Homer Tien

The immunomodulatory effects of hypertonic saline resuscitation in patients sustaining traumatic hemorrhagic shock: a randomized, controlled, double-blinded trial.

Objective:To investigate the potential immunologic and anti-inflammatory effects of hypertonic saline plus dextran (HSD) in hemorrhagic trauma patients. Background:Unbalanced inflammation triggered by shock has been linked to multiorgan dysfunction (MOD) and death. In animal and cellular models, HSD alters the inflammatory response to shock, attenuating MOD and improving outcome. It remains untested whether HSD has similar effects in humans. Methods:A single 250-mL dose of either HSD (7.5% NaCl, 6% dextran-70) or placebo (0.9% NaCl) was administered to adult blunt trauma patients in hemorrhagic shock. The primary outcome was to measure changes in immune/inflammatory markers, including neutrophil activation, monocyte subset redistribution, cytokine production, and neuroendocrine changes. Patient demographics, fluid requirements, organ dysfunction, infection, and death were recorded. Results:A total of 27 patients were enrolled (13 HSD) with no significant differences in clinical measurements. Hyperosmolarity was modest and transient, whereas the immunologic/anti-inflammatory effects persisted for 24 hours. HSD blunted neutrophil activation by abolishing shock-induced CD11b up-regulation and causing CD62L shedding. HSD altered the shock-induced monocyte redistribution pattern by reducing the drop in “classic” CD14++ and the expansion of the “pro-inflammatory” CD14+CD16+ subsets. In parallel, HSD significantly reduced pro-inflammatory tumor necrosis factor (TNF)-α production while increasing anti-inflammatory IL-1ra and IL-10. HSD prevented shock-induced norepinephrine surge with no effect on adrenal steroids. Conclusions:This first human trial evaluating the immunologic/anti-inflammatory effects of hypertonic resuscitation in trauma patients demonstrates that HSD promotes a more balanced inflammatory response to hemorrhagic shock, raising the possibility that similar to experimental models, HSD might also attenuate post-trauma MOD.

Abnormal Coagulation Tests Are Associated With Progression of Traumatic Intracranial Hemorrhage

BACKGROUND Intracranial hemorrhage (ICH) is common in traumatic brain injury (TBI) and a major determinant of death and disability. ICH commonly increases in size and coagulopathy has been implicated in such progression. We investigated the association between coagulopathy diagnosed by routine laboratory tests and ICH progression. METHODS Subgroup post hoc analysis from a randomized controlled trial including adult patients with blunt severe TBI (Glasgow Coma Scale score <or=8) and repeat computerized tomography scans in 48 hours. Coagulopathy was defined as international normalized ratio >or=1.3, activated partial thromboplastin time >or=35, or platelet count (PLT) <or=100 x 10/L any time in the first 24 hours. Progression was any size increase or new ICH. TBI-associated coagulopathy was investigated measuring soluble tissue factor (TF) and d-dimer. RESULTS The ICH progressed in 37 of 72 patients (51%), in 80% if any abnormal laboratory test (coagulopathic patients) versus 36% in noncoagulopathic (p = 0.0004). Abnormal international normalized ratio (odds ratio [OR] = 4.09; 95% confidence interval [CI] = 1.29-12.95; p = 0.017), PLT (OR = 12.59; 95% CI = 1.52-108.57; p = 0.019), head Abbreviated Injury Scale (AIS) (OR = 1.82; 95% CI = 1.15-2.88; p = 0.011) were significantly associated with progression (univariate analysis). In a multiple logistic regression, only head AIS (OR = 1.81; 95% CI 1.10-2.98; p = 0.0198) and PLT (OR = 11.8; 95% CI = 1.38-101.23; p = 0.024) correlated with progression. All patients with abnormal partial thromboplastin time experienced progression. ICH progression carried a 5-fold higher odds of death; 32% with progression died versus 8.6% without. Age, head AIS, Injury Severity Score, and d-dimer were also associated with mortality. Tissue factor was not associated with progression or mortality. CONCLUSION This study demonstrates an association between coagulopathy, diagnosed by routine laboratorial tests in the first 24 hours, with ICH progression; and ICH progression with mortality in patients with severe TBI. The causal relationship between coagulopathy and ICH progression will require further studies.

