Lorraine N. Tremblay

Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model.

We examined the effect of ventilation strategy on lung inflammatory mediators in the presence and absence of a preexisting inflammatory stimulus. 55 Sprague-Dawley rats were randomized to either intravenous saline or lipopolysaccharide (LPS). After 50 min of spontaneous respiration, the lungs were excised and randomized to 2 h of ventilation with one of four strategies: (a) control (C), tidal volume (Vt) = 7 cc/kg, positive end expiratory pressure (PEEP) = 3 cm H2O; (b) moderate volume, high PEEP (MVHP), Vt = 15 cc/kg; PEEP = 10 cm H2O; (c) moderate volume, zero PEEP (MVZP), Vt = 15 cc/kg, PEEP = 0; or (d) high volume, zero PEEP (HVZP), Vt = 40 cc/kg, PEEP = 0. Ventilation with zero PEEP (MVZP, HVZP) resulted in significant reductions in lung compliance. Lung lavage levels of TNFalpha, IL-1beta, IL-6, IL-10, MIP-2, and IFNgamma were measured by ELISA. Zero PEEP in combination with high volume ventilation (HVZP) had a synergistic effect on cytokine levels (e.g., 56-fold increase of TNFalpha versus controls). Identical end inspiratory lung distention with PEEP (MVHP) resulted in only a three-fold increase in TNFalpha, whereas MVZP produced a six-fold increase in lavage TNFalpha. Northern blot analysis revealed a similar pattern (C, MVHP < MVZP < HVZP) for induction of c-fos mRNA. These data support the concept that mechanical ventilation can have a significant influence on the inflammatory/anti-inflammatory milieu of the lung, and thus may play a role in initiating or propagating a local, and possibly systemic inflammatory response.

Injurious ventilation induces widespread pulmonary epithelial expression of tumor necrosis factor-α and interleukin-6 messenger RNA

ObjectiveWe examined the hypothesis that injurious strategies of mechanical ventilation alter the expression and distribution within the lung of tumor necrosis factor-&agr; and interleukin-6 that are both duration and ventilation strategy dependent. SubjectsMale Sprague Dawley rats. InterventionsLungs from rats were preserved immediately after death or were randomized to ex vivo ventilation with either a) noninjurious ventilation; b) high end-inspiratory lung volume with positive end-expiratory pressure (PEEP); c) high end-inspiratory lung volume without PEEP; or d) intermediate lung distension without PEEP, for periods ranging from 30 mins to 3 hrs. Measurement and Main ResultsChanges in cytokines were assessed by in situ hybridization, immunocytochemistry, simultaneous in situ hybridization and immunocytochemistry, Northern analysis, and enzyme-linked immunosorbent assay. Whereas minimal expression of tumor necrosis factor-&agr; and interleukin-6 mRNA was found in lungs subjected to noninjurious ventilation, the three injurious strategies resulted in a diffuse increase in expression of tumor necrosis factor-&agr; and interleukin-6. The principal cells involved were the bronchial, bronchiolar, and alveolar epithelium. The changes in tumor necrosis factor-&agr; mRNA and protein expression were dependent on both duration of ventilation and the ventilation strategy used. ConclusionsThe vast pulmonary epithelium is a major contributor to ventilation-induced changes in cytokine production and may play an important role in the pathogenesis of lung injury and systemic sequelae in ventilated subjects.

Pulmonary surfactant is altered during mechanical ventilation of isolated rat lung

