Ernest A. Gonzalez

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 ≥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 (≥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 (≥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.

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.

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.

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-1β, negatively correlated while one anti-inflammatory cytokine, IL-10, positively correlated with shed syndecan-1. These cytokines all play an important role in maintaining endothelial integrity. An in vitro model of endothelial injury then specifically examined endothelial permeability after treatment with fresh frozen plasma orlactated Ringers. Shock or endothelial injury disrupted junctional integrity and increased permeability, which was improved with fresh frozen plasma, but not lactated Ringers. Changes in endothelial cell permeability correlated with syndecan-1 shedding. These data suggest that plasma based resuscitation preserved endothelial syndecan-1 and maintained endothelial integrity, and may help to explain the protective effects of fresh frozen plasma after hemorrhagic shock.

Effect of high product ratio massive transfusion on mortality in blunt and penetrating trauma patients.

BACKGROUND Recent data suggest that massively transfused patients have lower mortality rates when high ratios (>1:2) of plasma or platelets to red blood cells (RBCs) are used. Blunt and penetrating trauma patients have different injury patterns and may respond differently to resuscitation. This study was performed to determine whether mortality after high product ratio massive transfusion is different in blunt and penetrating trauma patients. METHODS Patients receiving 10 or more units of RBCs in the first 24 hours after admission to one of 23 Level I trauma centers were analyzed. Baseline physiologic and biochemical data were obtained. Univariate and logistic regression analyses were performed. Adjusted mortality in patients receiving high (≥ 1:2) and low (<1:2) ratios of plasma or platelets to RBCs was calculated for blunt and penetrating trauma patients. RESULTS The cohort contained 703 patients. Blunt injury patients receiving a high ratio of plasma or platelets to RBCs had lower 24-hour mortality (22% vs. 31% for plasma, p = 0.007; 20% vs. 30% for platelets, p = 0.032), but there was no difference in 30-day mortality (40% vs. 44% for plasma, p = 0.085; 37% vs. 44% for platelets, p = 0.063). Patients with penetrating injuries receiving a high plasma:RBC ratio had lower 24-hour mortality (21% vs. 37%, p = 0.005) and 30-day mortality (29% vs. 45%, p = 0.005). High platelet:RBC ratios did not affect mortality in penetrating patients. CONCLUSION Use of high plasma:RBC ratios during massive transfusion may benefit penetrating trauma patients to a greater degree than blunt trauma patients. High platelet:RBC ratios did not benefit either group.

Update on postinjury nutrition.

Purpose of reviewNutritional 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 findingsNutrition 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. SummaryBuilding 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.

Differential effects of anesthetics on endotoxin-induced liver injury.

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

Gender-based differences in mortality in response to high product ratio massive transfusion.

BACKGROUND Recent data suggest that patients undergoing massive transfusion have lower mortality rates when ratios of plasma and platelets to red blood cells (RBCs) of ≥ 1:2 are used. This has not been examined independently in women and men. A gender dichotomy in outcome after severe injury is known to exist. This study examined gender-related differences in mortality after high product ratio massive transfusion. METHODS A retrospective study was conducted using a database containing massively transfused trauma patients from 23 Level I trauma centers. Baseline demographic, physiologic, and biochemical data were obtained. Univariate and logistic regression analyses were performed. Adjusted mortality in patients receiving high (≥ 1:2) or low (<1:2) ratios of plasma or platelets to RBCs was compared in women and men independently. RESULTS Seven hundred four patients were analyzed. In males, mortality was lower for patients receiving a high plasma:RBC ratio at 24 hours (20.6% vs. 33.0% for low ratio, p = 0.005) and at 30 days (34.9% vs. 42.8%, p = 0.032). Males receiving a high platelet:RBC ratio also had lower 24-hour mortality (17.6% vs. 31.5%, p = 0.004) and 30-day mortality (32.1% vs. 42.2%, p = 0.045). Females receiving high ratios of plasma or platelets to RBCs had no improvement in 24-hour mortality (p = 0.119 and 0.329, respectively) or 30-day mortality (p = 0.199 and 0.911, respectively). Use of high product ratio transfusions did not affect 24-hour RBC requirements in males or females. CONCLUSION Use of high plasma:RBC or platelet:RBC ratios in massive transfusion may benefit men more than women. This may be due to gender-related differences in coagulability. Further study is needed to determine whether separate protocols for women and men should be established.

Complete occlusion after blunt injury to the abdominal aorta.

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

A predictive model for mortality in massively transfused trauma patients

BACKGROUND Improvements in trauma systems and resuscitation have increased survival in severely injured patients. Massive transfusion has been increasingly used in the civilian setting. Objective predictors of mortality have not been well described. This study examined data available in the early postinjury period to identify variables that are predictive of 24-hour- and 30-day mortality in massively transfused trauma patients. METHODS Massively transfused trauma patients from 23 Level I centers were studied. Variables available on patient arrival that were predictive of mortality at 24 hours were entered into a logistic regression model. A second model was created adding data available 6 hours after injury. A third model evaluated mortality at 30 days. Receiver operating characteristic curves and the Hosmer-Lemeshow test were used to assess model quality. RESULTS Seven hundred four massively transfused patients were analyzed. The model best able to predict 24-hour mortality included pH, Glasgow Coma Scale score, and heart rate, with an area under the receiver operating characteristic curve (AUROC) of 0.747. Addition of the 6-hour red blood cell requirement increased the AUROC to 0.769. The model best able to predict 30-day mortality included the above variables plus age and Injury Severity Score with an AUROC of 0.828. CONCLUSION Glasgow Coma Scale score, pH, heart rate, age, Injury Severity Score, and 6-hour red blood cell transfusion requirement independently predict mortality in massively transfused trauma patients. Models incorporating these data have only a modest ability to predict mortality and should not be used to justify withholding massive transfusion in individual cases.