Effect of hypertonic saline solution and dextran on ventricular blood flow and heart-lung interaction after hemorrhagic shock.

BACKGROUND: Hypertonic saline solutions may have beneficial hemodynamic effects in the resuscitation of hemorrhagic shock. The effects on cardiac function and potential interaction with lung function are controversial and served as the basis for this study. METHODS: Domestic swine were resuscitated from hemorrhagic shock with equivalent sodium loads of lactated Ringer's solution (LR) or 7.5% NaCl plus 10% dextran (HSD). Hemodynamic data were obtained at baseline, shock, and after resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time (dP/dt) were used to index contractility. Regional myocardial blood flow was determined with microspheres. Lung water was determined gravimetrically. RESULTS: There were no differences in the ability to restore hemodynamic parameters with equivalent sodium loads of LR and HSD resuscitation. Right ventricular ejection fraction and left ventricular change in pressure with respect to time were only transiently affected by shock and resuscitation. Regional myocardial blood flow was increased above baseline values after HSD. The total resuscitation volumes were 1958 +/- 750 mL and 140 +/- 31 mL with LR and HSD, respectively. CONCLUSIONS: Although LR and HSD were equally effective in the early resuscitation of hemorrhagic shock, this occurred at the expense of significantly greater volume requirements for resuscitation with LR. This may contribute to cardiac dysfunction in this setting. Enhanced regional myocardial blood flow after HSD resuscitation may be beneficial against ongoing myocardial stress.

Differences in arterial and mixed venous IL-6 levels: the lungs as a source of cytokine storm in sepsis.

BACKGROUND: Several investigators have shown that blood levels of interleukin 6 (IL-6) correlate with the severity of illness in critically ill or injured patients. However, little is known about differential arterial and venous blood levels of the cytokine, especially across the lungs. METHODS: We measured differences in IL-6 levels in pulmonary and systemic arterial blood and then documented the production or elimination of IL-6 by the lungs in 19 patients with severe illness. Prospective data were obtained from multiple, simultaneous systemic arterial (ART) and mixed venous (MV) blood samples that were drawn for IL-6 analysis from systemic arterial and pulmonary artery catheters in 7 patients awaiting vascular operation and in 12 trauma patients being treated in the intensive care unit. RESULTS: A lung disorder was present in 5 patients (pneumonia [n = 1], lung trauma [n = 4]) and absent in the remaining 14 patients. The following data were obtained (mean +/- SD) from the highest MV IL-6 levels (pg/mL) in each patient. In patients with a lung disorder (n = 5) compared with those with no disorder (n = 14), ART IL-6 was 9309 +/- 12,521 versus 134 +/- 128 (P =.010), MV IL-6 was 5516 +/- 7420 versus 137 +/- 129 (P =.011), the absolute difference was 3793 +/- 5271 versus -3 +/- 15 (P =.011), and the percentage difference was 37.4% +/- 29.8% versus 1.5% +/- 12.3% (P =.001). The ART and MV IL-6 levels tended to be much higher in the 5 patients with pneumonia (n = 1) and lung injuries (n = 4) than in the patients without apparent pulmonary problems. In addition, the patients with a primary lung disorder demonstrated a net increase in IL-6 levels across the lungs, whereas there was no increase, but rather, a net reduction of IL-6 levels across the lungs in patients without a lung disorder. CONCLUSIONS: The lung appears to be a major producer of IL-6 in patients with an inflammatory lung process. There is a 39% increase in the level of IL-6 as it passes through inflamed lung, producing a marked difference in ART and MV IL-6 levels. Normal lung demonstrated little effect on either ART or MV IL-6 levels.

Prognostic factors with the use of the transjugular intrahepatic portosystemic shunt for bleeding varices.

