Reliability of transpulmonary pressure-time curve profile to identify tidal recruitment/hyperinflation in experimental unilateral pleural effusion.

The stress index (SI) is a parameter that characterizes the shape of the airway pressure-time profile (P/t). It indicates the slope progression of the curve, reflecting both lung and chest wall properties. The presence of pleural effusion alters the mechanical properties of the respiratory system decreasing transpulmonary pressure (Ptp). We investigated whether the SI computed using Ptp tracing would provide reliable insight into tidal recruitment/overdistention during the tidal cycle in the presence of unilateral effusion. Unilateral pleural effusion was simulated in anesthetized, mechanically ventilated pigs. Respiratory system mechanics and thoracic computed tomography (CT) were studied to assess P/t curve shape and changes in global lung aeration. SI derived from airway pressure (Paw) was compared with that calculated by Ptp under the same conditions. These results were themselves compared with quantitative CT analysis as a gold standard for tidal recruitment/hyperinflation. Despite marked changes in tidal recruitment, mean values of SI computed either from Paw or Ptp were remarkably insensitive to variations of PEEP or condition. After the instillation of effusion, SI indicates a preponderant over-distension effect, not detected by CT. After the increment in PEEP level, the extent of CT-determined tidal recruitment suggest a huge recruitment effect of PEEP as reflected by lung compliance. Both SI in this case were unaffected. We showed that the ability of SI to predict tidal recruitment and overdistension was significantly reduced in a model of altered chest wall-lung relationship, even if the parameter was computed from the Ptp curve profile.

Not only in trauma patients: hospital-wide implementation of a massive transfusion protocol.

OBJECTIVES: To review outcomes of massive transfusion protocol (MTP) activation and determine the impact of MTP implementation on blood bank use. BACKGROUND: MTP has been established to rapidly provide plasma and packed red blood cells in ratios approaching 1 : 1. Due to availability, MTP has been utilised in non-traumatic haemorrhage despite evidence of benefit in this population. Our hospital-wide implementation of MTP was reviewed for propriety, outcomes and effect on blood bank resources. METHODS: Retrospective cohort study of patients receiving transfusion after MTP activation from October 2009 to 2011. Underlying medical conditions and baseline medication use were determined. In-hospital and 24-h mortality were compared with evaluation for confounding by Acute Physiology And Chronic Health Evaluation (APACHE) score and duration of MTP activation. Blood product use before and after MTP implementation was reviewed. RESULTS: MTP activation occurred in 62 trauma and 63 non-trauma patients. Non-trauma patients were older, had more underlying medical conditions and higher APACHE scores compared with trauma patients; 24-h mortality was higher in trauma compared with non-trauma patients (27·4 vs 11·1%, P = 0·02). There was no significant difference of in-hospital mortality. Transfusion ratio did not differ between trauma and non-trauma patients and was not associated with mortality even when MTP activation duration and APACHE score were considered. Hospital-wide blood product use did not change with MTP implementation. CONCLUSIONS: MTP may be successfully used in trauma and non-trauma settings without significantly impacting overall blood product utilisation. Inclusion of non-trauma patients into prospective studies of resuscitation with blood products is warranted to ensure benefit in these patients.

Differential neutrophil traffic in gut and lung after scald injury.

Neutrophil recruitment to the lung after thermal injury has been reported by various laboratories. Changes in neutrophil populations in the gut and lung have not been examined simultaneously after burn injury. Mice aged 8 to 10 weeks were anesthetized and subjected to 15% topical scald injury. Animals were sacrificed at 30 minutes and 1, 2, 4, 8, 16, and 32 hours after injury with harvesting of terminal ileum and lung for myeloperoxidase (MPO) assay. Lungs were evaluated after bronchoalveolar lavage and lavage of the vascular bed to remove neutrophils in these compartments. Myeloperoxidase activity was compared between groups of sham-injured and burned animals. Although pulmonary neutrophil recruitment was obvious after scald burn; in the ileum, burned animals showed diminished MPO activity. Histology and bronchoalveolar lavage revealed no evidence of gross organ injury apart from obvious changes in cellular content in the lung. Thermal injury is associated with differential neutrophil movement in the lung and the gut in this model. Pulmonary neutrophil recruitment is confirmed, whereas the gut seems to lose neutrophils as indicated by diminished MPO activity in the initial hours after dorsal scald injury.

