Grant V. Bochicchio

Endotracheal intubation in the field does not improve outcome in trauma patients who present without an acutely lethal traumatic brain injury.

OBJECTIVES There is an absence of prospective data evaluating the impact of prehospital intubation in adult trauma patients. Our objectives were to determine the outcome of trauma patients intubated in the field who did not have an acutely lethal traumatic brain injury (death within 48 hours) compared with patients who were intubated immediately on arrival to the hospital. METHODS Prospective data were collected on 191 consecutive patients admitted to the trauma center with a field Glasgow Coma Scale score < or = 8 and a head Abbreviated Injury Scale score > or = 3 who were either intubated in the field or intubated immediately at admission to the hospital. Patients who died within 48 hours of admission and transfers were excluded from the study. RESULTS Of the 191 patients, 176 (92%) sustained blunt trauma and 25 (8%) were victims of penetrating trauma. Seventy-eight (41%) of the 191 patients were intubated in the field and 113 (59%) were intubated immediately at admission. There was no significant difference in age, Glasgow Coma Scale score, head Abbreviated Injury Scale score, or Injury Severity Score between the two groups. Patients who were intubated in the field had a significantly higher morbidity (ventilator days, 14.7 vs. 10.4; hospital days, 20.2 vs. 16.7; and intensive care unit days, 15.2 vs. 11.7) compared with patients intubated on immediate arrival to the hospital and nearly double the mortality (23% vs. 12.4). Field-intubated patients had a 1.5 times greater risk of nosocomial pneumonia compared with hospital-intubated patients. CONCLUSION Prehospital intubation is associated with a significant increase in morbidity and mortality in trauma patients with traumatic brain injury who are admitted to the hospital without an acutely lethal injury. A randomized, prospective study is warranted to confirm these results.

Early aggressive use of fresh frozen plasma does not improve outcome in critically injured trauma patients.

Objectives:Recent data from Iraq supporting early aggressive use of fresh frozen plasma (FFP) in a 1:1 ratio to packed red blood cells (PRBCs) has led many civilian trauma centers to adopt this resource intensive strategy. Methods:Prospective data were collected on 806 consecutive trauma patients admitted to the intensive care unit over 2 years. Patients were stratified by PRBC:FFP transfusion ratio over the first 24 hours. Stepwise regression models were performed controlling for age, gender, mechanism of injury, injury severity, and acute physiology and chronic health evaluation (APACHE) 2 score to determine if early aggressive use of PRBC:FFP improved outcome. Results:Seventy-seven percent of patients were male (N = 617) and 85% sustained blunt injury (n = 680). Mean age, injury severity score (ISS), and APACHE score were 43 ± 20 years, 29 ± 13, and 13 ± 7, respectively. Mean number of PRBCs and FFP transfused were 7.7 ± 12 U, 6 U, and 5 ± 12 U, respectively. Three hundred sixty-five (45%) patients were transfused in the first 24 hours. Sixty-eight percent (n = 250) of them received both PRBCs and FFP. Analyzing these patients by stepwise regression controlling for all significant variables, the PRBC:FFP ratio did not predict intensive care unit days, hospital days, or mortality even in patients who received massive transfusion (≥10 U). Furthermore, there was no significant difference in outcome when comparing patients who had a 1:1 PRBC:FFP ratio with those who did not receive any FFP. Conclusion:Early and aggressive use of FFP does not improve outcome after civilian injury. This may reflect inherent differences compared with military injury; however, this practice should be reevaluated.

