Search

Introduction Isolated hip fractures (IHFs) in the elderly are high-frequency, life-altering events. Definitive surgery ≤24 hours of admission is associated with improved outcomes. An IHF process management guideline (IHF-PMG) to expedite definitive surgery ≤24 hours was developed for a multihospital network. We report on its feasibility and subsequent patient outcomes. Methods This is a prospective multicenter cohort study, involving 85 levels 1, 2, 3, and 4 trauma centers. Patients with an IHF between 65 and 100 years old were studied. Four cohorts were examined: (1) hospitals that did not implement any PMG, (2) hospitals that used their own PMG, (3) hospitals that partially used the network IHF-PMG, and (4) hospitals that used the network's IHF-PMG. Multivariable logistic regression with reliability adjustment was used to calculate the expected value of observed to expected (O/E) mortality. Statistical significance was defined as p Results Data on 24,457 IHF were prospectively collected. Following implementation of the IHF-PMG, overall IHF O/E mortality ratios decreased within the hospital network, from 1.13 in 2017 to 0.87 in 2018 and 0.86 in 2019. Hospitals that developed their own IHF-PMG or used the enterprise-wide IHF-PMG had the lowest inpatient O/E mortality at 0.59 and 0.65, respectively. Conclusion Goal-directed IHF-PMG for definitive surgery ≤24 hours was implemented across a large hospital network. The IHF-PMG was associated with lower inpatient mortality. Level of evidence Therapeutic/ Care management, Level III.

Background Significant differences in outcomes have been demonstrated between Level I trauma centers. Usually these differences are ascribed to regional or administrative differences, although the influence of variation in clinical practice is rarely considered. This study was undertaken to determine whether differences in early mortality of patients receiving a massive transfusion (MT, ≥ 10 units pf RBCs within 24 hours of admission) persist after adjustment for patient and transfusion practice differences. We hypothesized differences among centers in 24-hour mortality could predominantly be accounted for by differences in transfusion practices as well as patient characteristics. Methods Data were retrospectively collected over a 1-year period from 15 Level I centers on patients receiving an MT. A purposeful variable selection strategy was used to build the final multivariable logistic model to assess differences between centers in 24-hour mortality. Adjusted odds ratios for each center were calculated. Results : There were 550 patients evaluated, but only 443 patients had complete data for the set of variables included in the final model. Unadjusted mortality varied considerably across centers, ranging from 10% to 75%. Multivariable logistic regression identified injury severity score (ISS), abbreviated injury scale (AIS) of the chest, admission base deficit, admission heart rate, and total units of RBC transfused, as well as ratios of plasma:RBC and platelet:RBC to be associated with 24-hour mortality. After adjusting for severity of injury and transfusion, treatment variables between center differences were no longer significant. Conclusions In the defined population of patients receiving an MT, between-center differences in 24-hour mortality may be accounted for by severity of injury as well as transfusion practices.

Background: The effect of blood component ratios on the survival of patients with traumatic brain injury (TBI) has not been studied. Methods: A database of patients transfused in the first 24 hours after admission for injury from 22 Level I trauma centers over an 18-month period was queried to find patients who (1) met different definitions of massive transfusion (5 units red blood cell [RBC] in 6 hours vs. 10 units RBC in 24 hours), (2) received high or low ratios of platelets or plasma to RBC units (1:2 vs. /=1:2), and (3) had severe TBI (head abbreviated injury score /=3) (TBI+). Results: Of 2,312 total patients, 850 patients were transfused with /= 5 RBC units in 6 hours and 807 could be classified into TBi+ (n = 281) or TBI- (n = 526). Six hundred forty-three patients were transfused with /=10 RBC units in 24 hours with 622 classified into TBI+ (n = 220) and TBi- (n = 402). For both high-risk populations, a high ratio of platelets:RBCs (not plasma) was independently associated with improved 30-day survival for patients with TBI+ and a high ratio of plasma:RBCs (not platelets) was independently associated with improved 30-day survival in TBI- patients. Conclusions: High platelet ratio was associated with improved survival in TBI+ patients while a high plasma ratio was associated with improved survival in TBI- patients. Prospective studies of blood product ratios should include TBI in the analysis for determination of optimal use of ratios on outcome in injured patients.

Since the promulgation of emergency department (ED) thoracotomy40 years ago, there has been an ongoing search to define when this heroic resuscitative effort is futile. In this era of health care reform, generation of accurate data is imperative for developing patient care guidelines. The purpose of this prospective multicenter study was to identify injury patterns and physiologic profiles at ED arrival that are compatible with survival.Eighteen institutions representing the Western Trauma Association commenced enrollment in January 2003; data were collected prospectively.During the ensuing 6 years, 56 patients survived to hospital discharge. Mean age was 31.3 years (15-64 years), and 93% were male. As expected, survival was predominant in those with thoracic injuries (77%), followed by abdomen (9%), extremity (7%), neck (4%), and head (4%). The most common injury was a ventricular stab wound (30%), followed by a gunshot wound to the lung (16%); 9% of survivors sustained blunt trauma, 34% underwent prehospital cardiopulmonary resuscitation (CPR), and the presenting base deficit was25 mequiv/L in 18%. Relevant to futile care, there were survivors of blunt torso injuries with CPR up to 9 minutes and penetrating torso wounds up to 15 minutes. Asystole was documented at ED arrival in seven patients (12%); all these patients had pericardial tamponade and three (43%) had good functional neurologic recovery at hospital discharge.Resuscitative thoracotomy in the ED can be considered futile care when (a) prehospital CPR exceeds 10 minutes after blunt trauma without a response, (b) prehospital CPR exceeds 15 minutes after penetrating trauma without a response, and (c) asystole is the presenting rhythm and there is no pericardial tamponade.

