Effect of Hypoxic Blood Infusion on Pulmonary Physiology.

The ability to store red blood cells (RBCs) and other components for extended periods of time has expanded the availability and use of transfusion as a life-saving therapy. However, conventional RBC storage has a limited window of effective preservation and is accompanied by the progressive accumulation of a series of biochemical and morphological modifications, collectively referred to as "storage lesions." These lesions have been associated with negative clinical outcomes (i.e., postoperative complications as well as reduced short-term and long-term survival) in patients transfused with conventionally stored blood with older and deteriorated transfused red cells. Hence, there is an increased unmet need for improved RBC storage. Hypoxic storage of blood entails the removal of large amounts of oxygen to low levels prior to refrigeration and maintenance of hypoxic levels through the entirety of storage. As opposed to conventionally stored blood, hypoxic storage can lead to a reduction of oxidative damage to slow storage lesion development and create a storage condition expected to result in enhanced efficacy of stored RBCs without an effect on oxygen exchange in the lung. Hypoxic blood transfusions appear to offer minimal safety concerns, even in patients with hypoxemia. This review describes the physiology of hypoxically stored blood, how it differs from conventionally stored blood, and its use in potential clinical application, such as massively transfused and critically ill patients with oxygenation/ventilation impairments.

Use of Thromboelastography (TEG) for Detection of New Oral Anticoagulants.

CONTEXT: The clinical introduction of new oral anticoagulants (NOACs) has stimulated the development of tests to quantify the effects of these drugs and manage complications associated with their use. Until recently, the only treatment choices for the prevention of venous thromboembolism in orthopedic surgical patients, as well as for stroke and systemic embolism in patients with atrial fibrillation, were vitamin K antagonists, antiplatelet drugs, and unfractionated and low-molecular-weight heparins. With the approval of NOACs, treatment options and consequent diagnostic challenges have expanded. OBJECTIVE: To study the utility of thromboelastography (TEG) in monitoring and differentiating between 2 currently approved classes of NOACs, direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban). DESIGN: Blood samples from healthy volunteers were spiked with each NOAC in both the presence and absence of ecarin, and the effects on TEG were evaluated. RESULTS: Both the kaolin test reaction time (R time) and the time to maximum rate of thrombus generation were prolonged versus control samples and demonstrated a dose response for apixaban (R time within the normal range) and dabigatran. The RapidTEG activated clotting time test allowed the creation of a dose-response curve for all 3 NOACs. In the presence of anti-Xa inhibitors, the ecarin test promoted significant shortening of kaolin R times to the hypercoagulable range, while in the presence of the direct thrombin inhibitor only small and dose-proportional R time shortening was observed. CONCLUSIONS: The RapidTEG activated clotting time test and the kaolin test appear to be capable of detecting and monitoring NOACs. The ecarin test may be used to differentiate between Xa inhibitors and direct thrombin inhibitors. Therefore, TEG may be a valuable tool to investigate hemostasis and the effectiveness of reversal strategies for patients receiving NOACs.

Traumatic intracranial hemorrhage correlates with preinjury brain atrophy, but not with antithrombotic agent use: a retrospective study.

BACKGROUND: The impact of antithrombotic agents (warfarin, clopidogrel, ASA) on traumatic brain injury outcomes is highly controversial. Although cerebral atrophy is speculated as a risk for acute intracranial hemorrhage, there is no objective literature evidence. MATERIALS AND METHODS: This is a retrospective, consecutive investigation of patients with signs of external head trauma and age ≥60 years. Outcomes were correlated with antithrombotic-agent status, coagulation test results, admission neurologic function, and CT-based cerebral atrophy dimensions. RESULTS: Of 198 consecutive patients, 36% were antithrombotic-negative and 64% antithrombotic-positive. ASA patients had higher arachidonic acid inhibition (p = 0.04) and warfarin patients had higher INR (p<0.001), compared to antithrombotic-negative patients. Antithrombotic-positive intracranial hemorrhage rate (38.9%) was similar to the antithrombotic-negative rate (31.9%; p = 0.3285). Coagulopathy was not present on the ten standard coagulation, thromboelastography, and platelet mapping tests with intracranial hemorrhage and results were similar to those without hemorrhage (p≥0.1354). Hemorrhagic-neurologic complication (intracranial hemorrhage progression, need for craniotomy, neurologic deterioration, or death) rates were similar for antithrombotic-negative (6.9%) and antithrombotic-positive (8.7%; p = 0.6574) patients. The hemorrhagic-neurologic complication rate was increased when admission major neurologic dysfunction was present (63.2% versus 2.2%; RR = 28.3; p<0.001). Age correlated inversely with brain parenchymal width (p<0.001) and positively with lateral ventricular width (p = 0.047) and cortical atrophy (p<0.001). Intracranial hemorrhage correlated with cortical atrophy (p<0.001) and ventricular width (p<0.001). CONCLUSIONS: Intracranial hemorrhage is not associated with antithrombotic agent use. Intracranial hemorrhage patients have no demonstrable coagulopathy. The association of preinjury brain atrophy with acute intracranial hemorrhage is a novel finding. Contrary to antithrombotic agent status, admission neurologic abnormality is a predictor of adverse post-admission outcomes. Study findings indicate that effective hemostasis is maintained with antithrombotic therapy.