Effect of a fixed-ratio (1:1:1) transfusion protocol versus laboratory-results–guided transfusion in patients with severe trauma: a randomized feasibility trial

Background: Hemorrhage coupled with coagulopathy remains the leading cause of preventable in-hospital deaths among trauma patients. Use of a transfusion protocol with a predefined ratio of 1:1:1 (1 each of red blood cells [RBC], frozen plasma [FP] and platelets) has been associated with improved survival in retrospective studies in military and civilian settings, but such a protocol has its challenges and may increase the risk of respiratory complications. We conducted a randomized controlled trial to assess the feasibility of a 1:1:1 transfusion protocol and its effect on mortality and complications among patients with severe trauma. Methods: We included 78 patients seen in a tertiary trauma centre between July 2009 and October 2011 who had hypotension and bleeding and were expected to need massive transfusion (≥ 10 RBC units in 24 h). We randomly assigned them to either the fixed-ratio (1:1:1) transfusion protocol (n = 40) or to a laboratory-results–guided transfusion protocol (control; n = 38). The primary outcome, feasibility, was assessed in terms of blood product ratios and plasma wastage. Safety was measured based on 28-day mortality and survival free of acute respiratory distress syndrome. Results: Overall, a transfusion ratio of 1:1:1 was achieved in 57% (21/37) of patients in the fixed-ratio group, as compared with 6% (2/32) in the control group. A ratio of 1:1 (RBC:FP) was achieved in 73% (27/37) in the fixed-ratio group and 22% (7/32) in the control group. Plasma wastage was higher with the intervention protocol (22% [86/390] of FP units v. 10% [30/289] in the control group). The 28-day mortality and number of days free of acute respiratory distress syndrome were statistically similar between the groups. Interpretation: The fixed-ratio transfusion protocol was feasible in our study, but it was associated with increased plasma wastage. Larger randomized trials are needed to evaluate the efficacy of such a protocol in trauma care. Trial registration: ClinicalTrials.gov, no. NCT00945542

Tourniquet use for peripheral vascular injuries in the civilian setting

BACKGROUND Haemorrhage in peripheral vascular injuries may cause life-threatening exsanguination. Tourniquets are used extensively by the military, with increased interest in the civilian setting to prevent deaths. This is a retrospective study of trauma patients at two large Canadian trauma centres with arterial injury after isolated extremity trauma. We hypothesized that tourniquet use may decrease mortality rate and transfusion requirements if applied early. METHODS The study group was all adult patients at two Level 1 Trauma Centres in two Canadian cities in Canada, who had arterial injuries from extremity trauma. The study period was from January 2001 to December 2010. We excluded patients with significant associated injuries. The intervention in this study was prehospital tourniquet use. The main outcome was in-hospital mortality. Secondary outcomes were length of stay, compartment syndrome, amputation, and blood product transfusion. RESULTS 190 patients were included in the study, and only 4 patients had a prehospital tourniquet applied. They arrived directly from the scene of injury, had improvised tourniquets by police or bystanders, and showed a trend to be more hypotensive and acidotic. Four other patients had tourniquets applied in the trauma bay within 1h of injury. There were no differences in age, sex, injury severity or physiologic presentation between patients who had an early tourniquet applied and those who died without a tourniquet. However, six patients died without a tourniquet, and all bled to death. Of the eight patients who had early tourniquets applied, none died. CONCLUSIONS Tourniquets may prevent exsanguination in the civilian setting for patients suffering either blunt or penetrating trauma to the extremity. Future studies will help determine the utility of deploying tourniquets in the civilian setting, given the rarity of exsanguinating haemorrhage from isolated extremity trauma in this setting.

Vitamin K‐dependent coagulation factor deficiency in trauma: a comparative analysis between international normalized ratio and thromboelastography (CME)

BACKGROUND: The use of international normalized ratio (INR) to diagnose vitamin K‐dependent coagulation factor (VitK‐CF) deficiency in trauma has limitations (inability to predict bleeding and long turnaround times). Thromboelastography (TEG) assesses the entire coagulation process. With TEG, reaction time (TEG‐R) is used to assess global coagulation factor activity and takes less than 10 minutes. We assessed the ability of TEG‐R to detect VitK‐CF deficiency in trauma, compared to the INR.

Tactical Combat Casualty Care in the Canadian Forces: lessons learned from the Afghan war

Tactical Combat Casualty Care (TCCC) is intended to treat potentially preventable causes of death on the battlefield, but acknowledges that application of these treatments may place the provider and even the mission in jeopardy if performed at the wrong time. Therefore, TCCC classifies the tactical situation with respect to health care provision into 3 phases (care under fire, tactical field care and tactical evacuation) and only permits certain interventions to be performed in specific phases based on the danger to the provider and casualty. In the 6 years that the Canadian Forces (CF) have been involved in sustained combat operations in Kandahar, Afghanistan, more than 1000 CF members have been injured and more than 150 have been killed. As a result, the CF gained substantial experience delivering TCCC to wounded soldiers on the battlefield. The purpose of this paper is to review the principles of TCCC and some of the lessons learned about battlefield trauma care during this conflict.