A computerized protocol was developed and used to standardize bedside clinician decision making for resuscitation of shock due to severe trauma during the first day in the intensive care unit (ICU) at a metropolitan Level I trauma center. We report overall performance of a computerized protocol for resuscitation of shock due to severe trauma, incorporating two options for resuscitation monitoring and intervention intensity, according to: (1) duration of use and (2) acceptance of computerized protocol-generated instructions.A computerized protocol operated by clinicians, using a personal computer (PC) at the bedside, was used to guide clinical decision making for resuscitation of patients meeting specific injury and shock criteria. The protocol generated instructions that could be accepted or declined. Clinician acceptance of the protocol instructions was stored by the PC software in a database for each patient. A rule-based, data-driven protocol was developed using literature evidence, expert opinion, and ongoing protocol performance analysis. Logic-flow diagrams were used to facilitate communication among multidisciplinary protocol development team members. The protocol was computerized using standard programming methods and implemented using cart-mounted PCs with a touch screen and keyboard interfaces. Protocol progression began with patient demographic data and criteria entry, confirmation of hemodynamic monitor instrumentation, request for specific hemodynamic performance data, and instructions for specific interventions (or no intervention). Use and performance of the computerized protocol was recorded in a protocol execution database. The protocol was continuously maintained with new literature evidence and database performance analysis findings. Initially implemented in 2000, the computerized protocol was refined in 2004 with two options for resuscitation intensity: pulmonary artery catheter- and central venous pressure-directed resuscitation.Over 2 years ending at August 2006, a total of 193 trauma patients (mean Injury Severity Score was 27, survival rate 89%) were resuscitated using the computerized protocol. Protocol duration was 4400 hours or 22.7 +/- 0.4 hours per patient. The computerized protocol generated 3724 instructions (19 +/- 1 per patient) that required a bedside clinician response. In all, 94% of these instructions were accepted by the bedside clinician users.A computerized protocol to guide decision making for trauma shock resuscitation in a Level 1 trauma center surgical ICU was developed and used as standard of care. During 2 years ending at August 2006, 94% of computer-generated instructions for specific interventions or measurements of hemodynamic performance were accepted by bedside clinicians, indicating appropriate, useful design and reliance on the computerized protocol system.

Previously, we developed a protocol for shock resuscitation of severe trauma patients to reverse shock and regain hemodynamic stability during the first 24 intensive care unit (ICU) hours. Key hemodynamic measurements of cardiac output and preload were obtained using a pulmonary artery catheter (PAC). As an alternative, we developed a protocol that used central venous pressure (CVP) to guide decision making for interventions to regain hemodynamic stability [mean arterial pressure (MAP)or= 65 mmHg and heart rate (HR)or= 130 bpm]. Either protocol was available and required for traumatic shock resuscitation using bedside computerized clinical decision support to standardize decision making, and PAC was available if CVP-directed resuscitation was inadequate. We hypothesized that patients would be appropriately assigned to either protocol by trauma surgeon assessment of hemodynamic stability upon ICU admission. High-risk patients admitted to a level-1 trauma center ICU underwent resuscitation. Criteria were 1) major torso trauma, 2) base deficit (BD)or= 6 mEq/L or systolic blood pressure90 mmHg, 3) transfusion ofor= 1 unit packed red blood cells (PRBC), oror= age 65 years with two of three criteria. Patients with brain injury were excluded. Data were recorded prospectively. In 24 months ending July 31, 2006, of 193 patients, 114 (59%) were assigned CVP- directed resuscitation, and 79 (41%) were assigned PAC-directed resuscitation. A subgroup of 11 (10%) initially assigned CVP was reassigned PAC-directed resuscitation (7 +/- 2 h after start) due to hemodynamic instability. Crystalloid fluid and PRBC resuscitation volumes for PAC (8 +/- 1 L lactated Ringer's [LR], 5 +/- 0.4 units PRBC) wereCVP (5 +/- 0.4 L LR, 3 +/- 0.3 units PRBC) and similar to CVP - PAC protocol subgroup patients (9 +/- 2 L LR, 5 +/- 1 units PRBC). Intensive care unit (ICU) stay and survival rate for PAC (18 +/- 2 days, 75%) were similar to CVP - PAC (17 +/- 4 days, 73%) and worse than CVP protocol subgroup patients (9 +/- 1 days, 98%). Traumatic shock resuscitation is feasible using CVP as a primary hemodynamic monitor as part of a protocol that includes explicit definition of hemodynamic instability and where PAC monitoring is readily available. Computerized decision support provides a technique to implement complex protocol care processes and analyze patient response.

Background Poloxamer 188 (P188), a nonionic block copolymer chemical surfactant known to have cytoprotective, rheologic, anti-inflammatory, and anti-thrombotic activity, has shown promise in the management of selected trauma patients. We studied human PMN oxidative burst and adhesion molecule expression when exposed to P188. Methods After RBC lysis of whole blood samples, white blood cell components were primed with phosphotidylcholine, primed and activated with fMLP, primed and activated with PMA, or left unstimulated. Each group was treated with vehicle or P188 (0.005–15 mg/ml concentrations). Flow cytometry quantified: (1) PMN superoxide anion production and (2) PMN marker expression of CD11b and L-selectin. Results Among non-PMA activated PMNs, P188 increased superoxide anion production. PMA-activated PMNs decreased superoxide anion production, proportional to P188 dose. Among fMLP-activated PMNs, the highest P188 dose increased the expression of CD11b. Among PMA-activated PMNs, decreased CD11b expression was seen for the mid-range doses. Conclusions PMNs altered their oxidative burst and marker expression after exposure to P188. When used at lower doses, P188 may increase the oxidative burst response and, when used at very high doses, increase CD11b expression. However, if PMNs are in a maximally activated state, a higher dose of P188 may decrease the oxidative burst response and decrease CD11b expression.