OBJECTIVES: To evaluate the outcome of patients undergoing the transjugular intrahepatic portosystemic shunt (TIPS) procedure for bleeding esophageal varices and to outline the factors affecting outcome. DESIGN: Uncontrolled, nonrandomized, retrospective study. SETTING: A 320-bed university-associated urban emergency adult hospital. PATIENTS: Thirty-three patients undergoing TIPS procedures for bleeding esophageal varices with at least 18 months of follow-up. Five patients (15%) had Child class B disease and 28 (85%) had Child class C disease. The mean transfusion requirements were 12.6 U of red blood cells, 18 U of fresh-frozen plasma, and 7 U of platelets. The mean portosystemic gradients before and after the initial TIPS procedure were 18 and 7 mm Hg, respectively. OUTCOME MEASURES: The incidence, time and causes of death, and recurrent variceal hemorrhage were correlated with various clinical and laboratory factors. RESULTS: By 18 months after the TIPS procedure, 16 patients (48%) died of rebleeding or hepatic failure. Subsequent upper gastrointestinal tract bleeding occurred in 14 patients (42%). Of 8 in whom occlusion or stenosis of the TIPS was promptly corrected, all 8 survived. Of 6 in whom occlusion or stenosis of the TIPS was not corrected, 5 (83%) died. Laboratory values (mean +/- SD) predictive of death before 18 months (compared with those of patients alive at 18 months) included a low initial serum albumin level (22 +/- 4 vs 29 +/- 5 g/L; P < .001); an increased initial total bilirubin level (68 +/- 75 vs 34 +/- 20 mumol/L [4.0 +/- 4.4 vs 2.0 +/- 1.2 mg/dL]; P = .001), and an elevated prothrombin time after attempts at correction (18.0 +/- 3.4 vs 14.6 +/- 1.2 seconds; P < .001). CONCLUSIONS: The TIPS procedure in patients with Child class C alcoholic cirrhosis was associated with a high incidence of death or rebleeding within 18 months. Prompt correction of TIPS abnormalities in patients with rebleeding increased survival. The albumin, bilirubin, and prothrombin time values obtained before performance of the TIPS procedure were predictive of outcome.

A trial of ciprofloxacin and metronidazole vs gentamicin and metronidazole for penetrating abdominal trauma.

OBJECTIVES: To determine whether a combination of ciprofloxacin hydrochloride and metronidazole hydrochloride would be as effective or more effective than a combination of gentamicin sulfate and metronidazole hydrochloride for preventing infection in patients with penetrating abdominal trauma, to evaluate the factors associated with increased risk of infection, and to determine the serum peak and trough levels of gentamicin with the dosage regimen of 2.5 mg/kg every 12 hours. DESIGN: Randomized double-blind study. SETTING: Level I trauma center. PATIENTS: Eighty-four patients with penetrating intra-abdominal injuries (gunshot wound, 69; stab wound, 15) thought to require laparotomy. INTERVENTIONS: The patients were randomized during treatment in the emergency department to be given a combination of ciprofloxacin hydrochloride, 400 mg every 12 hours, and metronidazole hydrochloride, 500 mg every 6 hours, or a combination of gentamicin sulfate, 2.5 mg/kg every 12 hours, and metronidazole hydrochloride, 500 mg every 6 hours. RESULTS: Of 68 patients with intra-abdominal injuries who could be observed for at least 48 hours after laparotomy, posttraumatic infections developed in 12 (18%), and nosocomial infections developed in 6 (9%). The incidence of posttraumatic infections in patients who were given gentamicin and metronidazole (5/33 [15%]) was not significantly lower than the incidence in patients who were given ciprofloxacin and metronidazole (7 of 35 [20%]; P=.75). The presence of any infection increased the mean+/-SD length of hospital stay from 8.7+/-3.5 days to 23.3+/-10.9 days and increased the mean+/-SD hospital charges from $24 507+/-$9860 to $104920+/-$49083 (P<.001). Univariate analysis showed the factors most significantly associated with infection were as follows: (1) the use of blood transfusions (P<.001), (2) the penetrating abdominal trauma index of 35 or more (P<.002), (3) injury to the colon requiring a colostomy (P=.004), and (4) a trauma score of less than 12 (P<.02). Multivariate analysis showed the only significant factor was the receipt of blood transfusions (F=10.165; P<.005). CONCLUSIONS: Ciprofloxacin and gentamicin, each in combination with metronidazole, were equivalent in their ability to prevent infections after penetrating abdominal trauma; other factors, especially the receipt of blood transfusions, had much more effect on the incidence of infection. Infection greatly increases the length of hospital stay and hospital charges. The use of an increased dosing regimen of 2.5 mg/kg every 12 hours of gentamicin sulfate was effective at obtaining a therapeutic peak serum concentration.

