Kristen C. Sihler

Complications of Massive Transfusion

Massive transfusion (MT) is a lifesaving treatment of hemorrhagic shock, but can be associated with significant complications. The lethal triad of acidosis, hypothermia, and coagulopathy associated with MT is associated with a high mortality rate. Other complications include hypothermia, acid/base derangements, electrolyte abnormalities (hypocalcemia, hypomagnesemia, hypokalemia, hyperkalemia), citrate toxicity, and transfusion-associated acute lung injury. Blood transfusion in trauma, surgery, and critical care has been identified as an independent predictor of multiple organ failure, systemic inflammatory response syndrome, increased infection, and increased mortality in multiple studies. Once definitive control of hemorrhage has been established, a restrictive approach to blood transfusion should be implemented to minimize further complications.

Comparison in humans of the potency and pharmacokinetics of intravenously injected cocaethylene and cocaine

Cocaethylene (the ethyl ester of benzoylecgonine) is a product of the interaction between ethanol and cocaine. The results of preclinical studies and of a pilot clinical study have shown cocaethylene to produce pharmacologic effects similar to those of cocaine. However, no information is available concerning the potency and pharmacokinetics of cocaethylene in comparison to those of cocaine in humans. We report the results of a single-blind, crossover study in which six male, healthy, paid volunteers, who were moderate users of cocaine, were intravenously injected with the water soluble fumarate salt of cocaethylene (0.25 mg/kg cocaethylene base) or an equivalent dose of the water soluble hydrochloride salt of cocaine (0.25 mg/kg cocaine base). Each dose was dissolved in normal saline and injected over a 1-min interval. Test sessions were separated by a 1-week interval. The variables measured were: cocaine and cocaethylene plasma concentrations, subjective and cardiovascular effects. The results indicate, that in comparison to cocaine, cocaethylene had a significant smaller elimination rate constant (0.42 versus 0.67 l/h), had a longer elimination half-life (1.68 versus 1.07 h), and induced ratings of “high” and changes in heart rate that were of lower magnitude (65%, and 43%, respectively). During the period of time that pharmacologic effects were present the plasma concentrations of cocaine and cocaethylene were statistically indistinguishable. This finding supports the conclusion that in humans cocaethylene is less potent than cocaine.

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.

Anemia of Inflammation in Critically Ill Patients

Anemia is seen frequently in critically ill patients and has several etiologies. This article reviews the causes with an emphasis on the effects of inflammation, examines the risks and benefits of current therapies, and discusses novel treatment options.

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.

Catheter-Related vs. Catheter-Associated Blood Stream Infections in the Intensive Care Unit: Incidence, Microbiology, and Implications

BACKGROUND Catheter-associated blood stream infections (CA-BSI) and catheter-related blood stream infections (CR-BSIs) differ in the degree of proof required to show that the catheter is the cause of the infection. The U.S. Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infections Surveillance [NNIS] group) collects data regarding CA-BSI nationally. We hypothesized that there would be a significant difference in the rates reported according to the definition. METHODS Prospective surveillance of CA-BSI (defined as bacteremia with no extravascular source identified) is performed in all intensive care units (ICUs) at our institution and reported as the rate per 1,000 catheter-days. In January 2006, we initiated cultures of all catheter tips to evaluate for CR-BSI (defined as a catheter tip culture with >15 colony-forming units of the same microorganism(s) found in the blood culture) in the surgical, trauma-burn, and medical ICUs. RESULTS The CA-BSI rate across all ICUs for the 24-mo study period was 1.4/1,000 catheter-days. The CR-BSI rate was 0.4/1,000 catheter days, for a rate difference of 1.0 infections/1,000 catheter-days (p < 0.001 vs. CA-BSI). The pathogens identified in CA-BSI included many organisms that are not associated with catheter-related BSIs. CONCLUSIONS The CR-BSI rate is significantly lower than the CA-BSI rate. The organisms identified in CA-BSI surveillance often are not common in catheter-related infections. Reporting CR-BSI thus is a more accurate measure of complications of central venous catheter use, and this rate may be more sensitive to catheter-specific interventions designed to reduce rates of BSI in the ICU.

Hepcidin in trauma: linking injury, inflammation, and anemia.

