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Genomic analyses from blood leukocytes have concluded that mouse injury poorly reflects human trauma at the leukocyte transcriptome. Concerns have focused on the modest severity of murine injury models, differences in murine compared with human age, dissimilar circulating leukocyte populations between species, and whether similar signaling pathways are involved. We sought to examine whether the transcriptomic response to severe trauma in mice could be explained by these extrinsic factors, by utilizing an increasing severity of murine trauma and shock in young and aged mice over time, and by examining the response in isolated neutrophil populations.Preclinical controlled in vivo laboratory study and retrospective cohort study.Laboratory of Inflammation Biology and Surgical Science and multi-institution level 1 trauma centers.Six- to 10-week-old and 20- to 24-month-old C57BL/6 (B6) mice and two cohorts of 167 and 244 severely traumatized (Injury Severity Score15) adult (18 yr) patients.Mice underwent one of two severity polytrauma models of injury. Total blood leukocyte and neutrophil samples were collected.Fold expression changes in leukocyte and neutrophil genome-wide expression analyses between healthy and injured mice (p0.001) were compared with human total and enriched blood leukocyte expression analyses of severe trauma patients at 0.5, 1, 4, 7, 14, and 28 days after injury (Glue Grant trauma-related database). We found that increasing the severity of the murine trauma model only modestly improved the correlation in the transcriptomic response with humans, whereas the age of the mice did not. In addition, the genome-wide response to blood neutrophils (rather than total WBC) was also not well correlated between humans and mice. However, the expression of many individual gene families was much more strongly correlated after injury in mice and humans.Although overall transcriptomic association remained weak even after adjusting for the severity of injury, age of the animals, timing, and individual leukocyte populations, there were individual signaling pathways and ontogenies that were strongly correlated between mice and humans. These genes are involved in early inflammation and innate/adaptive immunity.

Acute kidney injury (AKI) is a common and often catastrophic complication in hospitalized patients; however, the impact of AKI in surgical sepsis remains unknown. We used Risk, Injury, Failure, Loss, End stage (RIFLE) consensus criteria to define the incidence of AKI in surgical sepsis and characterize the impact of AKI on patient morbidity and mortality.Our prospective, institutional review board-approved sepsis research database was retrospectively queried for the incidence of AKI by RIFLE criteria, excluding those with chronic kidney disease. Patients were grouped into sepsis, severe sepsis, and septic shock by refined consensus criteria. Data including demographics, baseline biomarkers of organ dysfunction, and outcomes were compared by Student's t test and χ test. Multivariable regression analysis was performed for the effect of AKI on mortality adjusting for age, sex, African-American race, elective surgery, Acute Physiology and Chronic Health Evaluation II score, septic shock versus severe sepsis, and sepsis source.During the 36-month study period ending on December 2010, 246 patients treated for surgical sepsis were evaluated. AKI occurred in 67% of all patients, and 59%, 60%, and 88% of patients had sepsis, surgical sepsis, and septic shock, respectively. AKI was associated with Hispanic ethnicity, several baseline biomarkers of organ dysfunction, and a greater severity of illness. Patients with AKI had fewer ventilator-free and intensive care unit-free days and a decreased likelihood of discharge to home. Morbidity and mortality increased with severity of AKI, and AKI of any severity was found to be a strong predictor of hospital mortality (odds ratio, 10.59; 95% confidence interval, 1.28-87.35; p = 0.03) in surgical sepsis.AKI frequently complicates surgical sepsis, and serves as a powerful predictor of hospital mortality in severe sepsis and septic shock.Prognostic and epidemiologic study, level III.

For the past thirty years, since IL-1β and TNFα were first cloned, there have been efforts to measure plasma cytokine concentrations in patients with severe sepsis and trauma, and to use these measurements to predict clinical outcome and response to therapies. The numbers of cytokines and chemokines that have been measured in the plasma have literally exploded with the development of multiplex immune approaches. Dozens of relatively small cohort studies have shown plasma cytokine concentrations correlating with outcome in sepsis and trauma. Despite what appears to be a consensus that plasma cytokine concentrations should be useful in the clinical setting, only two cytokines, IL-6 and procalcitonin, have approached routine clinical use. IL-6 has been used as a research tool for entry into sepsis-intervention trials, while procalcitonin is being used clinically at a large number of institutions to distinguish sepsis from other inflammatory processes. For most cytokines, the relative lack of sensitivity and specificity of individual or multiplex cytokine measurements has hindered their utility to predict clinical trajectory in individual patients. The problem rests with a general misunderstanding of cytokine biology, failing to appreciate the general paracrine nature of these mediators, the presence of binding proteins, chaperones and inhibitors in the plasma, and the rapid clearance of these proteins by binding to cell receptors and clearance predominantly by the kidney. The future of using plasma cytokine measurements as an indicator of sepsis/trauma severity or predicting outcome is generally behind us, although there is optimism that procalcitonin measurements may ultimately prove to have utility in the diagnosis of severe sepsis.

Surgical intensive care unit (ICU) stay of greater than ten days is often described by the experienced intensivist as a ‘complicated clinical course’, and is frequently attributed to persistent immune dysfunction. ‘Systemic inflammatory response syndrome’ (SIRS) followed by ‘compensatory anti-inflammatory response syndrome’ (CARS) is a conceptual framework to explain the immunological trajectory that ICU patients with severe sepsis, trauma or emergency surgery for abdominal infection often traverse, but the causes, mechanisms and reasons for persistent immune dysfunction remain unexplained. Often involving multiple organ failure (MOF) and death, improvements in surgical intensive care have altered its incidence, phenotype and frequency, and have increased the number of patients who survive initial sepsis or surgical events and progress to a persistent inflammation, immunosuppression, and catabolism syndrome (PICS). Often observed, but rarely reversible, these patients may survive to transfer to a long-term care facility only to return to the ICU, but rarely to self sufficiency. We propose that PICS is the dominant pathophysiology and phenotype that has replaced late MOF, and prolongs surgical ICU stay, usually with poor outcome. This review details the evolving epidemiology of MOF, the clinical presentation of PICS, and our understanding of how persistent inflammation and immunosuppression defines the pathobiology of prolonged intensive care. Therapy for PICS will require efficacy for multiple immune system defects and protein catabolism, and will involve innovative interventions for immune system rebalance and nutritional support to regain physical function and well being.

Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes., Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.

Sepsis is increasing in hospitalized patients. Our purpose is to describe its current epidemiology in a general surgery (GS) intensive care unit (ICU) where patients are routinely screened and aggressively treated for sepsis by an established protocol.Our prospective, Institutional Review Board-approved sepsis research database was queried for demographics, biomarkers reflecting organ dysfunction, and mortality. Patients were grouped as sepsis, severe sepsis, or septic shock using refined consensus criteria. Data are compared by analysis of variance, Student's t test, and χ test (p0.05 significant).During 24 months ending September 2009, 231 patients (aged 59 years ± 3 years; 43% men) were treated for sepsis. The abdomen was the source of infection in 69% of patients. Several baseline biomarkers of organ dysfunction (BOD) correlated with sepsis severity including lactate, creatinine, international normalized ratio, platelet count, and d-dimer. Direct correlation with mortality was noted with particular baseline BODs including beta natriuretic peptide, international normalized ratio, platelet count, aspartate transaminase, alanine aminotransferase, and total bilirubin. Most patients present with severe sepsis (56%) or septic shock (26%) each with increasing multiple BODs. Septic shock has prohibitive mortality rate (36%), and those who survive septic shock have prolonged ICU stays.In general surgery ICU patients, sepsis is predominantly caused by intra-abdominal infection. Multiple BODs are present in severe sepsis and septic shock but are notably advanced in septic shock. Despite aggressive sepsis screening and treatment, septic shock remains a morbid condition.

