1. Utilize the appropriate ratio of fresh frozen plasma to packed red blood cells for hemostatic resuscitation of patients requiring massive transfusion.

2. Discuss the advantages of using factor VIIa.

3. Recognize and treat transfusion-related acute lung injury.

4. Describe the characteristics of commonly used hemoglobin-based O2 carriers.

5. Discuss the role of ultrasonography in traumatic injuries.

New Strategies for Trauma Resuscitation
Gregory J. Beilman, MD, Professor of Surgery and Chief, Surgical Critical Care and Trauma, University of Minnesota Medical School, Minneapolis

Introduction: best resuscitation for patient with trauma is stopping bleeding and aggressive resuscitation to normal physiologic end points

Coagulopathy of trauma: severe injury, shock, transfusion, and resuscitation may cause hemorrhage, hemodilution, hypothermia, and acidosis, resulting in coagulopathy and exacerbating process; as injury severity score (ISS) increases, incidence of coagulopathy increases; associated with increased mortality; especially common in combat setting

Ratio of fresh frozen plasma (FFP) to packed red blood cells (PRBCs): data from Iraq war (patients receiving massive transfusions); if ratio <1:4, mortality risk ≈66%; if ratio 1:4 to 1:2, mortality risk ≈33%; if ratio approached 1:1, mortality risk dropped to 20%; damage-control resuscitation—complementary to damage-control surgery; aggressive hemostatic resuscitation while tending patient’s surgical needs in operating room (OR); most important to recognize patients at risk for massive transfusion as soon as possible; requires PRBCs, FFP, platelets, and factor VIIa in OR and intensive care unit (ICU), repeated as needed; minimize use of crystalloid in resuscitation process; retrospective chart review—of 997 transfused patients (at multiple trauma centers), 466 received massive transfusion; low ratio of FFP to PRBCs associated with high mortality rate; mortality decreased as ratio increased; no decrement in mortality by pushing ratio to 1:1; ratio of FFP to PRBCs (>1:2) and ratio of platelets to PRBCs (>1:2) independently predicted survival to 30 days; 1:1:1 ratio suggested for patients likely to require massive transfusion

Whole blood: not currently available in civilian practice; used frequently in combat setting; disadvantages—not approved by Food and Drug Administration (FDA); collection resource-intensive; no screening for disease transmission; cannot be stored; white blood cells (WBCs) possibly increase risk for adverse events in some patients

Recombinant factor VIIa: FDA-approved for use in hemophilia patients who develop antibody to factor VIII; large multicenter trauma trial showed reduction in need for blood transfusion and massive transfusion in patients who received factor VIIa as initial therapy along with stabilization therapy for severe traumatic injury; retrospective review showed that combat trauma patients who received early administration of factor VIIa required fewer units of PRBCs and had no difference in mortality, acute respiratory distress syndrome (ARDS), infection, or thrombotic events; study—evaluated role of factor VIIa for rapid reversal of coagulopathy in patients who required surgery after traumatic brain injury; patients who received factor VIIa experienced significantly decreased time to surgical intervention, compared to patients who received FFP to reverse coagulopathy; patients receiving factor VIIa required fewer units of FFP (2 vs 6 U) before surgery; difference in mortality rate approached statistical significance; no difference in thrombotic episodes or other complications

Near infrared spectroscopy (NIRS): light shone on tissue bed of interest is reflected through spectroscope; computer analysis of data estimates O2 saturation of tissue; multicenter study—looked at tissue O2 saturation of skeletal muscle (StO2 ) in sick patients who were hypotensive with multiple injuries; StO2 correlated with development of multiple organ failure, mortality, and need for massive transfusion; found that StO2 as sensitive as base deficit and systolic blood pressure (BP) for predicting mortality within first 24 hr and development of multiple organ failure in trauma patients; StO2 also had good negative predictive value; StO2 was only retained predictor for death and multiple organ failure in patients who received massive transfusion; concluded that NIRS and StO2 measures reflect resuscitation status in severe traumatic injuries; low StO2 predicts poor outcome in trauma patient population

Hypertonic saline: described effects include immunomodulation and decreased cerebral edema; multiple trials show unclear benefit; study—blunt trauma patients with hypotension randomized to treatment with hypertonic saline and dextran vs lactated Ringer’s solution; study ended early because of futility; currently, 2 studies sponsored by National Institutes of Health comparing hypertonic saline and hypertonic saline plus dextran for treatment of trauma patients

Hypotensive resuscitation: pressure target of 65 mm Hg too low; 8 hr of hypotensive resuscitation too long; data forthcoming