BACKGROUND Anemia is almost universal in trauma patients admitted to the intensive care unit (ICU). Hepcidin is a liver-derived peptide that is a negative regulator of iron stores. Hepcidin synthesis is suppressed by erythropoiesis and iron deficiency and upregulated by iron overload and inflammation. Hepcidin has been shown to have an important role in the anemia of chronic inflammatory diseases but has not been previously studied in the setting of trauma. We sought to define the link between traumatic injury, hepcidin, and inflammation. METHODS One hundred fifty trauma patients admitted to the ICU were prospectively enrolled in the study. Urine was collected at regular time points for hepcidin measurement. Serum for iron studies and measurement of those cytokines associated with acute inflammation was also collected. RESULTS The study population comprised 73% men. Mean age was 46 years, with a median Injury Severity Score (ISS) of 27. The mean lactate level was 2.9 mmol/L, and mean hemoglobin was 12.4 g/dL. More than 50% of patients were anemic on ICU admission, and nearly all were anemic by postinjury day 10. Urinary hepcidin levels were among the highest reported to date and had a rightward skew. Iron studies confirmed functional iron deficiency. Log hepcidin values were positively correlated with ISS and negatively correlated with admission Pao₂/FiO₂. Every increase in ISS by 10 was associated with a 40% increase in hepcidin. Initial hepcidin levels were positively correlated with duration of anemia. CONCLUSIONS Hepcidin levels rise to extremely high but variable levels after trauma and are positively correlated with injury severity measured by ISS and duration of anemia and negatively correlated with hypoxia. Hepcidin is likely a key factor in the impaired erythropoiesis seen in critically injured trauma patients.

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.

Specific abbreviated injury scale values are responsible for the underestimation of mortality in penetrating trauma patients by the injury severity score.

BACKGROUND The Injury Severity Score (ISS) is widely used as a method for rating severity of injury. The ISS is the sum of the squares of the three worst Abbreviated Injury Scale (AIS) values from three body regions. Patients with penetrating injuries tend to have higher mortality rates for a given ISS than patients with blunt injuries. This is thought to be secondary to the increased prevalence of multiple severe injuries in the same body region in patients with penetrating injuries, which the ISS does not account for. We hypothesized that the mechanism-based difference in mortality could be attributed to certain ISS ranges and specific AIS values by body region. METHODS Outcome and injury scoring data were obtained from transfused patients admitted to 23 Level I trauma centers. ISS values were grouped into categories, and a logistic regression model was created. Mortality for each ISS category was determined and compared with the ISS 1 to 15 group. An interaction term was added to evaluate the effect of mechanism. Additional logistic regression models were created to examine each AIS category individually. RESULTS There were 2,292 patients in the cohort. An overall interaction between ISS and mechanism was observed (p = 0.049). Mortality rates between blunt and penetrating patients with an ISS between 25 and 40 were significantly different (23.6 vs. 36.1%; p = 0.022). Within this range, the magnitude of the difference in mortality was far higher for penetrating patients with head injuries (75% vs. 37% for blunt) than truncal injuries (26% vs. 17% for blunt). Penetrating trauma patients with an AIS head of 4 or 5, AIS abdomen of 3, or AIS extremity of 3 all had adjusted mortality rates higher than blunt trauma patients with those values. CONCLUSION Significant differences in mortality between blunt and penetrating trauma patients exist at certain ISS and AIS category values. The mortality difference is greatest for head injured patients.

Variations between level i trauma centers in 24-hour mortality in severely injured patients requiring a massive transfusion

BACKGROUND Significant differences in outcomes have been demonstrated between Level I trauma centers. Usually these differences are ascribed to regional or administrative differences, although the influence of variation in clinical practice is rarely considered. This study was undertaken to determine whether differences in early mortality of patients receiving a massive transfusion (MT, ≥ 10 units pf RBCs within 24 hours of admission) persist after adjustment for patient and transfusion practice differences. We hypothesized differences among centers in 24-hour mortality could predominantly be accounted for by differences in transfusion practices as well as patient characteristics. METHODS Data were retrospectively collected over a 1-year period from 15 Level I centers on patients receiving an MT. A purposeful variable selection strategy was used to build the final multivariable logistic model to assess differences between centers in 24-hour mortality. Adjusted odds ratios for each center were calculated. RESULTS : There were 550 patients evaluated, but only 443 patients had complete data for the set of variables included in the final model. Unadjusted mortality varied considerably across centers, ranging from 10% to 75%. Multivariable logistic regression identified injury severity score (ISS), abbreviated injury scale (AIS) of the chest, admission base deficit, admission heart rate, and total units of RBC transfused, as well as ratios of plasma:RBC and platelet:RBC to be associated with 24-hour mortality. After adjusting for severity of injury and transfusion, treatment variables between center differences were no longer significant. CONCLUSIONS In the defined population of patients receiving an MT, between-center differences in 24-hour mortality may be accounted for by severity of injury as well as transfusion practices.