Robert C. Mackersie

Acute Traumatic Coagulopathy: Initiated by Hypoperfusion Modulated Through the Protein C Pathway?

Objectives:Coagulopathy following major trauma is conventionally attributed to activation and consumption of coagulation factors. Recent studies have identified an acute coagulopathy present on admission that is independent of injury severity. We hypothesized that early coagulopathy is due to tissue hypoperfusion, and investigated derangements in coagulation associated with this. Methods:This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times, prothrombin fragments 1+2, fibrinogen, thrombomodulin, protein C, plasminogen activator inhibitor-1, and d-dimers. Base deficit (BD) was used as a measure of tissue hypoperfusion. Results:A total of 208 patients were enrolled. Patients without tissue hypoperfusion were not coagulopathic, irrespective of the amount of thrombin generated. Prolongation of the partial thromboplastin and prothrombin times was only observed with an increased BD. An increasing BD was associated with high soluble thrombomodulin and low protein C levels. Low protein C levels were associated with prolongation of the partial thromboplastin and prothrombin times and hyperfibrinolysis with low levels of plasminogen activator inhibitor-1 and high d-dimer levels. High thrombomodulin and low protein C levels were significantly associated with increased mortality, blood transfusion requirements, acute renal injury, and reduced ventilator-free days. Conclusions:Early traumatic coagulopathy occurs only in the presence of tissue hypoperfusion and appears to occur without significant consumption of coagulation factors. Alterations in the thrombomodulin-protein C pathway are consistent with activated protein C activation and systemic anticoagulation. Admission plasma thrombomodulin and protein C levels are predictive of clinical outcomes following major trauma.

Acute coagulopathy of trauma: hypoperfusion induces systemic anticoagulation and hyperfibrinolysis

BACKGROUND Coagulopathy is present at admission in 25% of trauma patients, is associated with shock and a 5-fold increase in mortality. The coagulopathy has recently been associated with systemic activation of the protein C pathway. This study was designed to characterize the thrombotic, coagulant and fibrinolytic derangements of trauma-induced shock. METHODS This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of partial thromboplastin and prothrombin times, prothrombin fragments 1 + 2 (PF1 + 2), fibrinogen, factor VII, thrombomodulin, protein C, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), and D-dimers. Base deficit was used as a measure of tissue hypoperfusion. RESULTS Two hundred eight patients were studied. Systemic hypoperfusion was associated with anticoagulation and hyperfibrinolysis. Coagulation was activated and thrombin generation was related to injury severity, but acidosis did not affect Factor VII or PF1 + 2 levels. Hypoperfusion-induced increase in soluble thrombomodulin levels was associated with reduced fibrinogen utilization, reduction in protein C and an increase in TAFI. Hypoperfusion also resulted in hyperfibrinolysis, with raised tPA and D-Dimers, associated with the observed reduction in PAI-1 and not alterations in TAFI. CONCLUSIONS Acute coagulopathy of trauma is associated with systemic hypoperfusion and is characterized by anticoagulation and hyperfibrinolysis. There was no evidence of coagulation factor loss or dysfunction at this time point. Soluble thrombomodulin levels correlate with thrombomodulin activity. Thrombin binding to thrombomodulin contributes to hyperfibrinolysis via activated protein C consumption of PAI-1.

The etiology of missed cervical spine injuries.

Missed or delayed diagnosis of cervical spine (C-spine) injuries may lead to extension of those injuries and subsequent preventable mortality or morbidity. Previous reports examining the incidence of missed C-spine injuries have not determined the nature of the causal clinical errors made or the extent to which these errors are avoidable. This study was undertaken to (1) determine the incidence of delayed or missed diagnosis of C-spine injuries and the consequences of those missed injuries; (2) define the clinical errors leading to the delays; and (3) to determine if these errors are the result of fundamental problems or a lack of advanced diagnostic skills or equipment. Between August 1985 and February 1991, 32,117 trauma patients were admitted to one of the six trauma centers in San Diego county. Cervical spine injuries were identified in 740 patients and the diagnosis was delayed or missed in 34 patients (4.6%). Ten of the 34 patients (29%) developed permanent sequelae as a result of these delays. The single most common error was the failure to obtain an adequate series of C-spine roentgenograms. Delayed diagnosis could have been avoided in at least 31 of 34 injuries by the appropriate use of a standard three-view C-spine series and careful interpretation of those roentgenograms. Patients at risk for C-spine injuries require a technically adequate three-view C-spine series and skilled radiographic interpretation. Cervical spine precautions should be maintained, particularly in high risk patients, until appropriate and expert review of the cervical spine roentgenograms can be obtained.

Blunt carotid artery dissection : incidence, associated injuries, screening, and treatment

Blunt carotid dissection (BCD) is a rare injury occurring in less than one in 1,000 victims of blunt injuries. Using a 4-year experience in a trauma system with 14 cases of BCD, we performed a matched blunt trauma patient case-control analysis to determine if there were patterns of injuries that were associated with increased risk of BCD. Patients with combinations of head, facial, and cervical spine injuries with or without extremity fractures proved to be at significantly increased risk for BCD. Duplex scanning appears to be a useful screening tool for these patients. Anticoagulation was the preferred treatment once neurologic deficits were present.

