Gregory P. Victorino

Does tachycardia correlate with hypotension after trauma

BACKGROUND Tachycardia is believed to be closely associated with hypotension and is often listed as an important sign in the initial diagnosis of hemorrhagic shock, but the correlation between heart rate and hypotension remains unproved. STUDY DESIGN Data were collected from all trauma patients, 16 to 49 years old, presenting to our university-based trauma center between July 1988 and January 1997. Moribund patients with a systolic blood pressure < or =50 or heart rate < or = 40 and patients with significant head or spinal cord injuries were excluded. Tachycardia was defined as a heart rate >or= 90 and hypotension as a systolic blood pressure < 90. RESULTS Hypotension was present in 489 of the 14,325 admitted patients that met the entry criteria. Of the hypotensive patients, 35% (169) were not tachycardic. Tachycardia was present in 39% of patients with systolic blood pressure 120 mmHg. Hypotensive patients with tachycardia had a higher mortality (15%) compared with hypotensive patients who were not tachycardic (2%, P = 0.003). Logistic regression analysis revealed tachycardia to be independently associated with hypotension (p = 0.0004), but receiver operating curve analysis demonstrated that the sensitivity and specificity of heart rate for predicting hypotension is poor. CONCLUSIONS Tachycardia is not a reliable sign of hypotension after trauma. Although tachycardia was independently associated with hypotension, its sensitivity and specificity limit its usefulness in the initial evaluation of trauma victims. Absence of tachycardia should not reassure the clinician about the absence of significant blood loss after trauma. Patients who are both hypotensive and tachycardic have an associated increased mortality and warrant careful evaluation.

Hydrolysis of Phosphatidylserine-exposing Red Blood Cells by Secretory Phospholipase A2 Generates Lysophosphatidic Acid and Results in Vascular Dysfunction

Secretory phospholipase A2 (sPLA2) type IIa, elevated in inflammation, breaks down membrane phospholipids and generates arachidonic acid. We hypothesized that sPLA2 will hydrolyze red blood cells that expose phosphatidylserine (PS) and generate lysophosphatidic acid (LPA) from phosphatidic acid that is elevated in PS-exposing red blood cells. In turn, LPA, a powerful lipid mediator, could affect vascular endothelial cell function. Although normal red blood cells were not affected by sPLA2, at levels of sPLA2 observed under inflammatory conditions (100 ng/ml) PS-exposing red blood cells hemolyzed and generated LPA (1.2 nm/108 RBC). When endothelial cell monolayers were incubated in vitro with LPA, a loss of confluence was noted. Moreover, a dose-dependent increase in hydraulic conductivity was identified in rat mesenteric venules in vivo with 5 μm LPA, and the combination of PS-exposing red blood cells with PLA2 caused a similar increase in permeability. In the presence of N-palmitoyl l-serine phosphoric acid, a competitive inhibitor for the endothelial LPA receptor, loss of confluence in vitro and the hydraulic permeability caused by 5 μm LPA in vivo were abolished. The present study demonstrates that increased sPLA2 activity in inflammation in the presence of cells that have lost their membrane phospholipid asymmetry can lead to LPA-mediated endothelial dysfunction and loss of vascular integrity.

Glucagon-like peptide-1 protects mesenteric endothelium from injury during inflammation

Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived hormone with cellular protective actions. We hypothesized that GLP-1 would protect the endothelium from injury during inflammation. Our aims were to determine the: (1) effect of GLP-1 on basal microvascular permeability, (2) effect of GLP-1 on increased microvascular permeability induced by lipopolysaccaride (LPS), (3) involvement of the GLP-1 receptor in GLP-1 activity, and (4) involvement of the cAMP/PKA pathway in GLP-1 activity. Microvascular permeability (L(p)) of rat mesenteric post-capillary venules was measured in vivo. First, the effect of GLP-1 on basal L(p) was measured. Second, after systemic LPS injection, L(p) was measured after subsequent perfusion with GLP-1. Thirdly, L(p) was measured after LPS injection and perfusion with GLP-1+GLP-1 receptor antagonist. Lastly, L(p) was measured after LPS injection and perfusion with GLP-1+inhibitors of the cAMP/PKA pathway. Results are presented as mean area under the curve (AUC)+/-SEM. GLP-1 had no effect on L(p) (AUC: baseline=27+/-1.4, GLP-1=1+/-0.4, p=0.08). LPS increased L(p) two-fold (AUC: LPS=54+/-1.7, p<0.0001). GLP-1 reduced the LPS increase in L(p) by 75% (AUC: LPS+GLP-1=34+/-1.5, p<0.0001). GLP-1 antagonism reduced the effects of GLP-1 by 60% (AUC: LPS+GLP-1+antagonist=46+/-2.0, p<0.001). The cAMP synthesis inhibitor reduced the effects of GLP-1 by 60% (AUC: LPS+GLP-1+cAMP inhibitor=46+/-1.5, p<0.0001). The PKA inhibitor reduced the effects of GLP-1 by 100% (AUC: LPS+GLP-1+PKA inhibitor=56+/-1.5, p<0.0001). GLP-1 attenuates the increase in microvascular permeability induced by LPS. GLP-1 may protect the endothelium during inflammation, thus decreasing third-space fluid loss.

Live transference of surgical subspecialty skills using telerobotic proctoring to remote general surgeons

BACKGROUND Certain clinical environments, including military field hospitals or rural medical centers, lack readily available surgical subspecialists. We hypothesized that telementoring by a surgical subspecialist using a robotic platform is feasible and can convey subspecialty knowledge and skill to a remotely located general surgeon. STUDY DESIGN Eight general surgery residents evaluated the effect of remote surgical telementoring by performing 3 operative procedures, first unproctored and then again when teleproctored by a surgical subspecialist. The clinical scenarios consisted of a penetrating right ventricular injury requiring suture repair, an open tibial fracture requiring external fixation, and a traumatic subdural hematoma requiring craniectomy. A robotic platform consisting of a pan-and-tilt camera with laser pointer attached to an overhead surgical light with integrated audio allowed surgical subspecialists the ability to remotely teleproctor residents. Performance was evaluated using an Operative Performance Scale. Satisfaction surveys were given after performing the scenario unproctored and again after proctoring. RESULTS Overall mean performance scores were superior in all scenarios when residents were proctored than when they were not (4.30 +/- 0.25 versus 2.43 +/- 0.20; p < 0.001). Mean performance scores for individual metrics, including tissue handling, instrument handling, speed of completion, and knowledge of anatomy, were all superior when residents were proctored (p < 0.001). Satisfaction surveys showed greater satisfaction and comfort among residents when proctored. Proctored residents believed the robotic platform facilitated learning and would be feasible if used clinically. CONCLUSIONS This study supports the use of surgical teleproctoring in guiding remote general surgeons by a surgical subspecialist in the care of a wounded patient in need of an emergency subspecialty operation.

The heart of the matter: utility of ultrasound of cardiac activity during traumatic arrest.