Editorial: "Formula-Driven" Versus "Lab-Driven" Massive Transfusion Protocols: At a State of Clinical Equipoise

From the Department of Clinical Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Department of Surgery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; and Canadian Forces Health Services, Toronto, ON, Canada. Address reprint requests to Jeannie L.Callum, BA,MD,FRCPC, CTBS, Transfusion Medicine and Tissue Banks, Sunnybrook Health Sciences Centre, B211, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5. E-mail: jeannie.callum@sunnybrook.ca 0887-7963/09/

Pulmonary emboli after blunt trauma: Timing, clinical characteristics and natural history

see front matter

Redefining "dead on arrival": Identifying the unsalvageable patient for the purpose of performance improvement.

BACKGROUND Venous thromboembolism (VTE) frequently complicates the recovery of trauma patients, and contributes to morbidity and mortality. Recent studies showed an increase in diagnosis of pulmonary embolism (PE) mainly in the early or immediate period after trauma. The clinical significance of those incidental PEs is unclear. METHODS The study cohort included all blunt trauma patients who had a contrast-enhanced CT of the chest performed as part of their initial trauma assessment from January 1, 2005 to January 31, 2007 in a large academic Canadian trauma centre. Patients diagnosed with PE at any point during admission were identified using our institutional trauma registry. All chest CT scans and electronic charts were reviewed. Patients were classified according to time of PE detection (immediate, early or late) and symptoms (asymptomatic or symptomatic). The clinical characteristics and hospital course of the patients who were diagnosed with immediate PE were described. RESULTS 1259 blunt trauma patients were reviewed. Six patients presented with immediate PE (0.5%); nine patients were found to have early PE (0.7%) and 13 had late PE (1.0%). All six of the patients with immediate PE were classified as asymptomatic. Five of the nine patients with early PE were symptomatic and all 13 patients who developed late PE were symptomatic. Amongst the six patients with immediate PE, five survived 24h hospitalisation. Four of them were managed with prophylactic low molecular weight heparin and no other thromboembolic events were observed during admission or after discharge. CONCLUSIONS The increased use of advanced CT technology in trauma patients has resulted in an increased diagnosis of incidental PEs that are asymptomatic. The clinical significance and management of these small, incidental PE are uncertain and further studies are needed to clarify the natural history of this controversial finding.

The marriage of surgical simulation and telementoring for damage-control surgical training of operational first responders: A pilot study.

BACKGROUND Significant variation exists across registries in the criteria used to identify patients with no chance of survival, with potential for profound impact on trauma center mortality. The purpose of this study was to identify the optimal case definition for the unsalvageable patient, for the purpose of exclusion from performance improvement (PI) endeavors. METHODS Data were derived from the American College of Surgeons’ Trauma Quality Improvement Program for 2012 to 2013. We proposed three potential case definitions for the unsalvageable patient: (1) no signs of life as determined by local providers (NSOL), (2) prehospital cardiac arrest (PHCA), and (3) a proxy definition (PROXY) based on presenting vital signs, defined as emergency department (ED) heart rate = 0, ED systolic blood pressure = 0, and Glasgow Coma Scale score motor component = 1. Case definitions were compared using standard predictive tests to determine specificity and positive predictive value (PPV) for in-hospital mortality. After the optimal definition was identified, hierarchical logistic regression was used to assess the impact of including unsalvageable patients on trauma center risk-adjusted mortality. The impact on trauma center performance was determined as change in outlier status and performance decile after exclusion of patients who met the optimal case definition. RESULTS During the study period, 223,643 patients met inclusion criteria across 192 trauma centers. Overall in-hospital mortality was 7.2%. The PROXY definition had excellent PPV for death, with less than 1% of patients meeting the PROXY criterion surviving. By contrast, NSOL and PHCA had PPVs low enough such that many of these patients went on to live (33% and 10%, respectively). After exclusion of patients who met the PROXY definition, 7% of trauma centers changed performance decile. This change was greatest for patients with penetrating injury and shock, with change in performance decile at 23% and 33% of centers, respectively. CONCLUSION The PROXY case definition has excellent predictive utility to identify patients who, based on presenting vital signs, will go on to die. PROXY should be used to exclude unsalvageable patients from PI endeavors.