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Objective: Recent interest has arisen in airway driving pressure (DP(AW)), the quotient of tidal volume (V(T)), and respiratory system compliance (C(RS)), which could serve as a direct and easily measured marker for ventilator-induced lung injury risk. We aimed to test the correspondence between DP(AW) and transpulmonary driving pressure (DP(TP))-the quotient of V(T) and lung compliance (C(L)), in response to intra-abdominal hypertension and changes in positive end-expiratory pressure during different models of lung pathology., Design: Well-controlled experimental setting that allowed reversible modification of chest wall compliance (C(CW)) in a variety of models of lung pathology., Setting: Large animal laboratory of a university-affiliated hospital., Subjects: Ten deeply anesthetized swine., Interventions: Application of intra-abdominal pressures of 0 and 20 cm H2O at positive end-expiratory pressure of 1 and 10 cm H2O, under volume-controlled mechanical ventilation in the settings of normal lungs (baseline), unilateral whole-lung atelectasis, and unilateral and bilateral lung injuries caused by saline lavage., Measurements and Main Results: Pulmonary mechanics including esophageal pressure and calculations of DP(AW), DP(TP), C(RS), C(L), and C(CW). When compared with normal intra-abdominal pressures, intra-abdominal hypertension increased DP(AW), during both "normal lung conditions" (p < 0.0001) and "unilateral atelectasis" (p = 0.0026). In contrast, DP(TP) remained virtually unaffected by changes in positive end-expiratory pressure or intra-abdominal pressures in both conditions. During unilateral lung injury, both DPA(W) and DP(TP) were increased by the presence of intra-abdominal hypertension (p < 0.0001 and p = 0.0222, respectively). During bilateral lung injury, intra-abdominal hypertension increased both DP(AW) (at positive end-expiratory pressure of 1 cm H2O, p < 0.0001; and at positive end-expiratory pressure of 10 cm H2O, p = 0.0091) and DP(TP) (at positive end-expiratory pressure of 1 cm H2O, p = 0.0510; and at positive end-expiratory pressure of 10 cm H2O, p = 0.0335)., Conclusions: Our data indicate that DP(AW) is influenced by reductions in chest wall compliance and by underlying lung properties. As with other measures of pulmonary mechanics that are based on unmodified P(AW), caution is advised in attempting to attribute hazard or safety to any specific absolute value of DP(AW).

Background: In emergent situations, access to the vascular bed is frequently required for fluid and medication administration. Central venous catheter placement is associated with risk and may slow resuscitation in the unstable patient. The purpose of this study was to determine whether intraosseous pressure (IOP) could be consistently recorded and how similar this pressure was to central venous and arterial pressure in a porcine hemorrhagic shock model., Materials and Methods: After sedation, eight female swine had catheters placed in the femoral vein, aorta via femoral artery, and superior vena cava. IOP lines were placed in the proximal humerus, distal femur, and proximal tibia. Pressure readings were recorded continuously through the five stages of progressive hypovolemia. Pressure data were descriptively summarized, with the percent of change of IOP at each stage compared with arterial pressure using a multilevel mixed effects linear model with log transformation., Results: The IOP baseline values were between 16 and 18 mm Hg, approximately 22% of baseline arterial pressure. The intraosseous (IO) waveform mostly closely resembled the arterial pressure waveform, including the presence of a dichroitic notch. Pressure variations caused by ventilation (respiratory variability) were also identified in all the tracings. The rate of pressure change in the humeral IO most closely matched the change in arterial pressure rate. IO blood gas analysis showed gas composition to most closely match venous blood., Conclusions: IOP was reliably obtained in this porcine model and suggests potential for clinical application in humans., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (© 2013 The Authors. Transfusion Medicine © 2013 British Blood Transfusion Society.)