BACKGROUND The clinical utility of determining cardiac motion on ultrasound has been reported for patients presenting in pulseless medical cardiac arrest. However, the relationship between ultrasound-documented cardiac activity and the probability of surviving pulseless electrical activity has not been examined in populations with trauma. We hypothesized that cardiac activity on ultrasound predicts survival for patients presenting in pulseless traumatic arrest. METHODS We conducted a retrospective analysis at our university-based urban trauma center of adult patients with trauma, who were pulseless on hospital arrival. Results of cardiac ultrasound performed during trauma resuscitations were compared with the electrocardiogram (EKG) rhythm and survival. RESULTS Among 318 pulseless patients with trauma, 162 had both EKG tracings and a cardiac ultrasound, and 4.3% of these 162 patients survived to hospital admission. Survival was higher for those with cardiac motion than for those without it (23.5% vs. 1.9% for patients with EKG electrical activity, p = 0.002, and 66.7% vs. 0% for patients without EKG electrical activity, p < 0.001). The sensitivity of ultrasound cardiac motion to predict survival to hospital admission was 86% (specificity, 91%; positive predictive value, 30%; negative predictive value, 99%). When examined by mechanism, sensitivity was 100% for the 111 patients with penetrating trauma and 75% for the 50 patients with blunt trauma. CONCLUSION Survival in pulseless traumatic arrest is very low, but survival for patients with no cardiac motion on ultrasound is also exceedingly rare. Cardiac ultrasound had a negative predictive value approaching 100% for survival to hospital admission. For patients with prolonged prehospital cardiopulmonary resuscitation, ultrasound evaluation of cardiac motion in pulseless patients with trauma may be a rapid way to help determine which patients have no chance of survival in the setting of lethal injuries, so that futile resuscitations can be stopped. (J Trauma Acute Care Surg. 2012;73: 102–110. Copyright

Insurance Coverage Is Associated with Mortality after Gunshot Trauma

BACKGROUND Poor access to adequate health care coverage is associated with poor outcomes for many chronic medical conditions. We hypothesized that insurance coverage is also associated with mortality after gunshot trauma. STUDY DESIGN The trauma records for gunshot victims and their insurance status were reviewed at our center from January 1998 to December 2007. Patient demographics (age, gender, race, and insurance coverage), injury severity, hospital care (operations and radiographic studies), and in-hospital mortality were analyzed. RESULTS There were 2,164 gunshot trauma activations reviewed during the study period. One-quarter (n = 544) of these patients had insurance and three-quarters (n = 1,620) were uninsured. The in-hospital mortality rate was significantly higher for uninsured patients than for insured patients (9% vs 6%, p = 0.02). After controlling for age, gender, race, and injury severity by logistic regression analysis, the odds ratio for death of uninsured patients was 2.2 (95% CI 1.1 to 4.5). Insured patients did not differ from uninsured patients with respect to mean Injury Severity Score ([ISS] 12.2 +/- 10.7 vs 12.6 +/- 12.4, p = 0.56); similar percentages of patients were severely injured (ISS 16 to 24, 17% vs 15%, p = 0.19) and most severely injured (ISS > 24, 15% vs 16%, p = 0.68). Insured patients did not differ from uninsured patients with respect to use of radiographic imaging (53% vs 50%, p = 0.15) or operative intervention (37% vs 35%, p = 0.35). CONCLUSIONS Despite similar injury severity, uninsured trauma patients were more likely to die after gunshot injury than insured patients. This difference could not be attributed to demographics or hospital resource use. Insurance coverage may reflect the many social determinants of health. Improving the social determinants of health in patients affected by violent trauma may be a step toward improving outcomes after trauma.

Effect of hypertonic saline on microvascular permeability in the activated endothelium.

