Challenges to effective research in acute trauma resuscitation: consent and endpoints.

Selection of study endpoints is one of the most important decisions in the design of effective clinical trials. Late mortality (e.g., 28 days) is an unambiguous endpoint, accepted by regulatory agencies, but it is viewed as problematic among researchers in the study of resuscitation for acute trauma injury with hemorrhagic shock. In February 2008, physicians, ethicists, statisticians, and research scientists from the military, academia, industry, the Federal Drug Administration, and the National Heart Lung and Blood Institute gathered to discuss the obstacles confronting the trauma community in their efforts to improve patient outcomes. The primary meeting objective was to generate preliminary suggestions for a series of follow-up meetings that will develop consensus guidelines for the design of large multicenter clinical trials. Twenty short presentations and discussions, summarized here, outlined the group's concerns and suggestions. Successful and failed, completed or ongoing, clinical studies provided insight as to endpoints that may be of value for future trauma and shock studies. In addition to the importance of appropriate endpoints in study design, other related topics were discussed, including trauma epidemiology, patient enrollment and inclusion criteria, community consultation and the difficulty of obtaining informed consent in acute trauma research, and the inclusion of quality of life in composite endpoints. The consensus was that more discussion was needed and that consideration of new endpoints for clinical trials in emergency trauma research was a worthwhile and necessary goal.

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

Polymerized human Hb use in acute chest syndrome: a case report.

BACKGROUND: Acute chest syndrome (ACS) is a complication of sickle cell disease that can cause significant morbidity. Transfusion therapy has been shown to significantly increase oxygenation in patients with ACS and RBC exchange is considered the standard of care in patients at high risk of respiratory failure. CASE REPORT: A patient with ACS and several high-risk features, including thrombocytopenia, profound anemia, bilateral pulmonary infiltrates, staphylococcal sepsis, and pulmonary embolism is presented. The patient refused transfusion on religious grounds and received 12 units of human polymerized Hb solution (poly SFH-P injection, PolyHeme, Northfield Laboratories) over the course of 13 days. The patient's respiratory status improved and she was discharged home without receiving RBC transfusions. CONCLUSION: This is the first reported case that describes the use of PolyHeme in a patient with sickle cell disease, ACS, and sepsis. This therapy is thought to have been lifesaving for this patient.

Mortality and morbidity in patients with very low postoperative Hb levels who decline blood transfusion.

BACKGROUND: Guidelines for allogeneic transfusion emphasize minimizing use to avoid transmission of serious illness. However, there is little information on the risks associated from withholding transfusion. STUDY DESIGN AND METHODS: A retrospective cohort study of patients who declined RBC transfusions for religious reasons was performed. This analysis was restricted to consecutive patients > or = 18 years old, who underwent surgery in the operating room from 1981 to 1994 and had a postoperative Hb count of 8 g per dL or less. The primary outcome was defined as any inhospital death occurring within 30 days of the surgery. Secondary outcome was 30-day mortality or in-hospital 30-day morbidity. Morbidity was defined as myocardial infarction, arrhythmia, congestive heart failure, or infection. RESULTS: Of 2083 eligible patients, 300 had postoperative Hb counts of 8 g per dL or less. The study population was predominantly female (70.3%) with a mean age of 57 years (SD, +/- 17.7). In patients with a postoperative Hb level of 7.1 to 8.0, 0 died (upper 95% CI, 3.7%), and 9.4 percent (95% CI, 4.4-17.0%) had a morbid event. In patients with a postoperative Hb level of 4.1 to 5.0, 34.4 percent (95% CI, 18.6-53.2%) died and 57.7 percent (95% CI, 36.9-76.6%) had a morbid event or died. After adjusting for age, cardiovascular disease, and Acute Physiology and Chronic Health Evaluation II score, the odds of death in patients with a postoperative Hb level of < or = 8 g per dL increased 2.5 times (95% CI, 1.9-3.2) for each gram decrease in Hb level. CONCLUSIONS: The risk of death was low in patients with postoperative Hb levels of 7.1 to 8.0 g per dL, although morbidity occurred in 9.4 percent. As postoperative blood counts fall the risk of mortality and/or morbidity rises and becomes extremely high below 5 to 6 g per dL.

The life-sustaining capacity of human polymerized hemoglobin when red cells might be unavailable.

BACKGROUND: Human polymerized hemoglobin (PolyHeme, Northfield Laboratories, Evanston, IL) is a universally compatible, immediately available, disease-free, oxygen-carrying resuscitative fluid being developed as a red cell substitute for use in urgent blood loss. PolyHeme should be particularly useful when red cells may be temporarily unavailable. This article assesses survival at life-threatening RBC hemoglobin concentration ([Hb]) in massively bleeding patients who do not receive red cells. STUDY DESIGN: There were 171 patients who received rapid infusion of 1 to 20 units (1,000 g, 10 L) of PolyHeme in lieu of red cells as initial oxygen-carrying replacement in trauma and urgent surgery. The protocol simulated the unavailability of red cells, and the progressive fall in RBC [Hb] in bleeding patients was quantified. Thirty-day mortality was compared with a historical control group of 300 surgical patients who refused red cells on religious grounds. RESULTS: A total of 171 patients received rapid infusion of 1 to 2 units (n = 45), 3 to 4 units (n = 45), 5 to 9 units (n = 47), or 10 to 20 units (n = 34) of PolyHeme. Forty patients had a nadir RBC [Hb] < or = 3 g/dL (mean, 1.5 +/- 0.7 g/dL). But total [Hb] was adequately maintained (mean, 6.8 +/- 1.2 g/dL) because of plasma [Hb] added by PolyHeme. The 30-day mortality was 25.0% (10/40 patients) compared with 64.5% (20/31 patients) in historical control patients at these RBC [Hb] levels. CONCLUSIONS: PolyHeme increases survival at life-threatening RBC [Hb] by maintaining total [Hb] in the absence of red cell transfusion. PolyHeme should be useful in the early treatment of urgent blood loss and resolve the dilemma of unavailability of red cells.