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: Sepsis is the leading cause of mortality in noncoronary intensive care units. Recent evidence based guidelines outline strategies for the management of sepsis and studies have shown that early implementation of these guidelines improves survival. We developed an extensive logic-based sepsis management protocol; however, we found that early recognition of sepsis was a major obstacle to protocol implementation. To improve this, we developed a three-step sepsis screening tool with escalating levels of decision making. We hypothesized that aggressive screening for sepsis would improve early recognition of sepsis and decrease sepsis-related mortality by insuring early appropriate interventions. Methods: Patients admitted to the surgical intensive care unit were screened twice daily by our nursing staff. The initial screen assesses the systemic inflammatory response syndrome parameters (heart rate, temperature, white blood cell count, and respiratory rate) and assigns a numeric score (0―4) for each. Patients with a score of ≥4 screened positive proceed to the second step of the tool in which a midlevel provider attempts to identify the source of infection. If the patients screens positive for both systemic inflammatory response syndrome and an infection, the intensivist was notified to determine whether to implement our sepsis protocol. Results: Over 5 months, 4,991 screens were completed on 920 patients. The prevalence of sepsis was 12.2%. The screening tool yielded a sensitivity of 96.5%, specificity of 96.7%, a positive predictive value of 80.2%, and a negative predictive value of 99.5%. In addition, sepsis-related mortality decreased from 35.1% to 23.3%. Conclusions: The three step sepsis screening tool is a valid tool for the early identification of sepsis. Implementation of this tool and our logic-based sepsis protocol has decreased sepsis-related mortality in our SICU by one third.

PURPOSE OF REVIEW To review what we learned through implementation of computerized decision support for ICU resuscitation of major torso trauma patients who arrive in shock. RECENT FINDINGS Overall, these patients respond well to preload-directed goal-orientated ICU resuscitation; however, the subset of patients destined to develop abdominal compartment syndrome do not respond well. In fact, this strategy precipitates the full-blown syndrome that is a new iatrogenic variant of multiple organ failure. The clinical trajectory of abdominal compartment syndrome starts early after emergency department admission and its course is fairly well defined by the time patients reach the ICU. It occurs in patients who arrive with severe bleeding that is not readily controlled. These patients require a very different emergency department management strategy. Hemorrhage control is paramount. Alternative massive transfusion protocols should be used with an emphasis on hemostasis and avoidance of excessive isotonic crystalloids. Finally, near-infrared spectroscopy that measures tissue hemoglobin saturation in skeletal muscle (StO2) is good at identifying high-risk patients. A falling StO2 in the setting of ongoing resuscitation is a harbinger of death from early exsanguination and multiple organ failure. SUMMARY Fundamental changes are needed in the care of trauma patients who arrive in shock and require a massive transfusion.

BACKGROUND: Damage control resuscitation (DCR) with early plasma in combat casualties requiring massive transfusion (MT) decreases early deaths from bleeding. METHODS: To ascertain the potential role of early plasma DCR in civilian MT, we queried a prospective traumatic shock database of 383 civilians. RESULTS: Ninety-three (24%) of the traumatic shock civilians received a MT, of which 26 (28%) died early, predominantly from bleeding within 6 hours. Comparatively, this early MT death cohort arrived in more severe shock and were coagulopathic (mean INR 2.4). In the critical period of MT (ie, the first 3 hours), these patients received 20 U of packed red blood cells (PRBCs) but only 4 U of fresh frozen plasma (FFP). They remained severely acidotic and their coagulopathy worsened as they exsanquinated. CONCLUSION: Civilians who arrived in traumatic shock, required a MT, and died early had worsening coagulopathy, which was not treated. DCR with FFP may have a role in civilian trauma.

The incidence of venous thromboembolism (VTE) without prophylaxis is as high as 80% after major trauma. Initiation of prophylaxis is often delayed because of concerns of injury-associated bleeding. As the effect of delays in the initiation of prophylaxis on VTE rates is unknown, we set out to evaluate the relationship between late initiation of prophylaxis and VTE.Data were derived from a multicenter prospective cohort study evaluating clinical outcomes in adults with hemorrhagic shock after injury. Analyses were limited to patients with an Intensive Care Unit length of stayor=7 days. The rate of VTE was estimated as a function of the time to initiation of pharmacologic prophylaxis. A multivariate stepwise logistic regression model was used to evaluate factors associated with late initiation.There were 315 subjects who met inclusion criteria; 34 patients (11%) experienced a VTE within the first 28 days. Prophylaxis was initiated within 48 hours of injury in 25% of patients, and another one-quarter had no prophylaxis for at least 7 days after injury. Early prophylaxis was associated with a 5% risk of VTE, whereas delay beyond 4 days was associated with three times that risk (risk ratio, 3.0, 95% CI [1.4-6.5]). Factors associated with late (4 days) initiation of prophylaxis included severe head injury, absence of comorbidities, and massive transfusion, whereas the presence of a severe lower extremity fracture was associated with early prophylaxis.Clinicians are reticent to begin timely VTE prophylaxis in critically injured patients. Patients are without VTE prophylaxis for half of all days within the first week of admission and this delay in the initiation of prophylaxis is associated with a threefold greater risk of VTE. The relative risks and benefits of early VTE prophylaxis need to be defined to better direct practice in this high-risk population.

Inflammation and the Host Response to Injury, a Large-Scale Collaborative Project: Patient-Oriented Research Core—Standard Operating Procedures for Clinical Care: III. Guidelines for Shock Resuscitation Frederick Moore;Bruce McKinley;Ernest Moore;Avery Nathens;Michael West;Michael Shapiro;Paul Bankey;Bradley Freeman;Brian Harbrecht;Jeffrey Johnson;Joseph Minei;Ronald Maier; The Journal of Trauma: Injury, Infection, and Critical Care

Ventilator-associated pneumonia (VAP*) is the most common nosocomial infection encountered in the ICU setting. Injured patients are particularly prone to VAP due in part to injuries such as direct chest trauma with pulmonary contusion and inability to control oropharyngeal secretions associated with traumatic brain injury. Post-injury immunosuppression is a recognized complicating factor of severe injury. Furthermore, common therapies used in caring for injured patients, such as blood transfusion, total parenteral nutrition and repeated trips to the operating room add to this immunocompromised state. The Centers for Disease Control (CDC), through the National Nosocomial Infections Surveillance System (NNIS), report that the median rate of VAP per 1000 ventilator days for patients in trauma ICU’s (11.4) was higher than any other individual type of surgical ICU (general surgery, cardiac surgery, neurosurgical, etc.). This rate was more than double that seen in medical (3.7) or coronary care (4.0) ICU’s. The mortality and morbidity attributable to VAP is difficult to ascertain. In a matched cohort study looking at a mixed population, the relative risk of death attributable to pneumonia was 32%. This increase was only significant in medical ICU patients where the relative risk of death attributable to pneumonia was 65%, suggesting an episode of VAP tips the balance for the medically frail. It is likely that surgical patients, by virtue of either being selected by surviving operative intervention (or their injuries) have adequate reserve such that an episode of VAP is less likely to be fatal. However, the additional length of stay (4–6 days) and associated costs, coupled with the detrimental effects of antimicrobial use on ICU ecology, calls for aggressive prevention strategies and a practical, evidence-based approach to managing VAP in critically ill trauma patients. Despite its common occurrence, there is still no agreed upon “gold standard” for the diagnosis of VAP and contro

Background This study reviews the efficacy of vacuum-assisted wound closure (VAWC) to obtain primary fascial closure of open abdomens after severe trauma. Methods The study population included shock resuscitation patients who had open abdomens treated with VAWC. The VAWC dressing was changed at 2- to 3-day intervals and downsized as fascial closure was completed with interrupted suture. The Trauma Research Database and the medical records were reviewed for pertinent data. Results Over 26 months, 35 patients with open abdomens were managed by VAWC. Six died early, leaving 29 patients who were discharged. Of these, 25 (86%) were successfully closed using VAWC at a mean of 7 +/- 1 days (range, 3-18 days). Of the four patients that failed VAWC, two developed fistulas. No patients developed evisceration, intra-abdominal abscess, or wound infection. Conclusion VAWC achieved early fascial closure in a high percentage of open abdomens, with an acceptable rate of complications.

