Effect of LFA-1beta antibody on leukocyte adherence in response to hemorrhagic shock in rats.

The activation and adherence of leukocytes to the venular endothelium are critical steps in the pathogenesis of generalized microvascular injury following hemorrhagic shock. Previous studies have shown that the integrins CD11/CD18 play a significant role in this interaction. The purpose of this study is to examine the efficacy of anti-LFA-1beta, an antibody to CD11a/CD18, in attenuating leukocyte adherence before, during, and after hemorrhagic shock. Following a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mm Hg for 30 min in urethane-anesthetized rats. Mesenteric venules in a transilluminated segment of the small intestines were examined to quantitate leukocyte adherence using intravital microscopy. In sham-operated rats (control), there was minimal to no leukocyte adherence throughout the experiment. Hemorrhagic shock resulted in significant leukocyte adherence during resuscitation (10.8 +/- 1.7 cells/100 microm, P < 0.01) when compared to control. Anti-LFA-1beta, when given before hemorrhagic shock, significantly attenuated leukocyte adherence during resuscitation (1.1 +/- 0.8, P < 0.01) when compared with hemorrhagic shock alone. This protective effect of anti-LFA-1beta on leukocyte adherence was even demonstrated when it was given during (1.6 +/- 0.3, P < 0.01) and 10 min after hemorrhagic shock (5.8 +/- 0.4, P < 0.05). These results suggest that anti-LFA-1beta may be of potential therapeutic benefit against microvascular injury caused by hemorrhagic shock.

The value of routine posttracheostomy chest radiography.

OBJECTIVE: This study proposes to evaluate the efficacy of routine posttracheostomy chest radiography. DESIGN: A retrospective chart review provided the framework of this study. SETTING: The study took place at a university teaching hospital-level one trauma center. PATIENTS: The study included 293 patients undergoing elective tracheostomy between 1989 and 1993. MEASUREMENTS AND RESULTS: Data extracted from the charts included indication for tracheostomy, immediate preoperative and postoperative chest radiograph reports, management changes made secondarily to radiographic findings, including chest tube placement, institution of chest physiotherapy, and need for tracheal tube reposition. Complications were defined as findings not noted on the preoperative radiographs; these were pneumothorax, tube malposition, atelectasis, or clinical information resulting in management changes. All patients received postoperative chest radiographs in the trauma ICU. Statistical analysis of our data was carried out using the chi2 test. Patients with chest tubes in place at the time of surgery were the only group who were excluded so as not to confuse whether pneumothorax developed postoperatively. Of the initial 293 patients, 25 patients were excluded on the basis of having a chest tube. The remaining 268 charts were analyzed; 220 (82%) patients underwent tracheostomy for ventilator-dependent respiratory failure, 31 (12%) due to multiple facial fractures, 6 (2.1%) secondary to penetrating neck wounds, and 11 (4%) as a result of refractory vocal cord edema. One (0.3%) patient was found to have a postoperative 10% apical pneumothorax. Eight (2.4%) patients were found to have postoperative subsegmental atelectasis. There were no significant (p>0.05) management changes implemented as a result of these findings. No new infiltrates, effusions, or malpositioned tubes were noted. Deletion of routine posttracheostomy radiographs would save $52.39 per patient (cost) or $15,350 for 293 patients and $35,453 in total patient charges. CONCLUSIONS: Abnormalities revealed by routine chest radiography after tracheostomy did not appear to alter patient management frequently enough to warrant the costs. A randomized, prospective study should be performed to analyze the safety of abandoning this practice.

Predictors of operative outcome in patients with human immunodeficiency virus infection and acquired immunodeficiency syndrome.

BACKGROUND: Plasma viral load has recently been associated with clinical outcome in patients with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). We hypothetized that, in addition to CD4 lymphocytes, plasma HIV-1 RNA counts are predictive of postoperative outcome. METHODS: HIV-infected and AIDS patients admitted to a major teaching hospital requiring invasive or surgical procedures were retrospectively analyzed for postoperative outcome. Preoperative and postoperative immune cell counts including plasma HIV-1 RNA counts were recorded. Chi-square analysis, Fisher's exact test, and multivariate regression were performed with statistical significance P

Jejunostomy tube feedings should not be stopped in the perioperative patient.

