In 2004, experts in the diagnosis and management of infection and sepsis from 11 international medical organizations published the first guidelines to improve the prognosis of severe sepsis and septic shock. These guidelines represent Phase II of the Save Sepsis Campaign (SSC), an international effort to raise awareness and improve prognosis in severe sepsis. In conjunction with several other organizations, this working group met again in 2006 and 2007 to update the guideline document using a new evidence-based methodological system to assess the quality of the evidence and the strength of the recommendations. These recommendations are intended to be used to guide clinicians in the treatment of patients with severe sepsis and septic shock. It is important to note that the recommendations in these guidelines are not a substitute for clinician decision-making when physicians are faced with the unique clinical indicators of a specific patient. GRADE SYSTEM 1. (Strong recommendation: do or don’t do) 2. (Weak recommendation: may or may not do) A. (High quality randomized controlled study (RCT) or meta-analysis study) B. (Moderate quality RCT or high quality observational and cohort study) C. (Well-completed, controlled, observational and cohort study) D. (Case summaries or expert opinion, low-quality study) A. Initial Resuscitation Septic shock is characterized by inadequate tissue perfusion, persistent low blood pressure, and blood lactate ≥ 4 mmol/L. Hypotension should be transferred to the ICU room as soon as possible after the onset of hypotension to receive treatment The first 6 hours of resuscitation should be aimed at a) Central Venous Pressure (CVP): 8-12 mmHg b) Mean Arterial Pressure (MAP) ≥ 65 mmHg c) Urine output ≥ 0.5 ml/kg/hd) Central Venous ( superior vena cava) oxygen saturation ≥70% or mixed arterial and venous oxygen saturation ≥65% (1C) e) CVP has reached the target, but ScvO2 still fails to reach 70% or SvO2 still fails to reach 65%, then transfuse concentrated erythrocytes in suspension with Hct ≥30% and/or transfuse dobutamine (maximum of 20 μg/kg.min) to reach this target (2C). B. Diagnosis 1. At least two blood cultures should be obtained before antibiotic administration! i.e., blood specimens from percutaneous puncture and from blood vessels with built-in tubes that have been left in place for more than 48 hours. Other culture specimens, including urine, cerebrospinal fluid, wounds, respiratory secretions, or other body fluids that may be the source of the infection, should be obtained before antibiotics are administered, if possible (1C). 2. Imaging should be performed as soon as possible to confirm underlying infection (1C) {E} C. Antibiotic therapy 1. Early intravenous antibiotic therapy is recommended within 1 hour of confirmation of septic shock (1B) or severe sepsis before septic shock (1D) develops. Retain an appropriate specimen before applying antibiotics, but do not delay antibiotic administration for the purpose of retaining a specimen (1D). 2a.It is recommended that initial empiric anti-infective therapy consist of one or more drugs against all suspected pathogenic microorganisms (bacteria and/or fungi) and that the concentration of the drug that penetrates the infected lesion causing sepsis is sufficiently high (1B){D} 2b.It is recommended that the antibiotic regimen be evaluated on a daily basis in order to achieve the desired clinical outcome, to prevent the emergence of bacterial resistance, to minimize toxicity, and to reduce costs (1C). . 2c.Combination therapy is recommended for patients with severe sepsis caused by known or suspected Pseudomonas spp. infection (2D) 2d.Empiric combination therapy is recommended for neutropenic patients (2D). 2e. For patients with severe sepsis when applying empiric therapy, it is recommended that combination therapy should not exceed 3-5 days. Once the pathogen has been identified, the most appropriate monotherapy should be selected (2D). 3. The recommended course of therapy is generally 7-10 days, but it should be appropriately prolonged in patients with slow clinical response to therapy, incomplete clearance of infected lesions, or immunodeficiency (including neutropenia) (1D). D. Infection source control 1a. For specific infections requiring urgent management such as necrotizing fasciitis, diffuse peritonitis, cholangitis, and intestinal infarction, the cause should be sought and the diagnosis established or ruled out as soon as possible (1C), and this should be accomplished within 6 hours of symptom onset (1D). 1b.All patients with severe sepsis should be evaluated to determine if a controllable source of infection is present. Means of control include drainage of abscesses or localized foci of infection, postinfectious necrotic tissue debridement, removal of medical devices that can cause infection, or source control of microbial infections that remain (1C). 2. It is recommended that in cases where peripancreatic necrosis has been identified and may be a potential focus of infection, it is best to wait until viable and necrotic tissue have been clearly delineated before intervening (2B). 3. When pathogenetic treatment is required, effective interventions that minimize physiologic compromise are recommended, such as percutaneous drainage of abscesses rather than surgical drainage (1D). 