Background We initiated a multidisciplinary clinical pathway targeting patients greater than 45 years of age with more than 4 rib fractures. The purpose of the current study was to evaluate the effect of this pathway on infectious morbidity and mortality. Methods This was a prospective cohort study. Data evaluated included patient demographics, injury characteristics, pain management details, lengths of stay, morbidity, and mortality. Univariate and multivariate analyses were performed using a significance level of P Results When adjusting for age, injury severity score, and number of rib fractures, the clinical pathway was associated with decreased intensive care unit length of stay by 2.4 days (95% confidence interval [CI] −4.3, −0.52 days, P = .01) hospital length of stay by 3.7 days (95% CI −7.1, −0.42 days, P = .02), pneumonias (odds ratio [OR] 0.12, 95% CI 0.04 to 0.34, P P = .06). Conclusions Implementation of a rib fracture multidisciplinary clinical pathway decreased mechanical ventilator-dependent days, lengths of stay, infectious morbidity, and mortality.

Background Hypertonic saline (HS) resuscitation prevents neutrophil mediated injury after shock. The optimal dose is not known, but appears as a result of osmotic stress. We hypothesized that a dose dependent effect exists related to increasing tonicity and that the optimal gut protective dose would provide better protection against remote organ injury than large volume isotonic crystalloids. Methods In experiment 1, rats were assigned to controls (sham/no resuscitation, sham/4 mL/kg 7.5% HS, superior mesenteric artery occlusion [SMAO]/no resuscitation), SMAO/equal volume (4 mL/kg 0.9% NS, 4 mL/kg 2.5% HS, 4 mL/kg 5% HS, 4 mL/kg 7.5% HS and 4 mL/kg 10% HS) or SMAO/equal sodium (33 mL/kg 0.9% NS, 12 mL/kg 2.5% HS, 6 mL/kg 5% HS, 4 mL/kg 7.5% HS, and 3 mL/kg 10% HS). In experiment 2, rats were assigned to the same control groups, and to either SMAO/NS (33 mL/kg 0.9% NS, equal salt load) or SMAO/HS (4 mL/kg 7.5% HS). The SMAO was clamped for 60 minutes and boluses given 5 minutes before clamp removal. After 6 hours of reperfusion, ileum and lungs were harvested for analysis of histologic injury, myeloperoxidase (MPO) as an index of neutrophil mediated injury, and serum ALT and AST drawn as markers of liver injury. Results In experiment 1, equal volume and equal sodium decreased injury and inflammation with increasing tonicity in a dose dependent fashion, with the optimal effect seen at 7.5%. In experiment 2, NS resuscitation resulted in minimal improvement of SMAO-induced lung injury and inflammation or increases in serum ALT and AST whereas HS resuscitation significantly decreased these parameters. Conclusion The protective effect of HS is related to increased tonicity. While NS had little effect on SMAO-induced remote organ injury, optimal dose HS resuscitation was quite protective. This supports the growing evidence that HS protection may be because of its gut protective effects.

Introduction Lipopolysacharide (LPS) causes gastrointestinal ileus and gastric luminal fluid accumulation. Ketamine, an anti-inflammatory anesthetic agent attenuates accumulation of luminal fluid. However, its effects on gastrointestinal transit induced by endotoxemia are unknown. The purpose of this study was to determine if the anti-inflammatory properties of ketamine improve impaired gastric emptying and gastrointestinal transit because of LPS. Materials and methods Rats were given ketamine (70 mg/kg i.p.) or saline 1 h before LPS (20 mg/kg, i.p.) or saline injection. Five hours after LPS injection, rats were gavaged with 1 cc consisting of 0.1 ml of 5 m m FITC Dextran added to 0.9 ml of saline. After 30 min, rats were sacrificed, and gastric emptying, gastrointestinal transit, and gastric fluid accumulation determined. Gastric and ileal mucosa were harvested for analysis of inducible nitric oxide synthase (iNOS) (Western immunoblot). Results are reported as mean ± SE (n ≥ 5 per group; ANOVA). Results Ketamine did not prevent LPS induced gastrointestinal ileus, nor did it improve gastric emptying. More importantly, it did not worsen gastrointestinal function or gastric emptying when compared to saline controls. However, it did decrease LPS induced gastric luminal fluid accumulation and blunted iNOS expression in both the stomach and ileum. Conclusion These data indicate that the ability of ketamine to attenuate gastric fluid accumulation is not because of improved gastric emptying or improved gastrointestinal transit. Moreover, while iNOS may play a role in LPS induced gastric luminal fluid accumulation, it does not appear to be a major mediator of the gastrointestinal ileus caused by LPS.

Background Endotoxic shock can cause end-organ dysfunction and liver injury. Critically ill patients frequently require surgical intervention under general anesthesia for source control. However, the effects of anesthetics on organ function during sepsis and their influence on inflammatory mediators such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) remain to be fully elucidated. Because ketamine anesthesia has anti-inflammatory effects in some tissues, we hypothesized that it would attenuate lipopolysaccharide (LPS)-induced liver injury. Methods Adult rats were given no anesthesia (saline), continuous isoflurane inhalation, or intraperitoneal (ip) injection of ketamine 70 mg/kg. One hour later, the rats received saline or LPS (20 mg/kg ip) for 5 hours. The rats were killed, and serum hepatocellular enzymes, liver COX-2, iNOS protein (Western immunoblot), and nuclear factor kappa B (NF-κB)–binding activity (electrophoretic mobility shift assay) determined. In a separate study, the role of COX-2 in LPS-induced liver injury was examined by pretreating rats with the selective COX-2 inhibitor NS-398 (3 mg/kg, ip) and the role of iNOS examined with the use of the selective inhibitor aminoguanidine (45 mg/kg, ip) 1 hour before LPS. Results LPS increased serum aspartate aminotransferase and alanine aminotransferase levels, hepatic iNOS and COX-2 protein, and nuclear factor NF-κB. Ketamine, but not isoflurane, attenuated these effects caused by LPS. COX-2 inhibition with NS-398 as well as iNOS inhibition with aminoguanidine diminished LPS-induced changes in aspartate aminotransferase and alanine aminotransferase levels. Conclusions These data indicate that anesthetics differ in their effects on liver injury caused by LPS. Ketamine has hepatoprotective effects, while isoflurane does not. Moreover, the protective effects of ketamine are mediated, at least in part, through a reduction in COX-2 and iNOS protein that could be regulated via changes in NF-κB–binding activity.

