Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012

To provide an update to the Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock, last published in 2008.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.The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). the potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations.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 a parts per thousand yen65 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 a parts per thousand currency sign100 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) 180 mg/dL, targeting an upper blood glucose a parts per thousand currency sign180 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 absoluteaEuro (TM) adrenal insufficiency (2C).Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe 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 this important group of critically ill patients.American Association of Critical-Care NursesAmerican College of Chest PhysiciansAmerican College of Emergency PhysiciansAmerican Thoracic SocietyAsia Pacific Association of Critical Care MedicineAustralian and New Zealand Intensive Care SocietyBrazilian Society of Critical CareCanadian Critical Care SocietyChinese Society of Critical Care MedicineChinese Society of Critical Care Medicine-China Medical AssociationEmirates Intensive Care SocietyEuropean Respiratory SocietyEuropean Society of Clinical Microbiology and Infectious DiseasesEuropean Society of Intensive Care MedicineEuropean Society of Pediatric and Neonatal Intensive CareInfectious Diseases Society of AmericaIndian Society of Critical Care MedicineInternational Pan Arabian Critical Care Medicine SocietyJapanese Association for Acute MedicineJapanese Society of Intensive Care MedicinePediatric Acute Lung Injury and Sepsis InvestigatorsSociety for Academic Emergency MedicineSociety of Critical Care MedicineSociety of Hospital MedicineSurgical Infection SocietyWorld Federation of Critical Care NursesWorld Federation of Pediatric Intensive and Critical Care SocietiesWorld Federation of Societies of Intensive and Critical Care MedicineGordon and Betty Irene Moore FoundationSpectral Diagnostics IncFerringEisai (Ocean State Clinical Coordinating Center)Novartis (Clinical Coordinating Center)EisaiAstra ZenecaAggenixInimexAtoxbioWyethSirtrisCellular Bioengineering Inc.Sirius Genomics IncArtisan PharmaEisai, CorpFerring Pharmaceuticals A/SHutchinson Technology IncorporatedNovartis CorpEisai CorporationTakedaArtisan Pharma/Asahi Kasei Pharma America CorpEli LillyEli Lilly (PROWESS Shock site)Eisai (study site)National Institutes of Health (ARDS Network)Accelr8 (VAP diagnostics)CCCTG (Oscillate Study)Hospira (Dexmedetomidine in Alcohol Withdrawal RCT)National Institutes of Health Research, Health Technology Assessment Programme-United KingdomNIHR governmentICNARCEisai, IncNational Institutes of HealthRobert Wood Johnson FoundationCIHRAdvanced Lifeline SystemSiemensBayerByk GuldenAstraZenecaFaron PharmaceuticalsCerus CorporationDHDOxford University PressHospiraCernerPfizerKCIAmerican Association for Respiratory CareBioMed CentralAlberta Heritage Foundation for Medical ResearchNHMRC project grant (ARISE RECT of EGDT)NHMRC project grantFresiniusRCT of steroid versus placebo for septic shockNHMRC project grant (BLISS study of bacteria detection by PRC in septic shock) Intensive Care Foundation-ANZ (BLING pilot RCT of betalactam administration by infusion)Hospira (SPICE programme of sedation delirium researchNHMRC Centres for Research Excellent GrantAstellasCuracyteGlaxoSmithKlineMerckCooper Univ Hosp, Camden, NJ USABrown Univ, Warren Alpert Med Sch, Providence, RI 02912 USASt George Hosp, London, EnglandHop Raymond Poincare, Garches, FranceVivantes Klinikum Neukolln, Berlin, GermanyBrown Univ, Mem Hosp Rhode Isl, Pawtucket, RI 02860 USAEmory Univ Hosp, Atlanta, GA 30322 USAHadassah Hebrew Univ, Med Ctr, Jerusalem, IsraelDenver Hlth Med Ctr, Denver, CO USAMcMaster Univ, Hamilton, ON, CanadaBarnes Jewish Hosp, St Louis, MO 63110 USAUniv Chicago, Med Ctr, Chicago, IL 60637 USACalif Pacific Med Ctr, San Francisco, CA USAUniv Jena, Jena, GermanyRush Univ, Med Ctr, Chicago, IL 60612 USAUniv Pittsburgh, Pittsburgh, PA USAUniv Penn, Perelman Sch Med, Philadelphia, PA 19104 USAUniversidade Federal de São Paulo, São Paulo, BrazilSunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, CanadaRoyal Perth Hosp, Perth, WA, AustraliaGuys & St Thomas Hosp Trust, London, EnglandErasme Univ Hosp, B-1070 Brussels, BelgiumCtr Hosp Lisboa Cent, EPE, Hosp Sao Jose, UCINC, Lisbon, PortugalUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc