Missed injuries in patients with multiple trauma.

BACKGROUND: Understanding the etiology of missed injuries is essential in minimizing its occurrence. A retrospective review was conducted to identify the incidence, contributing factors, and clinical outcomes of missed injuries. METHODS: All trauma patients assessed by St Michael's Hospital trauma service from April 1, 1995, to July 31, 1997, were included in the study. Demographic and medical data were compared and statistically analyzed in two patient groups to identify factors associated with missed injuries. RESULTS: Forty six of 567 patients (8.1%) had missed injuries. Patients with missed injuries had higher mean Injury Severity Scores and longer stays in the hospital and intensive care unit compared with patients without missed injuries (p < 0.05). Patients with missed injuries were more likely to have lower Glasgow Coma Scale scores and to have required pharmacologic paralysis (p < 0.05). Of the factors contributing to missed injuries, 56.3% were potentially avoidable and 43.8% were unavoidable. Seven patients with missed injuries had clinically significant outcomes, including one patient death. Of the seven clinically significant missed injuries, five were attributable to potentially avoidable factors. CONCLUSION: Patients with missed injuries tend to be more severely injured with initial neurologic compromise. The majority of missed injuries are potentially avoidable with repeat clinical assessments and a high index of suspicion.

Production of tumour necrosis factor alpha by primary cultured rat alveolar epithelial cells.

Tumour necrosis factor alpha(TNF-alpha) is one of the most important pro-inflammatory cytokines, which plays an important role in host defense and acute inflammation related to tissue injury. The major source of TNF-alpha has been shown to be immune cells such as macrophages and neutrophils. In the present study, we demonstrated that LPS-treatment on alveolar epithelial cells isolated from adult rat lungs also induced a dose- and time-dependent release of TNF-alpha. The purity and identity of these cells were examined by immunofluorescent staining and confocal microscopy with antibodies for cytokeratin and pro-surfactant protein C, markers for epithelial cells and type II pneumocytes respectively. Positive staining of TNF-alpha was observed throughout the cell layer and localized intracellularly. LPS-induced TNF-alpha production from alveolar epithelial cells was blocked not only by cycloheximide, an inhibitor of protein translation, but also by actinomycin D, an inhibitor of gene transcription. The mRNA of TNF-alpha rapidly increased within 1 h of LPS stimulation. These data suggest that LPS-induced TNF-alpha production from alveolar epithelial cells is primarily regulated at the transcriptional level, which is different from that of macrophages and neutrophils. TNF-alpha produced by alveolar epithelial cells may function as an alert signal in host defense to induce production of other inflammatory mediators.

Tumor necrosis factor-alpha mediates lipopolysaccharide-induced macrophage inflammatory protein-2 release from alveolar epithelial cells. Autoregulation in host defense.

Our recent studies have demonstrated that in response to lipopolysaccharide (LPS) challenge, alveolar epithelial cells produced tumor necrosis factor (TNF)-alpha, an early response cytokine in the inflammatory process. To investigate whether LPS-induced TNF-alpha release is related to other inflammatory mediators from the same cell type, we examined effects of LPS stimulation on macrophage inflammatory protein (MIP)-2 production by alveolar epithelial cells, and then examined the relationship between TNF-alpha and MIP-2 production. LPS stimulation induced a dose- and time-dependent release of MIP-2. The steady-state messenger RNA level of MIP-2 was significantly increased, with the MIP-2 protein localized within alveolar epithelial cells, as determined by confocal microscopy. The LPS-induced MIP-2 production is regulated at both the transcriptional and post-transcriptional levels. TNF-alpha also induced MIP-2 production from alveolar epithelial cells. Preincubation with an antisense oligonucleotide against TNF-alpha inhibited LPS-induced TNF-alpha in a dose-dependent and sequence-specific manner. The same antisense also inhibited MIP-2 production. The inhibitory effects were highly correlated. Polyclonal and monoclonal antibodies against TNF-alpha also attenuated LPS-induced MIP-2. These results suggest that LPS-induced MIP-2 release from alveolar epithelial cells may be mediated in part by TNF-alpha from the same cell type. This autoregulatory mechanism may amplify LPS-induced signals involved in host defense as well as in acute inflammatory reactions.

LPS-induced depolymerization of cytoskeleton and its role in TNF-alpha production by rat pneumocytes.

Lipopolysaccharide (LPS) polymerizes microfilaments and microtubules in macrophages and monocytes. Disrupting microfilaments or microtubules with cytochalasin D (CytoD) or colchicine can suppress LPS-induced tumor necrosis factor-alpha (TNF-alpha) gene expression and protein production from these cells. We have recently demonstrated that primary cultured rat alveolar epithelial cells can produce TNF-alpha on LPS stimulation. In the present study, we found that the LPS-induced increase in TNF-alpha mRNA level and protein production in alveolar epithelial cells was not inhibited by CytoD or colchicine (1 nM to 10 microM). In fact, LPS-induced TNF-alpha production was further enhanced by CytoD (1-10 microM) and inhibited by jasplakinolide, a polymerizing agent for microfilaments. Immunofluorescent staining and confocal microscopy showed that LPS (10 microg/ml) depolymerized microfilaments and microtubules within 15 min, which was prolonged until 24 h for microfilaments. These results suggest that the effects of LPS on the cytoskeleton and the role of the cytoskeleton in mediating TNF-alpha production in alveolar epithelial cells are opposite to those in immune cells. This disparity may reflect the different roles between nonimmune and immune cells in host defense.

Pneumonia in patients with multiple trauma.

This article examines the features of nosocomial pneumonia in the subpopulation of patients with multiple trauma. Epidemiology, trauma-associated risk factors, diagnosis, microbiology, therapy, and prevention are reviewed. While some issues may overlap with critically ill patients in general, differences in approach and management will be discussed.

Improved lung preservation with dextran 40 is not mediated by a superoxide radical scavenging mechanism.

Improved lung preservation with a low-potassium dextran-containing solution has been previously demonstrated. In a subsequent study, it was shown that dextran 40 contributes significantly to this improved preservation. In the current in vitro study, human neutrophils suspended in lung preservation solutions (low potassium with dextran and low potassium without dextran) were stimulated to produce superoxide radicals. The presence of dextran in the solution did not significantly alter the amount of superoxide measured in the assay (low potassium with dextran, 4.149 +/- 0.144 nmol/10(6) cells/20 min; low potassium without dextran, 3.896 +/- 0.215; p greater than 0.2). This suggests that dextran 40 did not appreciably scavenge superoxide radicals, nor did it alter the production of superoxide radicals by stimulated neutrophils. Thus the significantly improved lung preservation seen with the use of dextran 40 is probably not mediated by a superoxide radical scavenging process.

Effect of systemic fibrinogen depletion on intraabdominal abscess formation.

Deposition of fibrin within the peritoneal cavity is an integral host response to local infection. To directly assess the role of fibrin deposition in the pathogenesis of intraabdominal abscess formation, the ability to induce abscesses in fibrinogen-depleted mice was examined. We hypothesized that systemic defibrinogenation with ancrod would limit the availability of fibrinogen for deposition within the peritoneal cavity and would therefore impair intraabdominal abscess formation. A gelatin capsule containing 50% sterile feces plus Bacteroides fragilis 1 x 10(9) CFU was inserted IP into control or defibrinogenated mice. System defibrinogenation resulted in alteration of the character of abscess formation, as manifested by reduced abscess size and degree of purulence. Abscesses were significantly smaller (0.18 +/- 0.02 gm [n = 29] vs. 0.09 +/- 0.02 gm [n = 11], p less than 0.01) and less purulent (p less than 0.001) in the ancrod-treated mice than in control animals, despite equal numbers of bacteria in the abscesses recovered from both groups. The effect of ancrod was specific for defibrinogenation, because IP repletion with fibrinogen reversed the ancrod effect on abscess size. In addition to its local effects, systemic fibrinogen depletion resulted in a significant elevation in mortality following IP infection (1 of 30 control animals vs. 10 of 23 ancrod-treated animals, p less than 0.01). However, this was not due to an increase in the magnitude of the B. fragilis bacteremia. These studies demonstrate that fibrin deposition contributes to the pathogenesis of purulent abscess formation and that systemic depletion of fibrinogen may alter host susceptibility to the consequences of infection.

Expression and secretion of IL-2 receptor in trauma patients.

The high-affinity cell-surface receptor for interleukin-2 (IL-2R) consists of the 75-kilodalton (kd) chain and a 55-kd glycoprotein known as Tac. This report examines the cellular expression of IL-2R and secretion of the soluble form of Tac in immunosuppressed blunt trauma (n = 20, injury severity score -20) and thermally injured (n = 20, Total body surface area greater than 35%) patients. The percentage of IL-2R-expressing peripheral blood mononuclear cells (PBMC) in mitogen-stimulated cultures from patients and age-matched normal donors was determined by direct immunofluorescence with a monoclonal anti-Tac followed by flow cytometry analysis. Levels of soluble Tac in patient sera were measured by a monoclonal antibody-based enzyme-linked immunosorbent assay. Expression of Tac antigen by mitogen-activated PBMC cultures from blunt trauma patients was transiently reduced (by as much as 40%) in 4 of 14 patients examined. Levels of serum Tac were significantly elevated (p less than 0.05) in 15 of 20 blunt trauma patients ranging from 750 to 3000 U/mL compared with 180 to 420 U/mL in control subjects. All burn patients studied 10 to 50 days after the injury demonstrated a significant reduction (by 50% to more than 90%) in the percentage of IL-2 receptor-bearing cells. Similarly serum levels of IL-2R increased significantly (p less than 0.001 to 0.05) in all burn patients studied, reaching concentrations as high as 5500 U/mL. These results suggest that major trauma, whether mechanical or thermal, induces alterations in the T-lymphocyte activation process. However the degree and duration of such changes may vary based on the nature of the injury.