A seroma is the most frequent complication of breast cancer surgery, the etiology of which remains obscure. We reviewed our data to determine the factors related to the incidence of seroma formation in our patients. A retrospective analysis of the records of 359 consecutive patients (334 Hispanic; 93%) who underwent primary surgical therapy from January 1, 1996 to December 31, 2000, with either modified radical mastectomy (MRM) or wide local excision (WLE) and axillary lymph node dissection (ALND) was performed. In all cases, removal of the breast was performed using electrocoagulation, and sharp dissection was used in the axilla. One-eighth inch closed suction round drains were used. Early arm motion was encouraged. The seroma rate was compared to the age of the patient, the presence and number of positive axillary lymph nodes, the total number of axillary lymph nodes removed, tumor size, weight of the patient, the use of neoadjuvant chemotherapy, and the type of surgery performed. The overall seroma rate was 15.8%. Seromas occurred in 19.9% of patients undergoing MRM and in 9.2% of patients undergoing breast-conserving surgery (p = 0.01). The seroma rate was not influenced by any other tested variables. All seromas were easily managed with aspiration and pressure; this technical maneuver allowed seroma resolution in all patients except one following one to six aspirations. A seroma did not delay initiation of chemotherapy. No patient developed a capsule requiring excision. In our experience, a seroma is a “necessary evil;” it will occur unpredictably in a predictable number of patients.

PURPOSE OF REVIEW In the 1980s, we witnessed tremendous advances in trauma care including trauma system development, advanced trauma life support, damage control surgery and ICU resuscitation. As a result, patients who used to bleed to death in the operating room survived. However, many went on to develop multiple organ failure (MOF) and in the mid-1990s, an epidemic of abdominal compartment syndrome (ACS) that emerged in these MOF survivors stimulated fundamental changes in early management of patients arriving in shock with severe bleeding. RECENT FINDINGS In the early 2000s, a massive transfusion protocol (emphasizing aggressive use of fresh frozen plasma) coupled with hypotensive resuscitation and rapid hemorrhage control were implemented and refined at a busy level I trauma center in Houston, Texas, USA. These changes were associated with a 50% reduction in mortality in massive transfusion patients, and ACS virtually disappeared. SUMMARY ACS is a modifiable link in the MOF cascade to death after severe shock. However, as ACS disappears, MOF is still occurring. Although fewer patients are dying of MOF, it remains the leading cause of prolonged ICU stays and long-term disability. This experience underscores the importance of ongoing epidemiologic characterization of postinjury MOF.

BACKGROUND Recent data suggest that patients undergoing massive transfusion have lower mortality rates when ratios of plasma and platelets to red blood cells (RBCs) of ≥ 1:2 are used. This has not been examined independently in women and men. A gender dichotomy in outcome after severe injury is known to exist. This study examined gender-related differences in mortality after high product ratio massive transfusion. METHODS A retrospective study was conducted using a database containing massively transfused trauma patients from 23 Level I trauma centers. Baseline demographic, physiologic, and biochemical data were obtained. Univariate and logistic regression analyses were performed. Adjusted mortality in patients receiving high (≥ 1:2) or low (

The early use of fresh frozen plasma as a resuscitative agent after hemorrhagic shock has been associated with improved survival, but the mechanism of protection is unknown. Hemorrhagic shock causes endothelial cell dysfunction and we hypothesized that fresh frozen plasma would restore endothelial integrity and reduce syndecan-1 shedding after hemorrhagic shock. A prospective, observational study in severely injured patients in hemorrhagic shock demonstrated significantly elevated levels of syndecan-1 (554±93 ng/ml) after injury, which decreased with resuscitation (187±36 ng/ml) but was elevated compared to normal donors (27±1 ng/ml). Three pro-inflammatory cytokines, interferon-γ, fractalkine, and interleukin-1β, negatively correlated while one anti-inflammatory cytokine, IL-10, positively correlated with shed syndecan-1. These cytokines all play an important role in maintaining endothelial integrity. An in vitro model of endothelial injury then specifically examined endothelial permeability after treatment with fresh frozen plasma orlactated Ringers. Shock or endothelial injury disrupted junctional integrity and increased permeability, which was improved with fresh frozen plasma, but not lactated Ringers. Changes in endothelial cell permeability correlated with syndecan-1 shedding. These data suggest that plasma based resuscitation preserved endothelial syndecan-1 and maintained endothelial integrity, and may help to explain the protective effects of fresh frozen plasma after hemorrhagic shock.

Resuscitation with fresh frozen plasma (FFP) is associated with improved outcomes after hemorrhagic shock. Many trauma centers are using thawed plasma that has been stored for up to 5 days at 4°C (refrigeration), yet the effect of refrigeration on FFP is relatively unknown. Previously, our group showed that refrigeration of FFP changed its coagulation factors and diminished its beneficial effects on endothelial cell (EC) function and resuscitation in an animal model of hemorrhagic shock. We hypothesize that growth factor composition of FFP is altered during refrigeration, leading to a diminished beneficial effect on EC. Transforming growth factor (TGF-β) is a potent inhibitor of EC migration and is released during refrigeration of platelets. We found increased TGF-β1 protein levels and greater activation of downstream mediators Smad2/3 during refrigeration of FFP. Both day 0 FFP (used on the same day after being thawed) and day 5 FFP (used after being thawed and refrigerated for 5 days) stimulated EC migration in vitro; however, the EC migration in day 5 FFP was significantly reduced. Inhibition of TGF-β type I receptor blocked FFP-induced Smad3 signaling in EC cells and restored the effectiveness of day 5 FFP on EC migration to a comparable level seen in day 0 FFP. These data suggest that the increased TGF-β levels during FFP refrigeration contribute to the deterioration of refrigerated FFP's effects on EC migration. This study identifies a novel molecular mechanism contributing to the reduced efficacy of refrigerated FFP.