Prophylactic Chlorhexidine Oral Rinse Decreases Ventilator-Associated Pneumonia in Surgical ICU Patients

BACKGROUND Pneumonia is one of the most common nosocomial infections in hospitalized patients. The risk of nosocomial pneumonia increases with age, severity of acute illness and preexisting co-morbid conditions. Ventilator-associated pneumonia (VAP) significantly increases morbidity, length of stay, resource utilization and mortality. The purpose of this study was to determine whether adherence to a ventilator weaning protocol (WP) and the use of chlorhexidine gluconate (CH) oral rinse for oral hygiene would decrease the incidence of VAP in surgical ICU patients. METHODS A prospective study was conducted over a period of 10 months (October 1998-July 1999) in surgical ICU patients requiring mechanical ventilation (n = 95). During the first 5 months, a WP was applied to all patients requiring mechanical ventilation. During the following 5 months, a CH 0.12% oral rinse administered twice daily was added to the protocol, initiated on ICU admission in all intubated patients. The data collection included age, gender, race, risk factors, co-morbid conditions, severity of the acute illness (APACHE II) at admission, duration of ventilation, ICU and total-hospital length of stay, and incidence of VAP and in-hospital mortality rates. Both WP and WP+CH groups were compared using the National Nosocomial Infection Surveillance (NNIS) and hospital databases as historic controls. RESULTS The institution of the WP alone led only to a slight decrease in the incidence of VAP but a significant reduction in the median duration of mechanical ventilation by 40% (4.5 days, p < 0.008). The addition of CH to the WP led to a significant reduction and delay in the occurrence of VAP (37% overall, 75% for late VAP, p < 0.05). The median duration of mechanical ventilation in this group was similar to that of the WP group. There was no significant difference in the overall hospital or ICU length of stay between the groups. CONCLUSIONS Improved oral hygiene via topical CH application in conjunction with the use of a WP is effective in reducing the incidence of VAP and the duration of mechanical ventilation in surgical ICU patients.

A self-assembling hydrophobically modified chitosan capable of reversible hemostatic action

Blood loss at the site of a wound in mammals is curtailed by the rapid formation of a hemostatic plug, i.e., a self-assembled network of the protein, fibrin that locally transforms liquid blood into a gelled clot. Here, we report an amphiphilic biopolymer that exhibits a similar ability to rapidly gel blood; moreover, the self-assembly underlying the gelation readily allows for reversibility back into the liquid state via introduction of a sugar-based supramolecule. The biopolymer is a hydrophobically modified (hm) derivative of the polysaccharide, chitosan. When hm-chitosan is contacted with heparinized human blood, it rapidly transforms the liquid into an elastic gel. In contrast, the native chitosan (without hydrophobes) does not gel blood. Gelation occurs because the hydrophobes on hm-chitosan insert into the membranes of blood cells and thereby connect the cells into a sample-spanning network. Gelation is reversed by the addition of α-cyclodextrin, a supramolecule having an inner hydrophobic pocket: polymer hydrophobes unbind from blood cells and embed within the cyclodextrins, thereby disrupting the cell network. We believe that hm-chitosan has the potential to serve as an effective, yet low-cost hemostatic dressing for use by trauma centers and the military. Preliminary tests with small and large animal injury models show its increased efficacy at achieving hemostasis - e.g., a 90% reduction in bleeding time over controls for femoral vein transections in a rat model.

Tight glycemic control in critically injured trauma patients.

Objectives:Evaluate the impact of a tight glucose control (TGC) protocol during the first week of admission in critically injured trauma patients. Methods:A prospective quasi-experimental interrupted time-series design was used to evaluate the impact of TGC [24-month preintervention phase (no TGC) vs. 24-month postintervention phase]. Patients were stratified by serum glucose level on day 1 to 7 (low, 0–150 mg/dL; medium-high, 151–219 mg/dL; and high, ≥220 mg/dL), age, gender, and injury severity. Patients were further stratified by pattern of glucose control (all low, all medium high, all high, improving, worsening, highly variable). Outcome was measured by ventilator days, infection, hospital (HLOS) and ICU (ILOS) length of stay, and mortality. Results:One thousand twenty-one patients were evaluated in the preintervention phase as compared with 1108 patients in the postintervention phase. There was no significant difference in mechanism of injury (83% vs. 84% blunt), gender (74% vs. 73% male), age (44 vs. 43 years), and Injury Severity Score (ISS) (26 vs. 25). The TGC group was more likely to be in the all low and improving pattern of glucose control (P < 0.001). The incidence of infection significantly decreased (over the first 2 weeks) from 29% to 21% in the TGC group (P < 0.001). Ventilator days (OR = 3.9, 1.8, 8.1), ILOS (OR = 4.3, 2.1, 7.5), and HLOS (OR = 5.5, 2.2, 11) and mortality (OR = 1.4, 1.1, 10) were significantly higher in the non-TGC group when controlled for age, ISS, obesity, and diabetes (P < 0.01). Conclusion:The positive outcomes associated with the implementation of a TGC protocol necessitates further evaluation in a randomized prospective trial.