Dynamic behavior during noninvasive ventilation: chaotic support?

Acute noninvasive ventilation is generally applied via face mask, with modified pressure support used as the initial mode to assist ventilation. Although an adequate seal can usually be obtained, leaks frequently develop between the mask and the patient's face. This leakage presents a theoretical problem, since the inspiratory phase of pressure support terminates when flow falls to a predetermined fraction of peak inspiratory flow. To explore the issue of mask leakage and machine performance, we used a mathematical model to investigate the dynamic behavior of pressure-supported noninvasive ventilation, and confirmed the predicted behavior through use of a test lung. Our mathematical and laboratory analyses indicate that even when subject effort is unvarying, pressure-support ventilation applied in the presence of an inspiratory leak proximal to the airway opening can be accompanied by marked variations in duration of the inspiratory phase and in autoPEEP. The unstable behavior was observed in the simplest plausible mathematical models, and occurred at impedance values and ventilator settings that are clinically realistic.

Sublethal endotoxemia promotes pulmonary cytokine-induced neutrophil chemoattractant expression and neutrophil recruitment but not overt lung injury in neonatal rats.

Gram-negative sepsis and septic shock remain major causes of morbidity and mortality in the newborn. Respiratory failure is a common feature in neonatal sepsis regardless of the presence or absence of associated pneumonia. In adult animal models, cytokine-induced neutrophil chemoattractant (CINC) is a potent chemoattractant for neutrophils and believed to play a role in endotoxin-induced lung injury. We examined this in a neonatal model. Ten-day-old Sprague-Dawley rats were injected with Salmonella enteritidis endotoxin (ETX) 0.03 mg/kg i.p. and sacrificed at baseline, 30 min, 1, 2, 4, 8 and 16 h post-ETX. Blood was collected by cardiac puncture. After bronchoalveolar lavage, lung tissue was collected and evaluated for neutrophil (polymorphonuclear leukocyte) recruitment by myeloperoxidase assay (MPO). Lung CINC expression was measured by Northern blot and ELISA. Peripheral blood leukocytosis was noted at 1 h (p < 0.001) with counts below baseline at 2 and 4 h. Differential counts revealed neutrophilia at 8 h (p < 0.001). MPO revealed pulmonary PMN recruitment peaking at 1 h (p < 0.05) and CINC RNA and protein expression peaked slightly later at 2 h (p < 0. 001). No overt lung injury was noted by bronchoalveolar lavage cell counts or by histology. Therefore, pulmonary CINC expression and neutrophil recruitment follows LPS exposure in neonatal rats. This may represent priming of the lung tissue and a secondary event may be necessary for injury to occur.

Recent progress in advanced cardiac life support.

The revised guidelines for advanced cardiac life support (ACLS) from the American Heart Association are anticipated in the fall of 2000. Although dramatic changes in the approach to adult basic and ACLS are not anticipated, several controversies and new drugs on the horizon may radically change our approach to emergent cardiac resuscitation. This article features some of the evolving thinking on the emergent treatment of the adult with ventricular fibrillation or ventricular tachycardia, the critical rhythms seen in most cases of acute cardiac distress. Approaches to airway therapy drug administration and new agents also are described.

Blunt thoracic aortic injury: delayed or early repair?