Shock is a prime inciting event for postinjury multiple organ failure (MOF), believed to induce a state of injurious systemic inflammation. In animal models of hemorrhagic shock, early (24 hours) changes in cytokine production are an index of the systemic inflammatory response syndrome. However, their predictive value in trauma patients remains to be fully elucidated.In a prospective observational pilot study of1 year at an urban Level I trauma center, serial (every 4 hours) serum cytokine levels were determined during a 24-hour period using multiplex suspension immunoassay in patients with major torso trauma (excluding severe brain injury) who met criteria for standardized shock resuscitation. Temporal cytokine expression was assessed during shock resuscitation in severe trauma patients to predict risk for MOF. MOF was assessed with the Denver score.Of 48 study patients (mean age 39 +/- 3 years, 67% men, 88% blunt mechanism, mean Injury Severity Score 25 +/- 2), MOF developed in 11 (23%). MOF patients had a considerably higher mortality (64% versus 3%) and fewer ICU-free days (3.5 +/- 2 versus 17.8 +/- 1.3 days) compared with non-MOF patients. Traditional predictors of MOF, including age (45 +/- 7 versus 38 +/- 3 years; p=0.21), Injury Severity Score (26 +/- 3 versus 25 +/- 2; p=0.67), admission hemoglobin (11.4 +/- 0.9 versus 12.1 +/- 0.5 g/dL; p=0.22), international normalized ratio (1.6 +/- 0.2 versus 1.4 +/- 0.06; p=0.17), and base deficit (9.0 +/- 2 versus 7.1 +/- 0.8; p=0.19), were not significantly different between MOF and non-MOF patients. Statistical analysis identified six candidate predictors of MOF: inducible protein 10, macrophage inflammatory protein-1beta, interleukin-10, interleukin-6, interleukin-1Ra, and eotaxin.These data provide insight into cytokine expression during traumatic shock that can enable earlier identification of patients at risk for development of MOF.

Hypotensive resuscitation prolongs survival of patients with severe bleeding until they can undergo hemorrhage control. However, its value is limited by continuing ischemic injury. Purified poloxamer 188 (P188), a copolymer with rheological and cytoprotective activities, was known to reduce mortality of hemorrhagic shock when used as an adjunct to full resuscitation with fresh whole blood and crystalloid. Studies were undertaken to determine if it could prolong survival and reduce reperfusion injury during prolonged hypotensive resuscitation when added to the best regimen currently available. Unanesthetized rats were bled to a MAP of 30 mmHg for 30 min under computer control. They then received hypotensive resuscitation with Hextend or Hextend + P188 to maintain a MAP of 60 mmHg until death. Poloxamer 188 improved autoresuscitation, reduced fluid requirements, and increased the survivable duration of hypotensive resuscitation by more than 3 h (P0.01). Additional studies assessed tissue damage after shock and hypotensive resuscitation with Hextend followed by full resuscitation with crystalloid. In these studies, P188 blunted the no-reflow phenomenon and largely prevented myocardial injury, pulmonary inflammation, small bowel damage, renal tubular necrosis, hepatic central lobular necrosis, and apoptosis of splenic germinal centers that occurred during full resuscitation. Additional studies demonstrated that P188 increased survival from 0% to 75% in 50% volume-controlled hemorrhage (P0.001). Finally, P188 did not increase bleeding in uncontrolled hemorrhage produced by 75% tail amputation. Because P188 prolongs survival, decreases fluid requirements, and reduces tissue damage, it deserves further consideration as an adjunct to hypotensive resuscitation.

Nutritional supplementation is paramount to the care of severely injured patients. Despite its widespread use in trauma, many areas of clinical nutrition remain controversial and not well defined. The benefit of early enteral nutrition in the care of injured patients has been well established, with further benefit derived by the administration of immune-enhancing formulas supplemented with glutamine, arginine, nucleotides, and omega-3-fatty acids. A new paradigm of pharmaconutrition has been developed that separates the administration of immunomodulatory nutrients from that of nutritional support. The optimal utilization and benefit of pharmaconutrients, however, remains unclear, as does the need for full caloric provision in the early postinjury phase.Nutrition studies with the greatest reduction in morbidity and mortality are those utilizing specific nutrients. The use of pharmaconutrients to modulate the inflammatory and immune response associated with critical illness seems to provide benefit to critically ill and injured patients. Additionally, studies at least suggest that trauma patients derive comparable if not additional benefit from hypocaloric feeding during the acute phase of injury.Building upon previous well performed studies in trauma patients, the current focus of nutritional investigations center on the use of pharmaconutrients to modulate the inflammatory response and the use of hypocaloric feeds. These practices will be reviewed and evidence presented for their use in critically ill and injured patients.