Background: It is recommended that patients with impending abdominal compartment syndrome (ACS) should be volume loaded to insure the adequate preload. We evaluated our prospective resuscitation database to determine how patients who developed ACS differ from non-ACS patients in response to early volume loading. Methods: Over 36 months, 152 consecutive high-risk patients were resuscitated by a standard intensive care unit (ICU) protocol that escalates interventions in nonresponders. Interventions, responses, and outcomes are prospectively collected and the characteristics of ACS and non-ACS patients were compared. Results: Twenty-three patients (15%) developed ACS and were decompressed 8 ± 1 hours after ICU admission. The ACS and non-ACS patients had similar demographics and injury severity. The severity of pre-ICU shock tended to be greater in the ACS patients. During the first 8 hours of ICU resuscitation, patients who developed ACS received more blood transfusions (11 ± 2 versus 2 ± 0.2 units; P

Abdominal compartment syndrome (ACS) has emerged to be a significant problem in patients who develop postinjury multiple organ failure (MOF). Current laboratory research suggests that ACS could be a second hit for the development of MOF. Recent studies demonstrate that ACS is an independent predictor of MOF and that the prevention of ACS decreases the incidence of MOF. The Trauma Research Centers at the University of Colorado and the University of Texas-Houston Medical School are focused on defining the role of the gut in postinjury MOF. Because ACS is a plausible modifiable risk factor, our interest has been to 1) describe the epidemiology of ACS, 2) build prediction models, 3) provide strategies for prevention and treatment of ACS, and 4) develop relevant laboratory models. This review summarizes our findings.

Background: Postinjury small bowel ileus is poorly characterized and may be an important factor in intolerance to enteral nutrition (EN). We, therefore, placed jejunal manometry catheters in high-risk trauma patients. Our hypothesis was that the presence of fasting migrating motility complex (MMC) activity and conversion to a fed pattern at goal rate of EN would be present in those patients who tolerate jejunal feeding. Methods: After obtaining baseline fasting manometry pressure tracings, jejunal feeding was advanced stepwise to a set goal while tolerance was monitored and intolerance was treated by a standard approach. Results: Of the 10 study patients, 7 were able to be maintained on EN. Five (50%) had fasting MMCs and had good tolerance to early advancement of EN. The remaining five patients did not exhibit fasting MMCs and four had poor tolerance to early advancement of EN. Overall, nine patients reached goal rate of EN of which four converted to a fed pattern. This, however, was not associated with later tolerance to EN. Conclusion: EN is feasible following severe traumatic shock. Surprisingly, half of the patients had fasting MMCs. This requires intact neural and motor function and was associated with good tolerance of early EN.

Background: Damage control and decompressive laparotomies salvage severely injured patients who would have previously died. Unfortunately, many of these patients develop open abdomens. A variety of management strategies exist. The end result in many cases, however, is a large ventral hernia that requires a complex repair 6 to 12 months after discharge. We instituted vacuum-assisted wound closure (VAWC) to achieve early fascial closure and eliminate the need for delayed procedures. Methods: For 12 months ending June 2000, 14 of 698 trauma intensive care unit admissions developed open abdomens and were managed with VAWC dressing. This was changed every 48 hours in the operating room with serial fascial approximation until complete closure. Results: Fascial closure was achieved in 13 patients (92%) in 9.9 ± 1.9 days, and 2.8 ± 0.6 VAWC dressing changes were performed. There were 2 wound infections, no eviscerations, and no enteric fistulas. Conclusions: Use of VAWC can safely achieve early fascial closure in more than 90% of trauma patients with open abdomens.

Background: Variability and logistic complexity of mechanical ventilatory support of acute respiratory distress syndrome, and need to standardize care among all clinicians and patients, led University of Utah/LDS Hospital physicians, nurses, and engineers to develop a comprehensive computerized protocol. This bedside decision support system was the basis of a multicenter clinical trial (1993-1998) that showed ability to export a computerized protocol to other sites and improved efficacy with computer- versus physician-directed ventilatory support. The Memorial Hermann Hospital Shock Trauma intensive care unit (ICU) (Houston, TX; a Level I trauma center and teaching affiliate of The University of Texas Houston Medical School) served as one of the 10 trial sites and recruited two thirds of the trauma patients. Results from the trauma patient subgroup at this site are reported to answer three questions: Can a computerized protocol be successfully exported to a trauma ICU? Was ventilator management different between study groups? Was patient outcome affected? Methods: Sixty-seven trauma patients were randomized at the Memorial Hermann Shock Trauma ICU site. Protocol assigned patients had ventilatory support directed by the bedside respiratory therapist using the computerized protocol. Nonprotocol patients were managed by physician orders. Results: Of the 67 trauma patients randomized, 33 were protocol (age 40 ± 3; Injury Severity Score [ISS] 26 ± 3; 73% blunt) and 34 were nonprotocol (age 38 ± 2; ISS 25 ± 2; 76% blunt). For the protocol group, the computerized protocol was used 96% of the time of ventilatory support and 95% of computer-generated instructions were followed by the bedside respiratory therapist. Outcome measures (i.e., survival, ICU length of stay, morbidity, and barotrauma) were not significantly different between groups. FIO 2 ≥ 0.6 and Pplateau ≥ 35 cm H 2 O exposures were less for the protocol group. Conclusion: A computerized protocol for bedside decision support was successfully exported to a trauma center, and effectively standardized mechanical ventilatory support of trauma-induced acute respiratory distress syndrome without adverse effect on patient outcome.

Objective: Patients with thoracic aortic injury (TAI) usually have sustained other major trauma, and may require aggressive shock resuscitation. In the 24 hours after aortic repair and during resuscitation, our cardiothoracic surgeons request intravenous nitroprusside to maintain mean arterial pressure (MAP) less than 90 mm Hg to minimize bleeding at the repair. We compared the resuscitation response of patients who sustained major torso trauma (MTT) and TAI with that of patients who had MTT with no TAI to determine whether nitroprusside can effectively control MAP during resuscitation and whether use of nitroprusside, because of its peripheral vasodilatory effects, is associated with a favorable resuscitation response. Methods: During the 9-month study period, 11 patients who sustained TAI and 38 patients who sustained MTT with no TAI met multiple organ failure risk/shock criteria and were resuscitated by a standardized protocol emphasizing volume loading and hemoglobin replacement to maintain systemic oxygen delivery index (Do 2 I) ≥ 600 mL O 2 /min-m 2 for the first 24 intensive care unit hours. For TAI patients, postoperative management included intravenous nitroprusside infusion titrated by the bedside nurse to maintain mean arterial pressure (MAP) less than 90 mm Hg during the same 24 hours. Data were obtained prospectively during resuscitation. Retrospectively, the resuscitation response of TAI and non-TAI patients was compared. Results: For the TAI group, nitroprusside effectively controlled MAP (range, 77-87 mm Hg); for the non-TAI group, mean MAP exceeded 95 mm Hg within 5 hours. During the first 8 hours, MAP, pulmonary capillary wedge pressure, and systemic vascular resistance index were less, and Do 2 I was greater for the TAI than for the non-TAI group. The resuscitation goal of Do 2 I ≥ 600 mL O 2 / min-m 2 was attained at 4 hours for the TAI group, and was attained at 12 hours for the non-TAI group. No revisions of aortic repairs were required during or as a result of resuscitation. Conclusion: During aggressive shock resuscitation, control of MAP using nitroprusside is feasible and is associated with a favorable resuscitation response. Nitroprusside may be a useful adjunct during shock resuscitation of MTT as a vasoactive agent that promotes peripheral tissue perfusion.