Pulmonary artery diastolic and wedge pressure relationships in critically ill and injured patients.

To study pulmonary artery wedge pressure (PAWP) and pulmonary artery diastolic pressure (PADP) relationships, we measured these simultaneously with cardiac outputs 1922 times in 128 patients who were critically ill or in an intensive care unit. In 356 (18.5%) of the readings, the PAWP exceeded the PADP, indicating that the PAWP reading might be erroneous. In 106 (5.5%) of these readings, the PAWP was 6.0 mm Hg or more higher than the PADP, indicating that the PAWP was almost certainly erroneous. In virtually all instances in which this discrepancy was recognized, changing the position of the catheter tip provided a PAWP value equal to or lower than the PADP. On the other extreme, in 49 (30%) of the patients, the PADP was 6.0 mm Hg or more higher than the PAWP. The pulmonary vascular resistance in these patients averaged (+/- SD) 257 +/- 145 dyne/s/cm-5 (normal, 80 to 160 dyne/s/cm-5). The mean pulmonary vascular resistance in the other 74 patients was significantly lower (158 +/- 72 dyne/s/cm-5). The mortality rate with the increased PADP-PAWP gradients was 59% (24/49). This was significantly higher than the mortality rate (34%, or 27/79) seen with lower PAWP-PADP gradients. Thus, the relationship between the PADP and PAWP should be examined closely in critically ill patients. A PAWP higher than the PADP indicates that the PAWP measurement may be erroneous. On the other hand, if the PADP exceeds the PAWP by 6.0 mm Hg or more, the patient has probably developed pulmonary hypertension and has a much poorer prognosis.

Implementation and evaluation of guidelines for use of enoxaparin as deep vein thrombosis prophylaxis after major trauma.

Although enoxaparin is more efficacious than many other deep vein thrombosis (DVT) prevention strategies after trauma, its routine use in trauma patients at low risk for venous thrombosis is unlikely to be cost-effective and may be deleterious if risk factors for bleeding are present. By way of consensus of opinion of trauma surgeons and pharmacists, enoxaparin DVT prophylaxis guidelines were developed, implemented, and evaluated. Fifty patients with major orthopedic or spinal trauma were followed throughout hospitalization. Enoxaparin use and frequency of DVT, pulmonary embolism (PE), thrombocytopenia, and enoxaparin-related major bleeding (overt bleeding associated with a hemoglobin decrease > or = 2 g/dl, need for > or = 2 units of packed red blood cells, or need for surgery) were recorded. All pharmacist interventions pertaining to enoxaparin prophylaxis were collected. Average patient age was 45.6+/-19.5 years, average Injury Severity Score was 19.0+/-11.2, and average length of hospitalization was 14.3+/-10.0 days. Most injuries were related to motor vehicles (52%) and falls (30%). Sites of injury were femur or tibia (52%), pelvis or acetabulum (32%), hip (20%), and spinal cord (12%). Two-thirds (72%) of patients received enoxaparin during part of their hospital stay (on average, for 53% of the duration of hospitalization). Sequential compression devices and vena caval filters were used in 86% and 10% of patients, respectively. Duplex-proven DVT occurred in two patients, and angiography-proven PE developed in one patient. Enoxaparin-related major bleeding and thrombocytopenia occurred in three and one patient(s), respectively. Pharmacists recommended enoxaparin initiation in nine (18%) patients and discontinuation of the agent in seven (14%) patients (one for bleeding; six for lack of indication). Most recommendations (78%) were accepted. Data from the 50 patients in this study showed fewer thrombotic complications but more bleeding than the frequencies found in controlled studies. It is unclear whether the large number of days that patients did not receive enoxaparin was due to fears of enoxaparin-related bleeding or other factors.

Impact of trauma stress ulcer prophylaxis guidelines on drug cost and frequency of major gastrointestinal bleeding.

