C. Anne Morrison

BACKGROUND: Trauma is a leading cause of death worldwide and is thus a major public health concern. Previous studies have shown that limiting the amount of fluids given by following a strategy of permissive hypotension during the initial resuscitation period may improve trauma outcomes. This study examines the clinical outcomes from the first 90 patients enrolled in a prospective, randomized controlled trial of hypotensive resuscitation, with the primary aim of assessing the effects of a limited transfusion and intravenous (IV) fluid strategy on 30-day morbidity and mortality. METHODS: Patients in hemorrhagic shock who required emergent surgery were randomized to one of the two arms of the study for intraoperative resuscitation. Those in the experimental (low mean arterial pressure [LMAP]) arm were managed with a hypotensive resuscitation strategy in which the target mean arterial pressure (MAP) was 50 mm Hg. Those in the control (high MAP [HMAP]) arm were managed with standard fluid resuscitation to a target MAP of 65 mm Hg. Patients were followed up for 30 days. Intraoperative fluid requirements, mortality, postoperative complications, and other clinical data were prospectively gathered and analyzed. RESULTS: Patients in the LMAP group received a significantly less blood products and total i.v. fluids during intraoperative resuscitation than those in the HMAP group. They had significantly lower mortality in the early postoperative period and a nonsignificant trend for lower mortality at 30 days. Patients in the LMAP group were significantly less likely to develop immediate postoperative coagulopathy and less likely to die from postoperatively bleeding associated with coagulopathy. Among those who developed coagulopathy in both groups, patients in the LMAP group had significantly lower international normalized ratio than those in the HMAP group, indicating a less severe coagulopathy. CONCLUSIONS: Hypotensive resuscitation is a safe strategy for use in the trauma population and results in a significant reduction in blood product transfusions and overall IV fluid administration. Specifically, resuscitating patients with the intent of maintaining a target minimum MAP of 50 mm Hg, rather than 65 mm Hg, significantly decreases postoperative coagulopathy and lowers the risk of early postoperative death and coagulopathy. These preliminary results provide convincing evidence that support the continued investigation and use of hypotensive resuscitation in the trauma setting.

OBJECTIVE: To test the hypothesis that oral creatine supplements with exercise are more effective than exercise alone in improving muscle function in patients with established dermatomyositis or polymyositis receiving chronic medical therapies who are clinically weak yet stable. METHODS: In a 6-month, 2-center, double-blind, randomized controlled trial, patients were randomized to receive oral creatine supplements (8 days, 20 gm/day then 3 gm/day) or placebo. All patients followed a home exercise program. The primary outcome was aggregate functional performance time (AFPT), reflecting the ability to undertake high-intensity exercise. Secondary outcomes included a functional index measuring endurance and muscle bioenergetics on (31)P magnetic resonance spectroscopy ((31)P MRS). Patients were receiving stable immunosuppressive treatment and/or corticosteroids. RESULTS: A total of 37 patients with polymyositis or dermatomyositis were randomized (19 to creatine, 18 to placebo); 29 completed 6 months. Intent-to-treat analyses demonstrated that AFPT improved significantly at 6 months with creatine (median decrease 13%, range -32-8%) compared with placebo (median decrease 3%, range -13-16%; P = 0.029 by Mann-Whitney U test). A completer analysis also showed significant benefits from creatine (P = 0.014). The functional index improved significantly with both creatine and placebo (P < 0.05 by paired Wilcoxon's rank sum test), with a significant benefit between groups in the completer analysis only. Phosphocreatine/beta-nucleoside triphosphate ratios using MRS increased significantly in the creatine group (P < 0.05) but not in the control group. No clinically relevant adverse events were associated with creatine. CONCLUSION: Oral creatine supplements combined with home exercises improve functional performance without significant adverse effects in patients with polymyositis or dermatomyositis. They appear safe, effective, and inexpensive.

BACKGROUND: Hemorrhagic shock is responsible for one third of trauma related deaths. We hypothesized that intraoperative hypotensive resuscitation would improve survival for patients undergoing operative control of hemorrhage following penetrating trauma. METHODS: Between July 1, 2007, and March 28, 2013, penetrating trauma patients aged 14 years to 45 years with a systolic blood pressure of 90 mm Hg or lower requiring laparotomy or thoracotomy for control of hemorrhage were randomized 1:1 based on a target minimum mean arterial pressure (MAP) of 50 mm Hg (experimental arm, LMAP) or 65 mm Hg (control arm, HMAP). Patients were followed up 30 days postoperatively. The primary outcome of mortality; secondary outcomes including stroke, myocardial infarction, renal failure, coagulopathy, and infection; and other clinical data were analyzed between study arms using univariate and Kaplan-Meier analyses. RESULTS: The trial enrolled 168 patients (86 LMAP, 82 HMAP patients) before early termination, in part because of clinical equipoise and futility. Injuries resulted from gunshot wounds (76%) and stab wounds (24%); 90% of the patients were male, and the median age was 31 years. Baseline vitals, laboratory results, and injury severity were similar between groups. Intraoperative MAP was 65.5 ± 11.6 mm Hg in the LMAP group and 69.1 ± 13.8 mm Hg in the HMAP group (p = 0.07). No significant survival advantage existed for the LMAP group at 30 days (p = 0.48) or 24 hours (p = 0.27). Secondary outcomes were similar for the LMAP and HMAP groups: acute myocardial infarction (1% vs. 2%), stroke (0% vs. 3%), any renal failure (15% vs. 12%), coagulopathy (28% vs. 29%), and infection (59% vs. 58%) (p > 0.05 for all). Acute renal injury occurred less often in the LMAP than in HMAP group (13% vs. 30%, p = 0.01). CONCLUSION: This study was unable to demonstrate that hypotensive resuscitation at a target MAP of 50 mm Hg could significantly improve 30-day mortality. Further study is necessary to fully realize the benefits of hypotensive resuscitation. LEVEL OF EVIDENCE: Therapeutic study, level II.