Ease of dosing and simplicity of monitoring make new oral anticoagulants an attractive therapy in a growing range of clinical conditions. However, newer oral anticoagulants interact with the coagulation cascade in different ways than traditional warfarin therapy. Replacement of clotting factors will not reverse the effects of dabigatran, rivaroxaban, or apixaban. Currently, antidotes for these drugs are not widely available. Fortunately, withholding the anticoagulant and dialysis are freqnently effective treatments, particularly with rivaroxaban and dabigatran. Emergent bleeding, however, requires utilization of Prothrombin Complex Concentrates (PCCs). PCCs, in addition to recombinant factor VIIa, are used to activate the clotting system to reverse the effects of the new oral anticoagulants. In cases of refractory or emergent bleeding, the recommended factor concentrate in our protocols differs between the new oral anticoagulants. In patients taking dabigatran, we administer an activated PCC (aPCC) [FELBA] due to reported benefit in human in vitro studies. Based on human clinical trial evidence, the 4-factor PCC (Kcentra) is suggested for patients with refractory rivaroxaban- or apixaban-associated hemorrhage. If bleeding continues, recombinant factor VIIa may be employed. With all of these new procoagulant agents, the risk of thrombosis associated with administration of factor concentrates must be weighed against the relative risk of hemorrhage.

Objective: To clarify the effect of progressively increasing intra-abdominal pressure on esophageal pressure, transpulmonary pressure, and functional residual capacity., Design: Controlled application of increased intra-abdominal pressure at two positive end-expiratory pressure levels (1 and 10 cm H2O) in an anesthetized porcine model of controlled ventilation., Setting: Large animal laboratory of a university-affiliated hospital., Subjects: Eleven deeply anesthetized swine (weight 46.2 ± 6.2 kg)., Interventions: Air-regulated intra-abdominal hypertension (0-25 mm Hg)., Measurements: Esophageal pressure, tidal compliance, bladder pressure, and end-expiratory lung aeration by gas dilution., Main Results: Functional residual capacity was significantly reduced by increasing intra-abdominal pressure at both positive end-expiratory pressure levels (p ≤ 0.0001) without corresponding changes of end-expiratory esophageal pressure. Above intra-abdominal pressure 5 mm Hg, plateau airway pressure increased linearly by ~ 50% of the applied intra-abdominal pressure value, associated with commensurate changes of esophageal pressure. With tidal volume held constant, negligible changes occurred in transpulmonary pressure due to intra-abdominal pressure. Driving pressures calculated from airway pressures alone (plateau airway pressure--positive end-expiratory pressure) did not equate to those computed from transpulmonary pressure (tidal changes in transpulmonary pressure). Increasing positive end-expiratory pressure shifted the predominantly negative end-expiratory transpulmonary pressure at positive end-expiratory pressure 1 cm H2O (mean -3.5 ± 0.4 cm H2O) into the positive range at positive end-expiratory pressure 10 cm H2O (mean 0.58 ± 1.2 cm H2O)., Conclusions: Despite its insensitivity to changes in functional residual capacity, measuring transpulmonary pressure may be helpful in explaining how different levels of positive end-expiratory pressure influence recruitment and collapse during tidal ventilation in the presence of increased intra-abdominal pressure and in calculating true transpulmonary driving pressure (tidal changes of transpulmonary pressure). Traditional interpretations of respiratory mechanics based on unmodified airway pressure were misleading regarding lung behavior in this setting.

Background: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) may complicate monitoring of pulmonary mechanics owing to their impact on the respiratory system. However, recommendations for mechanical ventilation of patients with IAH/ACS and the interpretation of thoracoabdominal interactions remain unclear. Our study aimed to characterize the influence of elevated intra-abdominal pressure (IAP) and positive end-expiratory pressure (PEEP) on airway plateau pressure (PPLAT) and bladder pressure (PBLAD)., Methods: Nine deeply anesthetized swine were mechanically ventilated via tracheostomy: volume-controlled mode at tidal volume (VT) of 10 mL/kg, frequency of 15, inspiratory-expiratory ratio of 1:2, and PEEP of 1 and 10 cm H2O (PEEP1 and PEEP10, respectively). A tracheostomy tube was placed in the peritoneal cavity, and IAP levels of 5, 10, 15, 20, and 25 mm Hg were applied, using a continuous positive airway pressure system. At each IAP level, PBLAD and airway pressure measurements were performed during both PEEP1 and PEEP10., Results: PBLAD increased as experimental IAP rose (y = 0.83x + 0.5; R = 0.98; p < 0.001 at PEEP1). Minimal underestimation of IAP by PBLAD was observed (-2.5 ± 0.8 mm Hg at an IAP of 10-25 mm Hg). Applying PEEP10 did not significantly affect the correlation between experimental IAP and PBLAD. Approximately 50% of the PBLAD (in cm H2O) was reflected by changes in PPLAT, regardless of the PEEP level applied. Increasing IAP did not influence hemodynamics at any level of IAP generated., Conclusion: With minimal underestimation, PBLAD measurements closely correlated with experimentally regulated IAP, independent of the PEEP level applied. For each PEEP level applied, a constant proportion (approximately 50%) of measured PBLAD (in cm H2O) was reflected in PPLAT. A higher safety threshold for PPLAT should be considered in the setting of IAH/ACS as the clinician considers changes in VT. A strategy of reducing VT to cap PPLAT at widely recommended values may not be warranted in the setting of increased IAP.