Glial fibrillary acidic protein is highly correlated with brain injury.

BACKGROUND Glial fibrillary acidic protein (GFAP) is an intermediate filament protein found in the cytoskeleton of astroglia. Recent work has indicated that GFAP may serve as a serum marker of traumatic brain injury (TBI) that is released after central nervous system cell damage. METHODS Serum from 51 critically injured trauma patients was prospectively collected on admission and on hospital day 2. All patients underwent an admission head computed tomography (CT) scan as a part of their clinical evaluation. Patients with facial fractures in the absence of documented TBI and patients with spinal cord injury were excluded. Demographic and outcome data were collected prospectively. Serum GFAP was measured in duplicate using enzyme-linked immunosorbent assay techniques. RESULTS Thirty-nine (76%) of the 51 patients had CT-documented TBI. The study cohort was 72.5% men with a mean age of 43 years and mean Injury Severity Score (ISS) of 30.2. There were no statistically significant demographic differences between the two groups. At admission day, the mean GFAP level in non-TBI patients was 0.07 pg/mL compared with 6.77 pg/mL in TBI patients (p = 0.002). On day 2 the mean GFAP level was 0.02 in non-TBI patients compared with 2.17 in TBI patients (p = 0.003). Using regression analysis to control for age, sex, and ISS, the Head Abbreviated Injury Scale was predictive of the level of GFAP on both days 1 and 2 (p values 0.006 and 0.026, respectively). Although GFAP levels were not predictive of increased hospital length of stay, intensive care unit length of stay, or ventilator days, high GFAP levels on hospital day 2 were predictive of mortality when controlling for age, sex, and ISS (odds ratio 1.45, p value 0.028). The area under the receiver operating characteristic curve for GFAP was 0.90 for day 1 and 0.88 for day 2. A GFAP cutoff point of 1 pg/mL yielded 100% specificity and 50% to 60% sensitivity for TBI. CONCLUSIONS GFAP is a serum marker of TBI, and persistent elevation on day 2 is predictive of increased mortality. Excellent specificity for CT-documented brain injury was found using a cutoff point of 1 pg/mL.

Gene expression profiles differentiate between sterile SIRS and early sepsis.

Introduction:The systemic inflammatory response syndrome (SIRS) occurs frequently in critically ill patients and presents similar clinical appearances despite diverse infectious and noninfectious etiologies. Despite similar phenotypic expression, these diverse SIRS etiologies may induce divergent genotypic expressions. We hypothesized that gene expression differences are present between sepsis and uninfected SIRS prior to the clinical appearance of sepsis. Methods:Critically ill uninfected SIRS patients were followed longitudinally for the development of sepsis. All patients had whole blood collected daily for gene expression analysis by Affymetrix Hg_U133 2.0 Plus microarrays. SIRS patients developing sepsis were compared with those remaining uninfected for differences in gene expression at study entry and daily for 3 days prior to conversion to sepsis. Acceptance criteria for differentially expressed genes required: >1.2 median fold change between groups and significance on univariate and multivariate analysis. Differentially expressed genes were annotated to pathways using DAVID 2.0/EASE analysis. Results:A total of 12,782 (23.4%) gene probes were differentially expressed on univariate analysis 0 to 48 hours before clinical sepsis. 626 (1.1%) probes met acceptance criteria, corresponding to 459 unique genes, 65 (14.2%) down and 395 (85.8%) up expressed. These genes annotated to 10 pathways that functionally categorized to 4 themes involving innate immunity, cytokine receptors, T cell differentiation, and protein synthesis regulation. Conclusions:Sepsis has a unique gene expression profile that is different from uninfected inflammation and becomes apparent prior to expression of the clinical sepsis phenotype.

