A better understanding of why murine models of trauma do not recapitulate the human syndrome.

OBJECTIVE: 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. DESIGN: Preclinical controlled in vivo laboratory study and retrospective cohort study. SETTING: Laboratory of Inflammation Biology and Surgical Science and multi-institution level 1 trauma centers. SUBJECTS: 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 Score > 15) adult (> 18 yr) patients. INTERVENTIONS: Mice underwent one of two severity polytrauma models of injury. Total blood leukocyte and neutrophil samples were collected. MEASUREMENTS AND MAIN RESULTS: Fold expression changes in leukocyte and neutrophil genome-wide expression analyses between healthy and injured mice (p < 0.001) 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. CONCLUSIONS: 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.

Is there value in plasma cytokine measurements in patients with severe trauma and sepsis?

For the past thirty years, since IL-1ß 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.

The epidemiology of sepsis in general surgery patients.

BACKGROUND: 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. METHODS: 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 (p<0.05 significant). RESULTS: 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. CONCLUSION: 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.

Computer protocol facilitates evidence-based care of sepsis in the surgical intensive care unit.

BACKGROUND: 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. METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.

Performance of a computerized protocol for trauma shock resuscitation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Validation of a screening tool for the early identification of sepsis.

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 > or = 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.

Computerized clinical decision support for traumatic shock resuscitation.

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.

Enteral glutamine during active shock resuscitation is safe and enhances tolerance of enteral feeding.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Computerized clinical decision support: a technology to implement and validate evidence based guidelines.

UNLABELLED: 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. CONCLUSION: : CCDS to implement and refine EBG derived computerized protocols offers a method to decrease variability, test interventions, and validate improved quality of care.

A report on associations among gastric pH, bleeding, duodenogastric reflux, and outcomes after trauma.

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.

Massive transfusion in trauma patients: tissue hemoglobin oxygen saturation predicts poor outcome.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

The next generation in shock resuscitation.

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 optimization using "starling curve" generation during shock resuscitation: can it be done?

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.

Abdominal compartment syndrome: the cause or effect of postinjury multiple organ failure.

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.

Standardized trauma resuscitation: female hearts respond better.

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 > or = 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, chi(2), and t tests; P<.05 was considered significant. 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 > or = 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 > or = 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<.05), required less Starling curve intervention (42% vs 15%, P<.05), and maintained the DO(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.

Supranormal trauma resuscitation causes more cases of abdominal compartment syndrome.

HYPOTHESIS: Normal resuscitation (oxygen delivery index [DO2I] >/=500 mL/min per square meter), compared with supranormal trauma resuscitation (DO2I >/=600 mL/min per square meter), requires less crystalloid volume, thus decreasing the incidence of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS). DESIGN: Retrospective analysis of a prospective database. SETTING: Twenty-bed intensive care unit (ICU) in a regional level I trauma center. PATIENTS: Patients with major trauma (injury severity score >15, initial base deficit >/=6 mEq/L, or need for >/=6 units of packed red blood cells in the first 12 hours) or age 65 years or older with any 2 of the previous criteria. INTERVENTIONS: Shock/trauma resuscitation protocol: pulmonary artery catheter, gastric tonometry, urinary bladder pressure measurements, lactated Ringer infusion, packed red blood cell transfusion, and moderate inotrope support, as needed, in that sequence, to attain and maintain a DO2I greater than or equal to 600 mL/min per m2 (16 months, ending January 1, 2001, n = 85) or a DO2I greater than or equal to 500 mL/min per square meter (16 months, starting January 1, 2001, n = 71) for the first 24 hours in the ICU. MAIN OUTCOME MEASURES: Lactated Ringer infusion volume (liters) at ICU admission, gastric partial carbon dioxide minus end-tidal carbon dioxide(GAPCO2), IAH (urinary bladder pressure measurements >20 mm Hg), ACS (urinary bladder pressure measurements >25 mm Hg with organ dysfunction), multiple organ failure, and mortality. RESULTS: Demographics, injury severity, and shock severity parameters were similar in both groups. The supranormal resuscitation group required more lactated Ringer infusion volume in the first 24 hours in the ICU (mean +/- SD, 13 +/- 2 vs 7 +/- 1 L; P<.05) and had higher GAPCO2 (16 +/- 2 vs 7 +/- 1 mm Hg; P<.05). In the supranormal group, IAH (42% vs 20%; P<.05) and ACS (16% vs 8%; P<.05) were more frequent. The conventional trauma outcomes, such as multiple organ failure (22% vs 9%; P<.05) and mortality (27% vs 11%; P<.05) were less favorable in the supranormal resuscitation group. CONCLUSION: Supranormal resuscitation, compared with normal resuscitation, was associated with more lactated Ringer infusion, decreased intestinal perfusion (higher GAPCO2), and an increased incidence of IAH, ACS, multiple organ failure, and death.

Secondary abdominal compartment syndrome is an elusive early complication of traumatic shock resuscitation.

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.

Patients with impending abdominal compartment syndrome do not respond to early volume loading.

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<0.05) and crystalloids (13 +/- 2 versus 4 +/- 0.3 L; P<0.05). As a result, pulmonary capillary wedge pressure increased more in the ACS patients (20 +/- 1.5 versus 15 +/- 0.5 mm Hg; P<0.05), but comparatively the cardiac index did not (3.2 +/- 0.2 versus 4.2 +/- 0.1 L/min/m(2); P<0.05) and the ACS patients developed pathologic elevations of gastric regional CO(2) pressures (70 +/- 7 versus 48 +/- 1 mm Hg P<0.05). CONCLUSIONS: Conventional preload directed resuscitation to enhance cardiac function is not effective in patients with impending ACS, and this traditional resuscitation strategy is detrimental in this subgroup of patients.

Computer versus paper system for recognition and management of sepsis in surgical intensive care.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: Therapeutic study, level III.

Persistent inflammation, immunosuppression, and catabolism syndrome after severe blunt trauma.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: Epidemiologic study, level III.