Lung injury resulting from inhalation of smoke or chemical products of combustion continues to be associated with significant morbidity and mortality. Combined with cutaneous burns, inhalation injury increases fluid resuscitation requirements, incidence of pulmonary complications and overall mortality of thermal injury. While many products and techniques have been developed to manage cutaneous thermal trauma, relatively few diagnosis-specific therapeutic options have been identified for patients with inhalation injury. Several factors explain slower progress for improvement in management of patients with inhalation injury. Inhalation injury is a more complex clinical problem. Burned cutaneous tissue may be excised and replaced with skin grafts. Injured pulmonary tissue must be protected from secondary injury due to resuscitation, mechanical ventilation and infection while host repair mechanisms receive appropriate support. Many of the consequences of smoke inhalation result from an inflammatory response involving mediators whose number and role remain incompletely understood despite improved tools for processing of clinical material. Improvements in mortality from inhalation injury are mostly due to widespread improvements in critical care rather than focused interventions for smoke inhalation.Morbidity associated with inhalation injury is produced by heat exposure and inhaled toxins. Management of toxin exposure in smoke inhalation remains controversial, particularly as related to carbon monoxide and cyanide. Hyperbaric oxygen treatment has been evaluated in multiple trials to manage neurologic sequelae of carbon monoxide exposure. Unfortunately, data to date do not support application of hyperbaric oxygen in this population outside the context of clinical trials. Cyanide is another toxin produced by combustion of natural or synthetic materials. A number of antidote strategies have been evaluated to address tissue hypoxia associated with cyanide exposure. Data from European centers supports application of specific antidotes for cyanide toxicity. Consistent international support for this therapy is lacking. Even diagnostic criteria are not consistently applied though bronchoscopy is one diagnostic and therapeutic tool. Medical strategies under investigation for specific treatment of smoke inhalation include beta-agonists, pulmonary blood flow modifiers, anticoagulants and antiinflammatory strategies. Until the value of these and other approaches is confirmed, however, the clinical approach to inhalation injury is supportive.

Increasing age and number of rib fractures are thought to portend a worse outcome with blunt chest trauma, although this is not clearly substantiated in the literature. We hypothesized that these parameters have a significant and synergistic effect, worsening patient outcome. Using the National Trauma Data Bank, we evaluated patients from 2002 to 2006. Patients with a rib fracture International Classification of Diseases, 9th Revision code were included; those with sternal fractures were excluded. Data on demographics, injury, comorbidity, complications, intensive care unit duration, ventilator duration, length of stay, and death were collected. Significant univariate predictors were included in the multivariate logistic regression analysis to adjust for any potential confounders. We identified 35,467 patients who met the inclusion. The mean age was 45.5 years with a mean Injury Severity Score of 19.3. There were 2.1 per cent open rib fractures. Using univariate analysis, rib fracture number was significant. However, once multivariate analyses were applied, the number of rib fractures was not found to be an independent predictor of outcome. The number of rib fractures is not an independent predictor of outcome. Age and overall trauma burden are more powerful predictors of poor outcomes. Treatment focus should shift from the chest to the broader scope of injuries and comorbidities.

During the last 2 years, two new oral anticoagulants, dabigatran and rivaroxaban, have been approved in the United States. Phase II and Phase III clinical trials of dabigatran, rivaroxaban, and apixaban are summarized. Approach to perioperative management depends on the half-life of the medication, risk of surgical bleeding, and the patient's renal function. No reversal agent is available for any of the new oral anticoagulants. Management of bleeding patients is based on local measures and consideration of antifibrinolytic therapy and activated factor VII or prothrombin complex concentrate infusion based on healthy volunteer and animal studies. The new oral anticoagulants provide additional options to prevent venous thromboembolism in patients after orthopedic surgery or stroke in patients with atrial fibrillation but present unique challenges compared to warfarin.

