Increased platelet:RBC ratios are associated with improved survival after massive transfusion.

BACKGROUND: Several recent military and civilian trauma studies demonstrate that improved outcomes are associated with early and increased use of plasma-based resuscitation strategies. However, outcomes associated with platelet transfusions are poorly characterized. We hypothesized that increased platelet:red blood cells (RBC) ratios would decrease hemorrhagic death and improve survival after massive transfusion (MT). METHODS: A transfusion database of patients transported from the scene to 22 Level I Trauma Centers over 12 months in 2005 to 2006 was reviewed. MT was defined as receiving ≥ 10 RBC units within 24 hours of admission. To mitigate survival bias, 25 patients who died within 60 minutes of arrival were excluded from analysis. Six random donor platelet units were considered equal to a single apheresis platelet unit. Admission and outcome data associated with the low (>1:20), medium (1:2), and high (1:1) platelet:RBC ratios were examined. These groups were based on the median value of the tertiles for the ratio of platelets:RBC units. RESULTS: Two thousand three hundred twelve patients received at least one unit of blood and 643 received an MT. Admission vital signs, INR, temperature, pH, Glasgow Coma Scale, Injury Severity Score, and age were similar between platelet ratio groups. The average admission platelet counts were lower in the patients who received the high platelet:RBC ratio versus the low ratio (192 vs. 216, p = 0.03). Patients who received MT were severely injured, with a mean (± standard deviation) Injury Severity Score of 33 ± 16 and received 22 ± 15 RBCs and 11 ± 14 platelets within 24 hours of injury. Increased platelet ratios were associated with improved survival at 24 hours and 30 days (p < 0.001 for both). Truncal hemorrhage as a cause of death was decreased (low: 67%, medium: 60%, high: 47%, p = 0.04). Multiple organ failure mortality was increased (low: 7%, medium: 16%, high: 27%, p = 0.003), but overall 30-day survival was improved (low: 52%, medium: 57%, high: 70%) in the high ratio group (medium vs. high: p = 0.008; low vs. high: p = 0.007). CONCLUSION: Similar to recently published military data, transfusion of platelet:RBC ratios of 1:1 was associated with improved early and late survival, decreased hemorrhagic death and a concomitant increase in multiple organ failure-related mortality. Based on this large retrospective study, increased and early use of platelets may be justified, pending the results of prospective randomized transfusion data.

Differential induction of PPAR-gamma by luminal glutamine and iNOS by luminal arginine in the rodent postischemic small bowel.

Using a rodent model of gut ischemia-reperfusion (I/R), we have previously shown that the induction of inducible nitric oxide synthase (iNOS) is harmful, whereas the induction of heme oxygenase 1 (HO-1) and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is protective. In the present study, we hypothesized that the luminal nutrients arginine and glutamine differentially modulate these molecular events in the postischemic gut. Jejunal sacs were created in rats at laparotomy, filled with either 60 mM glutamine, arginine, or magnesium sulfate (osmotic control) followed by 60 min of superior mesenteric artery occlusion and 6 h of reperfusion, and compared with shams. The jejunum was harvested for histology or myeloperoxidase (MPO) activity (inflammation). Heat shock proteins and iNOS were quantitated by Western blot analysis and PPAR-gamma by DNA binding activity. In some experiments, rats were pretreated with the PPAR-gamma inhibitor G9662 or with the iNOS inhibitor N-[3(aminomethyl)benzyl]acetamidine (1400W). iNOS was significantly increased by arginine but not by glutamine following gut I/R and was associated with increased MPO activity and mucosal injury. On the other hand, PPAR-gamma was significantly increased by glutamine but decreased by arginine, whereas heat shock proteins were similarly increased in all experimental groups. The PPAR-gamma inhibitor G9662 abrogated the protective effects of glutamine, whereas the iNOS inhibitor 1400W attenuated the injurious effects of arginine. We concluded that luminal arginine and glutamine differentially modulate the molecular events that regulate injurious I/R-mediated gut inflammation and injury. The induction of PPAR-gamma by luminal glutamine is a novel protective mechanism, whereas luminal arginine appears harmful to the postischemic gut due to enhanced expression of iNOS.

Heme oxygenase-1 induction by hemin protects against gut ischemia/reperfusion injury.

