Assessing predictors of futility in patients receiving massive transfusions.

BACKGROUND: Massive transfusions are associated with a high mortality rate, but there is little evidence indicating when such efforts are futile. The purpose of this study was to identify clinical variables that could be used as futility indicators in massively transfused patients. METHODS: We retrospectively analyzed 138 adult surgical patients at our institution receiving a massive transfusion (2016-2019). Peak lactate and nadir pH within 24 h of massive transfusion initiation, along with other clinical variables, were assessed as predictors of the primary outcome, in-hospital mortality. RESULTS: The overall rate of in-hospital mortality among our patient population was 52.9% (n = 73). Increasing lactate and decreasing pH were associated with greater mortality among massively transfused patients. Mortality rates were ~2-fold higher for patients in the highest lactate category (≥10.0 mmol/L: 25 of 37; 67.6%) compared to the lowest category (0.0-4.9 mmol/L: 17 of 48; 35.4%) (p = .005), and ~2.5-fold higher for patients in the lowest pH category (<7.00: 8 of 9; 88.9%) compared to the highest category (≥7.40: 8 of 23; 34.7%) (p = .016). Increasing age was also associated with higher mortality (≥65 years: 24 of 33; 72.7%) when compared to younger patients (18-64 years: 49 of 105; 46.7%) (p = .010). CONCLUSIONS: Peak lactate ≥10.0 mmol/L, nadir pH <7.00, and age ≥65 years were significantly associated with higher rates of in-hospital mortality among massively transfused patients. Incorporating these clinical parameters into a futility index for massive transfusions will be useful in situations where blood products are scarce and/or mortality may be unavoidable.

Hemostatic properties of cold-stored whole blood leukoreduced using a platelet-sparing versus a non-platelet-sparing filter.

BACKGROUND: Whole blood (WB) is an appealing alternative to component-based transfusion in patients with significant bleeding. Historically, WB was transfused less than 48 hours after collection and was not leukoreduced (LR). However, LR components are now standard in many hospitals and LR WB is desirable. We investigated the effect of the type of LR filter used, as well as storage duration, on coagulation laboratory testing of WB. STUDY DESIGN AND METHODS: Ten units of LR WB-5 units manufactured with a Food and Drug Administration (FDA)-approved platelet (PLT)-sparing filter (WB-PS) and 5 units manufactured with an FDA-approved non-PLT-sparing filter (WB-NPS)-underwent complete blood count, PLT function analyzer (PFA [PFA-100]), thromboelastography (TEG), prothrombin time (PT), partial thromboplastin time (PTT), Factor (F)V activity, chromogenic FVIII, thrombin generation, and microparticle quantification on Storage Days 3, 5, 7, 10, and 14. RESULTS: WB-PS contains more PLTs than WB-NPS (mean, 71 × 109 /L vs. 1 × 109 /L, p < 0.001). WB-PS yielded essentially normal TEG tracings, while TEG tracings of WB-NPS were grossly abnormal (mean reaction time, 7.0 min for WB-PS vs. 9.7 min for WB-NPS, p < 0.001; mean alpha-angle 54.9° vs. 38.1°, p < 0.001; mean maximum amplitude, 54.9 mm vs. 13.9 mm, p < 0.001). PFA-100 closure was more common among units of WB-PS compared to units of WB-NPS (72% vs. 4%, p < 0.001). PT, PTT, and factor activities were not dramatically affected by the LR filter. CONCLUSION: The choice LR filter has a major impact on the hemostatic properties of WB. Although storage of WB is associated with a rapid decline in PLT count, hemostasis as assessed by TEG and PFA-100 is not diminished over a 2-week storage period.

Handheld Tissue Oximetry for the Prehospital Detection of Shock and Need for Lifesaving Interventions: Technology in Search of an Indication?

