Data-Driven Blood Transfusion Thresholds for Severely Injured Patients During Blood Shortages.

INTRODUCTION: Crises like the COVID-19 pandemic create blood product shortages. Patients requiring transfusions are placed at risk and institutions may need to judiciously administer blood during massive blood transfusions protocols (MTP). The purpose of this study is to provide data-driven guidance for the modification of MTP when the blood supply is severely limited. METHODS: This is a retrospective cohort study of 47 Level I and II trauma centers (TC) within a single healthcare system whose patients received MTP from 2017 to 2019. All TC used a unifying MTP protocol for balanced blood product transfusions. The primary outcome was mortality as a function of volume of blood transfused and age. Hemoglobin thresholds and measures of futility were also estimated. Risk-adjusted analyses were performed using multivariable and hierarchical regression to account for confounders and hospital variation. RESULTS: Proposed MTP maximum volume thresholds for three age groupings are as follows: 60 units for ages 16-30 y, 48 units for ages 31-55 y, and 24 units for >55 y. The range of mortality under the transfusion threshold was 30%-36% but doubled to 67-77% when the threshold was exceeded. Hemoglobin concentration differences relative to survival were clinically nonsignificant. Prehospital measures of futility were prehospital cardiac arrest and nonreactive pupils. In hospital risk factors of futility were mid-line shift on brain CT and cardiopulmonary arrest. CONCLUSIONS: Establishing MTP threshold practices under blood shortage conditions, such as the COVID pandemic, could sustain blood availability by following relative thresholds for MTP use according to age groups and key risk factors.

Timing and Type of Venous Thromboembolic Chemoprophylaxis Is Associated with Acute Traumatic Brain Injury Outcomes.

Venous thromboembolic (VTE) prophylaxis in acute traumatic brain injury (TBI) is a controversial topic with wide practice variations. This study examined the association of VTE chemoprophylaxis with inpatient mortality and VTE events among isolated TBI patients. This was a retrospective cohort study of 87 trauma centers within a large hospital system in the United States analyzing 23,548 patients with isolated TBI, 7977 of whom had moderate-to-severe TBI. Primary outcomes were inpatient mortality and VTE events. The control group received no chemoprophylaxis. Other groups received low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), and combined LMWH and UFH chemoprophylaxis. Multi-variable regression accounted for confounders. Outcomes were stratified by timing of administration, body mass index (BMI), and TBI type. Patients without VTE prophylaxis had the least VTE events. LMWH had the lowest mortality for both all-isolated and moderate-to-severe isolated TBI populations at adjusted odds ratio (aOR) 0.24 (95% confidence interval [CI], 0.14-0.43) and aOR 0.25 (95% CI, 0.14-0.44), respectively. Clinically significant progression of TBI was lowest among the LMWH group (0.1%; p value, 0.001). After stratifying by timing of VTE chemoprophylaxis, only patients with subdural hematoma and LMWH between 6 and 24 h (N = 62), as well as patients with ≥35 BMI and LMWH between 6 and 24 h (N = 65) or >24-48 h (N = 54), had no VTE events. VTE chemoprophylaxis timing may have prevented VTE in certain subgroups of isolated TBI patients. Though VTE chemoprophylaxis did not prevent VTE for most TBI patients, LMWH VTE chemoprophylaxis was associated with reduced mortality.

A multicenter study on definitive surgery for isolated hip fracture within 24 hours.

INTRODUCTION: Isolated hip fractures (IHFs) in the elderly are high-frequency, life-altering events. Definitive surgery ≤24 hours of admission is associated with improved outcomes. An IHF process management guideline (IHF-PMG) to expedite definitive surgery ≤24 hours was developed for a multihospital network. We report on its feasibility and subsequent patient outcomes. METHODS: This is a prospective multicenter cohort study, involving 85 levels 1, 2, 3, and 4 trauma centers. Patients with an IHF between 65 and 100 years old were studied. Four cohorts were examined: (1) hospitals that did not implement any PMG, (2) hospitals that used their own PMG, (3) hospitals that partially used the network IHF-PMG, and (4) hospitals that used the network's IHF-PMG. Multivariable logistic regression with reliability adjustment was used to calculate the expected value of observed to expected (O/E) mortality. Statistical significance was defined as p < 0.05. RESULTS: Data on 24,457 IHF were prospectively collected. Following implementation of the IHF-PMG, overall IHF O/E mortality ratios decreased within the hospital network, from 1.13 in 2017 to 0.87 in 2018 and 0.86 in 2019. Hospitals that developed their own IHF-PMG or used the enterprise-wide IHF-PMG had the lowest inpatient O/E mortality at 0.59 and 0.65, respectively. CONCLUSION: Goal-directed IHF-PMG for definitive surgery ≤24 hours was implemented across a large hospital network. The IHF-PMG was associated with lower inpatient mortality. LEVEL OF EVIDENCE: Therapeutic/ Care management, Level III.

Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation.

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

The association of blood component use ratios with the survival of massively transfused trauma patients with and without severe brain injury.

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

Increased transforming growth factor ß contributes to deterioration of refrigerated fresh frozen plasma's effects in vitro on endothelial cells.

Resuscitation with fresh frozen plasma (FFP) is associated with improved outcomes after hemorrhagic shock. Many trauma centers are using thawed plasma that has been stored for up to 5 days at 4°C (refrigeration), yet the effect of refrigeration on FFP is relatively unknown. Previously, our group showed that refrigeration of FFP changed its coagulation factors and diminished its beneficial effects on endothelial cell (EC) function and resuscitation in an animal model of hemorrhagic shock. We hypothesize that growth factor composition of FFP is altered during refrigeration, leading to a diminished beneficial effect on EC. Transforming growth factor (TGF-ß) is a potent inhibitor of EC migration and is released during refrigeration of platelets. We found increased TGF-ß1 protein levels and greater activation of downstream mediators Smad2/3 during refrigeration of FFP. Both day 0 FFP (used on the same day after being thawed) and day 5 FFP (used after being thawed and refrigerated for 5 days) stimulated EC migration in vitro; however, the EC migration in day 5 FFP was significantly reduced. Inhibition of TGF-ß type I receptor blocked FFP-induced Smad3 signaling in EC cells and restored the effectiveness of day 5 FFP on EC migration to a comparable level seen in day 0 FFP. These data suggest that the increased TGF-ß levels during FFP refrigeration contribute to the deterioration of refrigerated FFP's effects on EC migration. This study identifies a novel molecular mechanism contributing to the reduced efficacy of refrigerated FFP.

Defining the limits of resuscitative emergency department thoracotomy: a contemporary Western Trauma Association perspective.

BACKGROUND: Since the promulgation of emergency department (ED) thoracotomy>40 years ago, there has been an ongoing search to define when this heroic resuscitative effort is futile. In this era of health care reform, generation of accurate data is imperative for developing patient care guidelines. The purpose of this prospective multicenter study was to identify injury patterns and physiologic profiles at ED arrival that are compatible with survival. METHODS: Eighteen institutions representing the Western Trauma Association commenced enrollment in January 2003; data were collected prospectively. RESULTS: During the ensuing 6 years, 56 patients survived to hospital discharge. Mean age was 31.3 years (15-64 years), and 93% were male. As expected, survival was predominant in those with thoracic injuries (77%), followed by abdomen (9%), extremity (7%), neck (4%), and head (4%). The most common injury was a ventricular stab wound (30%), followed by a gunshot wound to the lung (16%); 9% of survivors sustained blunt trauma, 34% underwent prehospital cardiopulmonary resuscitation (CPR), and the presenting base deficit was >25 mequiv/L in 18%. Relevant to futile care, there were survivors of blunt torso injuries with CPR up to 9 minutes and penetrating torso wounds up to 15 minutes. Asystole was documented at ED arrival in seven patients (12%); all these patients had pericardial tamponade and three (43%) had good functional neurologic recovery at hospital discharge. CONCLUSION: Resuscitative thoracotomy in the ED can be considered futile care when (a) prehospital CPR exceeds 10 minutes after blunt trauma without a response, (b) prehospital CPR exceeds 15 minutes after penetrating trauma without a response, and (c) asystole is the presenting rhythm and there is no pericardial tamponade.

Resuscitation beyond the abdominal compartment syndrome.

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

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.

Central venous pressure versus pulmonary artery catheter-directed shock resuscitation.

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= 6 mEq/L or systolic blood pressure < 90 mmHg, 3) transfusion of >or= 1 unit packed red blood cells (PRBC), or >or= 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) were > CVP (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.

Early cytokine production risk stratifies trauma patients for multiple organ failure.

BACKGROUND: 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. STUDY DESIGN: In a prospective observational pilot study of > 1 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. RESULTS: 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. CONCLUSIONS: These data provide insight into cytokine expression during traumatic shock that can enable earlier identification of patients at risk for development of MOF.

Poloxamer 188 prolongs survival of hypotensive resuscitation and decreases vital tissue injury after full resuscitation.

