Bruce A. McKinley

A genomic storm in critically injured humans

Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes.

Both primary and secondary abdominal compartment syndrome can be predicted early and are harbingers of multiple organ failure

BACKGROUND 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. METHODS 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). RESULTS 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%). CONCLUSION 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.

Persistent inflammation and immunosuppression: A common syndrome and new horizon for surgical intensive care

ABSTRACT Surgical intensive care unit (ICU) stay of longer than 10 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 immunologic 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 define the pathobiology of prolonged intensive care. Therapy for PICS will involve innovative interventions for immune system rebalance and nutritional support to regain physical function and well-being.

Vacuum-assisted wound closure provides early fascial reapproximation in trauma patients with open abdomens

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.

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.

Tissue hemoglobin O2 saturation during resuscitation of traumatic shock monitored using near infrared spectrometry.

BACKGROUND Near infrared (NIR) spectrometry offers a noninvasive monitor of tissue hemoglobin O2 saturation and has been developed to report a quantitative clinical variable, StO2 [= HbO2/(HbO2 + Hb)]. In this study, a prototype NIR oximeter was used to investigate the hypothesis that changes in systemic O2 delivery index (D(O2)I) would be reflected by changes in StO2 in skeletal muscle, subcutaneous tissue, or both, as reperfusion occurs during shock resuscitation. StO2 was also compared with other indices of severity of shock or adequacy of resuscitation, including arterial base deficit, lactate, gastric mucosal P(CO2) (PgCO2), and mixed venous hemoglobin O2 saturation (S(VO2)). METHODS Skeletal muscle and subcutaneous tissue StO2 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 D(O2)I > or = 600 mL O2/min/m2 for 24 hours, and for an additional 12 hours during transition from resuscitation to standard intensive care unit care. RESULTS Skeletal muscle StO2 increased significantly from 15 +/- 2% (mean +/- SEM) at the start of resuscitation to 49 +/- 14% at 24 hours, and to approximately 55% from 25 to 36 hours. Subcutaneous tissue StO2 approximately 82% and was significantly greater than skeletal muscle StO2 throughout. D(O2)I increased significantly from 372 +/- 54 to 718 +/- 47 mL O2/min/m2 during resuscitation. Over 36 hours, mean D(O2)I and skeletal muscle StO2 were highly correlated (r = 0.95). Neither D(O2)I-PgCO2 nor D(O2)I-S(VO2) were significantly correlated; neither S(VO2) nor subcutaneous tissue StO2 changed significantly. CONCLUSION Hemoglobin O2 saturation was monitored noninvasively and simultaneously in skeletal muscle and subcutaneous tissues as StO2 (%) by using a prototype NIR oximeter. Skeletal muscle StO2 tracked systemic O2 delivery during and after resuscitation. As a rapidly deployable, noninvasive monitor of peripheral tissue oxygenation and O2 delivery, skeletal muscle StO2 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.

Vacuum-assisted wound closure achieves early fascial closure of open abdomens after severe trauma.

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.

Quantitative proteome analysis of human plasma following in vivo lypopolysaccharide administration using 16O/18O labeling and the accurate mass and time tag approach

Identification of novel diagnostic or therapeutic biomarkers from human blood plasma would benefit significantly from quantitative measurements of the proteome constituents over a range of physiological conditions. Herein we describe an initial demonstration of proteome-wide quantitative analysis of human plasma. The approach utilizes postdigestion trypsin-catalyzed 16O/18O peptide labeling, two-dimensional LC-FTICR mass spectrometry, and the accurate mass and time (AMT) tag strategy to identify and quantify peptides/proteins from complex samples. A peptide accurate mass and LC elution time AMT tag data base was initially generated using MS/MS following extensive multidimensional LC separations to provide the basis for subsequent peptide identifications. The AMT tag data base contains >8,000 putative identified peptides, providing 938 confident plasma protein identifications. The quantitative approach was applied without depletion of high abundance proteins for comparative analyses of plasma samples from an individual prior to and 9 h after lipopolysaccharide (LPS) administration. Accurate quantification of changes in protein abundance was demonstrated by both 1:1 labeling of control plasma and the comparison between the plasma samples following LPS administration. A total of 429 distinct plasma proteins were quantified from the comparative analyses, and the protein abundances for 25 proteins, including several known inflammatory response mediators, were observed to change significantly following LPS administration.

High Dynamic Range Characterization of the Trauma Patient Plasma Proteome

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 3654 different proteins with 1494 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 2910 different N-glycopeptides that correspond to 662 N-glycoproteins and 1553 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.

Nonocclusive bowel necrosis occurring in critically ill trauma patients receiving enteral nutrition manifests no reliable clinical signs for early detection

BACKGROUND Nonocclusive bowel necrosis (NOBN) has been associated with early enteral nutrition (EN). The purpose of this study was to determine the incidence of this complication in our trauma intensive care unit population and to define a typical patient profile vulnerable to NOBN. METHODS Thirteen cases of NOBN were identified among 4,311 patients (0.3%) over a 64-month period ending October 1998. Their charts were analyzed for a variety of clinical data, including prospective EN tolerance data in 4. RESULTS Twelve (92%) patients were enterally fed prior to diagnosis for 10 +/- 8 days (range 3 to 21). Tachycardia (n = 12, 92%); fever/hypothermia, (n = 12, 92%), and an abnormal white blood cell count (n = 11, 85%) were consistently present. Abdominal distention was common but tended to be a late sign (n = 12). Seven (56%) survived. In 4 patients with tolerance data, 3 reached the goal rate of feeds prior to diagnosis. Two became distended at >12 hours from diagnosis. Gastric tonometry demonstrated a decreased NgpHi (<7.30) after starting EN in all 3 in whom it was monitored. CONCLUSIONS NOBN developed in 0.3% of our trauma patients. Onset occurs in the second week in high-acuity patients who have had a period of EN tolerance. Clinical findings resemble bacterial sepsis with tachycardia, fever, and leukocytosis. Gastrointestinal specific signs are not consistent or occur late. Thus, we could not identify an early, useful clinical indicator. Gastric carbon dioxide tonometry may detect a vulnerable subgroup of patients.