Background: Near infrared (NIR) spectrometry offers a noninvasive monitor of tissue hemoglobin O 2 saturation and has been developed to report a quantitative clinical variable, Sto 2 [= HbO 2 /(HbO 2 + Hb)]. In this study, a prototype NIR oximeter was used to investigate the hypothesis that changes in systemic O 2 delivery index (Do 2 I) would be reflected by changes in Sto 2 in skeletal muscle, subcutaneous tissue, or both, as reperfusion occurs during shock resuscitation. Sto 2 was also compared with other indices of severity of shock or adequacy of resuscitation, including arterial base deficit, lactate, gastric mucosal Pco 2 (Pgco 2 ), and mixed venous hemoglobin O 2 saturation (Svo 2 ). Methods: Skeletal muscle and subcutaneous tissue Sto 2 were monitored simultaneously in eight severely injured trauma patients (88% blunt mechanism; age, 42 ± 6 years; Injury Severity Score, 27 ± 3) during standardized shock resuscitation in the intensive care unit with the primary goal of Do 2 I ≥ 600 mL O 2 /min/m 2 for 24 hours, and for an additional 12 hours during transition from resuscitation to standard intensive care unit care. Results: Skeletal muscle Sto 2 increased significantly from 15 ± 2% (mean ± SEM) at the start of resuscitation to 49 ± 14% at 24 hours, and to ∼55% from 25 to 36 hours. Subcutaneous tissue Sto 2 ∼ 82% and was significantly greater than skeletal muscle Sto 2 throughout. Do 2 I increased significantly from 372 ± 54 to 718 ± 47 mL O 2 /min/m 2 during resuscitation. Over 36 hours, mean Do 2 I and skeletal muscle Sto 2 were highly correlated (r = 0.95). Neither Do 2 I-Pgco 2 nor Do 2 I-Svo 2 were significantly correlated; neither Svo 2 nor subcutaneous tissue Sto 2 changed significantly. Conclusion: Hemoglobin O 2 saturation was monitored non-invasively and simultaneously in skeletal muscle and subcutaneous tissues as Sto 2 (%) by using a prototype NIR oximeter. Skeletal muscle Sto 2 tracked systemic O 2 delivery during and after resuscitation. As a rapidly deployable, noninvasive monitor of peripheral tissue oxygenation and O 2 delivery, skeletal muscle Sto 2 obtained using NIR spectrometry would be useful to guide resuscitation in the intensive care unit, to monitor resuscitation status in the operating room, and, potentially, in combination with indicators such as base deficit and lactate, to detect shock during initial assessment of the severe trauma patient in the emergency department.

To monitor PO2, PCO2, and pH in the interstitium of skeletal muscle (PmO2, PmCO2, and pHm) during hemorrhage, shock, and resuscitation using fiber-optic sensors and to compare Pco2 and pH in the interstitium of gastric mucosa (PrCO2 and pHi) obtained using gastric CO2 tonometry.Prospective, controlled observational study in an acute experimental preparation.Physiology laboratory in a university medical school.Nine mongrel dogs (20 to 35 kg).Anesthesia was induced with pentobarbital (25 mg/kg iv) and maintained (10 mg/hr) after hemorrhagic shock. Mechanical ventilation was established to maintain baseline PaCO2 approximately 35 torr. Arterial, venous, and pulmonary artery catheters were placed. Blood flow probes were placed around the right femoral artery and vein. A probe (0.5 mm in diameter) with fiber-optic PO2, PCO2, and pH sensors was placed percutaneously in the adductor muscle of the right thigh. A gastric tonometer catheter was placed in the stomach lumen. After baseline data collection, controlled hemorrhage to mean arterial pressure (MAP) of 45 to 50 mm Hg was maintained for 1 hr. Shed blood was then reinfused. Blood gas, hemodynamic, and gastric tonometric data were collected during shock and reinfusion at 30-min intervals and hourly after reinfusion for 4 hrs. Normothermia was maintained.PmO2 decreased rapidly from 42 +/- 13 torr (mean +/- sD) to 13 +/- 9 torr within 15 mins and to 6 +/-4 torr within 30 mins of MAP reaching 45 mm Hg, and it recovered to baseline with reinfusion. pHm decreased gradually from 7.23 +/-0.09 to 6.89 +/- 0.25 during the 1-hr shock period and increased slowly toward baseline after reinfusion. pHi decreased from 7.43 +/- 0.14 to 6.91 +/- 0.23, and on average it returned to baseline 2 hrs after reinfusion. PmCO2 increased from 50 +/- 12 to 113 +/- 49 torr, increased further to 124 +/- 73 torr during reinfusion, and returned slowly toward baseline after reinfusion. PrCO2 increased from 35 +/- 8 to 60 +/- 19 torr and returned to baseline within 15 mins after reinfusion. During shock and reinfusion, oxygen delivery, mixed venous PO2, mixed venous oxygen saturation, and PmO2 responded with similar time courses. After reinfusion, on average, PmO2 exceeded baseline PmO2 and mixed venous PO2, and oxygen availability exceeded demand, suggesting an oxygen consumption defect. On average, PmCO2 and pHm did not return to baseline values 4 hrs after reinfusion, suggesting the persistence of anaerobic metabolic effects in skeletal muscle beyond the relatively short time that is required to reestablish baseline MAP, blood flow rates, oxygen delivery, PrCO2, and pHi.PmO2, PmCO2, and pHm, monitored simultaneously using fiber-optic sensors in a single, small probe placed percutaneously, appear to indicate greater severity of shock and more prolonged resuscitation than conventional systemic or gastric tonometric variables.

Objective: To test a standardized protocol for management of intracranial pressure (ICP) after severe head injury (i.e., traumatic brain injury), consistent with published guidelines. Methods : We compared prospective use of a standardized protocol for ICP management in 12 patients with severe head injuries and retrospective ICP management using preprinted hospital orders in combination with ad hoc physician orders in 12 historical control patients with severe head injuries. With the standardized protocol, flow-chart decision logic diagrams were applied at patient bedside by critical care practitioners, with nursing shift review. Results: ICP and its variation during the first 6 intensive care unit days was less for the standardized protocol- than for the preprinted order-managed group (p

Purpose: The purpose of this study was to test the performance of a patient attached, on demand ex vivo arterial blood gas (ABG) monitor, and to compare the frequency of ABG analysis using the monitor, where the monitor was operated by intensive care unit (ICU) staff on shock trauma and neurosurgical intensive care patients for s6 days, with standard clinical laboratory analysis. Materials and Methods: The ABG monitor (SensiCath; Optical Sensors Inc., Minneapolis, MN) incorporates fiber optic pH, Pco2, Po2 and thermistor temperature sensors in a 0.3-mL sensor chamber that attaches in line with the patient's arterial pressure tubing and connects via a fiberoptic cable to a bedside instrument. The monitor and standard clinical laboratory performance were compared following an institutionally approved protocol. Adult ICU patients (n = 30) were studied for whom an arterial cannula was required, the expected ICU stay was >72 hours, ≥2 ABG analyses/day were anticipated, and informed consent had been obtained. Paired comparison ABG analyses and quality assurance checks were performed daily. The frequency of ABG analyses in this study, for which monitor values were used for clinical decision making, was compared with the frequency previously reported for the same ICUs, for which the monitor and laboratory results were compared but only the latter were used for clinical decision making. Results: Five hundred ABG analyses, 436 over the first 72 hours, were obtained using the monitor for patient management over 3,248 patient hours (85 ± 47 hours/ patient). Monitor-laboratory comparison ABG analyses (n = 258) indicated stable performance over 6 days: For pH, the range of laboratory measurements was 7.200 to 7.540, accuracy (mean difference between monitor and laboratory measurement) was +0.013, and precision (standard deviation of difference between monitor and laboratory measurements) was ±0.031. For Pco2, range: 18 to 78.5, accuracy: −0.8, precision: ±3.4 mm Hg. For P02, range: 41.0 to 344.0, accuracy: +2.3, precision: ±12.8 mm Hg. The frequency of ABG analyses obtained using the monitor (ie, 15.0 ± 11.6 ABGs/patient/72 hours) was significantly greater than that using the clinical laboratory (ie, 8.8 ± 4.2 ABGs/patient/72 hours) (P = .01). Conclusion: The ABG monitor provides performance comparable to standard clinical laboratory analysis for ≤6 days (≤144 hours), consistent with ICU arterial cannula changeout schedules. More frequent ABG analyses are obtained by critical care practitioners using the monitor compared with the clinical laboratory system, suggesting that clinical decision making based on ABG data may be limited by the frequency of ABG analysis.