To determine the effect of blood component ratios in massive transfusion (MT), we hypothesized that increased use of plasma and platelet to red blood cell (RBC) ratios would result in decreased early hemorrhagic death and this benefit would be sustained over the ensuing hospitalization.Civilian guidelines for massive transfusion (MTor =10 units of RBC in 24 hours) have typically recommend a 1:3 ratio of plasma:RBC, whereas optimal platelet:RBC ratios are unknown. Conversely, military data shows that a plasma:RBC ratio approaching 1:1 improves long term outcomes in MT combat casualties. There is little consensus on optimal platelet transfusions in either civilian or military practice. At present, the optimal combinations of plasma, platelet, and RBCs for MT in civilian patients is unclear.Records of 467 MT trauma patients transported from the scene to 16 level 1 trauma centers between July 2005 and June 2006 were reviewed. One patient who died within 30 minutes of admission was excluded. Based on high and low plasma and platelet to RBC ratios, 4 groups were analyzed.Among 466 MT patients, survival varied by center from 41% to 74%. Mean injury severity score varied by center from 22 to 40; the average of the center means was 33. The plasma:RBC ratio ranged from 0 to 2.89 (mean +/- SD: 0.56 +/- 0.35) and the platelets:RBC ratio ranged from 0 to 2.5 (0.55 +/- 0.50). Plasma and platelet to RBC ratios and injury severity score were predictors of death at 6 hours, 24 hours, and 30 days in multivariate logistic models. Thirty-day survival was increased in patients with high plasma:RBC ratio (or =1:2) relative to those with low plasma:RBC ratio (1:2) (low: 40.4% vs. high: 59.6%, P0.01). Similarly, 30-day survival was increased in patients with high platelet:RBC ratio (or =1:2) relative to those with low platelet:RBC ratio (1:2) (low: 40.1% vs. high: 59.9%, P0.01). The combination of high plasma and high platelet to RBC ratios were associated with decreased truncal hemorrhage, increased 6-hour, 24-hour, and 30-day survival, and increased intensive care unit, ventilator, and hospital-free days (P0.05), with no change in multiple organ failure deaths. Statistical modeling indicated that a clinical guideline with mean plasma:RBC ratio equal to 1:1 would encompass 98% of patients within the optimal 1:2 ratio.Current transfusion practices and survival rates of MT patients vary widely among trauma centers. Conventional MT guidelines may underestimate the optimal plasma and platelet to RBC ratios. Survival in civilian MT patients is associated with increased plasma and platelet ratios. Massive transfusion practice guidelines should aim for a 1:1:1 ratio of plasma:platelets:RBCs.

Background: Gastric function in trauma patients is poorly understood. In animals, shock causes gastric luminal alkalinization and bile reflux. In trauma patients, studies of stress gastritis prophylaxis demonstrated with continuous gastric pH monitoring that the stomach became alkaline even without antisecretory therapy. Therefore, we hypothesized that trauma patients have an alkaline gastric environment that may be because of bile reflux. Methods: A prospective observational study at an urban Level I trauma center was performed. All major torso trauma patients (severe head injuries excluded) who met the criteria for standardized shock resuscitation were eligible for inclusion. A 12.5 Fr silastic pH probe (Sandhill Scientific) was placed in the stomach and the gastric pH continuously monitored for 7 days. Patients received no stress gastritis prophylaxis. Gastric samples were obtained each day and assayed for total bile acids and pH. Results: Twelve patients were entered into the study. Mean age was 31 years ± 4 years, 67% men, 75% blunt mechanism of injury, and mean Injury Severity Score 28 ± 3. Three patients (25%) developed multiple organ failure and four acquired ventilator-associated pneumonia. During the first day of continuous pH monitoring, 9 of 12 patients had a gastric pH >4 for the majority of the day with 7 patients having essentially no acid production. During subsequent days, gastric pH began to drop and by the 4th day the majority of each day was spent at a pH

Background: The pathogenesis of multiple organ failure (MOF) in trauma patients may involve the gastrointestinal tract, but its exact origins remain elusive. In a prospective study, the gastric fluid of major torso trauma patients was examined for evidence of duodenogastric reflux and potential gastric injury, and was compared with patient outcomes regarding MOF. Methods: Patient samples were collected daily for 4 days by nasogastric tube and analyzed for pH, hemoglobin, and bile acid. Blood was collected for analysis of C-reactive protein (CRP). Outcomes were recorded for the presence or absence of MOF. Results: The results showed that most patients exhibited alkaline gastric contents (pH ≥ 4.9) and elevated levels of hemoglobin immediately after the trauma. Although non-MOF patients demonstrated a decline of both mean gastric pH and bleeding by day 4, MOF patients maintained significant elevations in pH during this time period. Mean total bile acid levels were increased in all patients, signifying the presence of duodenogastric reflux. However, there were no clear differences in mean bile acid concentrations between MOF and non-MOF patients over time, although MOF patients tended to exhibit higher levels. All patients showed a progressive rise in serum CRP during the first 24 hours after trauma, which was maintained for 4 days. The initial rise in serum CRP in MOF patients was delayed compared with that in non-MOF patients. Conclusions: We conclude that duodenogastric reflux occurs in trauma patients in the first few days after trauma and may contribute to elevated gastric pH and bleeding. Further study is needed to verify whether monitoring the gastric juice of trauma patients during the first several days of hospitalization, for alkaline pH and excessive blood in the gastric lumen, could lead to better assessments of patient status.

Acute lower extremity compartment syndrome (ALECS) is a devastating complication that often presents silently in critically injured patients; therefore, we developed a protocol to screen high-risk patients.This prospective observational study included all Shock Trauma intensive care unit patients who met specific high-risk criteria including pulmonary artery catheter-directed shock resuscitation, open or closed tibial shaft fracture, major vascular injury below the aortic bifurcation, abdominal compartment syndrome, or pelvic or lower extremity crush injury. Patients were screened at admission and every 4 hours thereafter for the first 48 hours of admission. Screening included physical examination (PE) and anterior or deep posterior calf compartment pressure measurements when PE was suspicious or unreliable. A positive screening, defined as a DeltaP30 mm Hg (where DeltaP is the difference between the diastolic blood pressure and the compartment pressure), mandated a four-compartment fasciotomy.During a 6-month period, the incidence of ALECS in screened patients was surprisingly high at 20% (9 patients). With diligent screening, it was diagnosed early in the patient's Shock Trauma intensive care unit course. These were patients with severe injuries with an Injury Severity Score of 32.0 +/- 12.5 who exhibited significant volume depletion, with a base deficit of 12.9 +/- 5.9 mEq/L and a lactate level of 13.0 +/- 5.2 mmol/L, requiring large volume resuscitation. Although aggressive fasciotomy resulted in no limb loss, ALECS was associated with an exceedingly high mortality rate at 67%.ALECS is an important clinical entity in critically injured patients with trauma associated with significant mortality. Aggressive screening may provide some diagnostic insight to those at risk.

