Splenic arterial neurovascular bundle stimulation in esophagectomy: A feasibility and safety prospective cohort study.

Introduction: The autonomic nervous system is a key regulator of inflammation. Electrical stimulation of the vagus nerve has been shown to have some preclinical efficacy. However, only a few clinical studies have been reported to treat inflammatory diseases. The present study evaluates, for the first time, neuromodulation of the splenic arterial neurovascular bundle (SpA NVB) in patients undergoing minimally invasive esophagectomy (MIE), in which the SpA NVB is exposed as part of the procedure. Methods: This single-center, single-arm study enrolled 13 patients undergoing MIE. During the abdominal phase of the MIE, a novel cuff was placed around the SpA NVB, and stimulation was applied. The primary endpoint was the feasibility and safety of cuff application and removal. A secondary endpoint included the impact of stimulation on SpA blood flow changes during the stimulation, and an exploratory point was C-reactive protein (CRP) levels on postoperative day (POD) 2 and 3. Results: All patients successfully underwent placement, stimulation, and removal of the cuff on the SpA NVB with no adverse events related to the investigational procedure. Stimulation was associated with an overall reduction in splenic arterial blood flow but not with changes in blood pressure or heart rate. When compared to historic Propensity Score Matched (PSM) controls, CRP levels on POD2 (124 vs. 197 mg/ml, p = 0.032) and POD3 (151 vs. 221 mg/ml, p = 0.033) were lower in patients receiving stimulation. Conclusion: This first-in-human study demonstrated for the first time that applying a cuff around the SpA NVB and subsequent stimulation is safe, feasible, and may have an effect on the postoperative inflammatory response following MIE. These findings suggest that SpA NVB stimulation may offer a new method for immunomodulatory therapy in acute or chronic inflammatory conditions.

An Interprofessional Senior Medical Student Preparation Course: Improvement in Knowledge and Self-Confidence Before Entering Surgical Training.

PURPOSE: Senior medical students are variably prepared to begin surgical training; and a national curriculum was established through the American College of Surgeons to better prepare senior medical students for surgical training. The purpose of our course is to prepare senior medical students to more effectively enter surgical training programs. We recently enhanced our independently developed surgical training preparation course by increasing exposure to surgical anatomy, medical physiology, surgical skills, and point-of-care ultrasound. We evaluated the impact of our interprofessional training course to increase confidence and readiness among senior medical students entering surgical training. METHODS: The course focused on pre- and post-operative patient care, surgical anatomy, human physiology, and bedside ultrasound. Didactic lectures in anatomy, human physiology, and bedside ultrasound were provided prior to all hands-on simulated patient care sessions and mock surgical procedures. To evaluate our interprofessional curriculum, we administered pre- and post-course surveys, pre- and post-course knowledge tests, and a final surgical anatomy laboratory practical examination to 22 senior medical students who were enrolled in the course. All students created a final surgical anatomy presentation. RESULTS: The students demonstrated a 100% pass rate in surgical anatomy. The knowledge test, which included assessment of knowledge on perioperative surgical decision making, human physiology, and bedside ultrasound, demonstrated an average improvement of 10%. Statistically significant improvements in median confidence values were identified in 10 of 32 surveyed categories, including surgical skills (p < 0.05); 84% of student goals for the course were achieved. The medical students' surveys confirmed increased confidence related to the use of point-of-care ultrasound, teamwork experience, and basic surgical skills through small group interactive seminars and surgical simulation exercises. CONCLUSION: Our preparation for surgical training course resulted in high student satisfaction and demonstrated an increased sense of confidence to begin surgical training. The 10% improvement in medical student knowledge, as evaluated by a written examination, and the significant improvement in confidence level self-assessment scores confirms this surgery preparation course for senior medical students successfully achieved the desired goals of the course.

Splenic artery loops: Potential splenic plexus stimulation sites for neuroimmunomodulatory-based anti-inflammatory therapy?