OBJECTIVE: To evaluate the safety and benefit of delayed repair of blunt thoracic aortic injury (BTAI) in trauma patients with multiple injuries and to assess the financial impact of delayed repair. METHODS: A retrospective review of charts was performed on 55 patients with the diagnosis of BTAI from January 1, 1992, through December 31, 1997, at our Level I trauma center. Early repair was defined as operative repair of BTAI within 12 hours of admission. Seven patients were excluded from analysis due to death before BTAI diagnosis (two deaths were from rupture in the emergency department and five were from massive blunt trauma without rupture). The groups were compared by using a McNemar chi2 test, for which p less than or equal to 0.05 is significant. RESULTS: There were 30 patients in the early repair (ER) group repaired at 5.3+/-2.4 hours, and 18 patients in the delayed repair (DR) group repaired at 8.5 days (range, 17 hours-67 days). There were no significant differences between the ER and DR groups in age (37+/-18 years vs. 41+/-19 years), Injury Severity Score (39+/-15 vs. 45+/-14), intensive care unit days (12+/-14 days vs. 18+/-11 days), hospital length of stay (21+/-19 days vs. 28+/-14 days), or mortality rates (7% vs. 6%). There was a trend toward longer lengths of stay in the DR group. Most DR patients required beta-blocker therapy and/or other antihypertensives for systolic BP more than 120 mm Hg during admission. There were no deaths from aortic rupture in either group. By using financial data that was available from July of 1994 onward, we performed a subset analysis of the direct costs associated with BTAI. Total direct and variable direct costs for patients undergoing delayed repair were over two times the costs for early repair patients (p < 0.05). CONCLUSION: The management of trauma patients with multiple injuries requires prioritization of injuries so that the outcomes from these injuries can be optimized. Although delayed aortic repair was safely practiced in this series, there was not an obvious outcome benefit to delayed repair. The patients undergoing late repair required increased attention to hemodynamics, and there was a trend toward increased length of stay. In addition, analysis of the costs associated with delayed repair demonstrated a twofold increase in the direct costs for delayed repair compared with early repair.

Fibrin sealant inhibits connective tissue deposition in a murine model of peritoneal adhesion formation.

BACKGROUND: Postoperative peritoneal adhesion formation causes a multitude of disorders, including bowel obstruction and infertility. METHODS: To test whether fibrin sealant inhibits adhesion formation, mice were given an intraperitoneal injection of talc (to induce adhesions) after which sealant was administered. Seven and 14 days later, the thickness of connective tissue between the fragmented mesothelium and the abdominal muscle was measured. RESULTS: At both 7 and 14 days after talc administration, talc-treated mice had a 6-fold increase in connective tissue thickness over vehicle alone (P < .05). Although fibrin sealant alone failed to trigger peritoneal pathologic conditions, administration of sealant to talc-treated mice inhibited connective tissue deposition by 80% at 7 and 14 days (P < .05). Additionally, delaying fibrin sealant administration up to and including 72 hours after talc treatment results in comparable inhibition of connective tissue deposition, as does treatment immediately after talc exposure. CONCLUSIONS: This study demonstrates that fibrin sealant inhibits peritoneal inflammation and peritoneal adhesion formation with use of a quantitative assay of connective tissue deposition. In addition, this is the first report to document the administration of fibrin sealant into the closed abdomen. The success of these studies suggests that fibrin sealant will block peritoneal adhesions when administered laparoscopically. Finally, because fibrin sealant is therapeutic even when administered after the initiation of peritoneal inflammation, it suggests that it may be efficacious in patients who present with adhesions or those undergoing multiple operations.

Prone positioning in acute lung injury.

More than 20 years ago, critical care workers first observed that oxygenation improved when patients with acute respiratory distress syndrome were ventilated in the prone position. In recent reports, on turning prone, from 50 to 100% of patients improve oxygenation to a degree sufficient to allow a reduction in the level of positive end-expiratory pressure or fraction of inspired oxygen. It appears that vascular conductance in lung regions previously in the dorsal position is augmented by an increase in air space volume, with the effect that prone position ventilation will reduce shunt and improve ventilation-perfusion mismatch. Factors determining which patients will respond have not yet been elucidated. Although many questions regarding the role of prone ventilation are unanswered, of greatest importance is whether this technique reduces morbidity and mortality of patients with acute respiratory failure. Only carefully conducted, randomized trials can answer this question.

