Ann V. Robinson

Role of gastric colonization in the development of pneumonia in critically ill trauma patients : results of a prospective randomized trial. Discussion

Critically ill trauma patients were entered in a prospective, randomized trial to determine the role of gastric colonization in the development of pneumonia. Trauma patients admitted to the SICU were randomized to receive antacids (n = 27), continuous IV cimetidine (n = 32), or sucralfate (n = 30). Quantitative nasogastric tube (NGT) cultures were obtained biweekly and correlated with gastric pH, the incidence of pneumonia, and the incidence of pneumonia caused by an organism previously isolated from the stomach (percentage of gastric source of pneumonia--% GSP). Patients receiving antacids had a significantly greater pH than those receiving cimetidine (5.6 +/- 1.03 vs. 4.7 +/- 1.03; p = 0.006). However, there was no significant difference between the overall incidence of pneumonia, the percentage of NGT isolates greater than 10(6)/ml, or the % GSP. The gastric bacteriology of the three subgroups was nearly identical, with Candida albicans, Enterococci, and beta-hemolytic Streptococci being the most frequently isolated organisms. Gastric growth of organisms preceding their appearance in the blood occurred in 5 of 89 (5.6%) patients. These results suggest that 1) in trauma patients, the incidence of pneumonia is not increased by the use of stress ulcer prophylactic agents that elevate gastric pH; 2) increases in gastric pH progressively increased the number of intragastric bacteria but this did not correlate with an increased incidence of % GSP; and 3) while organisms in the upper intestinal tract may be pathogens for pneumonia, they are uncommonly a source of bacteremia in seriously injured patients.

Should bariatric revisional surgery be avoided secondary to increased morbidity and mortality

BACKGROUND Revisional bariatric surgery may be necessary due to inadequate weight loss or postoperative complications of the primary operation. We sought to identify the reasons for revision, characteristics of the surgery, and outcomes. We hypothesize that revisional surgery, although technically challenging, can produce desirable outcomes. METHODS Patients undergoing bariatric surgery at our institution between 1998 and 2007 were reviewed from a prospective database. Patients who had revisional surgery were compared to those who had primary surgery. RESULTS We have identified 46 of 1,038 patients who underwent revisional surgery. Twenty of 46 had a primary Roux-en-Y gastric bypass. The most common indication for revisions is inadequate weight loss secondary to gastrogastric fistula (15/20). Leaks occurred more frequently following revisional surgeries (11% vs 1.2%), but intensive care unit (ICU) utilization was less (11% vs 4.4%) and mortality was lower (0% vs .3%) with bariatric revision surgery. CONCLUSIONS Although we saw a 9-fold increase in leaks, a 2-5 fold increase in ICU utilization, and 1.5-fold increase in length of stay, our mortality rate was zero. In experienced hands, bariatric revision surgery can be performed to produce desirable outcomes.

The use of the endothelin receptor antagonist, tezosentan, before or after renal ischemia protects renal function

Background. Utilization of organs subjected to ischemia/reperfusion (I/R) injury could expand the donor pool. Endothelin (ET) is implicated in renal I/R injury. Therefore, our study compared the effectiveness of pre- and postischemic administration of the ET receptor antagonist, Tezosentan, in preserving renal function. Methods. In a rat model, a kidney was subjected to 45 min of ischemia along with a contralateral nephrectomy. After 24 hr of reperfusion, renal function was assessed by serum creatinine (Scr), inulin clearance (glomerular filtration rate; GFR), and histology. ET-1 peptide expression was localized using immunohistochemistry. Three groups were studied: I/R untreated (n=17), I/R pretreated (n=11), and I/R posttreated (n=13) with Tezosentan (15 mg/kg, i.v.). Results. Tezosentan significantly decreased ( P <0.05) the rise in Scr from I/R injury (2.0±0.4 mg/dl, before and 2.9±0.4 mg/dl, after treatment) compared with untreated animals (4.2±0.4 mg/dl). GFR was significantly increased ( P <0.05) from 0.13±0.03 ml/min (untreated animals) to 0.74±0.16 and 0.47±0.14 ml/min (pre- and posttreated animals). Untreated animals had significant cortical acute tubular necrosis, which was almost completely prevented by pretreatment with Tezosentan and markedly reduced by posttreatment. Increased ET-1 peptide expression was noted in the renal vasculature and in the cortical tubular epithelium of kidneys exposed to I/R. Conclusions. The purpose of this study was to optimize the function of kidneys exposed to I/R injury. Pretreatment as well as posttreatment with Tezosentan successfully decreased Scr, increased GFR, and maintained renal architecture in kidneys after ischemia. Therefore, ET receptor antagonists may be useful to preserve renal function in the transplantation setting.