Trauma patients are routinely prescribed stress ulcer prophylaxis despite evidence suggesting such therapy be limited to patients with identifiable risk factors for bleeding. With surgeons' consensus, we developed and implemented trauma stress ulcer prophylaxis guidelines, and measured the impact of clinical pharmacists on implementing the guidelines and the effect of the guidelines on drug cost and frequency of major gastrointestinal bleeding. Two groups of 150 consecutive patients admitted with multiple trauma were evaluated before and after guideline implementation and stratified by Injury Severity Score (ISS) to minor (ISS < 9) or moderate to severe (ISS > or = 9) trauma groups. The number of patients prescribed stress ulcer prophylaxis, length and cost of this therapy, and number of patients experiencing major gastrointestinal bleeding (decrease in consecutive hemoglobin > or = 2 g/dl in conjunction with coffee-ground emesis, hematemesis, melena, or hematochezia) were measured. All pharmacist interventions pertaining to stress prophylaxis were collected. Fewer patients were prescribed stress ulcer prophylaxis after guideline implementation (105/150, 70% vs 39/150, 26%, p<0.0001), leading to a decrease in total drug cost of $4558. Use decreased more in patients with minor (40/54, 74% vs 9/59, 15%, p<0.0001) than moderate to severe (65/96, 68% vs 30/91, 33%, p<0.0001) trauma. Neither length of therapy nor agent of choice (> 95% cimetidine) differed between groups. Fifteen (38%) of 38 postguideline prophylaxis orders were determined by the pharmacist not to meet guideline criteria. Recommendations to discontinue therapy were accepted in 9 (60%) of 15 instances. The frequency of major gastrointestinal bleeding remained unchanged between groups (1/150 vs 0/150, p=1.0). Implementation of trauma stress ulcer prophylaxis guidelines limiting therapy to patients with risk factors for bleeding led to a 80% decrease in drug cost and did not affect the frequency of major gastrointestinal bleeding.

Management of patients with head injuries and multiple other trauma.

The management of patients with multiple trauma including head injuries is a complex task. The prime goal is to minimize secondary neuronal injury. Attention to establishment of an airway, assurance of adequate gas exchange, and circulatory resuscitation is mandatory to minimize any secondary neuronal injuries. Once these principles of resuscitation have been applied and the primary neuronal injury is treated, additional etiologies of secondary brain trauma, such as hypoglycemia and hypothermia, should be addressed. Continual monitoring of oxygenation and perfusion is mandatory optimizing the outcome of these patients.

The nutritional management of patients with head injuries.

Severe head injuries tend to be associated with hypermetabolism and hypercatabolism resulting in negative nitrogen balances which may exceed 30 grams day-1. Enteral feeding should begin as soon as the patient is hemodynamically stable, attempting to reach a non-protein caloric intake of at least 30-35 kcal kg-1 day-1 and a protein intake of 2.0-2.5 g kg-1 day-1 as soon as possible. With severe head injuries (Glasgow Coma Scale < 8), there is an increased tendency for gastric feeding to regurgitate into the upper airway. Keeping the patient upright and checking residuals is important in such patients. Jejunal feedings are less apt to be aspirated. If it is apparent that the gastro-intestinal tract cannot be used to reach the nutritional goals within three days, total parental nutrition is begun within 24-48 h so as to reach these nutrition goals by either one or both routes by the third or fourth day. Blood glucose levels exceeding 150-200 mg dl-1 tend to increase the severity of the neurologic problems and efforts should be made to prevent hyperglycemia by carefully regulating the glucose and insulin intake. Indirect calorimetry to determine the respiratory quotient and resting energy expenditure should be determined twice weekly. To determine N2 balance, urinary urea nitrogen should be measured in 24-h specimens. These tests should be performed once or twice weekly until it is clear that the nutrition is adequate.

Infectious complications following duodenal and/or pancreatic trauma.