INTRODUCTION: The splenic plexus might represent a novel neuroimmunomodulatory therapeutic target as electrical stimulation of this tissue has been shown to have beneficial anti-inflammatory effects. Tortuous splenic artery segments (splenic artery loops), including their surrounding nerve plexus, have been evaluated as potential stimulation sites in humans. At present, however, our understanding of these loops and their surrounding nerve plexus is incomplete. This study aims to characterize the dimensions of these loops and their surrounding nerve tissue. MATERIALS AND METHODS: Six formaldehyde fixed human cadavers were dissected and qualitative and quantitative macro- and microscopic data on splenic artery loops and their surrounding nerve plexus were collected. RESULTS: One or multiple loops were observed in 83% of the studied specimens. These loops, including their surrounding nerve plexus could be easily dissected free circumferentially thereby providing sufficient space for further surgical intervention. The splenic plexus surrounding the loops contained a significant amount of nerves that contained predominantly sympathetic fibers. CONCLUSION: The results of this study support that splenic artery loops could represent suitable electrical splenic plexus stimulation sites in humans. Dimensions with respect to loop height and width, provide sufficient space for introduction of surgical instruments and electrode implantation, and, the dissected neurovascular bundles contain a substantial amount of sympathetic nerve tissue. This knowledge may contribute to further development of surgical techniques and neuroelectrode interface design.

Morphometric analysis of the splenic artery using contrast-enhanced computed tomography (CT).

PURPOSE: To evaluate the morphology and course of the splenic artery, which might impact the surgical implantation of systems that stimulate the nerves surrounding the splenic artery. Experimental studies indicate that these nerves play an important part in immune modulation, and might be a potential target in the treatment of autoimmune diseases. METHODS: This retrospective cohort study made use of contrast-enhanced CT images from 40 male and 40 female patients (age 30-69) that underwent a CT examination of the aorta, kidneys or pancreas. Anatomic features were described including total splenic artery length, calibers, tortuosity, the presence of arterial loops and the branching pattern of the splenic artery. RESULTS: No age-gender-related differences could be found related to tortuosity or branching pattern. The length of splenic artery in contact with pancreatic tissue decreased with increasing age, but was not different between genders. Artery diameters were wider in male compared to female subjects. Loops of variable directions, that represent a part of the artery that curls out of the pancreatic tissue, were identified in each age-gender category and were present in nearly all subjects (86%). CONCLUSION: This study suggests that although some anatomic features of the splenic artery are subject to factors as age and gender, the tortuosity of the splenic artery is not age dependent. Most subjects had one or multiple loops, which can serve as a target for neuromodulatory devices. Future studies should investigate whether splenic nerve stimulation is safe and feasible.

Prolonged Baroreflex Activation Abolishes Salt-Induced Hypertension After Reductions in Kidney Mass.

Chronic electric activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure and is currently being evaluated for therapy in patients with resistant hypertension. However, patients with significant impairment of renal function have been largely excluded from clinical trials. Thus, there is little information on blood pressure and renal responses to baroreflex activation in subjects with advanced chronic kidney disease, which is common in resistant hypertension. Changes in arterial pressure and glomerular filtration rate were determined in 5 dogs after combined unilateral nephrectomy and surgical excision of the poles of the remaining kidney to produce ≈70% reduction in renal mass. After control measurements, sodium intake was increased from ≈45 to 450 mol/d. While maintained on high salt, animals experienced increases in mean arterial pressure from 102±4 to 121±6 mm Hg and glomerular filtration rate from 40±2 to 45±2 mL/min. During 7 days of baroreflex activation, the hypertension induced by high salt was abolished (103±6 mm Hg) along with striking suppression of plasma norepinephrine concentration from 139±21 to 81±9 pg/mL, but despite pronounced blood pressure lowering, there were no significant changes in glomerular filtration rate (43±2 mL/min). All variables returned to prestimulation values during a recovery period. These findings indicate that after appreciable nephron loss, chronic suppression of central sympathetic outflow by baroreflex activation abolishes hypertension induced by high salt intake. The sustained antihypertensive effects of baroreflex activation occur without significantly compromising glomerular filtration rate in remnant nephrons.

Prediction of blunt traumatic injuries and hospital admission based on history and physical exam.