Rapid progress in trauma care occurs when the results of translational research are promptly integrated into clinical practice. Experience with a high volume of severely injured casualties expedites the process. Historically, these conditions have converged during times of conflict, improving the care of combat casualties and subsequently that of civilian trauma patients. In the most severely injured casualties, we know that when the lethal triad of hypothermia, acidosis, and coagulopathy are present, death is imminent. Current teaching is to avoid reaching these conditions by using damage control surgery. However, conventional resuscitation practice for damage control focuses on rapid reversal of acidosis and prevention of hypothermia, and surgical techniques focus on controlling hemorrhage and contamination. Direct treatment of coagulopathy has been relatively neglected, viewed as a byproduct of resuscitation, hemodilution, and hypothermia, and delayed by blood banking logistics. Damage control resuscitation addresses the entire lethal triad immediately upon admission to a combat hospital. By demonstrating that in the severely injured the coagulopathy of trauma is present at admission, recent studies have brought back to light the importance of treating this disorder at an earlier stage. Reports of lactated Ringer s solution and normal saline increasing reperfusion injury and leukocyte adhesion lead one to conclude that the standard crystalloid based resuscitation guidelines in pre hospital trauma life support (PHTLS) and advanced trauma life support (ATLS) may worsen the presenting acidosis and coagulopathy in severely injured trauma patients, and possibly increase ARDS, SIRS, and MOF. The safety of withholding PRBCs in hemodynamically stable patients has been demonstrated,18 and the risks associated with blood transfusion are well described.

Background The study purpose was to identify early predictors of prolonged mechanical ventilation in major torso trauma patients. Methods This was a retrospective review of torso trauma patients who met specific criteria for shock resuscitation and required 48 hours of mechanical ventilation. Independent variables evaluated included patient demographics, injury characteristics, and initial 24-hour resuscitation parameters. Univariate and multivariate logistic regression analyses were performed using a significance level of P Results Over 59 months, 224 patients met study criteria. Age was 34 years (range 25 to 69), 68% were male, 78% sustained blunt trauma, and injury severity score was 27 (range 18 to 38). Thirty-three percent required prolonged mechanical ventilation. In the analysis, predictors of prolonged mechanical ventilation included total fluid resuscitation, facial trauma, age, positive end-expiratory pressure ≥10 mm Hg on admission, arterial partial pressure of oxygen divided by the fraction of inspired oxygen ratio less than 300 at 24 hours, and chest abbreviated injury scale score. Conclusions The need for prolonged mechanical ventilation can be accurately predicted and these predictors may assist clinicians in resource allocation and patient management decisions.

Background: We have previously demonstrated that hypertonic saline (HS) resuscitation decreased inflammation and mucosal injury after mesenteric ischemia/ reperfusion (I/R). In contrast to I/R cell necrosis, apoptosis provides controlled cell death that minimizes inflammation. We therefore hypothesized that HS resuscitation after mesenteric I/R would induce apoptosis and decrease mucosal injury. Methods: Rats underwent 60 minutes of superior mesenteric artery occlusion (SMAO) and then received no resuscitation or resuscitation with 4 mL/kg of HS, 4 mL/kg of lactated Ringer's (LR) solution (equal volume), or 32 mL/ke of LR solution (equal salt load). Rats were killed at 6 hours of reperfusion, and ileum was harvested for analysis. DNA fragmentation (apoptosis) was assessed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and mucosal injury by histology (Chiu score 0-5). Caspase-3 (proapoptotic mediator) and Bcl-xL (antiapoptotic mediator) protein expression were analyzed by Western immunoblot. Results: SMAO with no resuscitation, SMAO with 4 mL/kg of LR, and SMAO with 32 mL/kg of LR increased apoptosis (quantitated by TUNEL) and I/R-induced mucosal injury (quantitated by Chiu score). This was associated with an increase to similar levels in both proapoptotic caspase-3 and antiapoptotic Bcl-xL protein expression. Moreover, SMAO with 4 mL/kg of HS further increased apoptosis but decreased mucosal injury. This was associated with a differential expression of proapoptotic caspase-3 over antiapoptotic Bcl-xL. Conclusion: HS resuscitation after mesenteric I/R significantly increased ileal mucosal apoptosis while decreasing mucosal injury and may represent a novel mechanism by which HS resuscitation after mesenteric I/R reduces inflammation and imparts protection to the gut.

Background: The liver is both a source and a target of inflammatory and anti-inflammatory mediators during sepsis. The oxidative stress proteins inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) are upregulated in the liver during sepsis but have opposite roles. Up-regulation of HO-1 has hepatoprotective effects, whereas iNOS has injurious effects to the liver. Although recent studies indicate that ketamine anesthesia has anti-inflammatory effects during sepsis, the effects of other anesthetics are unknown. We hypothesized that ketamine, but not isoflurane, would attenuate lipopolysaccharide (LPS)-induced liver injury through differential modulation of iNOS and HO-1. Methods: Adult rats were given no anesthesia (saline), continuous isoflurane inhalation, or intraperitoneal ketamine (70 mg/ kg). One hour later, saline or LPS (20 mg/kg intraperitoneally) was given for 5 hours. Rats were killed, serum prepared for determination of hepatocellular enzymes, and the liver assessed for iNOS and HO-1 by Western immunoblot. Results: LPS significantly increased serum aspartate aminotransferase levels, iNOS, and HO-1 immunoreactivity in the liver. Ketamine but not isoflurane attenuated LPS-induced liver injury, upregulated HO-1, and downregulated iNOS. Conclusion: These data indicate that anesthetics differ in their effects on the liver in a rat model of sepsis with LPS. Ketamine has hepatoprotective effects against LPS-induced liver injury that appear to be mediated, at least in part, by differential modulation of the oxidative stress proteins iNOS and HO-1. Thus, ketamine may be the anesthetic agent of choice for septic patients requiring anesthesia.