Fluid resuscitation following burn injury must support organ perfusion with the least amount of fluid necessary and the least physiological cost. Under resuscitation may lead to organ failure and death. With adoption of weight and injury size-based formulas for resuscitation, multiple organ dysfunction and inadequate resuscitation have become uncommon. Instead, administration of fluid volumes well in excess of historic guidelines has been reported. A number of strategies including greater use of colloids and vasoactive drugs are now under investigation to optimize preservation of end organ function while avoiding complications which can include respiratory failure and compartment syndromes. Adjuncts to resuscitation, such as antioxidants, are also being investigated along with parameters beyond urine output and vital signs to identify endpoints of therapy. Here we briefly review the state-of-the-art and provide a sample of protocols now under investigation in North American burn centers.

Purpose: A quantitative measure of the airway pressure-time tracing during passive inflation [stress index (SI)] has been suggested as an indicator of tidal lung recruitment and/or overinflation. If reliable, this simple index could help guide positive end-expiratory pressure (PEEP) and tidal volume selection. The compartment surrounding the lungs should impact airway pressure and could, therefore, affect SI validity. To explore the possibility, we determined SI in a swine model of pleural effusion (PLEF)., Methods: Unilateral PLEF was simulated by instilling fluid (13 ml/kg-moderate, 26 ml/kg-large) into the right pleural space of five anesthetized, paralyzed, mechanically ventilated pigs. Animals were ventilated with constant flow ventilation: tidal volume (V (T)) 9 ml/kg, f set to end-tidal CO₂ (ETCO₂) of 30-40 mmHg, inspiratory to expiratory ratio (I/E) 1:2, PEEP 1 or 10 cmH₂O. Respiratory system mechanics and computed tomography (CT) were acquired at end-inspiration and end-expiration to determine % tidal recruitment and overinflation., Results: Prior to PLEF instillation, SI values derived at PEEP = 1 and 10 cmH₂O were 0.90 and 1.22, respectively. Moderate PLEF increased these SI values to 1.06 and 1.24 and large PLEF further increased SI to 1.23 and 1.27 despite extensive tidal recruitment and negligible overdistention by CT. The initial half of the tidal pressure curve produced SI values (range 0.82-1.17) that were significantly lower than those of the second half (0.98-1.37)., Conclusions: In the presence of pleural fluid, SI indicated overinflation when virtually none was present and tidal lung recruitment predominated. When the extrapulmonary environment is abnormal, caregivers are advised to interpret the SI with caution.

Introduction: There is renewed interest in blood product use for resuscitation stimulated by recent military experience and growing recognition of the limitations of large-volume crystalloid resuscitation., Methods: An editorial review of recent reports published by investigators from the United States and Europe is presented. There is little prospective data in this area., Results: Despite increasing sophistication of trauma care systems, hemorrhage remains the major cause of early death after injury. In patients receiving massive transfusion, defined as 10 or more units of packed red blood cells in the first 24 hours after injury, administration of plasma and platelets in a ratio equivalent to packed red blood cells is becoming more common. There is a clear possibility of time dependent enrollment bias. The early use of multiple types of blood products is stimulated by the recognition of coagulopathy after reinjury which may occur as many as 25% of patients. These patients typically have large-volume tissue injury and are acidotic. Despite early enthusiasm, the value of administration of recombinant factor VIIa is now in question. Another dilemma is monitoring of appropriate component administration to control coagulopathy., Conclusion: In patients requiring large volumes of blood products or displaying coagulopathy after injury, it appears that early and aggressive administration of blood component therapy may actually reduce the aggregate amount of blood required. If recombinant factor VIIa is given, it should be utilized in the fully resuscitated patient. Thrombelastography is seeing increased application for real-time assessment of coagulation changes after injury and directed replacement of components of the clotting mechanism.