Hypothermia: pig model of hemorrhagic shock—environmentally induced hypothermia (body temperature of 33°C) improved survival (≈100% vs ≈40%), compared to maintenance of normothermia; pigs with induced hypothermia also had lower lactate levels and required less fluids for resuscitation; beneficial effects of environmentally-induced hypothermia may be mediated by slowing metabolism and improving biochemical function; shock-induced hypothermia, resulting from metabolic failure, associated with acidosis and coagulopathy

Conclusions: consider early resuscitation and increasing amounts of FFP and platelets in patients likely to require massive transfusion; factor VIIa reduces need for transfusion and allows more rapid surgery in subset of trauma patients; NIRS predicts outcome and reflects resuscitation status in severely injured trauma patients

Current Concepts in Transfusion
Jonathan L. Marinaro, MD, Assistant Professor, Department of Surgery, University of New Mexico Health and Sciences Center School of Medicine, Albuquerque

Introduction: Canadian Critical Care Trials Group looked at level of hemoglobin (Hb) as indicator for transfusion; average Hb level in restrictive group, 8.5 g/dL at time of transfusion; decision to transfuse affected by physician preferences and experience

Anemia in critically ill patients: 95% of patients in ICU have anemia by day 3; most patients transfused by end of 1 wk; acute blood loss responsible for anemia in 35% of patients in ICU (other causes include drawing blood for laboratory tests and insufficient hematopoiesis); study showed that given same hematocrit (Hct), patients have different erythropoietin (EPO) levels; surgical patients and those with multiple trauma or sepsis do not mount same EPO response as outpatients with chronic anemia; factors contributing to anemia in critical care patients include occult gastrointestinal (GI) bleeding and bleeding from wounds and drains; anemia in critical care patients similar to anemia of chronic disease (eg, low iron; low total iron binding capacity)

Risks for disease transmission: some hospitals require consent to transfuse blood; transfusions associated with risk of acquiring hepatitis B (1 in 200,000), hepatitis C (1 in 800,000), and HIV (1 in 2 million)

Transfusion-related acute lung injury (TRALI): on chest x-ray, appears similar to ARDS or fluid overload; underrecognized problem in critical care; incidence in North America, 1 in 5000 to 1 in 1300 (but underrecognized); one of most common causes of transfusion-related death; most commonly associated with FFP or plasma-rich products; reported with intravenous (IV) immunoglobulin (rare); etiology—30% of marginated WBCs reside in pulmonary capillary endothelium; activated neutrophils phagocytize bacteria and cell wall, causing capillary leakage and ARDS; WBCs activated de novo in TRALI; interleukins or granulocyte colony-stimulating factor (GCSF) may trigger TRALI in neutropenic patients; normally, extravascular bacteria stimulate production of cytokines, which attract WBCs to area (eg, endothelium); WBCs adhere to and cross capillary endothelium to kill bacteria; in patient with inciting event, surface becomes activated without presence of bacteria; WBCs attracted to cytokine-rich endothelium; transfusion causes activation of WBCs, leading to “holes” in endothelium, leakage, and problems associated with TRALI; risk factors— massive transfusion; surgery; cytokine administration (eg, interleukin-2, GCSF); multiparous women (3 pregnancies) excluded from donating plasma (higher risk of causing TRALI); human leukocyte antigen (HLA)-2 antibodies (important in TRALI) produced during pregnancy; presentation—1 to 6 hr after transfusion; severe hypoxemia; moderate hypotension; pulmonary edema; fever; conditions confused with TRALI—transfusion-associated circulatory overload (treated with diuretics); anaphylactic reactions (wheezing, urticaria, and laryngeal edema; requires steroids); transfusion-related bacterial sepsis rare; treatment—aggressive respiratory support; high positive end-expiratory pressure (PEEP) helpful; diuresis not recommended (causes hypotension); steroids not indicated; duration and severity—72 hr (ARDS lasts longer and associated with higher mortality [≈40%]); mortality 5% to 25%; wide spectrum of illness; action—once recognized, replace blood and continue transfusion

Management of Jehovah’s Witness patient: legally, only adults allowed to refuse blood; legal precedent for transfusing pediatric patient in acute situation; patient may accept some products but not others (present list of products to adult patient); strategies to limit transfusion—limit phlebotomy; minimize surgical losses; consider use of high- dose EPO, iron, folate, vitamin B12 , and factor VII; maintain blood volume with crystalloid or synthetic colloid; study—high-dose EPO given IV (600 IU/kg 3 times/wk or on days 1, 3, 6, 8, 10, and 13) resulted in substantial increases in Hb and Hct; mortality increases with Hb <8 g/dL (eg, from 34% to 60% when Hb <5-6 g/dL)