Improved prehospital methods for assessing the need for lifesaving interventions (LSIs) are needed to gain critical lead time in the care of the injured. We hypothesized that threshold values using prehospital handheld tissue oximetry would detect occult shock and predict LSI requirements. This was a prospective observational study of adult trauma patients emergently transported by helicopter. Patients were monitored with a handheld tissue oximeter (InSpectra Spot Check; Hutchinson Technology Inc, Hutchinson, MN), continuous vital signs, and 21 laboratory measurements obtained both in the field with a portable analyzer and at the time of admission. Shock was defined as base excess ≥ 4 or lactate > 3 mmol/L. Eighty-eight patients were enrolled with a median Injury Severity Score of 16 (interquartile range, 5-29). The median hemoglobin saturation in the capillaries, venules, and arterioles (StO2) value for all patients was 82% (interquartile range, 76%-87%; range, 42%-98%). StO2 was abnormal (< 75%) in 18 patients (20%). Eight were hypotensive (9%) and had laboratory-confirmed evidence of occult shock. StO2 correlated poorly with shock threshold laboratory values (r = -0.17; 95% confidence interval, -0.33 to 1.0; P = .94). The area under the receiver operating curve was 0.51 (95% confidence interval, 0.39-0.63) for StO2 < 75% and laboratory-confirmed shock. StO2 was not associated with LSI need on admission when adjusted for multiple covariates, nor was it independently associated with death. Handheld tissue oximetry was not sensitive or specific for identifying patients with prehospital occult shock. These results do not support prehospital StO2 monitoring despite its inclusion in several published guidelines.

Blood utilization and mortality in victims of gun violence.

BACKGROUND: Blood transfusion can be lifesaving for patients with hemorrhage; however, transfusion requirements for victims of gun violence are poorly understood. STUDY DESIGN AND METHODS: In an urban, Level 1 trauma center, 23,422 trauma patients were analyzed in a retrospective cohort study. Patients with gunshot wounds (GSWs) (n = 2,672; 11.4% of trauma patients) were compared to those with non-GSW traumatic injuries from 2005 to 2017, to assess blood utilization. RESULTS: The GSW cohort was approximately five times more likely to require transfusion (538 of 2672 [20.1%] vs. 798 of 20,750 [3.9%]; p < 0.0001), and the number of blood component units transfused per patient was approximately 10 times greater (3.3 ± 13.5 vs. 0.31 ± 3.8 units/patient; p < 0.0001), compared to the non-GSW cohort. The risk-adjusted likelihood of requiring high-dose transfusion was greater in the GSW cohort (odds ratio, 2.38; 95% confidence interval, 1.14-5.80), and requirements were increased for all four blood components (red blood cells, platelets, plasma, and cryoprecipitate). Patients with GSWs had approximately 14 times greater overall mortality (653 of 2672 [24.4%] vs. 352 of 20,750 [1.7%]; p < 0.0001]. Compared to non-GSW penetrating injuries (e.g., stab wounds), those with GSWs had approximately four times higher transfusion requirements (3.3 ± 13.5 vs. 0.80 ± 3.8 units/patient; p < 0.0001), and approximately eight times greater overall mortality (653 of 2672 [24.4%] vs. 28 of 956 [2.9%]; p < 0.0001). CONCLUSIONS: Compared to other traumatic injuries, GSW injuries are associated with substantially greater blood utilization and mortality. Trauma centers treating GSW injuries should have ready access to all blood components and ability to implement massive transfusions.

Physiologic Considerations in Trauma Patients Undergoing Resuscitative Endovascular Balloon Occlusion of the Aorta.

Resuscitative endovascular balloon occlusion of the aorta is a new procedure for adjunctive management of critically injured patients with noncompressible torso or pelvic hemorrhage who are in refractory hemorrhagic shock, ie, bleeding to death. The anesthesiologist plays a critical role in management of these patients, from initial evaluation in the trauma bay to definitive care in the operating room and the critical care unit. A comprehensive understanding of the effects of resuscitative endovascular balloon occlusion of the aorta is essential to making it an effective component of hemostatic resuscitation.

Helicopter emergency medical services for adults with major trauma.