Patients with pancreatic and/or duodenal trauma often have a high incidence of infectious complications. In this study we attempted to find the most important risk factors for these infections. A retrospective review of the records of 167 patients seen over 7 years (1989 through 1996) at an urban Level I trauma center for injury to the duodenum and/or pancreas was performed. Fifty-nine patients (35%) had isolated injury to the duodenum (13 blunt, 46 penetrating), 81 (49%) had isolated pancreatic trauma (18 blunt, 63 penetrating), and 27 (16%) had combined injuries (two blunt, 25 penetrating). The overall mortality rate was 21 per cent and the infectious morbidity rate was 40 per cent. The majority of patients had primary repair and/or drainage as treatment of their injuries. Patients with pancreatic injuries (alone or combined with a duodenal injury) had a much higher infection rate than duodenal injuries. The patients with duodenal injuries had significantly lower penetrating abdominal trauma indices, number of intra-abdominal organ injuries, and incidence of hypothermia. On multivariate analysis independent factors associated with infections included hypothermia and the presence of a pancreatic injury. Although injuries to the pancreas and duodenum often coexist it is the pancreatic injury that contributes most to the infectious morbidity.

Delayed pneumothorax after central venous access: a potential hazard.

Percutaneous central venous catheter access is common-place in surgical patients. Though several major complications of this procedure have been described, pneumothorax is the most common. Pneumothorax is routinely assessed by a chest X-ray within 2 hours after catheter placement. During a recent 6-month interval, the authors identified five patients with delayed onset and diagnosis of pneumothorax following percutaneous central venous access. All immediate post-insertion chest X-rays were normal; however, subsequent chest X-ray showed evidence of pneumothoraxes. The pneumothorax contributed to the death of one patient on positive pressure ventilation. A review of the literature revealed a total of 18 patients in the English literature with this complication. Although the incidence of delayed pneumothorax is low, it is, in some instances, life threatening, particularly in patients on positive pressure ventilation. A high index of suspicion is required to diagnosis and treat this reversible condition.

Craniocervical necrotizing fasciitis: an 11-year experience.

OBJECTIVE: We review our experience and present our approach to treating craniocervical necrotizing fasciitis (CCNF). STUDY DESIGN: All cases of CCNF treated at Wayne State University/Detroit Receiving Hospital from January 1989 to April 2000 were reviewed. Patients were analyzed for source and extent of infection, microbiology, co-morbidities, antimicrobial therapy, hospital days, surgical interventions, complications, and outcomes. RESULTS: A review of 250 charts identified 10 cases that met the study criteria. Five cases (50%) had spread of infection into the thorax, with only 1 (10%) fatality. An average of 24 hospital days (7 to 45), 14 ICU days (6 to 21), and 3 surgical procedures (1 to 6) per patient was required. CONCLUSION: Aggressive wound care, broad-spectrum antibiotics, and multiple surgical interventions resulted in a 90% (9/10) overall survival and 80% (4/5) survival for those with thoracic extension. SIGNIFICANCE: This is the largest single institution report of CCNF with thoracic extension identified to date.

Metabolic responses and nutritional therapy in patients with severe head injuries.

The severe hypermetabolism and hypercatabolism seen in patients with severe head injuries results in malnutrition that occurs very rapidly and can cause impaired healing and an increased tendency to infection and multiple organ failure. Thus, early adequate nutritional support plays a role in functional outcome. Total enteral nutrition (TEN) is preferred over total parenteral nutrition (TPN), but TPN should be supplied promptly while increasing TEN to a goal of at least 25 to 35 nonprotein kcal/kg/d and 2.0 to 2.5 g protein/kg/d. Nutritional formulas high in branched chain amino acids, glutamine, arginine, vitamins E and C, and zinc may also have some advantages. Growth hormone may improve anabolism. Hyperglycemia, especially glucose levels exceeding 200 mg/dL, must be prevented and/or treated promptly with insulin or decreased glucose intake. Careful monitoring with indirect calorimetry and nitrogen balance studies should help prevent inadequate protein or excessive carbohydrate intake.

Effect of acute hemodilution on intestinal perfusion and intramucosal pH after shock.

