Objective: To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012". Design:A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. Methods:The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable.

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Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Objective: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. Design: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods: We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied.

Rationale: Lung injury caused by a ventilator results from nonphysiologic lung stress (transpulmonary pressure) and strain (inflated volume to functional residual capacity ratio). Objectives: To determine whether plateau pressure and tidal volume are adequate surrogates for stress and strain, and to quantify the stress to strain relationship in patients and control subjects.

In the prone position, computed tomography scan densities redistribute from dorsal to ventral as the dorsal region tends to reexpand while the ventral zone tends to collapse. Although gravitational influence is similar in both positions, dorsal recruitment usually prevails over ventral derecruitment, because of the need for the lung and its confining chest wall to conform to the same volume. The final result of proning is that the overall lung inflation is more homogeneous from dorsal to ventral than in the supine position, with more homogeneously distributed stress and strain. As the distribution of perfusion remains nearly constant in both postures, proning usually improves oxygenation. Animal experiments clearly show that prone positioning delays or prevents ventilation-induced lung injury, likely due in large part to more homogeneously distributed stress and strain. Over the last 15 years, five major trials have been conducted to compare the prone and supine positions in acute respiratory distress syndrome, regarding survival advantage. The sequence of trials enrolled patients who were progressively more hypoxemic; exposure to the prone position was extended from 8 to 17 hours/day, and lung-protective ventilation was more rigorously applied. Single-patient and meta-analyses drawing from the four major trials showed significant survival benefit in patients with PaO2/FiO2 lower than 100. The latest PROSEVA (Proning Severe ARDS Patients) trial confirmed these benefits in a formal randomized study. The bulk of data indicates that in severe acute respiratory distress syndrome, carefully performed prone positioning offers an absolute survival advantage of 10-17%, making this intervention highly recommended in this specific population subset.

In a model of acute lung injury, we showed that positive end-expiratory pressure (PEEP) and tidal volume (VT) are interactive variables that determine the extent of lung recruitment, that recruitment occurs across the entire range of total lung capacity, and that superimposed pressure is a key determinant of lung collapse. Aiming to verify if the same rules apply in a clinical setting, we randomly ventilated five ALI/ARDS patients with 10, 15, 20, 30, 35, and 45 cm H2O plateau pressure and 5, 10, 15, and 20 cm H2O of PEEP. For each PEEP-VT condition, we obtained computed tomography at end inspiration and end expiration. We found that recruitment occurred along the entire volume-pressure curve, independent of lower and upper inflection points, and that estimated threshold opening pressures were normally distributed (mode = 20 cm H2O). Recruitment occurred progressively from nondependent to dependent lung regions. Overstretching was not associated with hyperinflation. Derecruitment did not parallel deflation, and estimated threshold closing pressures were normally distributed (mode = 5 cm H2O). End-inspiratory and end-expiratory collapse were correlated, suggesting a plateau-PEEP interaction. When superimposed gravitational pressure exceeded PEEP, end-expiratory collapse increased. We concluded that the rules governing recruitment and derecruitment equally apply in an oleic acid model and in human ALI/ARDS.