A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development.
METHODS: Key recommendations and suggestions, listed by category, include: early quantitative
resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before
antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of
infection (UG); administration of broad-spectrum antimicrobials
therapy within 1 h of the recognition of
septic shock (1B) and
severe sepsis without
septic shock (1C) as the goal of
therapy; reassessment of antimicrobial
therapy daily for de-escalation, when appropriate (1B);
infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid
resuscitation with
crystalloid (1B) and consideration of the addition of
albumin in patients who continue to require substantial amounts of
crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of
hetastarch formulations (1B); initial fluid challenge in patients with
sepsis-induced tissue hypoperfusion and suspicion of
hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG);
norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B);
epinephrine when an additional agent is needed to maintain adequate blood pressure (2B);
vasopressin (0.03 U/min) can be added to
norepinephrine to either raise mean arterial pressure to target or to decrease
norepinephrine dose but should not be used as the initial vasopressor (UG);
dopamine is not recommended except in highly selected circumstances (2C);
dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and
low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous
hydrocortisone in adult
septic shock patients if adequate fluid
resuscitation and vasopressor
therapy are able to restore hemodynamic stability (2C);
hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic
coronary artery disease, or acute
hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for
acute respiratory distress syndrome (ARDS); application of at least a minimal amount of
positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with
sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in
sepsis patients with severe refractory
hypoxemia due to ARDS (2C); prone positioning in
sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of
neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of
neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) <150 mm Hg (2C); a protocolized approach to
blood glucose management commencing
insulin dosing when two consecutive
blood glucose levels are >180 mg/dL, targeting an upper
blood glucose ≤180 mg/dL (1A); equivalency of
continuous veno-venous hemofiltration or intermittent
hemodialysis (2B); prophylaxis for
deep vein thrombosis (1B); use of stress
ulcer prophylaxis to prevent upper gastrointestinal
bleeding in patients with
bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous
glucose within the first 48 h after a diagnosis of
severe sepsis/
septic shock (2C); and addressing goals of care, including treatment plans and
end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric
severe sepsis include:
therapy with face mask
oxygen, high flow
nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and
hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for
septic shock associated with
hypovolemia, the use of crystalloids or
albumin to deliver a bolus of 20 mL/kg of crystalloids (or
albumin equivalent) over 5-10 min (2C); more common use of inotropes and
vasodilators for
low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of
hydrocortisone only in children with suspected or proven "absolute"'
adrenal insufficiency (2C).
CONCLUSIONS: