In 2004, experts in the diagnosis and management of infection and sepsis from 11 international medical organizations published the first guidelines for improving the prognosis of severe sepsis and septic shock.
These guidelines represent Phase II of the Save Sepsis Campaign (SSC), an international effort to increase awareness of severe sepsis and improve its prognosis. In conjunction with several other organizations, this working group met again in 2006 and 2007 to update the guideline document with a new evidence-based methodological system to assess the quality of evidence and strength of 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 unique clinical indicators for specific patients.
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 done, controlled observational and cohort study) D, (case summary or expert opinion, low quality study)
A. Initial resuscitation
Sepsis shock is characterized by inadequate tissue perfusion, persistent hypotension, blood lactate ≥ 4 mmol/L, and hypotension should be transferred to the ICU unit as soon as possible after the onset of treatment initial 6-hour goal of resuscitation 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 venous) oxygen saturation ≥ 70% or mixed arteriovenous oxygen saturation ≥ 65% (1C) e) CVP has reached the target but ScvO2 still cannot reach 70% or SvO2 still cannot reach 65%, then infusion of concentrated red blood cell suspension Hct ≥ 30% and/or infusion of dobutamine (maximum amount of 20μg/kg.min) to reach this target (2C).
B. Diagnosis
1. At least two blood cultures should be obtained prior to antibiotic administration! That is, blood specimens from a percutaneous puncture and from an intravascular tube left in place for more than 48 hours, and other culture specimens, including urine, cerebrospinal fluid, wounds, respiratory secretions, or other body fluids that may be the source of infection, should be obtained prior to antibiotic administration whenever possible (1C).
2. Perform imaging as soon as possible to confirm the underlying infection (1C) {E}
C. Antibiotic therapy
1.Recommend early intravenous antibiotic treatment within 1 hour when septic shock (1B) or severe sepsis has not yet developed (1D) is confirmed. Appropriate specimens should be obtained prior to the application of antibiotics, but antibiotics should not be delayed for the purpose of obtaining specimens (1D).
2a. It is recommended that initial empirical anti-infective therapy include one or more drugs against all suspected pathogenic microorganisms (bacteria and/or fungi) and that the concentration of drug penetrating the infected lesion causing sepsis is sufficiently high (1B) {D}
2b. Recommend daily evaluation of antibiotic regimens to achieve desired clinical outcomes, prevent the development of bacterial resistance, reduce toxicity, and reduce costs (1C).
2c. Combination therapy is recommended for patients with severe sepsis due to known or suspected Pseudomonas spp. infection (2D)
2d.Empirical combination therapy is recommended for patients with neutropenia (2D).
2e. For patients with severe sepsis when applying empirical treatment, combination therapy is recommended for no more than 3-5 days. Once the pathogen is found, the most appropriate single treatment (2D) should be selected.
3. The recommended course of treatment is generally 7-10 days, but for patients with slow response to clinical treatment, incomplete clearance of the infected lesion or immunodeficiency (including neutropenia), the course of treatment should be extended appropriately (1D).
D. Infection source control
1a. Specific infections requiring urgent management such as necrotizing fasciitis, diffuse peritonitis, cholangitis, and intestinal infarction should be searched for an etiology and a diagnosis established or ruled out as soon as possible (1C) and completed within 6 hours of symptom onset (1D).
1b. All patients with severe sepsis should be evaluated to determine if a controllable source of infection exists. Means of control include drainage of abscesses or localized foci of infection, debridement of necrotic tissue after infection, removal of medical devices that can cause infection, or control of the source of microbial infection that remains (1C).
2.It is recommended that interventions for those identified with peripancreatic necrosis that may become potential foci of infection should preferably wait until viable tissue and necrotic tissue are clearly delineated (2B).
3. When pathogenic treatment is required, effective interventions with minimal physiologic damage, such as percutaneous drainage of abscesses rather than surgical drainage, are recommended (1D).