Objectives: High-dose insulin (HDI) has inotropic and vasodilatory properties in various clinical conditions associated with myocardial depression. The authors hypothesized that HDI will improve the myocardial depression produced by severe septic shock and have beneficial effects on metabolic parameters. In an animal model of severe septic shock, this study compared the effects of HDI treatment to normal saline (NS) resuscitation alone., Methods: Ten pigs were randomized to an insulin (HDI) or NS group. All were anesthetized and instrumented to monitor cardiovascular function. In both arms, Escherichia coli endotoxin lipopolysaccharide (LPS) and NS infusions were begun. LPS was titrated to 20 mug/kg/hour over 30 minutes and continued for 5 hours, and saline was infused at 20 mL/kg/hour throughout the protocol. Dextrose (50%) was infused to maintain glucose in the 60-150 mg/dL range, and potassium was infused to maintain a level greater than 2.8 mmol/L. At 60 minutes, the HDI group received an insulin infusion titrated from 2 to 10 units/kg/hour over 40 minutes and continued at that rate throughout the protocol. Survival, heart rate (HR), mean arterial pressure (MAP), pulmonary artery and central venous pressure, cardiac output, central venous oxygen saturation (SVO(2)), and lactate were monitored for 5 hours (three pigs each arm) or 7 hours (two pigs each arm) or until death. Cardiac index, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), O(2) delivery, and O(2) consumption were derived from measured data. Outcomes from the repeated-measures analysis were modeled using a mixed-effects linear model that assumed normally distributed errors and a random effect at the subject level., Results: No significant baseline differences existed between arms at time 0 or 60 minutes. Survival was 100% in the HDI arm and 60% in the NS arm. Cardiovascular variables were significantly better in the HDI arm: cardiac index (p < 0.001), SVR (p < 0.003), and PVR (p < 0.01). The metabolic parameters were also significantly better in the HDI arm: SVO(2) (p < 0.01), O(2) delivery (p < 0.001), and O(2) consumption (p < 0.001). No differences in MAP, HR, or lactate were found., Conclusions: In this animal model of endotoxemic-induced septic shock that results in severe myocardial depression, HDI is associated with improved cardiac function compared to NS resuscitation alone. HDI also demonstrated favorable metabolic, pulmonary, and peripheral vascular effects. Further studies may define a potential role for the use of HDI in the resuscitation of septic shock.

Background: The time course of the physiological derangements that result from ventilator-induced lung injury has not been adequately described. Similarly, the regional topographies of pleural pressure and tissue edema have not been carefully mapped for this injury process., Methods: Lung injury was induced in 9 normal pigs by ventilating for 6 hours at a transpulmonary pressure of 35 cm H(2)O, with the animals in the supine position. Eight additional normal pigs received right thoracotomy to place pleural-surface-pressure sensors prior to an identical period and intensity of injurious ventilation. Gas exchange and lung mechanics were tracked in all the animals. Cytokines (tumor necrosis factor alpha, interleukin 6, and interleukin 8) in peripheral blood were assayed at 2 hour intervals, beginning at the onset of mechanical ventilation, from all the animals., Results: After a brief "induction" period, P(aO(2)) and tidal volume declined steadily in the animals that were ventilated to induce lung injury. The rate of decline was greater in the animals that received thoracotomy. The pleural pressure gradient steadily increased from ventral to dorsal. The serum cytokine levels did not evolve with developing injury, but cytokines were elevated at the onset of ventilation. Tissue edema, as assessed by the ratio of wet weight to dry weight, was greater in the thoracotomized animals than in the nonthoracotomized animals, and tissue edema tended to be greater in the caudal lung regions than in the cephalad lung regions., Conclusions: Following the induction period, the development of ventilator-induced lung injury progressed steadily and then plateaued, as assessed by quantitative physiology variables during 6 hours of ventilation at a transpulmonary pressure of 35 cm H(2)O. Greater injury developed in animals that had a coexisting potential insult (thoracotomy). Injury development was not paralleled by bloodborne inflammatory cytokines.

Background: Lung injury associated with the acute respiratory distress syndrome can be exacerbated by improper mechanical ventilation creating a secondary injury known as ventilator-induced lung injury (VILI). We hypothesized that VILI could be caused in part by alveolar recruitment/derecruitment resulting in gross tearing of the alveolus., Objectives: The exact mechanism of VILI has yet to be elucidated though multiple hypotheses have been proposed. In this study we tested the hypothesis that gross alveolar tearing plays a key role in the pathogenesis of VILI., Methods: Anesthetized rats were ventilated and instrumented for hemodynamic and blood gas measurements. Following baseline readings, rats were exposed to 90 min of either normal ventilation (control group: respiratory rate 35 min(-1), positive end-expiratory pressure 3 cm H(2)O, peak inflation pressure 14 cm H(2)O) or injurious ventilation (VILI group: respiratory rate 20 min(-1), positive end-expiratory pressure 0 cm H(2)O, peak inflation pressure 45 cm H(2)O). Parameters studied included hemodynamics, pulmonary variables, in vivo video microscopy of alveolar mechanics (i.e. dynamic alveolar recruitment/derecruitment) and scanning electron microscopy to detect gross tears on the alveolar surface., Results: Injurious ventilation significantly increased alveolar instability after 45 min and alveoli remained unstable until the end of the study (electron microscopy after 90 min revealed that injurious ventilation did not cause gross tears in the alveolar surface)., Conclusions: We demonstrated that alveolar instability induced by injurous ventilation does not cause gross alveolar tears, suggesting that the tissue injury in this animal VILI model is due to a mechanism other than gross rupture of the alveolus., (Copyright (c) 2007 S. Karger AG, Basel.)