BACKGROUND: Anesthetic standard of care is to restrict oral intake for 8 hours before elective surgery. There is no research addressing appropriate preoperative discontinuation of jejunostomy tube (J-tube) feedings. We hypothesized that patients could be fed safely, via a J-tube, until the time of surgery. METHODS: Patients admitted to a Level I Trauma Center, having J-tubes and undergoing a nonabdominal operation, were prospectively evaluated. Group I patients received J-tube feedings until transport to the operating room. Group II patients had tube feedings discontinued for at least 8 hours before surgery. Data were compared using the Student's t test and contingency table analysis. RESULTS: There were 46 patients in group I and 36 in group II. There was no incidence of aspiration. Patient groups did not differ in age, mortality, length of stay, injury severity score, or ventilator days. Group I patients had tube feedings discontinued for fewer hours before and after surgery than group II patients (before surgery: 1.40 +/- 1.20 vs 11.61 +/- 5.01, respectively; p < .001; after surgery: 2.99 +/- 7.49 vs 7.11 +/- 9.03, respectively; p = .043); received more kilocalories/ grams of protein on the day of surgery (group I vs group II, 1676.15/89.57 +/- 1133.21/38.04 vs 791.14/57.58 +/-498.66/79.87, respectively; p = .001/p = .032) and more kilocalories/grams of protein on the first postoperative day (group I vs group II, 1580.74/92.57 +/- 600.53/37.96 vs 1152.47/63.53 +/- 733.96/39.40, respectively; p = .006/p = .001). CONCLUSIONS: Patients receiving J-tubes who are undergoing nonabdominal operations may safely continue enteral nutrition at maximum protein and caloric intake until surgery.

Central nervous system metabolic and physiologic effects of laparoscopy.

We set out to determine whether the increases in intracranial pressure (ICP) associated with CO2 insufflation had any metabolic effect on the central nervous system in a head injury when compared with gasless laparoscopy (GL). To test this hypothesis, we looked at both the ICP and jugular bulb venous saturation (JVS), with and without a coexisting cerebral mass lesion. Twenty-five kilogram male pigs had tracheostomy, epidural balloon, pulmonary arterial catheter, arterial line, and jugular bulb catheter placed. Intravenous Pentobarbital was used for anesthesia. Either CO2 laparoscopy (CL; n=7) or GL (n=7) were performed both with and without an epidural balloon inflated to a baseline ICP of 25. Data were analyzed using the Student's t test with a P value <0.05 being significant. Cerebral perfusion pressure and most hemodynamic values did not differ. Both central venous pressure and peak inspiratory pressure were significantly elevated whenever CO2 insufflation took place, reflecting an increased intrathoracic pressure. When comparing both study groups, the partial pressure of CO2 did not differ. CL increases ICP significantly above the gasless group in our head injury model. This is most likely secondary to increased intrathoracic pressure. The question still remains whether these changes are clinically significant. We could not demonstrate significant metabolic effects secondary to laparoscopy. In patients suffering head injury, GL rather than CL might be safer to avoid ICP elevation. Additional studies looking at central nervous system metabolic and objective histopathologic effects should be undertaken with larger numbers of study animals.

Challenges in the management of pancreatic and duodenal injuries.