Injury to the abdominal aorta after blunt trauma is uncommon. When this injury results in complete vessel occlusion, the presentation is dramatic. Timely intervention is essential.After a case report, we examined all reported cases of complete occlusion after blunt injury to the abdominal aorta and reviewed the cause, presentation, and management of this injury.Complete vessel occlusion arises from intimal injury. The most frequent mechanism is compression from a seat belt or steering wheel during a motor vehicle crash. Patients present with absent femoral and distal pulses in association with lower extremity neuropathy. Intervention commonly involves bypass grafting of the abdominal aorta.Complete occlusion after blunt trauma to the abdominal aorta is rare. Neurologic deficits most commonly arise from peripheral nerve ischemia. Reperfusion within 6 hours confers a greater chance of limb salvage and neurologic recovery.

ESULTS: 2258 patients included in the AO group, 2021 atients in the AO group. Demographics and injury severity ere similar. Incidence of VAP, sacral decubiti, wound dehisence, SIRS, renal failure and sepsis were similar between the roups. However, abdominal compartment syndrome (ACS) (90 s. 31, p 0.001), pulmonary failure (721 vs. 528, p 0.001), atheter related infections (75 vs. 50, p 0.004), and surgical site nfections (101 vs. 44, p 0.001) were significantly less in the O group.

Lactated Ringer’s is the standard of care trauma resuscitation, but the D-isomer of lactate has been shown to activate proinflammation. We have shown that superior mesenteric artery occlusion (SMAO) without resuscitation causes gastric dysfunction characterized by luminal fluid accumulation and alkalization. In the same model, LR resuscitation protected the ileum, but the presence of the D-isomer abrogated this effect. We, therefore, hypothesized that the isomeric composition of LR resuscitation would have a differential effect on gastric dysfunction and inflammation in this model. Rats underwent sham or SMAO for 60 min. Five minutes prior to clamp removal, SMAO animals received no resuscitation, 20 ml/kg IV (our standard) of either LL or LD isomer LR, or 17 ml/kg IV normal saline (NS) as equal salt load control. Animals were sacrificed at 6 h of reperfusion and gastric mucosa was harvested for analysis. Gastric dysfunction was quantitated by gastric volume and luminal pH. Heme-Oxygenase-1 (HO-1; index of anti-inflammation) and inducible Nitric Oxide Synthase (iNOS; index of proinflammation) protein expression were analyzed by Western immunoblot. Data are reported as mean ± SEM ( n > 6/group; ANOVA). Means with different letters are significantly different. SMAO (no resuscitation) increased gastric volume and pH. All three resuscitative regimens decreased gastric volume, had no effect on pH, and equally induced HO-1 and iNOS. In conclusion, isomeric composition of LR had no differential effect on gastric dysfunction and inflammation after SMAO in contradistinction to its previously observed effects in the ileum. The isomeric immunomodulatory effects of LR appear to be organ specific. TABLE—ABSTRACT P87 . Model Volume (ml) pH (pH) HO-1 (AU) iNOS (AU) Sham 0.30 ± 0.05 a 1.67 ± 0.16 a 0.36 ± 0.02 a 0.28 ± 0.03 a SMAO 2.22 ± 0.57 b 6.58 ± 0.20 b 0.43 ± 0.05 a 0.29 ± 0.07 a SMAO/LL 1.28 ± 0.31 c 5.58 ± 0.62 b 0.56 ± 0.04 b 0.50 ± 0.06 b SMAO/LD 0.80 ± 0.23 c 6.38 ± 0.38 b 0.57 ± 0.04 b 0.44 ± 0.03 b SMAO/NS 1.03 ± 0.12 c 5.83 ± 0.60 b 0.59 ± 0.05 b 0.49 ± 0.10 b

Introduction. LPS causes a gastrointestinal ileus and gastric luminal fluid accumulation. Ketamine, an antiinflammatory agent, attenuates accumulation of luminal fluid. However its effects on gastrointestinal transit during endotoxemia are unknown. The purpose of this study was to determine if the antiinflammatory properties of ketamine improve impaired gastrointestinal transit due to LPS. We hypothesized that ketamine would improve impaired GI transit caused by LPS. Methods. Rats were given ketamine (70 mg/kg ip) or saline 1 h prior to LPS (20 mg/kg, ip) or saline injection. Five hours following LPS injection, rats were gavaged with 0.1 ml of 5 mM FITC Dextran followed by 0.9 ml of saline. After 30 min rats were sacrificed; transit was determined as the mean geometric center of the FITC Dextran tracer signal; gastric fluid accumulation was determined, and gastric and ileal mucosa were harvested for analysis of iNOS as an inflammatory marker (Western immunoblot). Results are reported as mean ± SE (n ≥ 5 per group; ANOVA). Results. As shown in the table TABLE—ABSTRACT P84 . GI transit Gastric fluid Gastric iNOS Ileal iNOS Sal/Sal 6.35 ± .16 .21 ± .02 .03 ± .001 .02 ± .001 Sal/LPS 2.71 ± .34 ∗ 2.71 ± .46 ∗ .31 ± .13 ∗ .4 ± .08 ∗ Ket/Sal 6.33 ± .38 .24 ± .08 .02 ± .01 .01 ± .002 Ket/LPS 2.86 ± .28 ∗ 1.23 ± .4 ∗∗ .13 ± .02 ∗∗ .24 ± .02 ∗∗ ∗ P ∗∗ P above, ketamine did not reverse LPS-induced gastrointestinal ileus. However it did decrease LPS-induced gastric luminal fluid accumulation and blunted iNOS expression in both the stomach and the ileum. Conclusion. These data indicate that ketamine’s ability to attenuate gastric fluid accumulation is not due to improved gastric emptying. Moreover, while iNOS may play a role in LPS-induced gastric luminal fluid accumulation, it does not appear to play a significant role in the gastrointestinal ileus caused by LPS.