Background: Purpura fulminans is an acute illness commonly associated with meningococcemia or invasive streptococcal disease, and it is typically characterized by disseminated intravascular coagulation (DIC) and purpuric skin lesions. In this article, we report the first 5 cases (to our knowledge) of purpura fulminans directly associated with Staphylococcus aureus strains that produce high levels of the superantigens toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin serotype B (SEB), or staphylococcal enterotoxin serotype C (SEC)., Methods: Cases were identified in the Minneapolis-St. Paul, Minnesota, metropolitan area during 2000-2004. S. aureus infection was diagnosed on the basis of culture results, and susceptibility to methicillin was determined. The ability of the isolated organisms to produce TSST-1, SEB, SEC, and Panton-Valentine leukocidin (PVL) was determined. TSST-1, SEB, and SEC levels were also quantified after in vitro growth of the organisms., Results: In 3 of the 5 cases, the infecting S. aureus strain was isolated from the blood cultures. In 2 of the 5 cases, the infecting S. aureus strain was isolated only from the respiratory tract, indicating that purpura fulminans and toxic shock syndrome resulted from exotoxin and/or other host factors, rather than septicemia. One of these latter 2 patients also had necrotizing pneumonia, and the isolated S. aureus was a methicillin-resistant strain that produced both SEC and PVL. Only 2 of the 5 patients survived, and 1 of the survivors received activated protein C., Conclusions: Staphylococcal purpura fulminans may be a newly emerging illness associated with superantigen production. Medical practitioners should be aware of this illness.

Objective: Elevated lung volumes and increased pleural pressures associated with recruitment maneuvers (RM) may adversely affect pulmonary vascular resistance and cardiac filling or performance. We investigated the hemodynamic consequences of three RM techniques after inducing acute lung injury., Design: Prospective, randomized, controlled experimental study., Setting: Hospital research laboratory., Subjects: Thirteen anesthetized, mechanically ventilated pigs., Interventions: We induced three types of acute lung injury: oleic acid injury (n = 4); ventilator-induced lung injury (n = 4); and pneumonia (n = 5). All three models were designed to initiate a similar severity of oxygenation impairment. RM methods tested were sustained inflation, incremental positive end-expiratory pressure (PEEP) with a limited peak pressure, and pressure-controlled ventilation with increased PEEP and a fixed driving pressure. From a baseline PEEP of 8 cm H2O, all interventions were tested using post-RM PEEP levels of 8, 12, and 16 cm H2O. Cardiac output by thermodilution and systemic and pulmonary artery pressures were measured frequently during the RM and for 15 mins after its completion., Measurements and Main Results: During the RM, cardiac output decreased to a greater extent in the pneumonia model (0.49 of baseline cardiac output) than in the oleic acid injury (0.67 of baseline) or ventilator-induced lung injury (0.79 of baseline) models. Cardiac output recovered to the baseline value by 5 mins post-RM in oleic acid injury and ventilator-induced lung injury models. However, cardiac output remained decreased 15 mins post-RM in the pneumonia model. There were no differences in hemodynamic parameters among RM methods in oleic acid injury and ventilator-induced lung injury models. In the pneumonia model, however, cardiac output decreased to a greater extent during the RM with sustained inflation (to 0.33 of baseline cardiac output) compared with pressure-controlled ventilation (to 0.68 of baseline)., Conclusions: We conclude that RM transiently but profoundly depressed cardiac output in three models of acute lung injury. The results imply that a lung recruiting maneuver should be used with caution, especially when using sustained inflation in the setting of pneumonia.