A retrospective analysis of 44 consecutive patients with pancreatic or duodenal injuries admitted to an urban trauma center over a 6-year period was undertaken. Thirty-three patients had pancreatic injuries, including eight with combined duodenal injuries. Eleven patients had duodenal injuries. The mean age was 28 years, and 93% of the patients were male. Penetrating abdominal trauma accounted for the majority of injuries. Class I pancreatic injuries were the most common (55%), followed by those with class III (21%) and class II (18%). The majority (55%) of pancreatic injuries were managed by drainage with or without suturing; distal pancreatectomy was used in 39% of patients. Duodenal injuries were managed by primary repair in 50% of cases and pyloric exclusion/diverticulization techniques were used in 20% of cases. The mean first 24 hours transfusion requirement was 6.8 packed red blood cells. Complications were common, occurring in 61% of patients surviving longer than 24 hours. Intraabdominal abscess developed in 31% of all patients, 42% of whom required relaparotomy. Pancreatic fistulas occurred in 16% of patients with pancreatic injuries. Six patients died, 83% within 8 hours of admission, all as a result of gunshot wounds. Increased mortality was seen in patients with higher blood transfusion requirements, higher penetrating abdominal trauma index, shotgun wounds, the need for pancreaticoduodenectomy, hypotension on admission, and the presence of an associated major vascular injury. We conclude that early operation and efficacious control of hemorrhage is of prime importance in decreasing the mortality rate associated with these injuries.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of self-esteem in repeat assault victims.

Background characterization of assault-related injuries have demonstrated that lifestyle, substance abuse, education, employment, mental illness, and high-risk behavior contribute to low self-esteem in repeat assault victims. Recurrent-assault patients have never been studied with respect to self-esteem. This study evaluated self-esteem and assault-related injury in 28 consecutive male assault patients (11 first-assault and 17 recurrent-assault patients) and 19 controls with no previous assault history. Study participants were administered the Walmyr Assessment Scales Index of Self-Esteem (WASISE) as part of a three-item survey to determine the relationship between self-esteem and assault-related injury. No demographic differences were found between the groups. The mean (+/- standard error) WASISE score for recurrent-assault patients (34.9 +/- 3.4) was significantly higher than mean scores for no-assault and first-time assault-injured patients (14.7 +/- 1.4 and 15.0 +/- 2.3, respectively). The recurrent-assault patients had a lower mean education level than both no-assault and first-time assault-injured patients (2.1 +/- 0.26 and 1.9 +/- 0.57, respectively). Eighteen (2%) first-time assault-injured and 11 (7%) recurrent-assault patients were employed. These data suggest that self-esteem, education, and employment history need to be considered when evaluating and developing interventions for repeat-assault patients.

The accuracy of diagnostic laparoscopy in trauma patients: a prospective, controlled study.

BACKGROUND: Numerous studies advocate the use of diagnostic laparoscopy (DL) for abdominal trauma, but none have documented its ability to diagnose specific injuries. This study tests the hypothesis that DL can accurately identify all significant intra-abdominal injuries in trauma patients. METHODS: Of trauma patients requiring laparotomy for presumed injuries, 47 underwent DL followed by laparotomy. Injuries noted at laparoscopy were compared with those found at laparotomy. RESULTS: Of these, 14 patients had no significant injuries necessitating operative intervention noted at laparoscopy and celiotomy. The remaining 33 patients harbored 93 significant injuries at laparotomy, of which only 57.0% were found by DL. DL possessed poor sensitivity (<50%) for injuries to hollow viscera. Despite DL's poor performance in finding specific injuries, it possessed excellent sensitivity (96.2%), and specificity (100%) for determining the need for therapeutic celiotomy. CONCLUSIONS: DL offers no clear advantage over diagnostic peritoneal lavage and computed tomography in blunt trauma. Its utility lies in assessment of the need for laparotomy in patients with penetrating wounds. Currently, DL cannot consistently identify all abdominal injuries, disqualifying it as a therapeutic tool in abdominal trauma.

Effect of WEB 2086 on leukocyte adherence in response to hemorrhagic shock in rats.