BACKGROUND: We evaluated the ability of experienced trauma surgeons to accurately predict specific blunt injuries, as well as patient disposition from the emergency department (ED), based only on the initial clinical evaluation and prior to any imaging studies. It would be hypothesized that experienced trauma surgeons' initial clinical evaluation is accurate for excluding life-threatening blunt injuries and for appropriate admission triage decisions. METHODS: Using only their history and physical exam, and prior to any imaging studies, three (3) experienced trauma surgeons, with a combined Level 1 trauma experience of over 50 years, predicted injuries in patients with an initial GCS (Glasgow Coma Score) of 14-15. Additionally, ED disposition (ICU, floor, discharge to home) was also predicted. These predictions were compared to actual patient dispositions and to blunt injuries documented at discharge. RESULTS: A total of 101 patients with 92 blunt injuries were studied. 43/92 (46.7 %) injuries would have been missed by only performing an initial history and physical exam ("Missed injury"). A change in treatment, though often minor, was required in 19/43 (44.2 %) of the missed injuries. Only 1/43 (2.3 %) of these "missed injuries" (blunt aortic injury) required surgery. Sensitivity, specificity, and accuracy for injury prediction were 53.2, 95.9, and 92.3 % respectively. Positive and negative predictive values were 53.8 and 95.8 % respectively. Prediction of disposition from the ED was 77.8 % accurate. In 7/34 (20.6 %) patients, missed injuries led to changes in disposition. "Undertriage" occurred in 9/99 (9.1 %) patients (Predicted for floor but admitted to ICU). Additionally, 8/84 (9.5 %) patients predicted for floor admission were sent home from the ED; and 5/13 (38.5 %) patients predicted for ICU admission were actually sent to the floor after complete evaluations, giving an "overtriage" rate of 13/99 (13.1 %) patients. CONCLUSIONS: In a neurologically-intact group of trauma patients, experienced trauma surgeons would have missed 46.7 % of the actual injuries, based only on their history and physical exam. Once accurate diagnoses of injuries were completed, usually with the help of CT scans, admission dispositions changed in 20.6 % of patients. Treatment changes occurred in 44.2 % of the missed injuries, though usually minimal. Broad elimination of early imaging studies in alert, blunt trauma patients cannot be advocated.

Wells criteria for DVT is a reliable clinical tool to assess the risk of deep venous thrombosis in trauma patients.

BACKGROUND: Deep Vein Thrombosis (DVT) is a common complication in trauma patients. Venous duplex surveillance is used widely for the diagnosis of DVT, however, there is controversy concerning its appropriate use. The Wells criterion is a clinically validated scoring system in an outpatient setting, but its use in trauma patients has not been studied. This study evaluated the application of the Wells scoring system in trauma population. METHODS: Wells scores were calculated retrospectively for all patients who were admitted to the trauma service and underwent Venous Duplex Scanning (VDS) at the author's institution between 2012 and 2013. Correlation of Wells score with DVT and its efficacy in risk stratifying the patients after trauma was analyzed using linear correlation and receiver operating characteristic (ROC) curve. Sensitivity and specificity of Wells score in ruling out or ruling in DVT were calculated in various risk groups. RESULTS: Of 298 patients evaluated, 18 (6 %) patients were positive for DVT. A linear correlation was present between Wells score and DVT with R (2) = 0.88 (p = 0.0016). Median Wells score of patients without DVT was 1 (1-3) compared to a median score of 2 (1-5) in those with DVT (p < 0.0001). In low risk patients (scores <1), Wells scoring was able to rule out the possibility of DVT with a sensitivity of 100 % and NPV of 100 %, while in moderate-high risk patients (scores ≥2), it was able to predict DVT with a specificity of 90 %. Area under ROC curve was 0.859 (p < 0.0001) demonstrating the accuracy of Wells scoring system for DVT risk stratification in post trauma patients. CONCLUSIONS: A Wells score of <1 can reliably rule out the possibility of DVT in the trauma patients. Risk of developing DVT correlates linearly with Wells score, establishing it as a valid pretest tool for risk stratification.

Chronic Interactions Between Carotid Baroreceptors and Chemoreceptors in Obesity Hypertension.