A system to provide surveillance, diagnosis, and protocolized management of surgical intensive care unit (SICU) sepsis was undertaken as a performance improvement project. A system for sepsis management was implemented for SICU patients using paper followed by a computerized system. The hypothesis was that the computerized system would be associated with improved process and outcomes.A system was designed to provide early recognition and guide patient-specific management of sepsis including (1) modified early warning signs-sepsis recognition score (MEWS-SRS; summative point score of ranges of vital signs, mental status, white blood cell count; after every 4 hours) by bedside nurse; (2) suspected site assessment (vascular access, lung, abdomen, urinary tract, soft tissue, other) at bedside by physician or extender; (3) sepsis management protocol (replicable, point-of-care decisions) at bedside by nurse, physician, and extender. The system was implemented first using paper and then a computerized system. Sepsis severity was defined using standard criteria.In January to May 2012, a paper system was used to manage 77 consecutive sepsis encounters (3.9 ± 0.5 cases per week) in 65 patients (77% male; age, 53 ± 2 years). In June to December 2012, a computerized system was used to manage 132 consecutive sepsis encounters (4.4 ± 0.4 cases per week) in 119 patients (63% male; age, 58 ± 2 years). MEWS-SRS elicited 683 site assessments, and 201 had sepsis diagnosis and protocol management. The predominant site of infection was abdomen (paper, 58%; computer, 53%). Recognition of early sepsis tended to occur more using the computerized system (paper, 23%; computer, 35%). Hospital mortality rate for surgical ICU sepsis (paper, 20%; computer, 14%) was less with the computerized system.A computerized sepsis management system improves care process and outcome. Early sepsis is recognized and managed with greater frequency compared with severe sepsis or septic shock. The system has a beneficial effect as a clinical standard of care for SICU patients.Therapeutic study, level III.

We recently proffered that a new syndrome persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has replaced late multiple-organ failure as a predominant phenotype of chronic critical illness. Our goal was to validate this by determining whether severely injured trauma patients with complicated outcomes have evidence of PICS at the genomic level.We performed a secondary analysis of the Inflammation and Host Response to Injury database of adults with severe blunt trauma. Patients were classified into complicated, intermediate, and uncomplicated clinical trajectories. Existing genomic microarray data were compared between cohorts using Ingenuity Pathways Analysis. Epidemiologic data and outcomes were also analyzed between cohorts on admission, Day 7, and Day 14.Complicated patients were older, were sicker, and required increased ventilator days compared with the intermediate/uncomplicated patients. They also had persistent leukocytosis as well as low lymphocyte and albumin levels compared with uncomplicated patients. Total white blood cell leukocyte analysis in complicated patients showed that overall genome-wide expression patterns and those patterns on Days 7 and 14 were more aberrant from control subjects than were patterns from uncomplicated patients. Complicated patients also had significant down-regulation of adaptive immunity and up-regulation of inflammatory genes on Days 7 and 14 (vs. magnitude in fold change compared with control and in magnitude compared with uncomplicated patients). On Day 7, complicated patients had significant changes in functional pathways involved in the suppression of myeloid cell differentiation, increased inflammation, decreased chemotaxis, and defective innate immunity compared with uncomplicated patients and controls. Subset analysis of monocyte, neutrophil, and T-cells supported these findings.Genomic analysis of patients with complicated clinical outcomes exhibit persistent genomic expression changes consistent with defects in the adaptive immune response and increased inflammation. Clinical data showed persistent inflammation, immunosuppression, and protein depletion. Overall, the data support the hypothesis that patients with complicated clinical outcomes are exhibiting PICS.Epidemiologic study, level III.

Purpose : The purpose of this study was to test the analytical performance of a new ex vivo arterial blood gas (ABG) monitor based on fiberoptic sensor technology (SensiCath; Optical Sensors, Inc., Minneapolis, MN) when operated by critical care practitioners in intensive care environments. Materials and Methods : Arterial blood analyses using a new ex vivo ABG monitor and standard clinical laboratory bench top analyzers were compared according to an institutionally approved protocol. The subjects were adult intensive care unit (ICU) patients (n = 20) with an arterial cannula for pressure monitoring, expectation of ICU stay >72 hours, need for ≥2 ABG analyses per day, and written informed consent. The clinical setting was two ICUs, a shock trauma ICU, and a neurological ICU in a metropolitan area trauma center. Results : One hundred seventy-five paired ABG analyses were obtained over 1,146 hours of monitor use (52 ± 20 hours per patient). Comparison of ABG monitor and laboratory analyses of blood samples obtained at the time of measurement by the monitor provided the following results: For pH, the range of laboratory measurements was 7.197 – 7.512, accuracy (mean difference between the monitor and laboratory measurement) was +0.010, precision (standard deviation of the difference between monitor and laboratory measurements) was ±0.027, and the correlation coefficient (r) = 0.913. For P CO 2, the range of laboratory measurements was 24.5–61.5 mm Hg, accuracy was +1.4 mm Hg, precision was ±3.3 mm Hg, and r = 0.942. For P O 2, the range of laboratory measurements was 47.3 – 163.3 mm Hg, accuracy was +4.0 mm Hg, precision was ±7.9 mm Hg, and r = 0.970. No adverse events occurred associated with the monitor. Conclusion : A practical ex vivo ABG monitor has been developed that offers accurate data and potential advantages to the critical care practitioner and the critically ill patient over other ABG analysis systems: one 10-minute calibration procedure; 1-minute analysis time; no permanent blood removal from the patient; and a closed arterial monitoring system. Precision performance is comparable to standard laboratory ABG analysis. The ABG monitor offers reliability and ease of use, and the ability of the critical care practitioner (nurse, respiratory therapist, or physician) to obtain accurate ABG analyses as needed at bedside.

Care of sepsis has been the focus of intense research and guideline development for more than two decades. With ongoing success of computer protocol (CP) technology and with publication of Surviving Sepsis Campaign (SSC) guidelines, we undertook protocol development for management of sepsis of surgical intensive care unit patients in mid-2006.A sepsis protocol was developed and implemented in The Methodist Hospital (TMH) (Houston, TX) surgical intensive care unit (27 beds) together with a sepsis research database. We compare paper-protocol (PP) (2008) and CP (2009) performance and results of the SSC guideline performance improvement initiative (2005-2008). TMH surgical intensive care unit sepsis protocol was developed to implement best evidence and to standardize decision making among surgical intensivists, nurse practitioners, and resident physicians.The 2008 and 2009 sepsis protocol cohorts had very similar number of patients, age, % male gender, Acute Physiology and Chronic Health Evaluation scoring system II, and Sequential Organ Failure Assessment scores. The 2008 PP patients had greater baseline lactate concentration consistent with greater mortality rate. Antibiotic agents were administered to 2009 CP cohort patients sooner than 2008 PP cohort patients. Both cohorts received similar volume of intravenous fluid boluses. Comparing 6-hour resuscitation bundle compliance, the 2009 CP cohort was substantially greater than SSC eighth quarter and 2008 PP cohorts (79% vs. 31% vs. 29%), and mortality rate was much less when using the CP (14% vs. 31% vs. 24%).Our comprehensive sepsis protocol has enabled rapid and consistent implementation of evidence-based care, and, implemented as a bedside CP, contributed to decreased mortality rate for management of surgical sepsis.