BACKGROUND: The pathogenesis of generalized microvascular injury after hemorrhagic shock is known to involve the generation of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine [PAF]). The release of PAF is manifested in several ways, including by increased vascular permeability, altered vascular reactivity, and increased leukocyte adherence to the endothelium. WEB 2086 is a PAF antagonist that has been shown experimentally to improve survival after hemorrhagic shock. The purpose of this study was to examine the efficacy of WEB 2086 in attenuating leukocyte adherence before, during, and after hemorrhagic shock. METHODS: After a control period, blood was withdrawn to reduce the mean arterial pressure to 40 mm Hg for 30 minutes in urethane-anesthetized rats. Mesenteric venules in a transilluminated segment of the small bowel were examined to quantitate leukocyte adherence using intravital microscopy. RESULTS: In sham-operated rats (control), there was minimal to no leukocyte adherence throughout the experiment. Hemorrhagic shock resulted in a significant increase in leukocyte adherence postshock during resuscitation (10.9 +/- 1.8 cells/100 microm, p < 0.01) when compared with controls. WEB 2086, when given before shock, significantly attenuated leukocyte adherence (0.1 +/- 0.08 cells/100 microm, p < 0.01) when compared with hemorrhagic shock alone. This effect of WEB 2086 on adherence could be demonstrated even when it was given during (3.5 +/- 0.9 cells/100 microm, p < 0.01) and 10 minutes into (5.8 +/- 1.1 cells/100 microm, p < 0.05) hemorrhagic shock. CONCLUSION: Our findings suggest that WEB 2086 may be of therapeutic benefit against the microvascular damage sustained after hemorrhagic shock.

Carboxyhemoglobin elevation in trauma victims.

BACKGROUND: Products of the hemeoxygenase enzyme include carboxyhemoglobin (COH) and bilirubin, which have protective effects in stressed states. Hemeoxygenase-1 enzyme up-regulates in states of oxidative stress. We hypothesized that COH is elevated in septic trauma patients compared with nonseptic patients. METHODS: A prospective study was carried out at a Level I trauma center involving all patients admitted to the trauma intensive care unit. During a 3.5-month period, 45 patients were enrolled, with 76 samples being drawn on admission and at later time points. The samples were classified as septic (Bone's criteria), stressed (based on expired gas analysis), or nonstressed nonseptic. Correlations with Acute Physiology and Chronic Health Evaluation III score, white blood cell count, temperature, partial pressure of oxygen, and percentage of inspired oxygen were evaluated. RESULTS: COH levels in samples drawn from patients presenting in shock (systolic blood pressure < or =90 mm Hg) were significantly higher than levels in samples from patients not in shock (systolic blood pressure >90 mm Hg) (3.27+/-1.09 vs. 2.75+/-0.64; p = 0.013). Samples from septic patients with infection were associated with significantly higher Injury Severity Scores (34.1+/-11.2 vs. 21.8+/-18.3; p< or =0.05) and a lower percentage of inspired oxygen (41.6+/-10.3 vs. 61.0+/-26.3; p< or =0.05). CONCLUSION: COH was significantly elevated in samples drawn during stress, sepsis, and shock states. There was overlap between sepsis and stress COH sample values, limiting the clinical usefulness of the assays in predicting sepsis. Further studies focusing on hemeoxygenase-1 expression and the role of its by-products in the outcomes of trauma patients are warranted.

Relationship of admission plasma gelsolin levels to clinical outcomes in patients after major trauma.