Computed tomography before transfer to a level I pediatric trauma center risks duplication with associated increased radiation exposure

INTRODUCTION Community hospitals commonly obtain computed tomographic (CT) imaging of pediatric trauma patients before triaging to a level I pediatric trauma center (PTC). This practice potentially increases radiation exposure when imaging must be duplicated after transfer. METHODS A retrospective review of our level 1 PTC registry from January 1, 2004, to December 31, 2006, was conducted. Level I and II trauma patients were grouped based on whether they had undergone outside CT examination (head and/or abdomen) at a referring hospital (group 1) or received initial CT examination at our institution (group 2). Subgroups were analyzed based on whether duplicate CT examination was required at our PTC (Fischers Exact test). RESULTS A duplicate CT scan (within 4 hours of transfer) was required in 91% (30/33) of group 1 transfer patients, whereas no group 2 patient required a duplicate scan (0/55; P < .0001). There was no significant difference within the groups for weight, age, or intensive care unit length of stay. CONCLUSION A significant number of pediatric trauma patients who receive CT scans at referring hospitals before transfer to our level I PTC require duplicate scans of the same anatomical field(s) after transfer, exposing them to increase potential clinical risk and cost.

Inhibition of endothelin-converting enzyme attenuates transplant vasculopathy and rejection in rat cardiac allografts.

BACKGROUND Transplant vasculopathy in kidney and heart allografts is associated with marked elevation of endothelin-1 (ET-1), but a role for ET-1 in the pathogenesis of transplant vasculopathy and chronic rejection has not been established. We, therefore, tested whether inhibition of ET-1-converting enzyme by phosphoramidon (PA) would attenuate rejection in a rat model of chronic cardiac allograft rejection (Lewis [LEW] to F344). METHODS Donor LEW rats were pretreated 24 hr before transplantation with a bolus injection of vehicle (water) or PA. Twenty- four hour after transplantation, water or PA was continuously administered through an osmotic mini-pump. Plasma ET-1 levels in Fisher 344 (F344) recipients were 0.8+/-0.1 pg/ml in water-treated rats and 0.2+/-0.2 pg/ml (P<0.01) in PA-treated rats, demonstrating that the PA treatment protocol effectively lowered ET-1 biosynthesis. RESULTS LEW cardiac allografts treated with water survived (i.e., palpable heart beat) for 16.0+/-0.5 days (n=6). Inhibition of ET-1 secretion by PA improved allograft survival to 28.8+/-3.3 days (P<0.01, n=8). An analysis of cardiac arteries demonstrated that PA treatment attenuated transplant vasculopathy. A morphometric scale of neointima formation (0-5) was 1.4+/-0.2 and 3.6+/-0.2 in PA- or water-treated rats, respectively (P<0.01). The percent of luminal occlusion, as measured by microscopic image analysis, was 19+/-6% in PA-treated animals and 38+/-6% (P<0.01) in animals treated with water. PA treatment also reduced infiltration of ED-1-positive monocytes/macrophages into the vascular neointima. CONCLUSIONS We conclude that, even in the absence of concomitant immunosuppression, inhibition of ET-1 biosynthesis significantly attenuates transplant vasculopathy and improves survival of LEW to F344 cardiac allografts.

Inhibition of endothelin-1 improves survival and vasculopathy in rat cardiac transplants treated with cyclosporine.

Background. In animal models, endothelin-1 (ET-1) blockade attenuates transplant vasculopathy and chronic allograft dysfunction even in the absence of cyclosporine (CsA). As CsA has side effects and ET-1 antagonism alone has significant benefits, we postulated that allograft survival could be significantly improved by combining an endothelin-converting enzyme inhibitor with low-dose CsA. Methods. Survival of Lewis to Fisher 344 rat heterotopic cardiac allografts was determined in untreated animals and compared with those treated with high-dose CsA (62 mg/kg i.m. on day 2), low-dose CsA (25 mg/kg), an endothelin-converting enzyme inhibitor, phosphoramidon (PA, 10 mg/kg/day), or low-dose CsA + PA. Results. Untreated allografts had a median survival of 16 days compared with 20 days for low-dose CsA. Grafts treated with PA survived for 28 days, and combination of PA and low-dose CsA improved median survival to 47 days (P <0.01). Median survival with combination therapy was similar to that for high-dose CsA (42 days). To explore mechanisms underlying the benefits of combination therapy, cardiac allografts treated as above (n=4 each group) were explanted at 20 d and analyzed for parenchymal rejection, neointimal vasculopathy, myocardial fibrosis, and macrophage infiltration. Low-dose CsA alone but not PA improved parenchymal rejection; in contrast, PA alone but not low-dose CsA improved vasculopathy. Both parenchymal rejection and vasculopathy were improved by combination therapy with low-dose CsA and PA. Unlike CsA, inhibition of ET-1 biosynthesis significantly reduced myocardial fibrosis in allografts. Conclusions. These results suggest that the combination of low-dose CsA and endothelin-converting enzyme inhibition may prove useful to improve long-term graft survival while minimizing potential side effects of CsA.