B-type natriuretic peptide (BNP) is secreted in response to myocardial stretch and has been used clinically to assess volume overload and predict death in congestive heart failure. More recently, BNP elevation has been demonstrated with septic shock and is predictive of death. How BNP levels relate to cardiac function in sepsis remains to be established.Retrospective review of prospectively gathered sepsis database from a surgical ICU in a tertiary academic hospital. Initial BNP levels, patient demographics, baseline central venous pressure levels, and in-hospital mortality were obtained. Transthoracic echocardiography was performed during initial resuscitation per protocol.During 24 months ending in September 2009, two hundred and thirty-one patients (59 ± 3 years of age, 43% male) were treated for sepsis. Baseline BNP increased with initial sepsis severity (ie, sepsis vs severe sepsis vs septic shock, by ANOVA; p0.05) and was higher in those who died vs those who lived (by Fisher's exact test; p0.05). Of these patients, 153 (66%) had early echocardiography. Low ejection fraction (50%) was associated with higher BNP (by Fisher's exact test; p0.05) and patients with low ejection fraction had a higher mortality (39% vs 20%; odds ratio = 3.03). We found no correlation between baseline central venous pressure (12.7 ± 6.10 mmHg) and BNP (526.5 ± 82.10 pg/mL) (by Spearman's ρ, R(s) = .001) for the entire sepsis population.In surgical sepsis patients, BNP increases with sepsis severity and is associated with early systolic dysfunction, which in turn is associated with death. Monitoring BNP in early sepsis to identify occult systolic dysfunction might prompt earlier use of inotropic agents.

Clinical laboratory diagnostic capabilities are needed to guide health and medical care of astronauts during long-duration space missions. Clinical laboratory diagnostics, as defined for medical care on Earth, offers a model for space capabilities. Interpretation of laboratory results for health and medical care of humans in space requires knowledge of specific physiological adaptations that occur, primarily because of the absence of gravity, and how these adaptations affect reference values. Limited data from American and Russian missions have indicated shifts of intra- and extracellular fluids and electrolytes, changes in hormone concentrations related to fluid shifts and stresses of the missions, reductions in bone and muscle mass, and a blunting of the cellular immune response. These changes could increase susceptibility to space-related illness or injury during a mission and after return to Earth. We review physiological adaptations and the risk of medical problems that occur during space missions. We describe the need for laboratory diagnostics as a part of health and medical care in space, and how this capability might be delivered.

An experimental clinical chemistry analyzer system was designed and built to demonstrate the feasibility of clinical chemistry as part of a medical-care system at NASA's planned space station Freedom. We report the performance of the experimental analyzer, called a medical development unit (MDU), for selected analytes in a laboratory setting in preparation for a preliminary clinical trial at patients' bedsides in an intensive-care unit. Within-run CVs ranged from 0.7% for sodium to 7.1% for phosphorus; day-to-day CVs ranged from 1.0% for chloride to 23.4% for calcium. Correlation of patients' blood sample analyses compared well with those by Ektachem E700 and other high-volume central laboratory analyzers (r ranged from 0.933 for creatine kinase MB isoenzyme to 0.997 for potassium), except for hemoglobin (r = 0.901) and calcium (r = 0.823). Although several CVs obtained in this study exceeded theoretical desired precision limits based on biological variations, performance was adequate for clinical laboratory diagnosis. We examined the effect of potentially interfering concentrations of hemoglobin, bilirubin, and lipids: the only effect was negative interference with calcium analyses by high concentrations of bilirubin. We also examined the effects of preanalytical variables and the performance of experimental sample-transfer cups designed to retain sample and reference liquid in microgravity. Continued development of the MDU system is recommended, especially automation of sample processing.

The management of surgical sepsis is challenging because of the complexity of interventions. The authors therefore created a computerized clinical decision support program to facilitate this process, with the goal of improving abdominal sepsis mortality.The authors evaluated a prospective database for all patients requiring surgery for abdominal sepsis. Patient demographics, Acute Physiology and Chronic Health Evaluation II score, sepsis source, and hospital mortality data were obtained. Observed mortality was compared with predicted mortality using Fisher's exact test.Eighty-seven patients met the inclusion criteria. The average age was 59 ± 17.0 years, and 39% were men. The most common source of infection was the colon (45%). The average Acute Physiology and Chronic Health Evaluation II score was 27.6 ± 9.72. The overall actual mortality rate for the cohort was 24% compared with a predicted Acute Physiology and Chronic Health Evaluation II mortality of 62.5% (P.0001).The use of computerized clinical decision support results in significantly improved survival in patients with intra-abdominal surgical sepsis.

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.

Severely bleeding trauma patients requiring massive transfusion (MT) often experience poor outcomes. Our purpose was to determine the potential role of near infrared spectrometry derived tissue hemoglobin oxygen saturation (StO2) monitoring in early prediction of MT, and in the identification of those MT patients who will have poor outcomes.Data from a prospective multi-institution StO2 monitoring study were analyzed to determine the current epidemiology of MT (defined as transfusion volume/=10 units packed red blood cells in 24 hours of hospitalization). Multivariate logistic regression was used to develop prediction models.Seven US level I trauma centers (TC) enrolled 383 patients. 114 (30%) required MT. MT progressed rapidly (40% exceeded MT threshold 2 hours after TC arrival, 80% after 6 hours). One third of MT patients died. Two thirds of deaths were due to early exsanguination and two thirds of early exsanguination patients died within 6 hours. One third of the early MT survivors developed multiple organ dysfunction syndrome. MT could be predicted with standard, readily available clinical data within 30 minutes and 60 minutes of TC arrival (area under the receiver operating characteristic curve = 0.78 and 0.80). In patients who required MT, StO2 was the only consistent predictor of poor outcome (multiple organ dysfunction syndrome or death).MT progresses rapidly to significant morbidity and mortality despite level I TC care. Patients who require MT can be predicted early, and persistent low StO2 identifies those MT patients destined to have poor outcome. The ultimate goal is to identify these high risk patients as early as possible to test new strategies to improve outcome. Further validation studies are needed to analyze appropriate allocation and study appropriate use of damage control interventions.

Faced with a documented crisis of patients not receiving appropriate care, there is a need to implement and refine evidence-based guidelines (EBGs) to ensure that patients receive the best care available. Although valuable in content, among their deficiencies, EBGs do not provide explicit methods to bring proven therapies to the bedside. Computerized information technology, now an integral part of the US healthcare system at all levels, presents clinicians with information from laboratory, imaging, physiologic monitoring systems, and many other sources. It is imperative that we clinicians use this information technology to improve medical care and efficacy of its delivery. If we do not do this, nonclinicians will use this technology to tell us how to practice medicine. Computerized clinical decision support (CCDS) offers a powerful method to use this information and implement a broad range of EBGs. CCDS is a technology that can be used to develop, implement, and refine computerized protocols for specific processes of care derived from EBGs, including complex care provided in intensive care units. We describe this technology as a desirable option for the trauma community to use information technology and maintain the trauma surgeon/intensivist's essential role in specifying and implementing best care for patients. We describe a process of logical protocol development based on standardized clinical decision making to enable EBGs. The resulting logical process is readily computerized, and, when properly implemented, provides a stable platform for systematic review and study of the process and interventions.: CCDS to implement and refine EBG derived computerized protocols offers a method to decrease variability, test interventions, and validate improved quality of care.