Tissue plasminogen activator reverses the deleterious effect of infection on colonic wound healing.

Fibrin deposition in response to bacterial peritonitis appears to predispose to residual infection in the peritoneal cavity. Our previous studies have demonstrated that intraperitoneal fibrinolysis using human recombinant tissue plasminogen activator (t-PA) prevented abscess formation in a rat intra-abdominal sepsis model. To investigate the potential adverse side effects of its use in the peritoneal cavity, the effect of t-PA on colonic anastomotic wound healing and on systemic coagulation parameters was examined in the rat. T-PA did not adversely affect colonic healing five and ten days after anastomosis. In animals infected intraperitoneally at the time of the anastomosis, t-PA reversed the inhibition of healing induced by perianastomotic abscesses at five days. This effect was mediated by the ability of t-PA to prevent perianastomotic abscess formation. After intraperitoneal administration, t-PA had no effect on prothrombin and partial thromboplastin times in either uninfected or infected animals and there was no evidence of clinical bleeding related to its use. These studies suggest that intraperitoneal fibrinolysis using t-PA may provide a safe, effective form of adjuvant therapy in the management of fibrinopurulent peritonitis.

Impaired antibody production in blunt trauma. Possible role for T cell dysfunction.

This study investigates mechanisms of impaired humoral immune response in a well-defined population of blunt trauma patients (n = 18, Injury Severity Score greater than or equal to 20). Spontaneous and pokeweed mitogen-induced polyclonal immunoglobulin production were assessed in cultures of peripheral blood mononuclear cells. The proliferative response to alloantigen and mitogen was assessed in parallel by the mixed lymphocyte reaction and pokeweed mitogen-induced blastogenesis, respectively. Pokeweed mitogen-induced IgG and IgM production was significantly reduced in trauma patients compared with controls. This effect was not reversed by depletion of adherent cells or by the addition of indomethacin. Exogenous interleukin 2 was also ineffective. However, the addition of normal T cells or supernatants from isoantigen-stimulated cultures of these cells to patient B cell-enriched cultures significantly enhanced (by 1.4- to 5.1-fold) the antibody response to pokeweed mitogen. Thus, suppression of humoral antibody response in blunt trauma patients may be due to failure of T-cell mediated help, resulting in insufficient secretion or activity of cytokines required for adequate B cell activation, proliferation, or differentiation into immunoglobulin-secreting cells.

Delayed administration of tissue plasminogen activator reduces intra-abdominal abscess formation.

Previous studies demonstrated that intraperitoneal fibrinolysis using tissue plasminogen activator (t-PA) prevented intraabdominal abscess formation in a rat fibrin clot infection model when administered simultaneously with the infecting inoculum. To more closely mimic the clinical setting, the efficacy of delayed administration of t-PA on intra-abdominal abscess formation was examined. A delay of 2, 6, and 18 hours had no effect on the rate of abscess formation but did reduce abscess size, indicating partial fibrinolysis. Since fibrin clots dehydrate in vivo, we hypothesized that a higher concentration of t-PA might be necessary to effect complete abscess resolution. High-dose t-PA (0.1 mg/mL) prevented abscess formation following a 6-hour delay and reduced mean weight following an 18-hour delay. Since heparin sodium may prevent new fibrin deposition and enhance t-PA activity, it was combined with t-PA to investigate potential synergistic effects. Despite adequate anticoagulation with heparin, no synergy with t-PA could be documented. In addition, the combination of antibiotics with t-PA did not affect its efficacy in vivo. We demonstrate that delayed administration of t-PA is effective in preventing abscess formation and may have implications for the clinical setting where initial surgical intervention is usually delayed.

A method for safe twelve-hour pulmonary preservation.

The clinical application of lung transplantation is severely limited by the shortage of suitable donor organs. Current techniques of lung preservation allow a maximum of 4 to 6 hours of safe ischemic time. The function of canine left lung allografts stored for 12 hours after being cooled by pulmonary artery flush was studied. Two types of flush solution were used: group I; Euro-Collins solution; group II, low-potassium-dextran solution. Lung function was studied immediately and 3 days after transplantation. This protocol enables study of acute preservation-related lung injury and the delayed manifestations of ischemic and reperfusion injury after a 3-day period of recovery. Inflatable cuffs were placed around each pulmonary artery at operation and were attached to subcutaneous injection ports. Temporarily occluding either pulmonary artery allowed independent study of the native or transplanted lung. Using this model, we were able to demonstrate reliable and reproducible preservation of lungs for 12 hours. The low-potassium-dextran solution provided significantly better immediate function of the preserved lung than the Euro-Collins solution: arterial oxygen tension 509 +/- 15 mm Hg versus 111 +/- 16 mm Hg (p less than 0.0001). Function on the third day was excellent for both groups. Pulmonary artery pressure, pulmonary vascular resistance, and carbon dioxide tension were not significantly different between the groups immediately or on day 3.