Molecular markers of hemostatic activation and inflammation following major injury: effect of therapy with IFN-gamma.

Interferon-gamma (IFN-gamma) has shown promise in treatment of injured patients. However, reactive states marked by immunologic and inflammatory responses constitute a potential deleterious effect of IFN-gamma administration. IFN-gamma therapy has been associated with high levels of tumor necrosis factor-alpha (TNF-alpha), with potential enhancement of coagulopathy after injury. This study evaluated TNF-alpha production and markers of hemostatic activation in patients receiving IFN-gamma therapy. Seventy-three patients, part of a larger multicenter trial, with severe injuries were randomized to IFN-gamma (100 microg/day s.c. for 21 days) or placebo treatment. Enrollment criteria included injury severity score (ISS) > or = 25 or significant bacterial contamination with ISS > or = 20. TNF-alpha and other cytokine production was assessed at baseline and on days 3, 8, and 22 following injury. Markers of coagulation activation and fibrinolysis were also evaluated. Plasma TNF-alpha and interleukin-6 (IL-6) levels were higher in IFN-treated relative to placebo-treated patients before and after IFN administration. Markers of coagulation and fibrinolysis were elevated at all times studied following injury in both treatment and control groups but did not differ between patients receiving IFN and those receiving placebo. Activation of coagulation and fibrinolysis diminished in a time-related manner following injury. We conclude that (1) IFN-gamma therapy at the dose employed was not associated with a significant increase in TNF-alpha or other inflammatory cytokine production beyond that seen in patients receiving placebo, (2) coagulation and fibrinolytic markers were increased following injury but decreased significantly in surviving patients, and (3) no changes in coagulation and fibrinolytic parameters were noted in relation to IFN-gamma therapy. These findings support previous observations that trauma is associated with hemostatic activation and that treatment of patients at the dose of IFN-gamma studied is safe in the setting of injury.

Trauma and thermal injury: comparison of hemostatic and cytokine changes in the acute phase of injury.

BACKGROUND: Initiated either by thermal injury or mechanical trauma, the systemic inflammatory response syndrome stimulates activation of coagulation and fibrinolysis, evolving into a subclinical disseminated intravascular coagulation. METHOD: Hemostatic parameters, interleukin-6, and endothelin plasma levels were compared in burn and trauma patients. Nineteen patients with major burn injury (> or = 40% total body surface area) were compared with 35 trauma patients with Injury Severity Scores > 25 on day 1 and days 5 to 8. RESULTS: Thrombin-antithrombin levels were significantly higher in trauma patients than in burn patients (p < 0.0001) on day 1, and endothelin was significantly higher on days 1 and 5 (p < 0.0001) in trauma patients than in burn patients. Interleukin-6 plasminogen activator inhibitor-1, and tissue plasminogen activator levels were elevated above normal limits on both days in both groups. CONCLUSION: There was a difference in the degree and level to which homeostasis was perturbed between the two groups. The mechanism of injury did not affect the initiation of subclinical disseminated intravascular coagulation and cytokine release, and the physiologic response remained the same.

Weaning from mechanical ventilation.

Use of mechanical ventilation is associated with several major complications despite its lifesaving potential. Timely discontinuation of mechanical ventilation is critical to control of duration of intensive care unit stay and reduction of complications associated with mechanical ventilation. Difficulty in discontinuation (or weaning) of patients from mechanical ventilatory support is in part attributable to inadequate understanding of the mechanisms responsible for unsuccessful outcome and a lack of guidelines regarding the optimal approach to the process of discontinuation of mechanical ventilation. For the first time, results from prospective, randomized, multicenter trials are available comparing common means of discontinuation of mechanical ventilation. In addition, the physiologic basis for a weaning strategy in mechanical ventilation is also coming into better focus. Two recent trials of weaning suggest different optimal modes, one favoring T-piece trials and the other supporting the use of pressure support ventilation. In either case, the above weaning techniques appear to be superior to intermittent mandatory ventilation in separating patients from mechanical ventilatory support. Based on available clinical trials, pressure support ventilation or T-piece trials appear to be the preferred methods for discontinuation of mechanical ventilatory support. A method using a simple T-piece trial technique is described.