Base deficit as a guide to volume resuscitation.

The base deficit (BD), is a potentially useful indicator of volume deficit in trauma patients. To evaluate BD as an index for fluid resuscitation, the records of 209 trauma patients with serial arterial blood gases (ABGs) were reviewed. The patients were grouped according to initial BD: mild, 2 to -5; moderate, -6 to -14; and severe, less than -15. The volume of resuscitative fluid administered, change in BD, mean arterial pressure (MAP), and presence of ongoing hemorrhage were analyzed for differences between the BD groups. The MAP decreased significantly and the volume of fluid required for resuscitation increased with increasing severity of BD group. A BD that increased (became more negative) with resuscitation was associated with ongoing hemorrhage in 65%. The data suggest that the BD is a useful guide to volume replacement in the resuscitation of trauma patients.

External fixation or arteriogram in bleeding pelvic fracture: initial therapy guided by markers of arterial hemorrhage.

BACKGROUND Bleeding pelvic fractures (BPF) carry mortality as high as 60%, yet controversy remains over optimal initial management. Some base initial intervention on fracture pattern, with immediate external fixation (EX FIX) in amenable fractures aimed at controlling venous bleeding. Others feel ongoing hemodynamic instability indicates arterial bleeding, and prefer early angiography (ANGIO) before EX-FIX. Our aim was to evaluate markers of arterial bleeding in patients with BPF, thus identifying patients requiring early ANGIO regardless of fracture pattern. METHODS Patients with pelvis fracture were identified from a Level I trauma center registry over a 7-year period and records reviewed. From this group, two subsets were analyzed: those with initial hypotension related to pelvic fracture, and those without hypotension who underwent pelvic ANGIO. Data included hemodynamics, response to resuscitation, presence of contrast blush on CT, fracture treatment and outcome. Adequate response to initial resuscitation (R) was defined as a sustained (>2 hours) improvement of systolic blood pressure to >90 mm Hg systolic after the administration of < or = 2 units packed red blood cells. Those with repeated episodes of hypotension despite resuscitation were classified as non-responders (NR) RESULTS: From 1/94-1/01, 1171 patients were admitted with pelvic ring fracture. Thirty-five (0.3%) had hypotension attributable to pelvis fracture. 28 fell into the NR group, and 26 of these underwent ANGIO. Nineteen (73%) showed arterial bleeding while 3 resuscitation response patients underwent ANGIO with none demonstrating bleeding (p = 0.03). Sensitivity and specificity of inadequate response to initial resuscitation for predicting the presence of arterial bleeding on ANGIO were 100% and 30% respectively while negative and positive predictive value were 100% and 73%. In patients with fractures amenable to external fixation (n = 16), 44% had arterial bleeding on ANGIO, and all were in the NR group. An additional 17 patients without hypotension also underwent ANGIO. Contrast blush on admission CT was seen in 4, 3 of which had arterial bleeding seen on ANGIO (75%). Sensitivity and specificity for contrast blush in predicting bleeding on ANGIO were 60% and 92% with positive and negative predictive value being 75% and 85%. CONCLUSIONS In patients with hypotension and pelvic fracture, therapy selection based on initial response to resuscitation in BPF yields a 73% positive ANGIO rate in NR patients. Delay in ANGIO for EX FIX in patients with amenable fractures would have delayed embolization in the face of ongoing arterial bleeding in 44% of patients. In stable patients with pelvic fracture, contrast blush also indicates a high likelihood of arterial injury and ANGIO is indicated. Optimal therapy in the face of BPF requires early determination of the presence of arterial bleeding so that ANGIO can be rapidly obtained, and response to initial resuscitation as well as the presence of contrast blush aid in this decision.

Venous thromboembolism in patients with major trauma

The risk of venous thromboembolism after trauma is thought to be high, but the specific risk factors and the incidence of venous thromboembolism in the trauma population are poorly defined. Between October 1, 1987, and March 1, 1988, 719 patients were evaluated; 542 had no risk factors and 177 had at least 1 risk factor. No venous thromboembolism occurred in any of the 542 patients without a risk factor, whereas 12 of 177 patients (7%) with at least 1 risk factor had a venous thromboembolism. Pneumatic compression hose was the most common form of prophylaxis used, but it could not be applied to 35% of limbs because of plaster immobilizers, external fixators, complex wounds, or traction. In the high-risk group, 25 patients (14%) received no prophylaxis because of a physical impediment to application of these hose and a contraindication to anticoagulation. Age greater than 45 years was the only risk factor predictive of venous thromboembolism by logistic regression analysis. Patients with more than one risk factor had a significantly higher incidence of venous thromboembolism than those with only one risk factor. We conclude that a selected subgroup of trauma patients appears to be at risk of venous thromboembolism and should receive prophylaxis. Approximately one in seven high-risk patients cannot receive anticoagulant or mechanical prophylaxis because of their injuries.