Characteristics and outcomes of trauma patients with ICU lengths of stay 30 days and greater: a seven-year retrospective study.

INTRODUCTION: Prolonged intensive care unit lengths of stay (ICU LOS) for critical illness can have acceptable mortality rates and quality of life despite significant costs. Only a few studies have specifically addressed prolonged ICU LOS after trauma. Our goals were to examine characteristics and outcomes of trauma patients with LOS >or= 30 days, predictors of prolonged stay and mortality. METHODS: All trauma ICU admissions over a seven-year period in a level 1 trauma center were analyzed. Admission characteristics, pre-existing conditions and acquired complications in the ICU were recorded. Logistic regression was used to identify independent predictors of prolonged LOS and predictors of mortality among those with prolonged LOS after univariate analyses. RESULTS: Of 4920 ICU admissions, 205 (4%) had ICU LOS >30 days. These patients were older and more severely injured. Age and injury severity score (ISS) were associated with prolonged LOS. After logistic regression analysis, sepsis, acute respiratory distress syndrome, and several infectious complications were important independent predictors of prolonged LOS. Within the group with ICU LOS >30 days, predictors of mortality were age, pre-existing renal disease as well as the development of renal failure requiring dialysis. Overall mortality was 12%. CONCLUSIONS: The majority of patients with ICU LOS >or= 30 days will survive their hospitalization. Infectious and pulmonary complications were predictors of prolonged stay. Further efforts targeting prevention of these complications are warranted.

Human polymerized hemoglobin for the treatment of hemorrhagic shock when blood is unavailable: the USA multicenter trial.

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

The impact of hyperglycemia on patients with severe brain injury.

BACKGROUND: This study aimed to analyze the relation of hyperglycemia to outcome in cases of severe traumatic brain injury, and to examine factors that may be responsible for the hyperglycemic state. METHODS: A retrospective analysis in an intensive care unit of a level 1 trauma center investigated 77 patients with severe traumatic brain injury. Patients with a Glasgow Coma Scale (GCS) of 8 or lower who survived more than 5 days were reviewed. Serum glucose, base deficit, GCS, use of steroids, and amounts of insulin and carbohydrates were recorded for 5 days, along with age. The Injury Severity Score (ISS) and the Abbreviated Injury Score (AIS) for the head, chest, and abdomen also were recorded. A hyperglycemia score (HS) was calculated as follows. A value of 1 was assigned each day the glucose exceeded 170 mg/dL (range, 0-5). A hyperglycemia score for days 3, 4, and 5 (HS day 3-5) also was calculated (range, 0-3). Outcomes included mortality, day 5 GCS, intensive care unit length of stay, and hospital length of stay. RESULTS: Of the 77 patients, 24 (31.2%) died. Nonsurvivors had higher glucose levels each day. The HS was higher for those who died: 2.4 +/- 1.7 versus 1.5 +/- 1.4 (p = 0.02). Univariate analysis showed that only HS and ISS correlated with all four outcome variables studied. Cox's regression analysis showed that mortality was related to age and ISS. Head AIS and HS were independent predictors of lower day 5 GCS, whereas HS 3-5 and day 4 GCS were related to prolonged hospital length of stay. Older age, diabetes, and lower day 1 GCS were associated with higher HS, whereas carbohydrate infusion rate, ISS, head AIS, and steroid administration were not. CONCLUSIONS: Early hyperglycemia is associated with poor outcomes for patients with severe traumatic brain injury. Tighter control of serum glucose without reduction of nutritional support may improve the prognosis for these critically ill patients.