Hypotensive resuscitation prolongs survival of patients with severe bleeding until they can undergo hemorrhage control. However, its value is limited by continuing ischemic injury. Purified poloxamer 188 (P188), a copolymer with rheological and cytoprotective activities, was known to reduce mortality of hemorrhagic shock when used as an adjunct to full resuscitation with fresh whole blood and crystalloid. Studies were undertaken to determine if it could prolong survival and reduce reperfusion injury during prolonged hypotensive resuscitation when added to the best regimen currently available. Unanesthetized rats were bled to a MAP of 30 mmHg for 30 min under computer control. They then received hypotensive resuscitation with Hextend or Hextend + P188 to maintain a MAP of 60 mmHg until death. Poloxamer 188 improved autoresuscitation, reduced fluid requirements, and increased the survivable duration of hypotensive resuscitation by more than 3 h (P < 0.01). Additional studies assessed tissue damage after shock and hypotensive resuscitation with Hextend followed by full resuscitation with crystalloid. In these studies, P188 blunted the no-reflow phenomenon and largely prevented myocardial injury, pulmonary inflammation, small bowel damage, renal tubular necrosis, hepatic central lobular necrosis, and apoptosis of splenic germinal centers that occurred during full resuscitation. Additional studies demonstrated that P188 increased survival from 0% to 75% in 50% volume-controlled hemorrhage (P < 0.001). Finally, P188 did not increase bleeding in uncontrolled hemorrhage produced by 75% tail amputation. Because P188 prolongs survival, decreases fluid requirements, and reduces tissue damage, it deserves further consideration as an adjunct to hypotensive resuscitation.

Update on postinjury nutrition.

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

Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients.

OBJECTIVE: To determine the effect of blood component ratios in massive transfusion (MT), we hypothesized that increased use of plasma and platelet to red blood cell (RBC) ratios would result in decreased early hemorrhagic death and this benefit would be sustained over the ensuing hospitalization. SUMMARY BACKGROUND DATA: Civilian guidelines for massive transfusion (MT > or =10 units of RBC in 24 hours) have typically recommend a 1:3 ratio of plasma:RBC, whereas optimal platelet:RBC ratios are unknown. Conversely, military data shows that a plasma:RBC ratio approaching 1:1 improves long term outcomes in MT combat casualties. There is little consensus on optimal platelet transfusions in either civilian or military practice. At present, the optimal combinations of plasma, platelet, and RBCs for MT in civilian patients is unclear. METHODS: Records of 467 MT trauma patients transported from the scene to 16 level 1 trauma centers between July 2005 and June 2006 were reviewed. One patient who died within 30 minutes of admission was excluded. Based on high and low plasma and platelet to RBC ratios, 4 groups were analyzed. RESULTS: Among 466 MT patients, survival varied by center from 41% to 74%. Mean injury severity score varied by center from 22 to 40; the average of the center means was 33. The plasma:RBC ratio ranged from 0 to 2.89 (mean +/- SD: 0.56 +/- 0.35) and the platelets:RBC ratio ranged from 0 to 2.5 (0.55 +/- 0.50). Plasma and platelet to RBC ratios and injury severity score were predictors of death at 6 hours, 24 hours, and 30 days in multivariate logistic models. Thirty-day survival was increased in patients with high plasma:RBC ratio (> or =1:2) relative to those with low plasma:RBC ratio (<1:2) (low: 40.4% vs. high: 59.6%, P < 0.01). Similarly, 30-day survival was increased in patients with high platelet:RBC ratio (> or =1:2) relative to those with low platelet:RBC ratio (<1:2) (low: 40.1% vs. high: 59.9%, P < 0.01). The combination of high plasma and high platelet to RBC ratios were associated with decreased truncal hemorrhage, increased 6-hour, 24-hour, and 30-day survival, and increased intensive care unit, ventilator, and hospital-free days (P < 0.05), with no change in multiple organ failure deaths. Statistical modeling indicated that a clinical guideline with mean plasma:RBC ratio equal to 1:1 would encompass 98% of patients within the optimal 1:2 ratio. CONCLUSIONS: Current transfusion practices and survival rates of MT patients vary widely among trauma centers. Conventional MT guidelines may underestimate the optimal plasma and platelet to RBC ratios. Survival in civilian MT patients is associated with increased plasma and platelet ratios. Massive transfusion practice guidelines should aim for a 1:1:1 ratio of plasma:platelets:RBCs.

Effects of poloxamer 188 on human PMN cells.

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

Gastric alkalinization after major trauma.

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

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.

Acute lower extremity compartment syndrome (ALECS) screening protocol in critically ill trauma patients.