AN ANALYSIS OF ERRORS CAUSING MORBIDITY AND MORTALITY IN A TRAUMA SYSTEM: A GUIDE FOR QUALITY IMPROVEMENT

The purpose of auditing trauma care is to maintain quality assurance and to guide quality improvement. This study was conducted to identify the incidence, type, and setting of errors leading to morbidity and mortality in trauma patients. Determinations of the Medical Audit Committee of San Diego County were reviewed and classified by the authors for identification of preventable errors leading to morbidity or mortality. Errors were classified by type and categorized by phase of care. Errors were identified in the cases of 4% of all patients admitted for trauma care over a 4-year period. Of all trauma patient deaths, 5.9% were considered preventable or potentially preventable. The most common single error across all phases of care was failure to appropriately evaluate the abdomen. Although errors in the resuscitative and operative phases were more common, critical care errors had the greatest impact on preventable death. The detected error rate of 4% may represent the baseline error rate in a trauma system. While regionalized trauma care has dramatically reduced the incidence of preventable death after injury, efforts to further reduce preventable morbidity and mortality may be guided by an identification of common errors in a trauma system and their relationship to outcome.

the Development of Acute Lung Injury Is Associated with Worse Neurologic Outcome in Patients with Severe Traumatic Brain Injury

OBJECTIVE The purpose of this study was to determine the incidence of acute lung injury (ALI) in trauma patients with severe traumatic brain injury (TBI), to evaluate the impact of ALI on mortality and neurologic outcome after severe traumatic brain injury (TBI), and to identify whether the development of ALI correlates with the severity of TBI. METHODS Clinical data were collected prospectively over a 4-year period in a Level I trauma center. Patients included in the study met the following criteria: mechanical ventilation > 24 hours, head Abbreviated Injury Scale score >or= 3, no other body region Abbreviated Injury Scale score >or= 3, and age between 18 and 54 years. ALI was defined using international consensus criteria. Glasgow Outcome Scale scores were assessed at 3 and 12 months. Bivariate comparisons were made between ALI and non-ALI groups. Multivariate analysis with stepwise logistical regression was used to assess independent factors on mortality. The patients admission head computed tomographic (CT) scan was graded using the Marshall system, and the presence and size of specific intracranial abnormality was noted. Glasgow Coma Scale (GCS) score, Marshall CT scan score, and intracranial abnormality were correlated with the development of ALI. RESULTS One hundred thirty-seven patients with isolated head trauma were enrolled in the study over a 4-year period. Thirty-one percent of patients with severe TBI developed ALI. Head trauma patients with ALI had a significantly higher ISS, a greater number of days on the ventilator, and a worse neurologic outcome for those who survived their hospitalization. Mortality was 38% in the ALI group and 15% in the non-ALI group (p = 0.004). Only 3 of 16 (19%) of the deaths within the ALI group were directly related to ALI. By multivariate analysis, only the presence of ALI, older age, and lower initial GCS score were associated with higher mortality. There was no association between ISS, the presence of arterial hypotension (arterial systolic pressure < 90 mm Hg) at admission to the hospital, or the amount of blood transfused and mortality. No correlation was found between the severity of head injury (GCS score, Marshall score, or intracranial abnormality) and development of ALI. CONCLUSION The development of ALI is a critical independent factor affecting mortality in patients suffering traumatic brain injury and is associated with a worse long-term neurologic outcome in survivors. The risk of developing ALI is not associated with specific anatomic lesions diagnosed by cranial CT scanning.

Prospective Randomized Trial of LC+LCBDE vs ERCP/S+LC for Common Bile Duct Stone Disease

OBJECTIVE To compare outcome parameters for good-risk patients with classic signs, symptoms, and laboratory and abdominal imaging features of cholecystolithiasis and choledocholithiasis randomized to either laparoscopic cholecystectomy plus laparoscopic common bile duct exploration (LC+LCBDE) or endoscopic retrograde cholangiopancreatography sphincterotomy plus laparoscopic cholecystectomy (ERCP/S+LC). DESIGN Our study was a prospective trial conducted following written informed consent, with randomization by the serially numbered, opaque envelope technique. SETTING Our institution is an academic teaching hospital and the central receiving and trauma center for the City and County of San Francisco, California. PATIENTS We randomized 122 patients (American Society of Anesthesiologists grade 1 or 2) meeting entry criteria. Ten of these patients, excluded from outcome analysis, were protocol violators having signed out of the hospital against medical advice before 1 or both procedures were completed. INTERVENTIONS Treatment was preoperative ERCP/S followed by LC, or LC+LCBDE. MAIN OUTCOME MEASURES The primary outcome measure was efficacy of stone clearance from the common bile duct. Secondary end points were length of hospital stay, cost of index hospitalization, professional fees, hospital charges, morbidity and mortality, and patient acceptance and quality of life scores. RESULTS The baseline characteristics of the 2 randomized groups were similar. Efficacy of stone clearance was likewise equivalent for both groups. The time from first procedure to discharge was significantly shorter for LC+LCBDE (mean [SD], 55 [45] hours vs 98 [83] hours; P < .001). Hospital service and total charges for index hospitalization were likewise lower for LC+LCBDE, but the differences were not statistically significant. The professional fee charges for LC+LCBDE were significantly lower than those for ERCP/S+LC (median [SD],