Objective To test the hypothesis that the lung injury induced by certain mechanical ventilation strategies is associated with changes in the pulmonary surfactant system. Design Analysis of the pulmonary surfactant system from isolated rat lungs after one of four different ventilatory strategies. Setting A research laboratory at a university. Subjects A total of 45 Sprague-Dawley rats. Interventions Isolated lungs were randomized to either no ventilation (O-TIME) or to ventilation at 40 breaths/min in a humidified 37°C chamber for either 30 mins or 120 mins with one of the following four strategies: a) control (CON, 7 mL/kg, 3 cm H2O positive end-expiratory pressure); b) medium volume, zero end-expiratory pressure (MVZP, 15 mL/kg, O cm H2O end-expiratory pressure); c) medium volume, high positive end-expiratory pressure (MVHP, 15 mL/kg, 9 cm H2O positive end-expiratory pressure); and d) high volume, zero end-expiratory pressure (HVZP, 40 mL/kg, 0 cm H2O end-expiratory pressure). Measurements Pressure-volume curves were determined before and after the ventilation period, after which the lungs were lavaged for surfactant analysis. Main Results Compared with 0-TIME, 30 mins of ventilation with the HVZP strategy or 120 mins of ventilation with CON and MVZP strategies caused a significant decrease in compliance. Groups showing a decreased compliance had significant increases in the amount of surfactant, surfactant large aggregates, and total lavage protein compared with 0-TIME. Conclusions A short period of injurious mechanical ventilation can cause a decrease in lung compliance that is associated with a large influx of proteins into the alveolar space and with alterations of the pulmonary surfactant system. The changes of surfactant in these experiments are different from those seen in acute lung injury, indicating that they may represent an initial response to mechanical ventilation.

Partial liquid ventilation decreases serum tumor necrosis factor-alpha concentrations in a rat acid aspiration lung injury model

OBJECTIVEnTo examine the hypothesis that partial liquid ventilation (PLV) with perfluorocarbon would decrease serum tumor necrosis factor-alpha concentrations in a rat acid aspiration lung injury model.nnnDESIGNnProspective, controlled animal study.nnnSETTINGSnResearch laboratory in a university setting.nnnSUBJECTSnMale Sprague-Dawley rats.nnnINTERVENTIONSnTreatment with intratracheal perflubron or control mechanical ventilation beginning 30 mins after acid aspiration.nnnMEASUREMENTS AND MAIN RESULTSnPLV with perfluorocarbon compared with control ventilation resulted in significantly greater mean arterial blood pressures at 3 and 4 hrs and greater arterial Po2 at all times. Serum tumor necrosis factor-alpha at 2, 3, and 4 hrs was significantly less than that observed in the control group (4-hr values: 80+/-64 pg/mL vs. 658+/-688 pg/mL; p<.05), although no significant difference in tracheal fluid tumor necrosis factor-alpha concentrations (1425+/-1347 pg/mL vs. 2219+/-1933 pg/mL) was found.nnnCONCLUSIONnWe conclude that the effects of PLV with perfluorocarbon can extend beyond improvements in pulmonary physiology and that PLV may be beneficial in reducing systemic sequelae of acute lung injury and inflammation.

Ultrasound-guided tracheostomy - not for the many, but perhaps the few… or the one

Percutaneous tracheostomy has become a routine procedure in most intensive care units, and point of care ultrasound is becoming used with greater frequency to augment diagnosis and therapy for critically ill patients. The case series from Rajajee and colleagues incorporates real-time ultrasound in an effort to improve the safety of percutaneous tracheostomy. While their report does not prove that ultrasound should be used prior to or during all percutaneous tracheostomies, it does reinforce several important safety considerations concerning the anatomy of the neck, and in particular the potential to encounter bleeding complications during these procedures.

Surgisis® in the management of the complex abdominal wall in trauma: A case series and review of the literature

Managing complex abdominal wall injuries acutely or at the time of reconstruction is challenging. Contaminated surgical fields, devitalized tissue, intestinal fistula and tissues under tension contribute to clinical scenarios where closure is not possible or morbidity is unacceptable. The introduction of an absorbable extracellular matrix derived from porcine small intestinal submucosa (Surgisis) adds a potentially useful tool to the surgeons armamentarium. A retrospective case series of the initial experience in 5 patients with complex abdominal wall injury following trauma managed with Surgisis is described. A review of the literature describing the use of Surgisis in contaminated fields is also performed.