INTRODUCTION The effect of hypertonic saline (HTS) on microvascular permeability in microvessels with activated endothelial cells is unclear. We hypothesized that HTS and HTS with dextran would decrease hydraulic permeability after activation of the endothelium. METHODS Hydraulic permeability (L(p)) was measured in rat mesenteric venules using the modified Landis micro-occlusion technique. The effects of 185 mM HTS and HTS plus 2% dextran (HSD) were tested in the activated endothelium by measuring L(p) at baseline, after perfusion with ATP, and again after HTS (n = 6) or HSD (n = 6). ATP (10 microM) activated endothelial cells and increased L(p) 4-fold. Additional venules were used to test the effects of 135 mM NaCl (n = 6) and 235 mM (n = 6) NaCl after endothelial activation with ATP. RESULTS After endothelial activation with ATP, L(p) values were 6.05 +/- 1.63. Subsequent perfusion with HTS decreased L(p) to 2.05 +/- 0.52 (P = 0.01). In the HSD trails, L(p) values after ATP were 6.17 +/- 1.38. Perfusion with HSD decreased L(p) to 1.65 +/- 0.30 (P = 0.001). After endothelial activation, 135 mM NaCl had no effect on L(p); however, 185 mM NaCl decreased L(p) 3-fold and 235 mM NaCl decreased L(p) 6-fold. Units for L(p) are x10(-7) cm - s(-1). cmH(2)O(-1). CONCLUSIONS Both HTS and HSD decreased hydraulic permeability after endothelial activation. These findings suggest that HTS may decrease microvascular fluid loss during states of elevated microvascular leak. In addition to the ability of hypertonic solutions to withdraw intracellular water to increase plasma volume, these findings propose an endothelial barrier mechanism whereby HTS and HSD act to maintain intravascular volume.

A different view of lactate in trauma patients: protecting the injured brain.

BACKGROUND The relationship between lactate and head injury is controversial. We sought to determine the relationship between initial serum lactate, severity of head injury, and outcome. We hypothesized that lactate is elevated in head injured patients, and that initial serum lactate increases as the severity of head injury increases. Furthermore, lactate may be neuroprotective and improve neurologic outcomes. MATERIALS AND METHODS We identified normotensive adult patients over a 6-y period at our university-based urban trauma center with isolated blunt head injury. We performed univariate and multivariate analysis to examine the relationship between lactate and Glasgow coma scale (GCS). The correlation of admission lactate with survival and neurologic function was also examined. RESULTS There were 555 patients who met study criteria. While controlling for injury severity score and age, increased lactate was associated with more severe head injury (P<0.0001). The admission lactate was 2.2+/-0.07, 3.7+/-0.7, and 4.7+/-0.8 mmol/L in patients with mild, moderate, and severe head injury respectively (P<0.01). Patients with moderate or severe head injury and an admission lactate>5 were more likely to have a normal mental status on discharge (P<0.0001). CONCLUSIONS In normotensive isolated head injured patients, there was an increase in serum lactate as head injuries became more severe. Since lactate is a readily available fuel source of the injured brain, this may be a mechanism by which brain function is preserved in trauma patients. Elevations in lactate due to anaerobic metabolism in trauma patients may have beneficial effects by protecting the brain during injury.

Pan computed tomography versus selective computed tomography in stable, young adults after blunt trauma with moderate mechanism: a cost-utility analysis.

BACKGROUND Pan computed tomography (PCT) of the head, cervical spine, chest, abdomen, and pelvis is a valuable approach for rapid evaluation of severely injured blunt trauma patients. A PCT strategy has also been applied for the evaluation of patients with lower injury severity; however, the cost-utility of this approach is undetermined. The advantage of rapidly identifying all injuries via PCT must be weighed against the risk of radiation-induced cancer (RIC). Our objective was to compare the cost-utility of PCT with selective computed tomography (SCT) in the management of blunt trauma patients with low injury severity. METHODS A Markov model–based, cost-utility analysis of a hypothetical cohort of hemodynamically stable, 30-year-old males evaluated in a trauma center after motor vehicle crash was used. CT scans are performed based on the mechanism of injury. The analysis compared PCT with SCT over a 1-year time frame with an analytic horizon over the lifespan of the patients. The possible outcomes, utilities of health states, and health care costs including RIC were derived from the published medical literature and public data. Costs were measured in US 2010 dollars, and incremental effectiveness was measured in quality-adjusted life-years (QALYs) with 3% annual discounted rates. Multiway sensitivity analyses were performed on all variables. RESULTS The total cost for blunt trauma patients undergoing PCT was

Local Secretion of Urocortin 1 Promotes Microvascular Permeability during Lipopolysaccharide-Induced Inflammation

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