Management of extremity fasciotomy sites prospective randomized evaluation of two techniques.

INTRODUCTION: Morbidity from the treatment of extremity compartment syndrome is underappreciated. Closure technique effectiveness has yet to be definitively established. METHODS: A randomized non-blinded prospective study was performed involving patients who underwent an extremity fasciotomy following trauma. Shoelace wounds were strapped with vessel loops under tension and VAC wounds were treated with a standard KCI VAC dressing. After randomization, patients returned to the OR every 96 h until primarily closed or skin grafted. RESULTS: 21 patients were consented for randomization with 11 (52%) successfully closed at the first re-operation. After interim analysis the study was closed early with 5/5 (100%) of wounds treated with the shoelace technique closed primarily and only 1/9 (11%) of VAC wounds closed primarily (p = 0.003). Overall primary closure was achieved in 74% of patients. CONCLUSIONS: Aggressive attempts at wound closure lead to an increased early closure rate. For wounds that remain open after the first re-operation, a simple shoelace technique is more successful than a wound VAC for achieving same hospital stay skin closure.

Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients with Sepsis.

BACKGROUND: Doripenem is approved by the Food and Drug Administration for the treatment of patients with complicated intra-abdominal infections and complicated urinary tract infections. While studies have described the pharmacokinetics/pharmacodynamics (PK/PD) of doripenem in the critically ill, no study has described the probability of target attainment profile among trauma patients with sepsis. PATIENTS AND METHODS: This study was a prospective, open-label, pharmacokinetic study in the surgical intensive care unit (SICU) at Grady Health System. Thirty trauma patients with sepsis admitted to the SICU received doripenem 1 g infused over 4 hours every 8 hours for three doses. Blood samples were taken just before and after the third dose. A two-compartment model was fit to the data using non-parametric population PK modeling software. Embedded with the final PK model, a Monte Carlo Simulations (MCS) was performed to determine the PK/PD profile of doripenem 1 g, infused over 4 hours, every 8 hours after administration of the first and fourth doses. RESULTS: Overall, the model fit the data well, and mean (standard deviation) clearance and volume of the central compartment were 16.9 (11.4) L/h and 28.5 (16.0) L, respectively. In the MCS analyses, doripenem 1 g, infused over 4 hours, administered every 8 hours, conferred >90% probabilities of achieving 30-50% time greater than the minimum inhibitory concentration (30-50% T>MIC) for MICs ≤2 mg/L after infusion of both the first and fourth doses. The MCS indicated that more intensive doripenem dosing schemes should be considered for organisms with MIC values in excess of 2 mg/L. CONCLUSIONS: This is the first study to describe the doripenem PK/PD in critically ill patients with trauma. Among these patients, the MCS analyses suggest that current dosing strategies may be ineffective when the MIC value for the infecting pathogen is expected to be above 2 mg/L.

Effects of acute ethanol exposure on the early inflammatory response after excisional injury.

BACKGROUND: Alcohol consumption is involved in over half of all trauma-related injuries. These patients are known to exhibit a higher incidence of mortality and morbidity following injury compared with patients not exposed to ethanol. As studies from our laboratory demonstrated that ethanol exposure impairs re-epithelialization and angiogenesis after dermal wounding and because the earlier inflammatory phase of wound healing is likely to influence later responses, we chose to examine neutrophil infiltration and chemokine and proinflammatory cytokine levels in the skin following administration of a dermal excisional wound. METHODS: BALB/c mice were given ethanol at a dose designed to increase blood alcohol concentration to 100 to 120 mg/dL at 30 minutes after treatment. Mice were then subjected to a full-thickness excisional wound. Wounds from ethanol and saline-treated mice were collected within the first 24 hours postinjury to assess neutrophil infiltration and myeloperoxidase (MPO) activity, neutrophil chemoattractant macrophage inflammatory protein-2 (MIP-2) and KC levels, and proinflammatory cytokine interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) levels. RESULTS: At 12 and 24 hours after injury, MPO in wounds from ethanol-exposed mice was significantly reduced compared with wounds from vehicle-treated animals. Despite this, histological examination of wounds did not reveal a difference in neutrophil infiltration between the 2 groups. Peak levels of MIP-2 and KC observed at 12 hours postinjury were decreased in wounds from ethanol-treated mice by 32 and 45%, respectively, relative to wounds from control mice. Levels of TNFalpha and IL-1beta (potent inducers of MIP-2 and KC, as well as neutrophil activation) were also assessed. Levels of TNFalpha were not elevated in either group after injury. However, IL-1beta demonstrated significantly lower peak levels at 6 hours postinjury in wounds from ethanol-treated mice, 58% less than wounds from controls. CONCLUSION: These studies reveal that early dermal inflammatory responses including MPO activity, production of MIP-2, KC, and IL-1beta are impaired in mice given ethanol before injury, which may also have detrimental affects on later stages of wound healing.