Sepsis: state of the art

In recent years, we have considerably widened our knowledge of the pathophysiology of sepsis and some procedures, aiming both to relieve symptoms and control the inflammation/coagulation reaction, have proven to be effective in increasing survival. This improves when mechanical ventilation is applied with low tidal volumes, fluid replacement and the use of cardioactive drugs are titrated on the oxygen saturation of hemoglobin in the central venous system and blood glucose does not exceed certain limits. It is also evident that inflammation and coagulation are closely related to each other. The inhibition of only one pathway, such as the inhibition of inflammation with high dosage steroids or the inhibition of coagulation with antithrombin, does not produce a survival improvement. The only molecule which has proven to be notably effective in reducing mortality is Activated Protein C interacting on coagulation/fibrinolysis, as well as on inflammation processes. Multinodal modulation of several interdependent processes may be the probable reason for the proven effectiveness of this treatment

Physical and biological triggers of ventilator-induced lung injury and its prevention

Ventilator-induced lung injury is a side-effect of mechanical ventilation. Its prevention or attenuation implies knowledge of the sequence of events that lead from mechanical stress to lung inflammation and stress at rupture. A literature review was undertaken which focused on the link between the mechanical forces in the diseased lung and the resulting inflammation/rupture. The distending force of the lung is the transpulmonary pressure. This applied force, in a homogeneous lung, is shared equally by each fibre of the lung's fibrous skeleton. In a nonhomogeneous lung, the collapsed or consolidated regions do not strain, whereas the neighbouring fibres experience excessive strain. Indeed, if the global applied force is excessive, or the fibres near the diseased regions experience excessive stress/strain, biological activation and/or mechanical rupture are observed. Excessive strain activates macrophages and epithelial cells to produce interleukin-8. This cytokine recruits neutrophils, with consequent full-blown inflammation. In order to prevent initiation of ventilator-induced lung injury, transpulmonary pressure must be kept within the physiological range. The prone position may attenuate ventilator-induced lung injury by increasing the homogeneity of transpulmonary pressure distribution. Positive end-expiratory pressure may prevent ventilator-induced lung injury by keeping open the lung, thus reducing the regional stress/strain maldistribution. If the transpulmonary pressure rather than the tidal volume per kilogram of body weight is taken into account, the contradictory results of the randomised trials dealing with different strategies of mechanical ventilation may be better understood

Physiologic rationale for ventilator setting in acute lung injury/acute respiratory distress syndrome patients

OBJECTIVES: To review the physiologic approach to setting mechanical ventilation in acute lung injury/acute respiratory distress syndrome. DATA SOURCES: MEDLINE search from 1979 to the present. DATA SELECTION: Personal selection of some articles we believe relevant for understanding acute lung injury/acute respiratory distress syndrome physiopathology and its physiologic management. DATA SUMMARY: Knowing the underlying pathology is key to estimating the potential for recruitment. The potential for recruitment is rather low when the consolidation of pulmonary units exceeds collapse, as in diffuse pneumonia. In contrast, when pulmonary unit collapse exceeds consolidation, as in acute lung injury/acute respiratory distress syndrome from extrapulmonary origin, the potential for recruitment may be high. To exploit the potential for recruitment, a transpulmonary pressure greater than the opening pressure must be applied to the lung. To do so, chest wall elastance must be measured or estimated. To avoid collapse after recruitment, a positive end-expiratory pressure greater than the compressive forces operating on the lung and an alveolar ventilation sufficient to prevent absorption atelectasis must be provided. Indeed, avoidance of stretch (low airway plateau pressure) and prevention of cyclic collapse and reopening (adequate positive end-expiratory pressure and alveolar ventilation) are the physiologic cornerstones of mechanical ventilation in acute lung injury/acute respiratory distress syndrome. When considering all the randomized clinical trials reported so far, it is tempting to speculate that transpulmonary pressure and stresses, rather than tidal volume per se, are the key factors that may have an impact on mortality. CONCLUSIONS: The majority of physiologic, experimental, and clinical trial data converge on one simple concept: treat the lung gently

Decrease in PaCO2 with prone position is predictive of improved outcome in acute respiratory distress syndrome

OBJECTIVE: To determine whether gas exchange improvement in response to the prone position is associated with an improved outcome in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). DESIGN: Retrospective analysis of patients in the pronation arm of a controlled randomized trial on prone positioning and patients enrolled in a previous pilot study of the prone position. SETTING: Twenty-eight Italian and two Swiss intensive care units. PATIENTS: We studied 225 patients meeting the criteria for ALI or ARDS. INTERVENTIONS: Patients were in prone position for 10 days for 6 hrs/day if they met ALI/ARDS criteria when assessed each morning. Respiratory variables were recorded before and after 6 hrs of pronation with unchanged ventilatory settings. MEASUREMENTS AND MAIN RESULTS: We measured arterial blood gas alterations to the first pronation and the 28-day mortality rate. The independent risk factors for death in the general population were the Pao2/Fio2 ratio (odds ratio, 0.992; confidence interval, 0.986-0.998), the minute ventilation/Paco2 ratio (odds ratio, 1.003; confidence interval, 1.000-1.006), and the concentration of plasma creatinine (odds ratio, 1.385; confidence interval, 1.116-1.720). Pao2 responders (defined as the patients who increased their Pao2/Fio2 by > or =20 mm Hg, 150 patients, mean increase of 100.6 +/- 61.6 mm Hg [13.4 +/- 8.2 kPa]) had an outcome similar to the nonresponders (59 patients, mean decrease -6.3 +/- 23.7 mm Hg [-0.8 +/- 3.2 kPa]; mortality rate 44% and 46%, respectively; relative risk, 1.04; confidence interval, 0.74-1.45, p =.65). The Paco2 responders (defined as patients whose Paco2 decreased by > or =1 mm Hg, 94 patients, mean decrease -6.0 +/- 6 mm Hg [-0.8 +/- 0.8 kPa]) had an improved survival when compared with nonresponders (115 patients, mean increase 6 +/- 6 mm Hg [0.8 +/- 0.8 kPa]; mortality rate 35.1% and 52.2%, respectively; relative risk, 1.48; confidence interval, 1.07-2.05, p =.01). CONCLUSION: ALI/ARDS patients who respond to prone positioning with reduction of their Paco2 show an increased survival at 28 days. Improved efficiency of alveolar ventilation (decreased physiologic deadspace ratio) is an important marker of patients who will survive acute respiratory failure