BACKGROUND: We have shown that both intraischemic hypothermia and hypertonic saline resuscitation provide dramatic protection against gut ischemia/reperfusion (I/R) injury that is in part mediated by heme oxygenase-1 (HO-1). We therefore hypothesized that induction of HO-1 by hemin would lessen damage and improve function after gut I/R. MATERIALS AND METHODS: Male Sprague-Dawley rats were treated with 50 micromol/kg hemin (HO-1 inducer ferric protoporphyrin IX chloride) sq or vehicle 2 h before superior mesenteric artery occlusion for 60 min or sham laparotomy. After 6 h of reperfusion, transit was determined by quantitation of percentage of tracer in 10 equal segments of small intestine 30 min following injection into the duodenum (expressed as mean geometric center). Ileum was harvested for assessment of mucosal histologic injury (Chiu score 0-5 by blinded observer), myeloperoxidase activity (MPO, index of inflammation), and HO-1 protein expression. RESULTS: Hemin treatment was associated with increased HO-1 protein expression, lessened mucosal injury, decreased MPO activity, and improved intestinal transit following gut I/R. CONCLUSION: These data corroborate that HO-1 plays an important role in protecting the gut against I/R-induced injury.

Migrating motility complexes persist after severe traumatic shock in patients who tolerate enteral nutrition.

BACKGROUND: Postinjury small bowel ileus is poorly characterized and may be an important factor in intolerance to enteral nutrition (EN). We, therefore, placed jejunal manometry catheters in high-risk trauma patients. Our hypothesis was that the presence of "fasting migrating motility complex (MMC)" activity and conversion to a "fed pattern" at goal rate of EN would be present in those patients who tolerate jejunal feeding. METHODS: After obtaining baseline fasting manometry pressure tracings, jejunal feeding was advanced stepwise to a set goal while tolerance was monitored and intolerance was treated by a standard approach. RESULTS: Of the 10 study patients, 7 were able to be maintained on EN. Five (50%) had "fasting MMCs" and had good tolerance to early advancement of EN. The remaining five patients did not exhibit "fasting MMCs" and four had poor tolerance to early advancement of EN. Overall, nine patients reached goal rate of EN of which four converted to a "fed pattern." This, however, was not associated with later tolerance to EN. CONCLUSION: EN is feasible following severe traumatic shock. Surprisingly, half of the patients had fasting MMCs. This requires intact neural and motor function and was associated with good tolerance of early EN.

Underappreciation of sleep disorders as a cause of motor vehicle crashes.

Despite an increased risk of motor vehicle crashes (MVC) in patients with obstructive sleep apnea (OSA), we hypothesized that OSA was not considered in drivers admitted to trauma centers after an injury-producing MVC. A retrospective study on drivers involved in MVCs admitted to a level 1 trauma center was performed, with crash cause determined and the frequency of sleep studies recorded. A questionnaire was also mailed to 240 trauma centers seeking information on evaluation of patients with unexplained causes for MVCs, including screening for OSA. There were 122 drivers of MVCs admitted to our hospital, 60/122 (49%) had unexplained crashes and no sleep studies were performed. There were 70 survey respondents (30% return rate), 35/70 (50%) centers routinely screened for syncope after unexplained MVC, however, no center screened for OSA. US trauma centers do not screen for sleep disorders despite the associated increased crash risk and the high prevalence of crashes that can not be explained by other causes. We believe this reflects a lack of awareness of sleep disorders by health care professionals caring for trauma victims and education is of utmost importance.

Inducible nitric oxide synthase mediates gut ischemia/reperfusion-induced ileus only after severe insults.

Inducible nitric oxide synthase (NOS 2) is thought to play a role in gut motility disorders that occur under proinflammatory conditions. Clinically, ileus occurs after sepsis and shock-induced gut ischemia/reperfusion (I/R). The purpose of this study was to determine if NOS 2 mediates impaired intestinal transit in well-established models of both moderate and severe gut ischemia/reperfusion. At laparotomy, Sprague-Dawley rats had duodenal catheters placed. Small intestinal transit was determined by quantitating the percentage tracer (FITC-dextran) in 10 equal segments of intestine 30 min after catheter injection [expressed as the mean geometric center (MGC) of distribution]. Transit was assessed at 6 and 24 h after gut ischemia [45 or 75 min of superior mesenteric artery occlusion (SMAO) with sham laparotomy as control]. In a separate set of experiments, N(6)-(iminoethyl)-L-lysine (L-NIL), a selective NOS 2 antagonist, was administered 1 h prior to laparotomy and transit was determined after 6 h as described above. Ileal NOS 2 expression was assessed by Western immunoblot and quantitative "real-time" RT-PCR. We observed that both 45 and 75 min of SMAO decreased intestinal transit at 6 h of reperfusion compared to sham. Ileal NOS 2 mRNA and protein were increased after 75, but not 45, min of SMAO. In addition, L-NIL improved transit after 75, but not 45, min of SMAO. We conclude that (1) NOS 2 is upregulated in the gut only after more severe ischemic insults, and (2) ileus is mediated, at least in part, by NOS 2 under these conditions.