BACKGROUND: Although helicopters are presently an integral part of trauma systems in most developed nations, previous reviews and studies to date have raised questions about which groups of traumatically injured people derive the greatest benefit. OBJECTIVES: To determine if helicopter emergency medical services (HEMS) transport, compared with ground emergency medical services (GEMS) transport, is associated with improved morbidity and mortality for adults with major trauma. SEARCH METHODS: We ran the most recent search on 29 April 2015. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library (Cochrane Central Register of Controlled Trials; CENTRAL), MEDLINE (OvidSP), EMBASE Classic + EMBASE (OvidSP), CINAHL Plus (EBSCOhost), four other sources, and clinical trials registers. We screened reference lists. SELECTION CRITERIA: Eligible trials included randomized controlled trials (RCTs) and nonrandomized intervention studies. We also evaluated nonrandomized studies (NRS), including controlled trials and cohort studies. Each study was required to have a GEMS comparison group. An Injury Severity Score (ISS) of at least 15 or an equivalent marker for injury severity was required. We included adults age 16 years or older. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and assessed the risk of bias of included studies. We applied the Downs and Black quality assessment tool for NRS. We analyzed the results in a narrative review, and with studies grouped by methodology and injury type. We constructed 'Summary of findings' tables in accordance with the GRADE Working Group criteria. MAIN RESULTS: This review includes 38 studies, of which 34 studies examined survival following transportation by HEMS compared with GEMS for adults with major trauma. Four studies were of inter-facility transfer to a higher level trauma center by HEMS compared with GEMS. All studies were NRS; we found no RCTs. The primary outcome was survival at hospital discharge. We calculated unadjusted mortality using data from 282,258 people from 28 of the 38 studies included in the primary analysis. Overall, there was considerable heterogeneity and we could not determine an accurate estimate of overall effect.Based on the unadjusted mortality data from six trials that focused on traumatic brain injury, there was no decreased risk of death with HEMS. Twenty-one studies used multivariate regression to adjust for confounding. Results varied, some studies found a benefit of HEMS while others did not. Trauma-Related Injury Severity Score (TRISS)-based analysis methods were used in 14 studies; studies showed survival benefits in both the HEMS and GEMS groups as compared with MTOS. We found no studies evaluating the secondary outcome, morbidity, as assessed by quality-adjusted life years (QALYs) and disability-adjusted life years (DALYs). Four studies suggested a small to moderate benefit when HEMS was used to transfer people to higher level trauma centers. Road traffic and helicopter crashes are adverse effects which can occur with either method of transport. Data regarding safety were not available in any of the included studies. Overall, the quality of the included studies was very low as assessed by the GRADE Working Group criteria. AUTHORS' CONCLUSIONS: Due to the methodological weakness of the available literature, and the considerable heterogeneity of effects and study methodologies, we could not determine an accurate composite estimate of the benefit of HEMS. Although some of the 19 multivariate regression studies indicated improved survival associated with HEMS, others did not. This was also the case for the TRISS-based studies. All were subject to a low quality of evidence as assessed by the GRADE Working Group criteria due to their nonrandomized design. The question of which elements of HEMS may be beneficial has not been fully answered. The results from this review provide motivation for future work in this area. This includes an ongoing need for diligent reporting of research methods, which is imperative for transparency and to maximize the potential utility of results. Large, multicenter studies are warranted as these will help produce more robust estimates of treatment effects. Future work in this area should also examine the costs and safety of HEMS, since multiple contextual determinants must be considered when evaluating the effects of HEMS for adults with major trauma.

Tranexamic acid: from trauma to routine perioperative use.

PURPOSE OF REVIEW: Optimizing hemostasis with antifibrinolytics is becoming a common surgical practice. Large clinical studies have demonstrated efficacy and safety of tranexamic acid (TXA) in the trauma population to reduce blood loss and transfusions. Its use in patients without pre-existing coagulopathies is debated, as thromboembolic events are a concern. In this review, perioperative administration of TXA is examined in nontrauma surgical populations. Additionally, risk of thromboembolism, dosing regimens, and timing of dosing are assessed. RECENT FINDINGS: Perioperative use of TXA is associated with reduced blood loss and transfusions. Thromboembolic effects do not appear to be increased. However, optimal dosing and timing of TXA administration is still under investigation for nontrauma surgical populations. SUMMARY: As part of a perioperative blood management programme, TXA can be used to help reduce blood loss and mitigate exposure to blood transfusion.

Wild-Type KRAS Is Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer.