Relationship of serum C-reactive protein and blood glucose levels with injury severity and patient morbidity in a pediatric trauma population

PURPOSE Serum markers of inflammation and of glucose production are known to reflect the immediate metabolic response to injury. We hypothesized that monitoring of the early C-reactive protein (CRP) and blood glucose (BG) concentrations would correlate with clinical morbidity and outcome measures in pediatric trauma patients. METHODS A five-year retrospective chart review of pediatric trauma patients admitted to our Level I pediatric trauma center was conducted to establish the relationships between early (first 3 hospital days) serum CRP and BG concentrations, Injury Severity Score (ISS), and hospital length of stay (HLOS). Statistical significance (P < 0.05) was determined using Students t-test. RESULTS Forty-two trauma patients (8.0 +/- 5.2 years) were evaluated. The early inflammatory response (CRP >or= 10 vs <10 mg/dl) was significantly correlated to the glycemic response (BG;121 +/- 24 vs 97.3 +/- 14.2 mg/dl, P < 0.05). Severely injured patients (ISS >or= 25 vs <25) were significantly more hyperglycemic (BG;156 +/- 56.9 vs 125 +/- 31.6 mg/dL, P = 0.003). Both increased inflammatory response (CRP;8.1 +/- 6.4 vs 2.5 +/- 3.5 mg/dL) and increased glycemic response (BG;111 +/- 15.9 vs 97.4 +/- 11.7 mg/dL) were independently and significantly associated with prolonged hospitalization (HLOS > 7 vs <or=7 days, P < 0.05). CONCLUSION This study establishes a significant relationship between the early inflammatory and glycemic injury response and the association of that response with pediatric trauma patient morbidity and outcome measures.

Effect of hypoxia on renal flow.

The isolated perfused rat kidney was used to characterize the renal response to hypoxia while flow was maintained. Hypoxia resulted in an 85% reduction in glomerular filtration rate (GFR) without any change in total renal vascular resistance. There was an initial 85% increase in urine flow rate (UV) and a 45% decrease in percent sodium reabsorption due to hypoxic metabolic inhibition of solute reabsorption. As GFR decreased, UV declined to 50% of control. GFR did not increase on reoxygenation. These results suggest that an intrinsic protective tubuloglomerular feedback mechanism is activated during hypoxia that redistributes intrarenal flow to reduce the filtered load and to reduce oxygen demand for solute reabsorption. Delivery of oxygen to the hypoxia-sensitive medulla would also be improved. Decreases in GFR observed with ischemic models of acute renal failure may reflect this protective mechanism in addition to the effects of ischemic injury.

Relationship of critical uptake volume to energy production and endotoxemia in late hemorrhagic shock

Abstract The appearance of endotoxemia and uncoupling of oxidative phosphorylation coincided with progressive uptake from the reservoir in a murine model of late hemorrhagic shock. Reinfusion with Ringers lactate rather than shed blood suggested that the endotoxemia was causally related to mitochondrial dysfunction. The mitochondrial dysfunction per se did not appear related to the uptake phenomenon. The shed blood in the reservoir had a high frequency of detectable endotoxin. The animals to be infused with Ringers lactate had a significantly more rapid appearance of the uptake phenomenon, probably due to intrinsic, variation in the biologic model.

A model of hypoxic renal failure.

Models of ischemic acute renal failure (ARF) must consider the combination of tissue hypoxia, insufficient nutrient flow, and anaerobic waste product accumulation. This study utilized isolated perfused rat kidneys to characterize the renal response to a graded hypoxic insult while maintaining flow. Kidneys were perfused at 37 degrees C with an asanguineous Krebs-buffered saline. After a 40-min baseline period, 10 or 30 min of hypoxia was rapidly achieved by reducing perfusate oxygen tension from approximately 550 to 50 mm Hg. Ten minutes of hypoxia resulted in tubular dysfunction evidenced by a 50% increase in urine flow (UV) and a 10% decrease in percent sodium reabsorption (%Na). Glomerular filtration rate (GFR) decreased by 40% during 10 min of hypoxia and returned to control levels after reoxygenation. Thirty minutes of hypoxia caused an irreversible 85% decrease in GFR accompanied by a 50% decrease in UV. This insult also caused more severe tubular dysfunction evidenced by a 20% decrease in %Na and a 35% decrease in oxygen consumption. These results demonstrate a spectrum of renal dysfunction that corresponds to the clinical spectrum from nonoliguric to oliguric ARF. This model of hypoxic ARF allows more specific investigation into the hypoxic component of postischemic renal dysfunction.