Carotid bodies play a critical role in protecting against hypoxemia, and their activation increases sympathetic activity, arterial pressure, and ventilation, responses opposed by acute stimulation of the baroreflex. Although chemoreceptor hypersensitivity is associated with sympathetically mediated hypertension, the mechanisms involved and their significance in the pathogenesis of hypertension remain unclear. We investigated the chronic interactions of these reflexes in dogs with sympathetically mediated, obesity-induced hypertension based on the hypothesis that hypoxemia and tonic activation of carotid chemoreceptors may be associated with obesity. After 5 weeks on a high-fat diet, the animals experienced a 35% to 40% weight gain and increases in arterial pressure from 106±3 to 123±3 mm Hg and respiratory rate from 8±1 to 12±1 breaths/min along with hypoxemia (arterial partial pressure of oxygen=81±3 mm Hg) but eucapnia. During 7 days of carotid baroreflex activation by electric stimulation of the carotid sinus, tachypnea was attenuated, and hypertension was abolished before these variables returned to prestimulation values during a recovery period. After subsequent denervation of the carotid sinus region, respiratory rate decreased transiently in association with further sustained reductions in arterial partial pressure of oxygen (to 65±2 mm Hg) and substantial hypercapnia. Moreover, the severity of hypertension was attenuated from 125±2 to 116±3 mm Hg (45%-50% reduction). These findings suggest that hypoxemia may account for sustained stimulation of peripheral chemoreceptors in obesity and that this activation leads to compensatory increases in ventilation and central sympathetic outflow that contributes to neurogenically mediated hypertension. Furthermore, the excitatory effects of chemoreceptor hyperactivity are abolished by chronic activation of the carotid baroreflex.

Non-weight-based enoxaparin dosing subtherapeutic in trauma patients.

BACKGROUND: We report our experience dosing and monitoring enoxaparin with anti-factor Xa activity (anti-FXaA) levels for venous thromboembolism prophylaxis in trauma patients (TP). MATERIALS AND METHODS: TP receiving standard, non-weight-based dosed enoxaparin administered every 12 h for venous thromboembolism prophylaxis with peak anti-FXaA levels measured were prospectively monitored and evaluated and those whose first anti-FXaA levels ≥ or <0.2 IU/mL were compared. Anti-FXaA levels and enoxaparin dose (mg/kg actual body weight) were evaluated for correlation. RESULTS: Of the fifty-one TP included, initial anti-FXaA levels were <0.2 IU/mL in 37 (72.5%) whose dose was lower than those within target range (0.38 [0.32-0.42] mg/kg versus 0.45 [0.39-0.48] mg/kg, P = 0.003). Thirty-seven TP achieved anti-FXaA level ≥0.2 IU/mL (23 requiring dose increases) at a dose of 0.49 [0.44-0.54] mg/kg. Correlation between dose and anti-FXaA levels for the initial 51 anti-FXaA levels (r = 0.360, P = 0.009) and for all 103 anti-XaA levels (r = 0.556, P < 0.001) was noted. CONCLUSIONS: Non-weight-based enoxaparin dosing did not achieve target anti-FXaA levels in most TP. Higher anti-FXaA levels correlated with larger weight-based enoxaparin doses. Weight-based enoxaparin dosing (i.e., 0.5 mg/kg subcutaneously every 12 h) would better achieve target anti-FXaA levels.

Global- and renal-specific sympathoinhibition in aldosterone hypertension.

Recent technology for chronic electric activation of the carotid baroreflex and renal nerve ablation provide global and renal-specific suppression of sympathetic activity, respectively, but the conditions for favorable antihypertensive responses in resistant hypertension are unclear. Because inappropriately high plasma levels of aldosterone are prevalent in these patients, we investigated the effects of baroreflex activation and surgical renal denervation in dogs with hypertension induced by chronic infusion of aldosterone (12 µg/kg per day). Under control conditions, basal values for mean arterial pressure and plasma norepinephrine concentration were 100±3 mm Hg and 134±26 pg/mL, respectively. By day 7 of baroreflex activation, plasma norepinephrine was reduced by ≈40% and arterial pressure by 16±2 mm Hg. All values returned to control levels during the recovery period. Arterial pressure increased to 122±5 mm Hg concomitant with a rise in plasma aldosterone concentration from 4.3±0.4 to 70.0±6.4 ng/dL after 14 days of aldosterone infusion, with no significant effect on plasma norepinephrine. After 7 days of baroreflex activation at control stimulation parameters, the reduction in plasma norepinephrine was similar but the fall in arterial pressure (7±1 mm Hg) was diminished (≈55%) during aldosterone hypertension when compared with control conditions. Despite sustained suppression of sympathetic activity, baroreflex activation did not have central actions to inhibit either the stimulation of vasopressin secretion or drinking induced by increased plasma osmolality during chronic aldosterone infusion. Finally, renal denervation did not attenuate aldosterone hypertension. These findings suggest that aldosterone excess may portend diminished blood pressure lowering to global and especially renal-specific sympathoinhibition during device-based therapy.

Computed tomography scans with intravenous contrast: low incidence of contrast-induced nephropathy in blunt trauma patients.