PURPOSE: Panitumumab, a fully human antibody against the epidermal growth factor receptor (EGFR), has activity in a subset of patients with metastatic colorectal cancer (mCRC). Although activating mutations in KRAS, a small G-protein downstream of EGFR, correlate with poor response to anti-EGFR antibodies in mCRC, their role as a selection marker has not been established in randomized trials. PATIENTS AND METHODS: KRAS mutations were detected using polymerase chain reaction on DNA from tumor sections collected in a phase III mCRC trial comparing panitumumab monotherapy to best supportive care (BSC). We tested whether the effect of panitumumab on progression-free survival (PFS) differed by KRAS status. RESULTS: KRAS status was ascertained in 427 (92%) of 463 patients (208 panitumumab, 219 BSC). KRAS mutations were found in 43% of patients. The treatment effect on PFS in the wild-type (WT) KRAS group (hazard ratio [HR], 0.45; 95% CI: 0.34 to 0.59) was significantly greater (P < .0001) than in the mutant group (HR, 0.99; 95% CI, 0.73 to 1.36). Median PFS in the WT KRAS group was 12.3 weeks for panitumumab and 7.3 weeks for BSC. Response rates to panitumumab were 17% and 0%, for the WT and mutant groups, respectively. WT KRAS patients had longer overall survival (HR, 0.67; 95% CI, 0.55 to 0.82; treatment arms combined). Consistent with longer exposure, more grade III treatment-related toxicities occurred in the WT KRAS group. No significant differences in toxicity were observed between the WT KRAS group and the overall population. CONCLUSION: Panitumumab monotherapy efficacy in mCRC is confined to patients with WT KRAS tumors. KRAS status should be considered in selecting patients with mCRC as candidates for panitumumab monotherapy.

Phase 1b dose-finding study of motesanib with docetaxel or paclitaxel in patients with metastatic breast cancer.

The purpose of this study was to investigate the safety, tolerability, and pharmacokinetics of motesanib when combined with docetaxel or paclitaxel in patients with metastatic breast cancer. In this open-label, dose-finding, phase 1b study, patients received motesanib 50 or 125-mg orally once daily (QD), beginning day 3 of cycle 1 of chemotherapy, continuously in combination with either paclitaxel 90 mg/m(2) on days 1, 8, and 15 every 28-day cycle (Arm A) or docetaxel 100 mg/m(2) on day 1 every 21-day cycle (Arm B). Dose escalation to motesanib 125 mg QD occurred if the incidence of dose-limiting toxicities (DLTs, primary endpoint) was ≤ 33 %. If the maximum tolerated dose (MTD) of motesanib was established in Arm B, additional patients could receive motesanib at the MTD plus docetaxel 75 mg/m(2). Forty-six patients were enrolled and 45 received ≥ 1 dose of motesanib. The incidence of DLTs was <33 % in all cohorts; thus, motesanib 125 mg QD was established as the MTD. Seven patients (16 %) had grade 3 motesanib-related adverse events including cholecystitis (2 patients) and hypertension (2 patients). Pharmacokinetic parameters of motesanib were similar to those reported in previous studies. The objective response rate was 56 % among patients with measurable disease at baseline who received motesanib in combination with taxane-based chemotherapy. The addition of motesanib to either paclitaxel or docetaxel was generally tolerable up to the 125-mg QD dose of motesanib. The objective response rate of 56 % suggests a potential benefit of motesanib in combination with taxane-based chemotherapy.

Towards a proteome-scale map of the human protein-protein interaction network.

Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.

Changing paradigms in surgical resuscitation.

Patients undergoing emergency surgery typically require resuscitation, either because they are hemorrhaging or because they are experiencing significant internal fluid shifts. Intravascular hypovolemia is common at the time of anesthesia induction and can lead to hemodynamic collapse if not promptly treated. Central pressure monitoring is associated with technical complications and does not improve outcomes in this population. Newer modalities are in use, but they lack validation. Fluid resuscitation is different in bleeding and septic patients. In the former group, it is advisable to maintain a deliberately low blood pressure to facilitate clot formation and stabilization. If massive transfusion is anticipated, blood products should be administered from the outset to prevent the coagulopathy of trauma. Early use of plasma in a ratio approaching 1:1 with red blood cells (RBCs) has been associated with improved outcomes. In septic patients, early fluid loading is recommended. The concept of "goal-directed resuscitation" is based on continuing resuscitation until venous oxygen saturation is normalized. In either bleeding or septic patients, however, the most important goal remains surgical control of the source of pathology, and nothing should be allowed to delay transfer to the operating room. We review the current literature and recommendations for the resuscitation of patients coming for emergency surgery procedures.

