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      Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

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          Abstract

          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. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

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          Most cited references351

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          Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome.

          In patients with the acute respiratory distress syndrome, massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury. We determined whether a ventilatory strategy designed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome. We randomly assigned 53 patients with early acute respiratory distress syndrome (including 28 described previously), all of whom were receiving identical hemodynamic and general support, to conventional or protective mechanical ventilation. Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure (PEEP) for acceptable oxygenation, with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels (35 to 38 mm Hg). Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve, a tidal volume of less than 6 ml per kilogram, driving pressures of less than 20 cm of water above the PEEP value, permissive hypercapnia, and preferential use of pressure-limited ventilatory modes. After 28 days, 11 of 29 patients (38 percent) in the protective-ventilation group had died, as compared with 17 of 24 (71 percent) in the conventional-ventilation group (P<0.001). The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group (P=0.005): the rates of clinical barotrauma were 7 percent and 42 percent, respectively (P=0.02), despite the use of higher PEEP and mean airway pressures in the protective-ventilation group. The difference in survival to hospital discharge was not significant; 13 of 29 patients (45 percent) in the protective-ventilation group died in the hospital, as compared with 17 of 24 in the conventional-ventilation group (71 percent, P=0.37). As compared with conventional ventilation, the protective strategy was associated with improved survival at 28 days, a higher rate of weaning from mechanical ventilation, and a lower rate of barotrauma in patients with the acute respiratory distress syndrome. Protective ventilation was not associated with a higher rate of survival to hospital discharge.
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            Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial.

            Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients, but a clear definition of an adequate treatment dose has not been established. We undertook a prospective randomised study of the impact different ultrafiltration doses in continuous renal replacement therapy on survival. We enrolled 425 patients, with a mean age of 61 years, in intensive care who had acute renal failure. Patients were randomly assigned ultrafiltration at 20 mL h(-1) kg(-1) (group 1, n=146), 35 mL h(-1) kg(-1) (group 2, n=139), or 45 mL h(-1) kg(-1) (group 3, n=140). The primary endpoint was survival at 15 days after stopping haemofiltration. We also assessed recovery of renal function and frequency of complications during treatment. Analysis was by intention to treat. Survival in group 1 was significantly lower than in groups 2 (p=0.0007) and 3 (p=0.0013). Survival in groups 2 and 3 did not differ significantly (p=0.87). Adjustment for possible confounding factors did not change the pattern of differences among the groups. Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors. 95%, 92%, and 90% of survivors in groups 1, 2, and 3, respectively, had full recovery of renal function. The frequency of complications was similarly low in all groups. Mortality among these critically ill patients was high, but increase in the rate of ultrafiltration improved survival significantly. We recommend that ultrafiltration should be prescribed according to patient's bodyweight and should reach at least 35 mL h(-1) kg(-1).
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              A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group.

              Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal may improve outcomes in critically ill patients. We studied whether increasing the cardiac index to a supranormal level (cardiac-index group) or increasing mixed venous oxygen saturation to a normal level (oxygen-saturation group) would decrease morbidity and mortality among critically ill patients, as compared with a control group in which the target was a normal cardiac index. A total of 10,726 patients in 56 intensive care units were screened, among whom 762 patients belonging to predefined diagnostic categories with acute physiology scores of 11 or higher were randomly assigned to the three groups (252 to the control group, 253 to the cardiac-index group, and 257 to the oxygen-saturation group). The hemodynamic targets were reached by 94.3 percent of the control group, 44.9 percent of the cardiac-index group, and 66.7 percent of the oxygen-saturation group (P < 0.001). Mortality was 48.4, 48.6, and 52.1 percent, respectively (P = 0.638), up to the time of discharge from the intensive care unit and 62.3, 61.7, and 63.8 percent (P = 0.875) at six months. Among patients who survived, the number of dysfunctional organs and the length of the stay in the intensive care unit were similar in the three groups. No differences in mortality among the three groups were found for any diagnostic category. A subgroup analysis of the patients in whom hemodynamic targets were reached revealed similar mortality rates: 44.8, 40.4, and 39.0 percent, respectively (P = 0.478). Hemodynamic therapy aimed at achieving supranormal values for the cardiac index or normal values for mixed venous oxygen saturation does not reduce morbidity or mortality among critically ill patients.
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                Author and article information

                Journal
                Intensive Care Medicine
                Intensive Care Med
                Springer Science and Business Media LLC
                0342-4642
                1432-1238
                January 2008
                December 4 2007
                January 2008
                : 34
                : 1
                : 17-60
                Article
                10.1007/s00134-007-0934-2
                8a5ebba6-eae3-4fb5-be25-964ffce6ed4c
                © 2008
                History

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