Objective: To compare the relative efficacy of three forms of recruitment maneuvers in diverse models of acute lung injury characterized by differing pathoanatomy., Design: We compared three recruiting maneuver (RM) techniques at three levels of post-RM positive end-expiratory pressure in three distinct porcine models of acute lung injury: oleic acid injury; injury induced purely by the mechanical stress of high-tidal airway pressures; and pneumococcal pneumonia., Setting: Laboratory in a clinical research facility., Subjects: Twenty-eight anesthetized mixed-breed pigs (23.8 +/- 2.6 kg)., Interventions: The RM techniques tested were sustained inflation, extended sigh or incremental positive end-expiratory pressure, and pressure-controlled ventilation., Primary Measurements: Oxygenation and end-expiratory lung volume., Main Results: The post-RM positive end-expiratory pressure level was the major determinant of post-maneuver PaO2, independent of the RM technique. The pressure-controlled ventilation RM caused a lasting increase of PaO2 in the ventilator-induced lung injury model, but in oleic acid injury and pneumococcal pneumonia, there were no sustained oxygenation differences for any RM technique (sustained inflation, incremental positive end-expiratory pressure, or pressure-controlled ventilation) that differed from raising positive end-expiratory pressure without RM., Conclusions: Recruitment by pressure-controlled ventilation is equivalent or superior to sustained inflation, with the same peak pressure in all tested models of acute lung injury, despite its lower mean airway pressure and reduced risk for hemodynamic compromise. Although RM may improve PaO2 in certain injury settings when traditional tidal volumes are used, sustained improvement depends on the post-RM positive end-expiratory pressure value.

Background: Mechanical ventilation is the defining event of intensive care unit management. To reduce use, a literature-based protocol was introduced to facilitate weaning. The effect of protocol-driven ventilator weaning on ventilator use, ventilator-associated pneumonia (VAP), and intensive care unit (ICU) length of stay (LOS) is described in a survey of 2 years' activity in a multidisciplinary surgical ICU., Methods: Data were gathered from April to September 2000 and from April to September 2002 before and after introduction of nurse/therapist-driven weaning. VAP was identified by chest radiography, clinical presentation, Gram's stains, and cultures from tracheal aspirates or bronchoalveolar lavage. Infection control practitioners diagnosed VAP. Failed extubation was defined as reintubation within 72 hours., Results: Overall, there was a 2:1 ratio of male patients to female patients. The total number of patients and days of mechanical ventilation increased, but the use ratio (ventilator days/ICU days) fell from 0.47 to 0.33. Patients failing extubation fell from 43 (in 2000) to 25 (in 2002). From these patients, 17 cases of VAP occurred in 2000 and 5 in 2002. Mean age (40 years), Injury Severity Score (24), and ICU LOS (5.7-7.4 days; p = not significant) were unchanged in injured patients. ICU discharge was frequently delayed because of the need for subsequent respiratory care., Conclusion: Protocol-driven weaning reduces use of mechanical ventilation and VAP. Injured and general surgical patients show reduction in complications, but shorter ICU LOS depends on resources elsewhere in the health care system.

Objective: To determine the influence of clinician-adjustable ventilator settings on the development of ventilator-induced lung injury, as assessed by changes in gas exchange (Pao2), compliance, functional residual capacity, and wet weight to dry weight ratio., Design: Randomized in vivo rabbit study., Setting: Hospital research laboratory., Subjects: Forty-four anesthetized, mechanically ventilated adult rabbits., Interventions: Ventilation for 2 hrs with pressure control ventilation at 45 cm H2O, Fio2 = 0.6, and randomization to one of five ventilatory strategies using combinations of positive end-expiratory pressure (3 or 12 cm H2O), inspiratory time (0.45, 1.0, or 2.0 secs), and frequency (9 or 23/min)., Measurements and Main Results: Among the ventilator strategies applied, PEEP at 12 cm H2O (elevated positive end-expiratory pressure) and inspiratory time at 0.45 secs (reduced inspiratory time) best preserved Pao2 (p <.003) and compliance (p <.035). During injury development, two consistent changes were observed: Tidal volume increased, and airway pressure waveform was transformed by extending the time to attain target pressure., Conclusions: In this preclinical model, lung injury was attenuated by decreasing inspiratory time. As lung injury occurred, tidal volume increased and airway pressure waveform changed.