Clinical Utility of Autologous Salvaged Blood: a Review.

INTRODUCTION: Autologous salvaged blood, commonly referred to as "cell saver" or "cell salvage" blood, is an important method of blood conservation. Understanding the mechanism of action and summarizing the existing evidence regarding the safety, efficiency, and the relative costs of cell salvage may help educate clinicians on how and when to best utilize autotransfusion. METHODS: This review focuses on issues concerning the quality of red blood cells (RBC), efficiency, and the cost effectiveness relative to autotransfusion. The key considerations of safe use and clinical applicability are described along with the challenges for wider dissemination. RESULTS: Cell salvage can reduce requirements for allogeneic transfusions, along with the associated risks and costs. Autologous salvaged RBCs provide high-quality transfusion, since the cells have not been subjected to the adverse effects of storage as occurs with banked blood. The risks for RBC alloimmunization and transfusion-related infectious diseases are also avoided. With a careful selection of cases, salvaged blood can be more cost effective than donor blood. Cell salvage may have a role in cardiac, major vascular, orthopedic, transplant, and trauma surgeries. However, there remain theoretical safety concerns in cases with bacterial contamination or in cancer surgery. CONCLUSION: In addition to other methods of blood conservation used in patient blood management programs, autologous salvaged blood adds value and is cost effective for appropriate surgical cases. Evidence suggests that autologous salvaged blood may be of higher quality and confer a cost reduction compared with the allogeneic banked blood, when used appropriately.

Prehospital Point of Care Testing for the Early Detection of Shock and Prediction of Lifesaving Interventions.

INTRODUCTION: Early diagnosis and treatment are essential for enhancing outcomes for the traumatically injured. In this prospective prehospital observational study, we hypothesized that a variety of laboratory results measured in the prehospital environment would predict both the presence of early shock and the need for lifesaving interventions (LSIs) for adult patients with traumatic injuries. METHODS: Adult trauma patients flown by a helicopter emergency medical service were prospectively enrolled. Using an i-STAT portable analyzer, data from 16 laboratory tests were collected. Vital signs data were also collected. Outcomes of interest included detection of shock, mortality, and requirement for LSIs. Logistic regression, including a Bayesian analysis, was performed. RESULTS: Among 300 patients screened for enrollment, 261 had complete laboratory data for analysis. The majority of patients were male (75%) with blunt trauma (91.2%). The median injury severity score was 29 (IQR, 25-75) and overall mortality was 4.6%. A total of 170 LSIs were performed. The median lactate for patients who required an LSI was 4.1 (IQR, 3-5.4). The odds of requiring an LSI within the first hour of admission to the trauma center was highly associated with increases in lactate and glucose. A lactate level > 4 mmol/L was statistically associated with greater sensitivity and specificity for predicting the need for a LSI compared with shock index. CONCLUSIONS: In this prospective observational trial, lactate outperformed static vital signs, including shock index, for detecting shock and predicting the need for LSIs. A lactate level > 4 mmol/L was found to be highly associated with the need for LSIs.

Tenosynovial Giant Cell Tumor: Incidence, Prevalence, Patient Characteristics, and Recurrence. A Registry-based Cohort Study in Denmark.

OBJECTIVE: Tenosynovial giant cell tumor (TGCT) is a rare benign proliferative and inflammatory disease arising from synovia of joints, bursae, or tendon sheaths. We aimed to estimate incidence rate and prevalence of TGCT in Denmark, to describe patient characteristics and treatment modalities among patients with TGCT, and to estimate risk of TGCT recurrence. METHODS: Using registry data on pathology examinations and inpatient and outpatient hospital diagnoses, we identified adult patients with diagnoses of diffuse TGCT (D-TGCT) or localized TGCT (L-TGCT) between 1997 and 2012, followed through 2012. We described patients' characteristics, treatment modalities, and recurrence. RESULTS: We identified 2087 patients with L-TGCT and 574 patients with D-TGCT. Their incidence rates per million person-years were 30.3 (95% CI 29.1-31.7) and 8.4 (95% CI 7.7-9.1), respectively. At the end of 2012, prevalence per 100,000 persons was 44.3 (95% CI 42.4-46.3) for L-TGCT and 11.5 (95% CI 10.6-12.6) for D-TGCT. Women made up 61% of the patients with L-TGCT and 51% of the patients with D-TGCT. Median age at diagnosis was 47 years. Ten-year risk of recurrence was 9.8% (95% CI 8.4-11.3%) after L-TGCT and 19.1% (95% CI 15.7-22.7%) after D-TGCT. CONCLUSION: This study contributes evidence about epidemiology of TGCT based on routinely collected population-based data gathered in a setting of universal equal access to healthcare and complete followup.