4. Endovascular appliances that may become foci of infection in severe sepsis or septic shock should be removed immediately after other vascular access is established (1C). E. Fluid therapy 1. Fluid resuscitation with natural/artificial colloidal or crystalloid fluids is recommended. There is no evidence to support the superiority of one fluid over another (1B). a. The use of albumin has been shown experimentally to be safe and equivalent to crystalloid fluids. b.The use of colloidal fluids significantly reduced mortality (P=0.09). c. There was no difference in the effectiveness of crystalloid and colloid resuscitation. d. To achieve the same therapeutic goal, the amount of crystalloid fluid was significantly greater than the amount of colloid fluid. e. Crystals are cheaper. 2. The recommended initial therapeutic goal of fluid resuscitation is to achieve a CVP of at least 8 mmHg (12 mmHg for mechanically ventilated patients), after which further fluid therapy is usually required (1C). 3a.Fluid shock therapy is recommended, with continuous fluid replacement until hemodynamics (e.g., arterial pressure, heart rate, urine output) improve (1D). 3b.Fluid shocks in patients with suspected hypovolemia should be administered with at least 1000 ml of crystalloid or 300-500 ml of colloid within the first 30 minutes. In patients with inadequate organ perfusion due to sepsis, faster and higher doses of fluids should be given (1D). 3c. In the absence of hemodynamic improvement, the rate of rehydration should be reduced when there is only an increase in cardiac filling pressure (CVP or pulmonary wedge pressure) (1D). F. Vasopressor Drugs It is recommended that MAP be maintained at ≥65 mmHg (1C). When hypovolemia is not corrected, vasopressors should be used to ensure perfusion during hypotension. Norepinephrine should be gradually increased until MAP reaches 65 mm Hg to maintain tissue perfusion. In addition, the patient’s pre-existing complications should be taken into account when setting goals for MAP therapy. 2. Norepinephrine or dopamine is recommended as the vasopressor of choice for correcting hypotension in septic shock (and should be administered as soon as possible after central venous access is established) (1C). 3a.Epinephrine, phenylephrine, or antidiuretic hormone is not recommended as the preferred vasopressor in septic shock (2C).0.03 U/min of antidiuretic hormone combined with norepinephrine is equivalent to norepinephrine alone. 3b.Epinephrine is recommended as the drug of choice if norepinephrine or dopamine is not effective (2B). 4. Low-dose dopamine is not recommended as a renoprotective drug (1A). A large randomized clinical trial and meta-analysis showed no significant difference in comparing the effects of low-dose dopamine and placebo. Therefore, there is no evidence to support that low-dose dopamine protects renal function. 5. It is recommended that arterial access (1D) be established as soon as possible for patients requiring vasopressor medications, when conditions permit. In shock, arterial catheterization is more accurate, the data can be reanalyzed, and continuous monitoring data can help one develop the next treatment plan based on blood pressure. G. Positive inotropic drugs should be administered intravenously with dobutamine (1C) in the presence of elevated cardiac filling pressures and decreased cardiac output suggestive of myocardial dysfunction. 2. against the use of methods that increase cardiac index to supranormal levels. G. Positive Inotropic Drugs Dobutamine is the cardiac contractile drug of choice when the patient’s LV filling pressures and MAP are sufficiently high (or when fluid resuscitation therapy has been clinically assessed as adequate) and low cardiac output is also measured or suspected. If cardiac output is not monitored, a combination of a cardiac contractile/vasopressor such as norepinephrine or dobutamine is recommended. A vasopressor such as norepinephrine alone may be used to achieve target MAP and cardiac output when cardiac output and blood pressure can be monitored. d. Two large prospective clinical studies of critically ill ICU patients with sepsis did not show a benefit of using dobutamine to increase oxygen delivery to extraordinary levels. H. Glucocorticoids In adults with septic shock, intravenous hydrocortisone is recommended only for patients whose blood pressure is insensitive to fluid resuscitation and vasopressor therapy (2C). 2. The ACTH stimulation test is not recommended for the identification of subgroups of adult septic patients who must receive glucocorticoids (2B). 3. Dexamethasone is not recommended if hydrocortisone is available (2B). 4. If hydrocortisone is not available and the alternative hormonal agent does not have significant hydrocorticoid activity, it is recommended to increase the daily oral dose of fludrocortisone (50 μg). If hydrocortisone is used, fluticasone is optional (2C). 5. When the patient no longer requires vasopressors, it is recommended that glucocorticoid therapy be discontinued (2D). 6. For the purpose of treating sepsis, it is recommended that the daily glucocorticoid dosage in patients with severe sepsis or septic shock be no greater than 300 mg equivalent of hydrocortisone (1A). 7, for patients with sepsis without shock, the application of hormones is not recommended. However, there are no contraindications to hormone maintenance therapy or to the use of stress doses of hormones if the patient requires endocrine or glucocorticoid therapy (1D).