BACKGROUND: Acute lower extremity compartment syndrome (ALECS) is a devastating complication that often presents silently in critically injured patients; therefore, we developed a protocol to screen high-risk patients. METHODS: This prospective observational study included all Shock Trauma intensive care unit patients who met specific high-risk criteria including pulmonary artery catheter-directed shock resuscitation, open or closed tibial shaft fracture, major vascular injury below the aortic bifurcation, abdominal compartment syndrome, or pelvic or lower extremity crush injury. Patients were screened at admission and every 4 hours thereafter for the first 48 hours of admission. Screening included physical examination (PE) and anterior or deep posterior calf compartment pressure measurements when PE was suspicious or unreliable. A positive screening, defined as a DeltaP <30 mm Hg (where DeltaP is the difference between the diastolic blood pressure and the compartment pressure), mandated a four-compartment fasciotomy. RESULTS: During a 6-month period, the incidence of ALECS in screened patients was surprisingly high at 20% (9 patients). With diligent screening, it was diagnosed early in the patient's Shock Trauma intensive care unit course. These were patients with severe injuries with an Injury Severity Score of 32.0 +/- 12.5 who exhibited significant volume depletion, with a base deficit of 12.9 +/- 5.9 mEq/L and a lactate level of 13.0 +/- 5.2 mmol/L, requiring large volume resuscitation. Although aggressive fasciotomy resulted in no limb loss, ALECS was associated with an exceedingly high mortality rate at 67%. CONCLUSIONS: ALECS is an important clinical entity in critically injured patients with trauma associated with significant mortality. Aggressive screening may provide some diagnostic insight to those at risk.

Fresh frozen plasma should be given earlier to patients requiring massive transfusion.

BACKGROUND: Acidosis, hypothermia, and coagulopathy were identified more than 20 years ago as a deadly triad for patients presenting with exsanguinating hemorrhage. This led to fundamental changes in initial management of severely injured patients. Despite major advances, hemorrhage remains a leading cause of early death in trauma patients. Recent studies report most severely injured patients to be coagulopathic at admission, before resuscitation interventions, and that traditional massive transfusion practice grossly underestimates needs. The hypothesis for this study is that our pre-intensive care unit (ICU) massive transfusion (MT) protocol does not adequately correct coagulopathy, and that early uncorrected coagulopathy is predictive of mortality. METHODS: Data maintained in our Trauma Research Database were reviewed. Univariate logistic regression analysis was used to analyze the association of early ICU international normalized ratio (INR) and outcomes, including survival. RESULTS: Ninety-seven of 200 patients admitted during 51 months (ending January 2003) and resuscitated using our standardized ICU shock resuscitation protocol received MT (> or =10 units packed red blood cells [PRBC]) during hospital day 1 (age, 39 +/- 2; ISS, 29 +/- 1; survival, 70%.) All patients required emergency operating room and/or interventional radiology procedures and arrived in the ICU 6.8 +/- 0.3 hours after admission. Coagulopathy, present at hospital admission (pre-ICU INR, 1.8 +/- 0.2), persisted at ICU admission (initial ICU INR, 1.6 +/- 0.1). Pre-ICU resuscitation, 9 +/- 1 L crystalloid fluid, 12 +/- 1 units PRBC, 5 +/- 0.4 units fresh frozen plasma (FFP), was consistent with our MT protocol by which FFP was not given until after 6 units PRBC. ICU resuscitation involved 11 +/- 1 L lactated Ringer's solution (LR) and 10 +/- 1 units PRBC. Mean pH was normal within 8 hours. Mean temperature increased from approximately 35 degrees C to >37 degrees C within 4 hours. In the ICU during resuscitation, patients received 10 +/- 1 units FFP for coagulopathy; the ratio of FFP:PRBC was 1:1. Mean INR decreased to 1.4 +/- 0.03 within 8 hours and remained nearly constant for the remaining 16 hours of ICU resuscitation, indicating moderate coagulopathy. Statistical analysis found severity of coagulopathy (INR) at ICU admission associated with survival outcome (p = 0.02; area under receiver operator curve [ROC] = 0.71.) CONCLUSION: These data indicate acidosis and hypothermia to be well managed. Coagulopathy was not corrected in the ICU despite adherence to pre-ICU MT and ICU protocols, likely because of inadequate pre-ICU intervention. More aggressive pre-ICU intervention to correct coagulopathy may be effective in decreasing PRBC requirement during ICU resuscitation, and, because of the association with increased mortality, could improve outcome. We have revised our pre-ICU MT protocol to emphasize early FFP in a FFP:PRBC ratio of 1:1. We think that treatment of coagulopathy can be improved with the development of standardized protocols, both empiric and data driven.