BACKGROUND: Restoration of oxygen delivery, especially to the splanchnic bed, is of critical importance during trauma resuscitation. Acute normovolemic hemodilution (ANH) has been used to reduce blood transfusion requirement during elective surgery. The effect of hemodilution on the splanchnic circulation during hemorrhagic shock (HS) is not well defined. METHODS: Swine were instrumented to measure systemic and splanchnic circulation effects of ANH after HS. The adequacy of the splanchnic circulation was assessed by changes in measured mucosal blood flow, mucosal tonometry, as well as by portal venous blood O2 saturation, portal venous CO2 saturation, and lactate. RESULTS: ANH after HS resulted in a final hematocrit of 18+/-2%. Superior mesenteric artery blood flow was returned to baseline levels; however, mucosal blood flow was still only 64% of baseline levels. However, at the same time mucosal PCO2 and intramucosal pH as well as portal venous O2 and CO2 saturation had normalized. CONCLUSION: As long as an adequate intravascular volume is maintained, hemodilution is well tolerated by the gut after HS. Concern about the adequacy of gut perfusion should not be a transfusion trigger after HS.

Incidence of pneumothorax from intercostal nerve block for analgesia in rib fractures.

BACKGROUND: The incidence of pneumothorax (PTX) after individual intercostal nerve block (INB) for postoperative pain reportedly varies from 0.073% to 19%.1-3 This study investigated the incidence of PTX after INB for rib fractures. METHODS: We conducted a retrospective chart review of patients admitted between January 1996 and December 1999 with rib fractures who received INB. RESULTS: One hundred sixty-one patients received 249 intercostal nerve block procedures (INBPs). An INBP is one session where a set of intercostal nerves are blocked. A total of 1,020 individual intercostal nerves were blocked. There were 14 pneumothoraces. The overall incidence of PTX per patient was 8.7%, with an incidence of PTX per INBP of 5.6%. The incidence of PTX was 1.4% for each individual intercostal nerve blocked. CONCLUSION: The incidence of PTX per individual intercostal nerve blocked is low. INB is an effective form of analgesia, and for most patients with rib fractures one INBP is sufficient to allow adequate respiratory exercises and discharge from the hospital.

Factors affecting prognosis with penetrating wounds of the heart.

OBJECTIVE: To determine factors affecting prognosis for patients with penetrating wounds of the heart. METHODS: A retrospective review of 302 patients with penetrating heart wounds undergoing emergency thoracotomy (August of 1980 through June of 1997) in a Level I trauma center. RESULTS: There were 148 patients with gunshot wounds (GSW) and 154 patients with stab wounds with 23% and 58% survival rates, respectively. Of 43 patients having no signs of life at the scene, 5 patients (12%) achieved some cardiac activity and were brought to the operating room (OR), but none survived. Of 67 patients "arresting" in the ambulance, 23 got to the OR, but only 3 patients (4%) survived. Of 27 patients "arresting" in the emergency department (ED), 18 patients reached the OR, but only 5 patients (19%) survived. Of 15 patients having an ED thoracotomy because of rapid deterioration there, 4 patients (27%) survived. Thus, of the 152 patients with an ED thoracotomy, 93 patients had gunshot wounds and none survived; of the 59 with stab wounds, 12 (20%) survived (p < 0.001). Of 150 patients having an OR thoracotomy, 111 (74%) survived. Single-chamber injuries had a survival rate of 51% (112 of 219 patients), but multiple chamber and/or intrapericardial great vessel injuries had only a 13% survival rate (11 of 83 patients) (p < 0.001). Intrapericardial aortic injuries were uniformly fatal in 15 patients. In patients with stab wounds, pericardial tamponade was associated with a higher survival rate (66%; 56 of 84 patients) than in those without tamponade (47%; 33 of 70 patients). CONCLUSION: The physiologic status of the patient at presentation, mechanism of injury, and presence of a tamponade were significant prognostic factors in this series of penetrating cardiac injuries. Multiple-chamber injuries, especially with great vessel involvement, were associated with a high mortality rate. ED thoracotomies for gunshot wounds of the heart were uniformly fatal.

Lipopolysaccharide induces relaxation in lung pericytes by an iNOS-independent mechanism.

