Studies examining large-volume blood transfusions should use CAT to identify patients, to accurately identify cohorts of interest.
Diagnostic tests, level II.
OBJECTIVE:To review the history of the innovation of damage control (DC) for management of trauma patients.
BACKGROUND:DC is an important development in trauma care that provides a valuable case ...study in surgical innovation.
METHODS:We searched bibliographic databases (1950–2015), conference abstracts (2009–2013), Web sites, textbooks, and bibliographies for articles relating to trauma DC. The innovation of DC was then classified according to the Innovation, Development, Exploration, Assessment, and Long-term study model of surgical innovation.
RESULTS:The “innovation” of DC originated from the use of therapeutic liver packing, a practice that had previously been abandoned after World War II because of adverse events. It then “developed” into abbreviated laparotomy using “rapid conservative operative techniques.” Subsequent “exploration” resulted in the application of DC to increasingly complex abdominal injuries and thoracic, peripheral vascular, and orthopedic injuries. Increasing use of DC laparotomy was followed by growing reports of postinjury abdominal compartment syndrome and prophylactic use of the open abdomen to prevent intra-abdominal hypertension after DC laparotomy. By the year 2000, DC surgery had been widely adopted and was recommended for use in surgical journals, textbooks, and teaching courses (“assessment” stage of innovation). “Long-term study” of DC is raising questions about whether the procedure should be used more selectively in the context of improving resuscitation practices.
CONCLUSIONS:The history of the innovation of DC illustrates how a previously abandoned surgical technique was adapted and readopted in response to an increased understanding of trauma patient physiology and changing injury patterns and trauma resuscitation practices.
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