BACKGROUND: Computed tomography (CT) with intravenous (IV) contrast is an important step in the evaluation of the blunt trauma patient; however, the risk for contrast-induced nephropathy (CIN) in these patients still remains unclear. The goal of this study was to describe the rate of CIN in blunt trauma patients at a Level 1 trauma center and identify the risk factors of developing CIN. METHODS: After internal review board approval, we reviewed our Level 1 trauma registry to identify blunt trauma patients admitted during a 1-year period. Chart review was used to identify patient demographics, creatinine levels, and vital signs. CIN was defined as an increase in creatinine by 0.5 mg/dL from admission after undergoing CT with IV contrast. RESULTS: Four percent of patients developed CIN during their admission following receipt of IV contrast for CT; 1% had continued renal impairment on discharge. No patients required dialysis during their admission. Diabetic patients had an increased rate of CIN, with 10% rate of CIN during admission and 4% at discharge. In multivariate analysis, only preexisting diabetes and Injury Severity Score (ISS) of greater than 25 were independently associated with risk for CIN. CONCLUSION: The rate of CIN in trauma patients following CT scan with IV contrast is low. Diabetes and ISS were independent risk factors of development of CIN in trauma patients. LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III.

Regulation of renin secretion and arterial pressure during prolonged baroreflex activation: influence of salt intake.

Chronic electric activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure and is currently being evaluated as antihypertensive therapy for patients with resistant hypertension. However, the influence of variations in salt intake on blood pressure lowering during baroreflex activation (BA) has not yet been determined. As the sensitivity of arterial pressure to salt intake is linked to the responsiveness of renin secretion, we determined steady-state levels of arterial pressure and neurohormonal responses in 6 dogs on low, normal, and high salt intakes (5, 40, 450 mmol/d, respectively) under control conditions and during a 7-day constant level of BA. Under control conditions, there was no difference in mean arterial pressure at low (92±1) and normal (92±2 mm Hg) sodium intakes, but pressure increased 9±2 mm Hg during high salt. Plasma renin activity (2.01±0.23, 0.93±0.20, 0.01±0.01 ng angiotensin I/mL/h) and plasma aldosterone (10.3±1.9, 3.5±0.5, 1.7±0.1 ng/dL) were inversely related to salt intake, whereas there were no changes in plasma norepinephrine. Although mean arterial pressure (19-22 mm Hg) and norepinephrine (20%-40%) were lower at all salt intakes during BA, neither the changes in pressure nor the absolute values for plasma renin activity or aldosterone in response to salt were different from control conditions. These findings demonstrate that suppression of sympathetic activity by BA lowers arterial pressure without increasing renin release and indicate that changes in sympathetic activity are not primary mediators of the effect of salt on renin secretion. Consequently, blood pressure lowering during BA is independent of salt intake.

Comparison of 3-Factor Prothrombin Complex Concentrate and Low-Dose Recombinant Factor VIIa for Warfarin Reversal.

INTRODUCTION: Prothrombin complex concentrate (PCC) and recombinant Factor VIIa (rFVIIa) have been used for emergent reversal of warfarin anticoagulation. Few clinical studies have compared these agents in warfarin reversal. We compared warfarin reversal in patients who received either 3 factor PCC (PCC3) or low-dose rFVIIa (LDrFVIIa) for reversal of warfarin anticoagulation. METHODS: Data were collected from medical charts of patients who received at least one dose of PCC3 (20 units/kg) or LDrFVIIa (1000 or 1200 mcg) for emergent warfarin reversal from August 2007 to October 2011. The primary end-points were achievement of an INR 1.5 or less for efficacy and thromboembolic events for safety. RESULTS: Seventy-four PCC3 and 32 LDrFVIIa patients were analyzed. Baseline demographics, reason for warfarin reversal, and initial INR were equivalent. There was no difference in the use of vitamin K or fresh frozen plasma. More LDrFVIIa patients achieved an INR of 1.5 or less (71.9% vs. 33.8%, p =0.001). The follow-up INR was lower after LDrFVIIa (1.25 vs. 1.75, p < 0.05) and the percent change in INR was larger after LDrFVIIa (54.1% vs. 38.8%, p = 0.002). There was no difference in the number of thromboembolic events (2 LDrFVIIa vs. 5 PCC3, p = 1.00), mortality, length of hospital stay, or cost. CONCLUSIONS: Based on achieving a goal INR of 1.5 or less, LDrFVIIa was more likely than PCC3 to reverse warfarin anticoagulation. Thromboembolic events were equivalent in patients receiving PCC3 and LDrFVIIa.