Treatment of Complicated Skin and Soft Tissue Infections

BACKGROUND Skin and soft tissue infections (SSTIs) may produce substantial morbidity and mortality rates, particularly those classified as complicated or necrotizing. OBJECTIVE To weigh the strength of recommendations using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology and to provide evidence-based recommendations for diagnosis and management for SSTIs. DATA SOURCES Computerized identification of published research and review of relevant articles. STUDY SELECTION All published reports on the management of complicated and necrotizing SSTIs were evaluated by an expert panel of members of the Surgical Infection Society according to published guidelines for evidence-based medicine. The quality of the evidence was judged by the GRADE methodology and criteria. Practice surveys, pharmacokinetic studies, and reviews or duplicative publications presenting primary data already considered were excluded from analysis. DATA EXTRACTION Information on demographics, study dates, microbiology findings, antibiotic type, surgical interventions, infection-related outcomes, and the methodologic quality of the studies was extracted. Results were submitted to the Therapeutic Agents Committee of the Surgical Infection Society for review prior to creation of the final consensus document. DATA SYNTHESIS Current surgical and antibiotic management of complicated SSTIs is based on a small number of studies that often have insufficient power to draw well-supported conclusions, with the exception of antimicrobial therapy for non-necrotizing soft tissue infections, for which ample data are available.

Early hyperglycemic control is important in critically injured trauma patients

BACKGROUND Our objectives were to determine whether persistent hyperglycemia when compared with normoglycemia was predictive of outcome in the later stages of hospitalization in critically injured trauma patients. METHODS A prospective study was conducted on 896 consecutive trauma patients admitted to the intensive care unit during a 2-year period. Patients were stratified by serum glucose level on day 1 to day 28 (low = 0-139 mg/dL, medium to high = 140-219 mg/dL, and high = >220 mg/dL), age, gender, race, insulin dependent diabetes, obesity, and Injury Severity Score (ISS). Patients were further stratified by pattern of glucose control (all low, all moderate, all high, improving, worsening, highly variable. Outcome was measured by ventilator days, infection, hospital and intensive care unit length of stay, and mortality. Multiple variable logistic and linear regression models were used to determine level of significance. RESULTS Eighty-three percent were victims of blunt trauma. The majority (74%) were male, with a mean ISS of 26 +/- 12. Hyperglycemia (moderate, worsening, and highly variable) in the first week was associated with significantly greater hospital and intensive care unit length of stay, ventilator time, infection, and mortality when controlling for age, race, gender, ISS, mechanism of injury, obesity, and insulin dependent diabetes (p < 0.03). However, hyperglycemia in later weeks was not associated with infection and only weakly associated with mortality when analyzed by the same model. When controlling for glucose levels in subsequent weeks, patients who were normoglycemic in the first week had a lower infection rate and were less likely to die even when controlling for age, ISS, and obesity (p < 0.05). CONCLUSIONS Early euglycemia is associated with improved outcome and appears to be protective regardless of glucose levels in subsequent weeks. Further studies are warranted to determine the etiology of this protective effect.

Controversy in Trauma Resuscitation: Do Ratios of Plasma to Red Blood Cells Matter?

Since a report in October 2007 of dramatic improvements in trauma mortality in a military population when massive transfusion of red blood cells (RBC) was accompanied by plasma replacement at 1:1 proportions, interest in the plasma-to-RBC ratio during resuscitation in both the trauma and transfusion communities has been intense. Over the 7-month period from August 2008 through February 2009, a further 9 major studies examining experience with plasma replacement in massively transfused civilian trauma patients have been published. This flood of observational studies is likely to continue. In this review, the authors examine the findings of these initial studies, highlighting the epidemiologic and analytic methodologies used, and the likely influence of these methodologies on the reported outcomes.