Lipopolysaccharide (LPS)-regulated contractility in pericytes may play an important role in mediating pulmonary microvascular fluid hemodynamics during inflammation and sepsis. LPS has been shown to regulate inducible nitric oxide (NO) synthase (iNOS) in various cell types, leading to NO generation, which is associated with vasodilatation. The purpose of this study was to test the hypothesis that LPS can regulate relaxation in lung pericytes and to determine whether this relaxation is mediated through the iNOS pathway. As predicted, LPS stimulated NO synthesis and reduced basal tension by 49% (P < 0.001). However, the NO synthase inhibitors N (omega)-nitro-L-arginine methyl ester, aminoguanidine, and N (omega)-monomethyl-L-arginine did not block the relaxation produced by LPS. In fact, aminoguanidine and N (omega)-monomethyl-L-arginine potentiated the LPS response. The possibility that NO might mediate either contraction or relaxation of the pericyte was further investigated through the use of NO donor compounds; however, neither sodium nitroprusside nor S-nitroso-N-acetylpenicillamine had any significant effect on pericyte contraction. The inhibitory effect of aminoguanidine on LPS-stimulated NO production was confirmed. This ability of LPS to inhibit contractility independent of iNOS was also demonstrated in lung pericytes derived from iNOS-deficient mice. This suggests the presence of an iNOS-independent but as yet undetermined pathway by which lung pericyte contractility is regulated.

Pericytes augment the capillary barrier in in vitro cocultures.

UNLABELLED: Most in vitro studies of capillary permeability focus on endothelial cell (MVEC) monolayers and ignore the second cell that forms the capillary wall: the microvascular pericyte (PC). We describe a model to study the permeability characteristics of MVEC, PC, and MVEC:PC cocultures. METHODS: Semipermeable culture inserts were coated with collagen and then plated with early passage bovine pulmonary MVEC. On Day 3, bovine pulmonary PC were added at concentrations to approximate MVEC:PC ratios of 1:1, 5:1, and 10:1. Electrical resistance was measured on subsequent days and fluorescently labeled (FITC) albumin was used in a permeability assay to calculate an albumin clearance for each culture. RESULTS: The results for electrical resistance measurements and albumin assays showed a similar pattern. Resistance for endothelial cell monolayers was significantly higher and albumin permeability was significantly lower than that of controls. Addition of pericytes at a 10:1 and 5:1 ratios increased the permeability barrier compared to endothelial cells alone, although these cultures were not significantly different from one another. Cocultures at a 1:1 ratio had the best barrier, significantly better than all other cultures. CONCLUSIONS: Endothelial cell monolayers are an inadequate model of the microcirculation. As PC form a key component of the capillary wall in vivo and as addition of PC to MVEC monolayers in vitro, optimally at a 1:1 ratio, increase their barrier effect to large and small molecules, we believe it is necessary to include both cells in future in vitro studies.

Factors affecting mortality rates in patients with abdominal vascular injuries.

BACKGROUND: Major vessel injury is seen in 5% to 25% of patients admitted to hospitals with abdominal trauma, and this is the most common cause of death in these patients. METHODS: Data on 470 patients with abdominal vascular injuries seen at a Level I trauma center were reviewed retrospectively. RESULTS: The overall mortality rate was 45%. The incidence of various types of trauma were blunt in 51 patients (11%), gunshot wounds in 329 patients (70%), shotgun wounds in 21 patients (4%), and stab wounds in 69 patients (15%). The three vessels with the highest mortality rates were aorta (at and proximal to the renals) (32 of 35 [91%]), hepatic veins and/or retrohepatic vena cava (36 of 41 [88%]), and portal vein (25 of 36 [69%]). The most significant risk factors (p < 0.001) for death were a trauma score of 9 or less, initial operating room (OR) systolic blood pressure (SBP) < 90 mm Hg, final OR core temperature < 34 degrees C, 10 or more blood transfusions in the first 24 hours, and an initial emergency department SBP < 70 mm Hg. Of 120 patients with an initial OR SBP < 70 mm Hg, 103 (86%) died. Of 29 patients with a good response to a prelaparotomy thoracotomy with thoracic aortic cross-clamping (SBP > 90 mm Hg within 5 minutes), 11 (38%) survived. Of the remaining 87 patients, only 6 (7%) survived (p = 0.01). CONCLUSION: Rapid control of bleeding sites (to keep blood transfusions to < 10 units) and urgent correction of hypothermia seem to be the main factors improving survival over which the surgeon has some control.