Laparoscopic repair of traumatic diaphragmatic injuries.

BACKGROUND: Laparoscopy has been proposed as a diagnostic and potentially therapeutic modality for penetrating diaphragmatic lacerations. The purpose of this study was to assess the technical feasibility and strength of various laparoscopic repairs of diaphragmatic injuries. METHODS: Swine underwent either open suture repair or laparoscopic repair by staple, suture, or patch technique of a 2-cm laceration to both the right and the left muscular or tendinous diaphragmatic leaflets. Six weeks after operation, diaphragms were harvested for either histologic analysis or bursting strength measurements. RESULTS: All methods of repair proved technically feasible. There was no significant difference in bursting strength measurements between treatment groups. Bursting was due to tissue failure either at or adjacent to the repair site. Histologic analysis confirmed healing of all specimens with the laparoscopic patch technique inciting less inflammation and greater fibroblastic proliferation than the other techniques. CONCLUSIONS: Laparoscopic repair of diaphragmatic lacerations can be accomplished using any of the currently available techniques. Laparoscopic stapling, suturing, or patch techniques all result in complete healing with a strong and durable repair. When selecting a particular technique, familiarity of the surgeon should be used as a guideline.

Vacuum-assisted wound closure provides early fascial reapproximation in trauma patients with open abdomens.

BACKGROUND: Damage control and decompressive laparotomies salvage severely injured patients who would have previously died. Unfortunately, many of these patients develop open abdomens. A variety of management strategies exist. The end result in many cases, however, is a large ventral hernia that requires a complex repair 6 to 12 months after discharge. We instituted vacuum-assisted wound closure (VAWC) to achieve early fascial closure and eliminate the need for delayed procedures. METHODS: For 12 months ending June 2000, 14 of 698 trauma intensive care unit admissions developed open abdomens and were managed with VAWC dressing. This was changed every 48 hours in the operating room with serial fascial approximation until complete closure. RESULTS: Fascial closure was achieved in 13 patients (92%) in 9.9 +/- 1.9 days, and 2.8 +/- 0.6 VAWC dressing changes were performed. There were 2 wound infections, no eviscerations, and no enteric fistulas. CONCLUSIONS: Use of VAWC can safely achieve early fascial closure in more than 90% of trauma patients with open abdomens.

[Enteral feeding of glucose increases intestinal mucosal blood flow during intestinal ischemia/reperfusion injury].

OBJECTIVE: To explore the relationship between enteral nutrition and the change in intestinal mucosal blood flow during intestinal ischemia/reperfusion injury. METHODS: Thirty-six Sprague-Dawley rats were randomly divided into alanine (12 rats), glucose (14 rats) and mannitol control (10 rats) groups. Jejunal sac was prepared with the filling of either 10 mM alanine, glucose or mannitol in the three groups. The laser doppler probe and intestinal mucosal tonometry were placed at the both ends of the sac. The superior mesenteric artery was occluded by arterial clamp for 60 mins and released thereafter for another 60 mins. Intestinal mucosal blood flow and regional pressure of CO(2) (PrCO(2)) were determined every 30 mins. RESULTS: During the process of ischemia/reperfusion, the intestinal mucosal blood flow in glucose group increased evidently and the PrCO(2) in glucose group decreased obviously (P < 0.01) when comparcd with those in mannitol group. CONCLUSION: During the process of ischemia/reperfusion, enteral feeding of glucose could increase intestinal mucosal blood flow, which provided guarding effects on the intestine suffering from ischemic/reperfusion injury.

Antioxidant enzymes are induced during recovery from acute lung injury.