A prospective study of the role of sleep related disordered breathing as a risk factor for motor vehicle crashes and the development of systemic complications in non-commercial drivers.

INTRODUCTION: Sleep related disordered breathing (SRDB), is an established risk factor for motor vehicle crashes (MVCs) involving commercial drivers. The role of SRDB in motor vehicle crashes involving non-commercial drivers is not well established. METHODS: Drivers involved in MVCs who were admitted to an American College of Surgeons accredited Level I trauma center for treatment of their injuries, and who could give informed consent and provide verbal responses to screening questionnaires were eligible for enrolment in this study. Two questionnaires previously validated for screening patients at risk for sleep disturbances (The Epworth Sleepiness Scale (ESS) and The Berlin Questionnaire (BQ)) were administered. Questionnaire results associated with an 85% sensitivity for predicting obstructive sleep apnea were considered positive. In this study we tested the hypothesis that patients at risk for SRDB, as measured by validated questionnaires, are at an increased risk being involved in MVCs. RESULTS: Between March and October 2010, 71 consecutive patients were offered enrolment in this study with 56 agreeing to participate in this study. Six were previously diagnosed with SRDB with only one being compliant and effectively treated at the time of their MVC. Forty-two patients (75%) had responses to the questionnaires that indicated that the patients were at high risk for SRDB. Six patients suffered systemic complications, including pleural effusions, pneumonia and arrhythmias, during their hospitalization with five (83%) having abnormal questionnaire responses indicating that the patient was at high risk for SRDB. CONCLUSIONS: The high incidence of positive responses to the sleep questionnaires is consistent with the hypothesis that SRDB is potentially a significant risk factor for MVCs. Furthermore the observation that systemic complications were seen more commonly in those with SRDB, while not unexpected, is a novel observation. Further studies are needed to validate these findings in a larger cohort of patients as well as determining if these patients are truly at a greater risk for systemic complications. If replicated these observations would suggest that effective therapy for disordered sleep could play a significant role in an injury prevention process.

Chronic baroreflex activation restores spontaneous baroreflex control and variability of heart rate in obesity-induced hypertension.

The sensitivity of baroreflex control of heart rate is depressed in subjects with obesity hypertension, which increases the risk for cardiac arrhythmias. The mechanisms are not fully known, and there are no therapies to improve this dysfunction. To determine the cardiovascular dynamic effects of progressive increases in body weight leading to obesity and hypertension in dogs fed a high-fat diet, 24-h continuous recordings of spontaneous fluctuations in blood pressure and heart rate were analyzed in the time and frequency domains. Furthermore, we investigated whether autonomic mechanisms stimulated by chronic baroreflex activation and renal denervation-current therapies in patients with resistant hypertension, who are commonly obese-restore cardiovascular dynamic control. Increases in body weight to ∼150% of control led to a gradual increase in mean arterial pressure to 17 ± 3 mmHg above control (100 ± 2 mmHg) after 4 wk on the high-fat diet. In contrast to the gradual increase in arterial pressure, tachycardia, attenuated chronotropic baroreflex responses, and reduced heart rate variability were manifest within 1-4 days on high-fat intake, reaching 130 ± 4 beats per minute (bpm) (control = 86 ± 3 bpm) and ∼45% and <20%, respectively, of control levels. Subsequently, both baroreflex activation and renal denervation abolished the hypertension. However, only baroreflex activation effectively attenuated the tachycardia and restored cardiac baroreflex sensitivity and heart rate variability. These findings suggest that baroreflex activation therapy may reduce the risk factors for cardiac arrhythmias as well as lower arterial pressure.

Prospective, protocolized study evaluating effects of antibiotics on sputum culture results in injured patients.