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.

Feeding the hemodynamically unstable patient is increasingly practiced, yet few data exist on its safety. Because enteral glutamine is protective to the gut in experimental models of shock and improves clinical outcomes, it may benefit trauma patients undergoing shock resuscitation and improve tolerance if administered early. This pilot study aimed to evaluate gastrointestinal tolerance and safety of enteral feeding with glutamine, beginning during shock resuscitation in severely injured patients.In a prospective randomized trial, 20 patients were randomly assigned to either an enteral glutamine group (n = 10) or a control group (n = 10). Patients with severe trauma meeting standardized shock resuscitation criteria received enteral glutamine 0.5 g/kg/d during the first 24 hours of resuscitation and 10 days thereafter. Immune-enhancing diet began on postinjury day 1, with a target of 25 kcal/kg/d. Control patients received isonitrogenous whey powder plus immune-enhancing diet. Tolerance (vomiting, nasogastric output, diarrhea, and distention) was assessed throughout the study.Glutamine was well tolerated and no adverse events occurred. Treated patients had significantly fewer instances of high nasogastric output (5 vs 23; p = .010), abdominal distention (3 vs 12; p = .021), and total instances of intolerance (8 vs 42; p = .011). Intensive care unit (ICU) and hospital length of stay were comparable. Control patients required supplemental parenteral nutrition (PN) to meet goals at day 7.Enteral glutamine administered during active shock resuscitation and through the early postinjury period is safe and enhances gastrointestinal tolerance. A large clinical trial is warranted to determine if enteral glutamine administered to the hemodynamically unstable patient can reduce infectious morbidity and mortality.

Near-infrared spectroscopy (NIRS) can continuously and noninvasively monitor tissue oxygen saturation (StO2) in muscle and may be an indicator of shock severity. Our purpose was to evaluate how well StO2 predicted outcome in high-risk torso trauma patients presenting in shock.The primary outcome in this prospective study was multiple organ dysfunction syndrome (MODS). StO2 data were obtained upon hospital arrival and for 24 hours along with other known predictors of hypoperfusion and clinical outcomes. Clinicians were blinded to StO2 measurements.Seven Level I trauma centers enrolled 383 patients, 50 of whom developed MODS. Minimum StO2 performed similarly to maximum base deficit (BD) in discrimination of MODS patients. The sensitivity for both measures (StO2 cutoff = 75%; BD cutoff = 6 mEq/L) was 78%, the specificity was 34% to 39%, the positive predictive value was 18% to 20% and the negative predictive value was 88% to 91%. StO2 and BD were also comparable in predicting death.NIRS-derived muscle StO2 measurements perform similarly to BD in identifying poor perfusion and predicting the development of MODS or death after severe torso trauma, yet have the additional advantages of being continuous and noninvasive.

Monitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for the future of medicine. Patients with injuries severe enough to develop multiple organ dysfunction syndrome have multiple immune derangements, including T cell apoptosis and anergy combined with depressed monocyte antigen presentation. Genome-wide expression analysis of highly enriched circulating leukocyte subpopulations, combined with cell-specific pathway analyses, offers an opportunity to discover leukocyte regulatory networks in critically injured patients. Severe injury induced significant changes in T cell (5,693 genes), monocyte (2,801 genes), and total leukocyte (3,437 genes) transcriptomes, with only 911 of these genes common to all three cell populations (12%). T cell-specific pathway analyses identified increased gene expression of several inhibitory receptors (PD-1, CD152, NRP-1, and Lag3) and concomitant decreases in stimulatory receptors (CD28, CD4, and IL-2Rα). Functional analysis of T cells and monocytes confirmed reduced T cell proliferation and increased cell surface expression of negative signaling receptors paired with decreased monocyte costimulation ligands. Thus, genome-wide expression from highly enriched cell populations combined with knowledge-based pathway analyses leads to the identification of regulatory networks differentially expressed in injured patients. Importantly, application of cell separation, genome-wide expression, and cell-specific pathway analyses can be used to discover pathway alterations in human disease.

Although human plasma represents an attractive sample for disease biomarker discovery, the extreme complexity and large dynamic range in protein concentrations present significant challenges for characterization, candidate biomarker discovery, and validation. Herein we describe a strategy that combines immunoaffinity subtraction and subsequent chemical fractionation based on cysteinyl peptide and N-glycopeptide captures with two-dimensional LC-MS/MS to increase the dynamic range of analysis for plasma. Application of this "divide-and-conquer" strategy to trauma patient plasma significantly improved the overall dynamic range of detection and resulted in confident identification of 22,267 unique peptides from four different peptide populations (cysteinyl peptides, non-cysteinyl peptides, N-glycopeptides, and non-glycopeptides) that covered 3,654 different proteins with 1,494 proteins identified by multiple peptides. Numerous low abundance proteins were identified, exemplified by 78 "classic" cytokines and cytokine receptors and by 136 human cell differentiation molecules. Additionally a total of 2,910 different N-glycopeptides that correspond to 662 N-glycoproteins and 1,553 N-glycosylation sites were identified. A panel of the proteins identified in this study is known to be involved in inflammation and immune responses. This study established an extensive reference protein database for trauma patients that provides a foundation for future high throughput quantitative plasma proteomic studies designed to elucidate the mechanisms that underlie systemic inflammatory responses.

Resuscitation of the severely injured patient who presents in shock has improved greatly, following focused wartime experience and insight from laboratory and clinical studies. Further benefit is probable from technologies that are being brought into clinical use, especially hypertonic saline dextran, haemoglobin-based oxygen carriers, less invasive early monitors, and medical informatics. These technologies could improve the potential of prehospital and early hospital care to pre-empt or more rapidly reverse hypoxaemia, hypovolaemia, and onset of shock. Damage control surgery and definitive interventional radiology will probably combine with more real-time detection and intervention for hypothermia, coagulopathy, and acidosis, to avoid extreme pathophysiology and the "bloody vicious cycle". Although now widely practised as standard of care in the USA and Europe, shock resuscitation strategies involving haemoglobin replacement and fluid volume loading to regain tissue perfusion and oxygenation vary between trauma centres. One of the difficulties is the scarcity of published evidence for or against seemingly basic intervention strategies, such as early or large-volume fluid loading. Standardised protocols for resuscitation, representing the best and most current knowledge of the clinical process, could be devised and widely implemented as interactive computerised applications among trauma centres in the USA and Europe. Prevention of injury is preferable and feasible, but early care of the severely injured patient and modulation of exaggerated systemic inflammatory response due to transfusion and other complications of traditional strategies will probably provide the next generation of improvements in shock resuscitation.

Preload-directed resuscitation is the standard of care in U.S. trauma centers. As part of our standardized protocol for traumatic shock resuscitation, patients who do not respond to initial interventions of hemoglobin replacement and fluid volume loading have optimal preload determined using a standardized algorithm to generate a "Starling curve." We retrospectively analyzed data from 147 consecutive resuscitation protocol patients during the 24 months ending August 2002. Fifty (34%) of these patients required preload optimization, of which the optimization algorithm was completed in 36 (72%). The average age of those who required preload optimization was 44 +/- 3 years vs. 34 +/- 1 years for patients who did not. Execution of the algorithm caused PCWP to increase from 18 +/- 1 mmHg to a maximum of 25 +/- 2 mmHg and CI to increase from 3.2 +/- 0.1 L/min m(-2) to 4.5 +/- 0.4 L/min m(-2). Algorithm logic determined PCWP = 24 +/- 2 to be optimal preload at the maximum CI = 4.8 +/- 0.4, and as the volume loading threshold for the remaining time of the resuscitation process. Starling curve preload optimization was begun 6.5 +/- 0.8 h after start of the resuscitation protocol and required 36 +/- 5 min and 4 +/- 0.4 fluid boluses (1.6 +/- 0.2 L). Comparison of early response of those patients who required preload optimization and those who did not indicated hemodynamic compromise apparent in the 1st 4 h of standardized resuscitation. We conclude that preload optimization using sequential fluid bolus and PCWP-CI measurement to generate a Starling curve is feasible during ICU shock resuscitation, but that there is the disadvantage that increasing and maintaining high PCWP may contribute to problematic tissue edema.