The Advanced Trauma Operative Management course—a two student to one faculty model

BACKGROUNDnThe internationally recognized Advanced Trauma Operative Management (ATOM) course uses a 1:1 student-to-faculty teaching model. This study examines a two student to one faculty ATOM teaching model.nnnMATERIALS AND METHODSnWe randomly assigned 16 residents to four experienced ATOM faculty members. Half started with the one-student model and the other half with the two-student model and then switched using the same faculty. Students and faculty completed forms on the educational value of the two models (1 = very poor; 2 = poor; 3 = average; 4xa0=xa0good; and 5 = excellent) and identified educational preferences and recommendations.nnnRESULTSnWe assigned educational values for the 13 procedures as follows: All faculty rated the one-student model as excellent; six members rated the two-student model as excellent, and seven as good. Students rated 50%-75% as excellent and 12%-44% as good for the two-student model, and 56%-81% as excellent and 12%-44% as good for the one-student model. Given resource constraints, all faculty and 88% of students preferred the two-student model. With no resource constraints, 75% of students and 50% of faculty chose the two-student model. All faculty and students rated both models acceptable. Overall, 81% of students and 50% of faculty rated the two-student model better. All faculty members recommended that the models be optional; 94% of students recommended that they be either optional (50%) or a two-student model (44%). Performing or assisting on each procedure twice was considered an advantage of the two-student model.nnnCONCLUSIONSnThe two-student teaching model was acceptable and generally preferred in this study. With appropriately trained faculty and students, the two-student model is feasible and should result in less animal usage and possibly wider promulgation.

Reply to the comment by Dr. Jardin on “Ventilator-induced lung injury: from the bench to the bedside”

Once upon a time the existence of ventilator-induced lung injury (VILI) was debated. After all, most patients with lung dysfunction requiring mechanical ventilation had other potential causes of lung injury, and many patients appeared to tolerate mechanical ventilation for prolonged periods without any adverse sequelae. However, as a result of numerous studies over the past century, and especially during the past 20 years it is now generally accepted that mechanical ventilation per se can initiate as well as exacerbate lung injury and contribute to patient morbidity and mortality. This review examines the seminal bench and bedside studies that contributed to our current understanding of VILI, and that form the basis for current recommendations for mechanical ventilation of the critically ill. Figure 1 schematically depicts a timeline of bench to bedside research on VILI. Included in this review are many of the most frequently cited studies (with the number of citations, N, from the Institute for Science Information Citation Index as of August 2005 included in parentheses), as well as those studies which the authors feel have had a particularly significant impact on subsequent research and/or clinical practice.

Ventilator-Induced Lung Injury in Patients with Ards

Background Protective ventilatory strategies have resulted in a decreased mortality rate in acute respiratory distress syndrome, but the underlying mechanisms remain unclear. The authors hypothesized that (1) mechanical ventilation modulates activation of polymorphonuclear leukocytes (PMNs), (2) the consequent release of proteinases is correlated with a systemic inflammatory response and with multiple organ dysfunction, and (3) these deleterious effects can be minimized by a protective ventilatory strategy. Methods Human PMNs were incubated with bronchoalveolar lavage fluid obtained from patients at entry or 36 h after randomization to ventilation with either a conventional (control) or a lung-protective strategy. PMN oxidant production and surface expression of adhesion molecules and granule markers, including CD18, CD63, and L-selectin, were measured by flow cytometry. Extracellular elastase activity was quantified using a fluorescent substrate. Results Bronchoalveolar lavage obtained from both groups of patients at entry showed similar effects on PMN oxidant production and expression of surface markers. At 36 h, exposure of PMNs to bronchoalveolar lavage fluid from the control group resulted in increased PMN activation as manifested by a significant increase in oxidant production, CD18, and CD63 surface expression, and shedding of L-selectin. By contrast, these variables were unchanged at 36 h in the lung-protective group. There was a significant correlation between the changes of the variables and changes in interleukin-6 level and the number of failing organs. Conclusions Polymorphonuclear leukocytes can be activated by mechanical ventilation, and the consequent release of elastase was correlated with the degree of systemic inflammatory response and multiple organ failure. This result may possibly explain the decreased mortality in acute respiratory distress syndrome patients treated with a lung-protective strategy.

Effect of Ventilation Strategy on Cytokine Expression in an Ex Vivo Lung Model

Although mechanical ventilation is an indispensable therapeutic intervention for the treatment of respiratory failure, it can also initiate andJor exacerbate underlying lung injury. The precise mechanisms remain unclear. We hypothesized that one mechanism by which injurious ventilation strategies lead to lung injury, is via increased production of inflammatory cytokines within the lung1.