Hypotensive resuscitation.

While the mechanism remains unclear, a growing body of experimental and clinical evidence suggests that aggressive crystalloid resuscitation in near fatal uncontrolled hemorrhage is associated with poor outcome. Limited attempts to restore blood pressure improve cardiac output, tissue perfusion, and survival while attempts to restore normal tension with crystalloid result in increased hemorrhage volume and higher mortality. The current standard of therapy for treatment of hemorrhagic shock includes initial aggressive crystalloid resuscitation. This mini-review summarizes some of the experimental and clinical data suggesting that this approach may not be desirable in the presence of uncontrolled hemorrhage following injury.

Interferon gamma in trauma-related infections.

OBJECTIVE: The efficacy of interferon gamma therapy in reducing infection and improving outcome from infection in patients sustaining major injury was examined. DESIGN: Randomized double-blind placebo control trial SETTING: Nine level one university affiliated trauma centers in the United States. PATIENTS AND PARTICIPANTS: Four hundred sixteen patients with injury severity score (ISS) > or = 25 or ISS > or = 20 with evidence of wound contamination. INTERVENTION: Recombinant human interferon gamma 100 ug or placebo was given subcutaneously daily for up to 21 days in addition to standard antibiotic therapy. MEASUREMENTS AND RESULTS: Comparable rates of major and minor infections were observed. Among the patients treated with interferon gamma there were fewer deaths related to major infection regardless of type [7-(3%) vs 18-(9%)]. The results, however, were dominated by one center which had the highest enrollment, infection and death rates. CONCLUSIONS: Further studies are warranted to investigate the role of interferon gamma therapy in improving outcome with major infection.

Activation of the clotting system and complement after trauma.

The traditional approach to hemostatic disorders in the injured patient has focused on bleeding rather than a hypercoagulable state. This strategy continues despite growing evidence from studies of coagulation disorders in other patient groups highlighting loss of organ function secondary to inappropriate coagulation rather than hemorrhage. While traditional testing is useful in screening for low levels of coagulation factors or platelet dysfunction, only obvious bleeding or significant fibrinolysis is identified. Cellular interactions, in particular those of the vascular endothelium, are not taken into account by these assays. More than 20 years have passed since coagulation abnormalities were reported in patients with severe infection. Despite recognition of this association in sepsis, we are only beginning to understand how coagulation abnormalities develop in injury and to consider strategies to counter them. While hemorrhage may be successfully treated in patients following trauma, thrombosis in the microcirculation often contributes to end-organ damage with irreversible ischemic changes that may lead to death.

Assessment of two clinical trials: interferon-gamma therapy in severe injury.

Two recent studies have examined the efficacy of interferon-gamma in reducing infection and death in patients sustaining severe injury. Both included multi-center, randomized, double-blinded placebo-control design. The first trial, conducted at four university trauma centers, enrolled 213 patients, while the second trial involved nine university trauma centers and 416 subjects. Recombinant human interferon-gamma (100 micrograms) was administered subcutaneously daily for 10 days in the first trial and 21 days in the second, in addition to standard supportive therapy. In both trials infection rates were similar in the treatment arms. Although the death rate related to infection was not affected in the first study, the second trial suggested an improved outcome from this complication. The outcome of the larger trial was flawed by dominant findings at one center that had the highest enrollment, infection, and death rates. Confounding variable analysis presented here explains much of the difference between center findings in the larger trial. Thus, the benefit of interferon-gamma as an immune adjuvant in severe injury is clouded by study design flaws evaluating its use and by the inability to identify appropriate subjects using clinical criteria.