Shock resuscitation is an obligatory intervention for severely injured patients who present in shock. During the past 15 years, with widespread acceptance of "damage control" surgery and early triage to the intensive care unit (ICU) to optimize resuscitation, the lives of many major trauma victims have been saved, and much has been learned about shock resuscitation. Due largely to the work of Shoemaker et al., a resuscitation strategy based on a standardized process using O(2) delivery index (DO(2)I) as an endpoint and physiologic performance goal for interventions has been developed, studied, and refined for resuscitation of shock caused by major trauma. DO(2)Ior=600 mL O(2)/min-m2 is the only resuscitation endpoint variable that has been tested in prospective randomized trials (PRTs) of trauma patient outcome. These PRTs are limited, and their results are not conclusive. Results from other investigators, including our group, using similar process and endpoints, are indicating similar performance and outcomes. We believe that DO(2)I is a useful endpoint because it integrates three important variables, ie, hemoglobin concentration [Hb], arterial hemoglobin O(2) saturation, and cardiac output. We have found DO(2)Ior=500 mL O(2)/min-m2 to be an endpoint with more general applicability, but we believe that the standardized process is more important than the specific endpoint. To standardize our process, we have developed a computerized decision support tool for shock resuscitation. This technology has provided novel data collection and has permitted refinement of the bedside process. Our data analysis indicates that the next challenge will be to develop a similar pre ICU resuscitation process that will use less invasive monitors and different endpoints. Identification of the high-risk resuscitation nonresponders early in the resuscitation process will be needed to redirect their clinical trajectories. As an endpoint for interventions for goal-directed resuscitation in the critically injured trauma patient, systemic O(2) delivery is the current state of the art and the basis for near future development of clinical processes for resuscitation of shock due to major trauma.

Primary abdominal compartment syndrome (ACS) is a known complication of damage control. Recently secondary ACS has been reported in patients without abdominal injury who require aggressive resuscitation. The purpose of this study was to compare the epidemiology of primary and secondary ACS and develop early prediction models in a high-risk cohort who were treated in a similar fashion.Major torso trauma patients underwent standardized resuscitation and had prospective data collected including occurrence of ACS, demographics, ISS, urinary bladder pressure, gastric tonometry (GAP(CO2) = gastric regional CO(2) minus end tidal CO(2)), laboratory, respiratory, and hemodynamic data. With primary and secondary ACS as endpoints, variables were tested by uni- and multivariate logistic analysis (MLA).From 188 study patients during the 44-month period, 26 (14%) developed ACS-11 (6%) were primary ACS and 15 (8%) secondary ACS. Primary and secondary ACS had similar demographics, shock, and injury severity. Significant univariate differences included: time to decompression from ICU admit (600 +/- 112 vs. 360 +/- 48 min), Emergency Department (ED) crystalloid (4 +/- 1 vs. 7 +/- 1 L), preICU crystalloid (8 +/- 1 vs. 12 +/- 1L), ED blood administration (2 +/- 1 vs. 6 +/- 1 U), GAP(CO2) (24 +/- 3 vs. 36 +/- 3 mmHg), requiring pelvic embolization (9 vs. 47%), and emergency operation (82% vs. 40%). Early predictors identified by MLA of primary ACS included hemoglobin concentration, GAP(CO2), temperature, and base deficit; and for secondary ACS they included crystalloid, urinary output, and GAP(CO2). The areas under the receiver-operator characteristic curves calculated upon ICU admission are primary= 0.977 and secondary= 0.983. Primary and secondary ACS patients had similar poor outcomes compared with nonACS patients including ventilator days (primary= 13 +/- 3 vs. secondary= 14 +/- 3 vs. nonACS = 8 +/- 2), multiple organ failure (55% vs. 53% vs. 12%), and mortality (64% vs. 53% vs. 17%).Primary and secondary ACS have similar demographics, injury severity, time to decompression from hospital admit, and bad outcome. 2 degrees ACS is an earlier ICU event preceded by more crystalloid administration. With appropriate monitoring both could be accurately predicted upon ICU admission.

Background The term secondary abdominal compartment syndrome (ACS) has been applied to describe trauma patients who develop ACS but do not have abdominal injuries. The purpose of this study was to describe major trauma victims who developed secondary ACS during standardized shock resuscitation. Methods Our prospective database for standardized shock resuscitation was reviewed to obtain before and after abdominal decompression shock related data for secondary ACS patients. Focused chart review was done to confirm time-related outcomes. Results Over the 30 months period ending May 2001, 11 (9%) of 128 standardized shock resuscitation patients developed secondary ACS. All presented in severe shock (systolic blood pressure 85 ± 5 mm Hg, base deficit 8.6 ± 1.6 mEq/L), with severe injuries (injury severity score 28 ± 3) and required aggressive shock resuscitation (26 ± 2 units of blood, 38 ± 3 L crystalloid within 24 hours). All cases of secondary ACS were recognized and decompressed within 24 hours of hospital admission. After decompression, the bladder pressure and the systemic vascular resistance decreased, while the mean arterial pressure, cardiac index, and static lung compliance increased. The mortality rate was 54%. Those who died failed to respond to decompression with increased cardiac index and did not maintain decreased bladder pressure. Conclusions: Secondary ACS is an early but, if appropriately monitored, recognizable complication in patients with major nonabdominal trauma who require aggressive resuscitation.

Hypothesis Women respond better to standardized shock resuscitation compared with similarly severely injured men. Design Severely injured patients who met specific criteria were resuscitated using a standardized protocol with no adjustment for gender. The resuscitation protocol was used to attain and to maintain an oxygen delivery index of 600 mL/min · m 2 or greater (DO 2 I ≥600) for the first 24 hours in the intensive care unit (ICU). Interventions, responses, and outcomes for the 2 cohorts were compared. Data were analyzed using analysis of variance, χ 2 , and t tests; P Setting A 20-bed regional level I trauma center ICU. Patients Patients at high risk of postinjury multiple organ failure (major organ or vascular injury and/or skeletal fractures, initial arterial base deficit of 6 mEq/L or greater, requirement for 6 units or more of packed red blood cells in the first 12 hours after hospital admission, or age ≥65 years with any 2 previous criteria). Interventions Pulmonary artery catheter, packed red blood cell transfusion, crystalloid fluid infusion, inotrope, and vasopressor support, as needed, in that sequence, to maintain DO 2 I ≥600. Main Outcome Measures Hemodynamic response to resuscitation, fluid, and packed red blood cell volume. Results During 2000, 58 patients (38 men, 20 women) met criteria and were resuscitated using our standardized protocol. Demographics and outcomes were similar for both cohorts. Requirements for and responses to standardized resuscitation were also similar, except for volume loading. The female cohort required less lactated Ringer solution volume (12 ± 1 vs 8 ± 2 L, P P 2 I goal with average pulmonary capillary wedge pressure that was less than that of the male cohort. Conclusion Review of prospective data from standardized shock resuscitation for female and male cohorts demonstrates that women respond better to standardized resuscitation compared with similarly severely injured men.