Actin-scavenging proteins, e.g., plasma gelsolin, counteract the pathophysiological consequences of actin leaked into the circulation from dying cells, but the capacity of this defense system can be overwhelmed by massive tissue injury. We examined the prognostic implications of plasma gelsolin levels obtained near the time of admission to our level I Trauma Unit on the subsequent clinical course in a group of patients with severe traumatic injuries. Blood samples were obtained from 13 patients shortly after major trauma and 11 healthy volunteers who served as the control group. Plasma gelsolin levels were assayed by quantitative Western blotting. Duration of mechanical ventilation, stay in the Trauma Intensive Care Unit, and development of acute respiratory distress syndrome (ARDS) were measured as clinical outcomes reflecting the complexity of the hospital course. Subsequently, we evaluated an additional 52 patients after major and minor trauma to extend our earlier observations. Plasma gelsolin concentrations were significantly lower in our 13 original patients compared with healthy controls. Levels below 250 mg/L (> 2 standard deviations below the mean of the control group) were associated with prolonged mechanical ventilation and a stay in the intensive care unit >/= 13 days. Both patients whose gelsolin level was < 100 mg/L in this first series developed ARDS. Including all 65 patients, 6 of the 10 patients who developed ARDS had admission gelsolin levels less than 250 mg/L, compared with only 7 of the 55 patients without ARDS (p = 0.0028). The mean gelsolin levels were 193 and 400 mg/L in patients with and without ARDS, respectively (p < 0.0001) and 398 mg/L in survivors versus 259 mg/L for patients who expired (p < 0.0001). Ten of the 13 patients (77%) with gelsolin levels at the time of admission more than 2 SD below the control mean had "bad outcomes," defined as mechanical ventilation for >/= 13 days in the Trauma Intensive Unit, ARDS, and/or death. Plasma gelsolin levels appear to be an early prognostic marker in patients experiencing major trauma. Whether circulating gelsolin serves a biologically vital function or is simply depleted after massive trauma cannot be determined from our study. The potential therapeutic benefits of infusions of recombinant human plasma gelsolin for patients in whom multiorgan dysfunction commonly follows a serious but self-limited insult have not yet been investigated.

Bactericidal/permeability-increasing protein (rBPI21) in patients with hemorrhage due to trauma: results of a multicenter phase II clinical trial. rBPI21 Acute Hemorrhagic Trauma Study Group.

BACKGROUND: Infection and organ failure are the most common causes of death or serious complication in trauma patients surviving initial resuscitation and operation. Of the many possible causes of these complications, bacterial translocation and release of harmful cytokines and oxygen free radicals may play an important role in the pathogenesis of the complications associated with traumatic hemorrhage. Recombinant human bactericidal/permeability-increasing protein (rBPI21) has antibacterial and antiendotoxin properties, reduces cytokine levels, and increases survival in animal models of hemorrhagic shock. The primary objective of this study was to evaluate the safety and efficacy of prophylactic rBPI21 infusion in patients with hemorrhage due to trauma. METHODS: This was a phase II, multicenter, randomized, double-blind, placebo-controlled trial. Patients who required at least 2 U of blood were randomized to receive rBPI21 (4 mg x kg(-1) x d(-1) for 2 consecutive days) or an equivalent volume of placebo by continuous infusion within 12 hours of injury. The primary efficacy end point was mortality or serious complication occurring during the first 15 days of the study. Safety was monitored clinically and by laboratory panels during the study period. RESULTS: A total of 401 patients were treated (202 in the rBPI21 group and 199 in the placebo group). The composite end point rate of mortality or serious complication through day 15 was 46% in the placebo group and 39% in the rBPI21 group (hazard ratio = 0.79; p = 0.13). Secondary analysis, which adjusted for age, mechanism of injury, Injury Severity Score (1990 version), and units of blood received before study drug infusion showed similar results (hazard ratio = 0.79; p = 0.14). The proportion of patients who developed at least one serious organ dysfunction was 22% in the placebo group and 16% in the rBPI21 group (hazard ratio = 0.71; p = 0.14). The proportion of patients who developed either pneumonia or acute respiratory distress syndrome was 32% in the placebo group and 22% in the rBPI21 group (hazard ratio = 0.66; post hocp = 0.03). The beneficial trends of rBPI21 were observed in both blunt and penetrating trauma and were generally observed across different age groups, Injury Severity Scores, and units of blood transfused. No treatment difference was observed in mortality or resource utilization in this phase II study. CONCLUSION: rBPI21 was well-tolerated and demonstrated a favorable trend in reducing the composite primary end point of mortality or serious complication through day 15, especially respiratory complications, in patients with hemorrhage due to trauma. A phase III study is currently in progress.