OBJECTIVE: To determine the contribution of the pulmonary antioxidant defense enzymes of the hexose monophosphate (HMP) shunt and glutathione systems to recovery from oxidant-mediated lung injury in an animal model shown to closely resemble the clinical syndrome of acute respiratory distress syndrome. DESIGN: Prospective, controlled laboratory study on phorbol myristate acetate (PMA)-induced lung injury in rabbits. SETTING: Animal research laboratory. SUBJECTS: Rabbits were injected with PMA (80 microg/kg) for 3 consecutive days. Control animals received normal saline. MEASUREMENTS AND MAIN RESULTS: Lungs were harvested at 24, 48, 72, and 96 hrs (n = 5/time point) after PMA injection or after the third injection of normal saline in control animals (n = 6). The cytosolic fraction from lung and bronchial alveolar lavage (BAL) fluid was used for measurements of HMP shunt and glutathione enzymes. Pulmonary activity peaked at 48 hrs post-PMA injury with a 40% increase in glucose-6-phosphate dehydrogenase activity and a 32% increase in 6-phosphogluconate dehydrogenase activity over control levels. BAL activity was maximal at 72 hrs with an increase of 98% in glucose-6-phosphate dehydrogenase and 346% in 6-phosphogluconate dehydrogenase activities. Glutathione peroxidase was maximally induced by 77% at 48 hrs in BAL and by 107% at 24 hrs in lung. Glutathione reductase activity did not increase significantly in either lung or BAL. CONCLUSIONS: The observed induction of the antioxidant enzymes in response to PMA suggests that both the HMP shunt and the glutathione systems contribute to the recovery phase of oxidant-mediated lung injury. The inability of natural host defenses to regenerate reduced glutathione may explain failure of recovery from acute respiratory distress syndrome and suggests an avenue for clinical intervention.

Traumatic hematuria in patients with polycystic kidney disease.

Autosomal dominant polycystic kidney disease (PKD) is the most prevalent hereditary disorder in this country and a common cause of chronic renal failure. Patients frequently present with hematuria as the initial manifestation of PKD. We describe a patient with gross hematuria after blunt trauma who was found to have previously undiagnosed PKD. We review present diagnostic and treatment modalities and suggest potential management strategies for surgeons caring for patients presenting with traumatic hematuria and PKD.

Free radical-induced alterations in endothelial cell function.

Free radical-induced injury to the arterial wall has been implicated in the pathogenesis and progression of atherosclerosis. To model the in vitro effects of free radicals on endothelial cell function, protein and lipid synthesis were measured after exposing cells to a superoxide generating system of xanthine (X = 100 microM) and xanthine oxidase (XO = 0.2 units). Total protein synthesis, measured by [35S]methionine uptake, decreased by 87.65 +/- 2.04% over 4 hr compared to controls (P < 0.05). Examination of lipid synthesis by high-performance liquid chromatography in cells prelabeled with either [3H]oleic acid or [3H]sodium acetate revealed alterations in all lipid classes. Phospholipid and neutral glyceride synthesis significantly decreased in a time- and dose-dependent fashion compared to controls (two-way ANOVA). In contrast, cholesterol synthesis and lipid peroxidation increased in a time- and dose-dependent fashion. When X = 200 microM and XO = 0.3 units, there was a statistically significant increase in cholesterol synthesis and lipid peroxidation within 24 hr (Tukey's HSD). We conclude that there is evidence of endothelial cell injury as measured by decreases in protein, glyceride, and phospholipid synthesis. The concurrent increases in lipid peroxidation and cholesterol synthesis may explain the relationship between free radical injury and the pathogenesis of atherosclerosis.

Mechanism of cellular phospholipid efflux.

Plasma phospholipid binding to cell-derived cholesterol is important in reverse cholesterol transport, a key step in the regression of atherosclerosis. However, the mechanism by which phospholipids are transferred from cells to plasma remains unclear. [3H]Choline-labeled phospholipid efflux from fibroblasts has been studied using plasma and its components as acceptors. The kinetics were resolved into a fast component (k1 = 0.119 +/- 0.23 min-1) that corresponded to high-affinity binding of high-density lipoproteins (HDL) to the cell surface and a slow component (k2 = 0.0047 +/- 0.0009 min-1) due to protein-mediated desorption (n = 3). Altering the donor charge with heparinase or the acceptor charge by acetylation abolished the fast component, while the slow phase was unchanged. Only HDL displayed biexponential kinetics, comparable to whole plasma. Half-lives for low-density lipoprotein and very-low-density lipoprotein were t1/2 = 278 +/- 22 min and t1/2 = 1003 +/- 147 min, respectively. In the absence of transfer factor, HDL alone significantly reduced phospholipid efflux (t1/2 = 663 min). Phospholipid transfer protein restored biexponential kinetics. We conclude that cell membranes are a potentially important source of plasma phospholipids and that protein-mediated transfer to HDL is the major route for cell-to-plasma transfer. This step represents a locus for anti-atherosclerotic intervention.