BACKGROUND: Appropriate utilization of antibiotics for critically ill patients involves tailoring the drug to culture results; however, the culture results must be reliable. We hypothesized that antimicrobial agents reduce significantly the reliability of cultures obtained between 1 and 24 h after antibiotic administration. METHODS: Patients were eligible for the study if they were ventilated mechanically and were suspected to have pneumonia. After enrollment, sputum cultures were obtained, and broad-spectrum antibiotics were started. Sputum cultures were repeated at 1, 6, 12, and 24 h after delivery of the first dose of antibiotic. Twenty-one patients whose initial culture was positive were included in the analysis. Their average age was 49.4 years, and the average Injury Severity Score was 27.7 points. RESULTS: The average intensive care unit and hospital lengths of stay were 20.2 days and 24.7 days, respectively. All of the organisms grown from the pre-antibiotic cultures also grew in the cultures obtained 1 h after antibiotics were given. However, a significant number of these organisms were unable to be grown in subsequent cultures. The rate of negative cultures increased to 21%, 32%, and 42% in the 6-, 12-, and 24-h groups (p<0.01), respectively. Gram-positive organisms accounted for 42.9% of infections, with Staphylococcus aureus being the most common. All patients positive for S. aureus prior to antibiotic administration remained positive at each subsequent time. By 6 h, 21.5% of the gram-negative organisms could no longer be cultured. At 12 h, among the gram-positive organisms, 11 of 12 cultures were still positive, whereas only 50% of gram-negative organisms were still recoverable. CONCLUSION: Antibiotics have a substantial effect on culture results that is most pronounced in gram-negative organisms and is observed in cultures obtained beginning 1 h after antibiotics are given. As a result, cultures obtained more than 1 h after antibiotics are started cannot be used to tailor antibiotic choice in injured patients with suspected infections.

Therapeutic anticoagulation can be safely accomplished in selected patients with traumatic intracranial hemorrhage.

INTRODUCTION: Therapeutic anticoagulation is an important treatment of thromboembolic complications, such as DVT, PE, and blunt cerebrovascular injury. Traumatic intracranial hemorrhage has traditionally been considered to be a contraindication to anticoagulation. HYPOTHESIS: Therapeutic anticoagulation can be safely accomplished in select patients with traumatic intracranial hemorrhage. METHODS: Patients who developed thromboembolic complications of DVT, PE, or blunt cerebrovascular injury were stratified according to mode of treatment. Patients who underwent therapeutic anticoagulation with a heparin infusion or enoxaparin (1 mg/kg BID) were evaluated for neurologic deterioration or hemorrhage extension by CT scan. RESULTS: There were 42 patients with a traumatic intracranial hemorrhage that subsequently developed a thrombotic complication. Thirty-five patients developed a DVT or PE. Blunt cerebrovascular injury was diagnosed in four patients. 26 patients received therapeutic anticoagulation, which was initiated an average of 13 days after injury. 96% of patients had no extension of the hemorrhage after anticoagulation was started. The degree of hemorrhagic extension in the remaining patient was minimal and was not felt to affect the clinical course. CONCLUSION: Therapeutic anticoagulation can be accomplished in select patients with intracranial hemorrhage, although close monitoring with serial CT scans is necessary to demonstrate stability of the hemorrhagic focus.

Renal responses to chronic suppression of central sympathetic outflow.

Chronic electric activation of the carotid baroreflex produces sustained reductions in sympathetic activity and arterial pressure and is currently being evaluated as hypertension therapy for patients with resistant hypertension. However, the chronic changes in renal function associated with natural suppression of sympathetic activity are largely unknown. In normotensive dogs, we investigated the integrative cardiovascular effects of chronic baroreflex activation (2 weeks) alone and in combination with the calcium channel blocker amlodipine, which is commonly used in the treatment of resistant hypertension. During baroreflex activation alone, there were sustained decreases in mean arterial pressure (17±1 mmHg) and plasma (norepinephrine; ≈35%), with no change in plasma renin activity. Despite low pressure, sodium balance was achieved because of decreased tubular reabsorption, because glomerular filtration rate and renal blood flow decreased 10% to 20%. After 2 weeks of amlodipine, arterial pressure was also reduced 17 mmHg, but with substantial increases in norepinephrine and plasma renin activity and no change in glomerular filtration rate. In the presence of amlodipine, baroreflex activation greatly attenuated neurohormonal activation, and pressure decreased even further (by 11±2 mmHg). Moreover, during amlodipine administration, the fall in glomerular filtration rate with baroreflex activation was abolished. These findings suggest that the chronic blood pressure-lowering effects of baroreflex activation are attributed, at least in part, to sustained inhibition of renal sympathetic nerve activity and attendant decreases in sodium reabsorption before the macula densa. Tubuloglomerular feedback constriction of the afferent arterioles may account for reduced glomerular filtration rate, a response abolished by amlodipine, which dilates the preglomerular vasculature.