Supplemental Perioperative Oxygen to Reduce Surgical Site Infection After High-Energy Fracture Surgery (OXYGEN Study).

Supplemental perioperative oxygen (SPO) therapy has been proposed as one approach for reducing the risk of surgical site infection (SSI). Current data are mixed regarding efficacy in decreasing SSI rates and hospital inpatient stays in general and few data exist for orthopaedic trauma patients. This study is a phase III, double-blind, prospective randomized clinical trial with a primary goal of assessing the efficacy of 2 different concentrations of perioperative oxygen in the prevention of SSIs in adults with tibial plateau, pilon (tibial plafond), or calcaneus fractures at higher risk of infection and definitively treated with plate and screw fixation. Patients are block randomized (within center) in a 1:1 ratio to either treatment group (FiO2 80%) or control group (FiO2 30%) and stratified by each study injury location. Secondary objectives of the study are to compare species and antibacterial sensitivities of the bacteria in patients who develop SSIs, to validate a previously developed risk prediction model for the development of SSI after fracture surgery, and to measure and compare resource utilization and cost associated with SSI in the 2 study groups. SPO is a low cost and readily available resource that could be easily disseminated to trauma centers across the country and the world if proved to be effective.

Opioid use among same-day surgery patients: Prevalence, management and outcomes.

OBJECTIVES: To determine whether the prevalence of opioid use among patients requiring elective same-day admission (SDA) surgery is greater than the 2.5% prevalence found in the general population. Secondary objectives were to assess compliance with expert recommendations on acute pain management in opioid-tolerant patients and to examine clinical outcomes. METHODS: A retrospective review of 812 systematically sampled adult SDA surgical cases between April 1, 2008 and March 31, 2009 was conducted. RESULTS: Among 798 eligible patients, 148 (18.5% [95% CI 15.9% to 21.2%]) were prescribed opioids, with 4.4% prescribed long-acting opioids (95% CI 3.0% to 5.8%). Use of opioids was most prevalent among orthopedic and neurosurgery patients. Among the 35 patients on long-acting opioids who had a high likelihood of being tolerant, anesthesiologists correctly identified 33, but only 13 (37%) took their usual opioid preoperatively while 22 (63%) had opioids continued postoperatively. Acetaminophen, nonsteroidal anti-inflammatory drugs and pregabalin were ordered preoperatively in 18 (51%), 15 (43%) and 18 (51%) cases, respectively, while ketamine was used in 15 (43%) patients intraoperatively. Acetaminophen, nonsteroidal anti-inflammatory drugs and pregabalin were ordered postoperatively in 31 (89%), 15 (43%) and 17 (49%) of the cases, respectively. No differences in length of stay, readmissions and emergency room visits were found between opioid-tolerant and opioid-naive patients. CONCLUSION: Opioid use is more common in SDA surgical patients than in the general population and is most prevalent within orthopedic and neurosurgery patients. Uptake of expert opinion on the management of acute pain in the opioid tolerant patient population is lacking.

Blood far forward: Time to get moving!

In planning for future contingencies, current problems often crowd out historical perspective and planners often turn to technological solutions to bridge gaps between desired outcomes and the reality of recent experience. The US Military, North Atlantic Treaty Organization, and other allies are collectively taking stock of 10-plus years of medical discovery and rediscovery of combat casualty care after the wars in Iraq and Afghanistan. There has been undeniable progress in the treatment of combat wounded during the course of the conflicts in Southwest Asia, but continued efforts are required to improve hemorrhage control and provide effective prehospital resuscitation that treats both coagulopathy and shock. This article presents an appraisal of the recent evolution in medical practice in historical context and suggests how further gains in far forward resuscitation might be achieved using existing technology and methods based on whole-blood transfusion while research on new approaches continues.