4. After establishing other vascular access, intravascular devices that may become foci of severe sepsis or septic shock infection should be removed immediately (1C).
E. Fluid therapy
1. Fluid resuscitation with natural/artificial colloid or crystalloid fluids is recommended. There is no evidence to support the superiority of one fluid over the other (1B).
a. Experiments have shown that the use of albumin is safe and equivalent to crystalloids. b. The use of colloidal fluids significantly reduced mortality (P=0.09). c. There was no difference in the effect of crystalloid and colloid resuscitation.
d. The amount of crystalloid was significantly greater than the amount of colloid to achieve the same treatment goal. e. Crystalloids were cheaper.
2. The recommended initial therapeutic goal for 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 with continuous fluid replacement until hemodynamics (e.g., arterial pressure, heart rate, urine output) improve is recommended (1D).
3b. For fluid shocks in patients with suspected hypovolemia, a minimum of 1000 ml of crystalloid or 300-500 ml of colloid should be administered within the first 30 minutes.
colloidal fluid. In patients with sepsis resulting in inadequate organ perfusion, a faster and higher dose of fluid must be administered (1D). 3c. If only cardiac filling pressure (CVP or pulmonary artery wedge pressure) increases without hemodynamic improvement, the rate of rehydration should be reduced (1D).
F. Vasopressors
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. The use of norepinephrine should be gradually increased until MAP reaches 65 mmHg in order to maintain tissue perfusion. In addition, the patient’s pre-existing complications should be taken into account when setting MAP treatment goals.
2. Norepinephrine or dopamine is recommended as the vasopressor drug of choice for correction of 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 drug in septic shock (2C). 0.03 U/min of antidiuretic hormone combined with norepinephrine is equivalent to norepinephrine alone.
3b. If norepinephrine or dopamine is not effective, epinephrine is recommended as the drug of choice (2B).
4. Low-dose dopamine is not recommended as a renal protective agent (1A).
A large randomized clinical trial and meta-analysis showed no significant differences when 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 drugs.
In shock, arterial catheterization is more accurate, the data can be analyzed repeatedly, and continuous monitoring data can help one to 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 reduced cardiac output suggestive of myocardial dysfunction.
2. Oppose the use of methods that increase cardiac index to supernormal levels.
G. Positive inotropic drugs When the patient’s left ventricular 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, dobutamine is the preferred myocardial contraction drug.
If cardiac output is not monitored, a combination of a myoconstrictor/vasopressor such as norepinephrine or dobutamine is recommended.
When cardiac output and blood pressure can be monitored, a vasopressor such as norepinephrine alone may be used to achieve target MAP and cardiac output. d. Two large prospective clinical studies of critically ill ICU patients with sepsis did not show benefit from the use of dobutamine to elevate patient oxygen delivery to supernormal levels.
H. Glucocorticoids
In adult patients with septic shock, intravenous hydrocortisone is recommended only for patients whose blood pressure is insensitive to fluid resuscitation and vasopressant therapy (2C).
2. For the identification of subgroups of adult septic patients subject to glucocorticoids, ACTH excitation tests are not recommended (2B).
3.If hydrocortisone is available, dexamethasone (2B) is not recommended.
4. If hydrocortisone is not available and the alternative hormone preparation has no significant salt corticosteroid activity, it is recommended to increase the daily oral fludrocortisone (50 μg). If hydrocortisone is used, fludrocortisone is optional (2C).
5.When patients no longer need vasopressors, it is recommended to discontinue glucocorticoid therapy (2D).
6.For the purpose of treating sepsis, it is recommended that the daily glucocorticoid dosage for patients with severe sepsis or septic shock should be no more than 300 mg equivalent of hydrocortisone (1A).
7.For patients with sepsis without shock, the application of hormones is not recommended. However, there is no contraindication to hormone maintenance therapy or the use of stress doses of hormones in cases where the patient requires endocrine or glucocorticoid therapy (1D).