Case: man, 21 yr of age, dragged by car; emergent hemostasis performed (received 2 U of blood); later identified as Jehovah’s Witness; mother did not allow transfusion; on day 7, Hct 9%, with worsening respiratory failure; bovine blood substitute (Hemopure) given as compassionate-use on days 8, 9, and 10; on day 11, family decided to discontinue; results—Hb increased from 3 to 10 mg/dL; Hct fell initially, then increased; mixed venous O2 saturation SvO2 increased from 55% to low 70s; brain tissue saturation normalized; creatinine improved; on day 10, ≈6 hr after transfusion, BP spiked, frothy pulmonary edema developed, and brain SvO2 dropped dramatically; computed tomography (CT) of head showed massive brain edema; patient became bradycardic; family gave do-not-resuscitate order and care withdrawn; massive reperfusion injury to brain (similar to that which may occur when giving thrombolytics after stroke) likely occurred

Hb-based O2 carriers (HBOCs): from bovine, human, and recombinant sources; refined versions much less likely to cause side effects; Hemopure has half-life of 19 hr in body and lasts 36 mo at room temperature; Polyheme has half- life of 24 hr in body and shelf life of 6 wk; human blood has half-life of 31 days and shelf life of 6 hr; P50 of Polyheme closer to that of blood; trial showed that, among trauma patients with Hb <1 g/dL, Polyheme improved survival (75% vs 16% of controls); Hemopure approved in United States for animals only; meta-analysis showed that patients who received HBOCs had higher risk for myocardial infarction and subsequent death (trials stopped); risk-benefit analysis necessary

Protocol for massive transfusion: from University of New Mexico Hospital; transfusion ratio of FFP to PRBCs of 1:1 or 1:2 reduces coagulopathy; coagulation factors decrease (as low as 25%) with increasing amount of transfused blood; massive transfusion—>1 blood volume (≈10 U) in 24 hr or >4 U in 1 hr; protocol—patient given 6 U of FFP, 6 U of PRBCs, and 1 pheresis pack (6 U) of platelets (repeated as necessary)

Trauma Ultrasonography
Margaret Knudson, MD, Professor of Surgery, University of California, San Francisco, School of Medicine

Echocardiography: for, eg, looking at pericardial fluid and in trauma room during cardiopulmonary resuscitation (CPR); absence of cardiac activity on ultrasonography (US) or electrocardiography indication for stopping CPR and not opening chest

US in penetrating chest wounds: positive findings warrant surgery; several options available when examination equivocal or small amount of fluid present (in stable patient); pericardial window may be appropriate; observation appropriate when examination negative

Pneumothorax: 7.5-Mhz transducer superior to 3.5-MHz transducer for visualization; US almost 100% accurate for identifying pneumothorax (shown in multiple studies); identified by lack of movement on US; not useful if patient stable and x-ray shows pneumothorax; useful if patient develops tension in ICU or during surgery, after removal of chest tube, and in environments where x-ray limited

Abdominal trauma: clear role in unstable patients (affects management); eg, positive findings in right upper quadrant (in unstable patient) indication for surgery; does not rule out all injuries; has very limited use in stable patient with penetrating trauma

Pediatric trauma: reduces dose of radiation; false-negatives—in children, blunt injuries to spleen and liver may not result in free fluid (not identified)

Other trauma: false-negative results possible with pelvic fractures; pelvic hematoma partially displaces bladder, obscuring shadow; Bedside Organ Assessment with Sonography for Trauma (BOAST) study—patients with solid-organ injuries identified by CT; candidates for nonoperative management received baseline BOAST examination; US used for identifying injury and amount of fluid present in intra-abdominal cavity (score of 1-3); follow-up BOAST examination 48 hr later looked for increase in fluid or size of injury or other findings (eg, pseudoaneurysm); if findings positive, CT repeated or visceral angiography performed, if indicated; of 135 solid-organ injuries, only 34 seen by both imaging techniques; after 48 hr, Hct decreased in 56 patients, but hematoperitoneal scores generally did not; sonography identified 13 of 15 complications, including intra-abdominal abscesses and psuedoaneurysms

Education: courses developed through American College of Surgeons; teaching modules (basic and advanced) and documentation available; level 1, attendance of course; level 2, objectives of course met (by, eg, passing written test); level 3, monitored clinical experience demonstrated; efficacy—study looking at learning curves for use of US in trauma setting showed no deterioration of skills (sensitivity, specificity, accuracy, and predictive value) over 24 mo

Other uses: measuring diameter of inferior vena cava; helps determine amount of fluid to be removed during hemodialysis; injury assessment (eg, cardiac, bone) on space station