The treatment of heart failure with angiotensin-converting enzyme inhibitors has resulted in substantial improvements in morbidity and mortality due to heart failure. Varying reports in the literature have suggested that African Americans respond less well to angiotensin-converting enzyme inhibitors, but careful reanalysis of major clinical trials in heart failure, especially the Studies of Left Ventricular Dysfunction (SOLVD), demonstrates a similar mortality benefit for African Americans as for whites. Morbidity, measured as hospitalizations, may not be as favorably impacted. African Americans do respond to angiotensin-converting enzyme inhibitors as a preemptive strategy to prevent heart failure, but the incidence of heart failure is still higher in this population. Mechanisms for these potential nuances in the response to angiotensin-converting enzyme inhibitors are not yet clear. The exaggerated benefit of nitrates and hydralazine implicates alterations in nitric oxide homeostasis. Race is an inadequate model to explain the observed differences. Careful translational research focusing on genetic patterns of disease may help resolve these outstanding questions.

Ventilator-induced lung injury has been established as a significant risk to patients receiving PPV. Animal studies have provided definitive experimental data that support the existence of VILI. Clinical studies have implied the role of VILI in ARDS and ALI patients. In patients who have ARDS or ALI, however, VILI cannot be distinguished from exacerbation of the primary condition. Animal and clinical studies that clearly show elevated levels of cytokines when PPV is applied beyond certain limits support the concept that an inflammatory process is activated by PPV. Whether the induction of inflammatory mediators contributes to the mortality or morbidity of the ventilated patient has not been established. A potential role for anti-inflammatory therapeutic agents is promising. Therefore, the following considerations can guide the clinical care of ventilator patients: Alveolar pressure exposure (plateau pressure) should be limited to less than 32 cm H2O. Positive end-expiratory pressure should be applied to avoid end-expiratory collapse and reopening. Tidal volume should be set at approximately 6 mL/kg or further guided by plateau pressure limitation. Although studies suggest that reducing Ti, flow, and f may be important in avoiding VILI, there are no current guidelines. The results of preliminary studies investigating the preventative potential of respiratory acidosis, prone positioning, or careful vascular pressure management seem promising. Inflammatory response in VILI has been established, but a role for intervention, such as general or specific suppression of the response, has not been established.

Objective: To present electron micrographs of lung tissue obtained from a patient exposed to high ventilatory pressures in the context of pulmonary dysfunction and pulmonary hypertension., Design: Case report., Setting: Adult intensive care unit of a university-affiliated teaching hospital., Patients: A patient exposed to high-pressure mechanical ventilation during support for acute respiratory distress syndrome; the acute respiratory distress syndrome in this case was secondary to septic shock., Measurements and Main Results: Scanning electron micrographs of lung tissue, focusing on the internal alveolar surfaces., Findings: Multiple gross disruptions of the alveolar walls, suggestive of stress fractures., Conclusion: High-pressure mechanical ventilation may promote fracturing of the alveolar blood:airspace barrier.

With additional international input, recent changes in emergency life support are reflected in updated guidelines for Advanced Cardiac Life Support (ACLS) from the American Heart Association and new technology in the arena of vascular access and emergency airway management. These changes will expand nurses' ability to provide advanced levels of care, even in the prehospital situation, and represent a more rigorous evidence-based approach than ever before. As early morbidity and mortality in emergency situations are frequently associated with complications associated with airway management and vascular access, recent development in these areas are reviewed along with evolution in ACLS guidelines.

Pressure support ventilation (PSV) is almost universally employed in the management of actively breathing ventilated patients with acute respiratory failure. In this partial support mode of ventilation, a fixed pressure is applied to the airway opening, and flow delivery is monitored by the ventilator. Inspiration is terminated when measured inspiratory flow falls below a set fraction of the peak flow rate (flow cutoff); the ventilator then cycles to a lower pressure and expiration commences. We used linear and nonlinear mathematical models to investigate the dynamic behavior of pressure support ventilation and confirmed the predicted behavior using a test lung. Our mathematical and laboratory analyses indicate that pressure support ventilation in the setting of airflow obstruction can be accompanied by marked variations in tidal volume and end-expiratory alveolar pressure, even when subject effort is unvarying. Unstable behavior was observed in the simplest plausible linear mathematical model and is an inherent consequence of the underlying dynamics of this mode of ventilation. The mechanism underlying the observed instability is "feed forward" behavior mediated by oscillatory elevation in end-expiratory pressure. In both mathematical and mechanical models, unstable behavior occurred at impedance values and ventilator settings that are clinically realistic.

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.

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.

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.

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.