ARTICULO MEDICO:Manejo y Tratamiento de la sepsis grave

GUIAS INTERNACIONALES PARA EL MANEJO Y TRATAMIENTO DE LA SEPSIS GRAVE Y CHOQUE SEPTICO 


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Guideline Summary NGC-6316
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Guideline Title
Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008.
Bibliographic Source(s)
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R,
Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT,
Townsend S, Vender JS, Zimmerman JL, Vincent JL. Surviving Sepsis Campaign: International guidelines for
management of severe sepsis and septic shock: 2008. Intensive Care Med 2008 Jan;34(1):17-60. [341 references]
PubMed
Guideline Status
This is the current release of the guideline.
This guideline updates a previous version: Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-
Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM. Surviving sepsis
campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004 Mar;32(3):858-73.
Scope
Disease/Condition(s)
l Severe sepsis
l Septic shock
Guideline Category
Management
Treatment
Clinical Specialty
Critical Care
Emergency Medicine
Internal Medicine
Nursing
Pediatrics
Intended Users
Advanced Practice Nurses
Emergency Medical Technicians/Paramedics
Health Care Providers
Hospitals
Nurses
Physician Assistants
Physicians
Guideline Objective(s)
l 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
l To provide guidance for the clinician caring for a patient with severe sepsis or septic shock
Target Population
Adult and pediatric patients in intensive care unit (ICU) and non-ICU settings with severe sepsis or septic shock
Interventions and Practices Considered
1. Initial resuscitation
2. Diagnostic studies, as indicated
l Blood culture and cultures from other sites, such as urine, cerebrospinal fluid, wounds respiratory secretions,
or other body fluids, as indicated
l Imaging studies, such as ultrasound, as indicated
3. Antibiotic therapy
4. Source identification and control measures
5. Fluid therapy
Natural or artificial colloids or crystalloids
Interventions and Practices Considered
1. Initial resuscitation
2. Diagnostic studies, as indicated
l Blood culture and cultures from other sites, such as urine, cerebrospinal fluid, wounds respiratory secretions,
or other body fluids, as indicated
l Imaging studies, such as ultrasound, as indicated
3. Antibiotic therapy
4. Source identification and control measures
5. Fluid therapy
l Natural or artificial colloids or crystalloids
l Fluid challenge in patients with suspected hypovolemia
6. Vasopressor therapy (norepinephrine, dopamine, vasopressin, epinephrine)
7. Inotropic therapy (dobutamine infusion)
8. Corticosteroids (hydrocortisone, dexamethasone, fludrocortisones)
9. Recombinant human activated protein C (rhAPC)
10. Blood product administration (red blood cells, erythropoietin, fresh frozen plasma, antithrombin*, platelets)
11. Mechanical ventilation of sepsis-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS)
12. Sedation, analgesia, and neuromuscular blockade
13. Glucose control (intravenous insulin)
14. Renal replacement
15. Bicarbonate therapy*
16. Deep vein thrombosis prophylaxis (low-dose unfractionated heparin [UFH], low-molecular weight heparin
[LMWH], mechanical prophylactic devices)
17. Stress ulcer prophylaxis (H2 blockers, proton pump inhibitors [PPIs])
18. Selective digestive tract decontamination (no recommendation made for or against)
19. Advance care planning
20. Considerations for pediatric patients
*Guideline developers considered but did not recommend these interventions.
Major Outcomes Considered
l Survival of patients with severe sepsis and septic shock
l Length of stay in intensive care unit (ICU)
Methodology
Methods Used to Collect/Select the Evidence
Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence
The current clinical practice guidelines build on the first and second editions from 2001 and 2004. The 2001 publication
incorporated a MEDLINE search for clinical trials in the preceding 10 years, supplemented by a manual search of other
relevant journals. The 2004 publication incorporated the evidence available through the end of 2003. The current
publication is based on an updated search into 2007.
Subgroups were formed, each charged with updating recommendations in specific areas, including corticosteroids, blood
products, activated protein C, renal replacement therapy, antibiotics, source control, and glucose control, etc. Each
subgroup was responsible for updating the evidence (into 2007, with major additional elements of information
incorporated into the evolving manuscript throughout 2006 and 2007). A separate search was performed for each clearly
defined question. The committee chair worked with subgroup heads to identify pertinent search terms that always
included, at a minimum, sepsis, severe sepsis, septic shock and sepsis syndrome crossed against the general topic
area of the subgroup as well as pertinent key words of the specific question posed. All questions of the previous
guidelines publications were searched, as were pertinent new questions generated by general topic related search or
recent trials.
Number of Source Documents
Not stated
Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence
Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) System
Grade A: Randomized controlled trial (RCT)
Grade B: Downgraded RCT or upgraded observational studies
Grade C: Well-done observational studies
Grade D: Case series or expert opinion
Factors that may decrease the strength of the evidence:
Rating Scheme for the Strength of the Evidence
Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) System
Grade A: Randomized controlled trial (RCT)
Grade B: Downgraded RCT or upgraded observational studies
Grade C: Well-done observational studies
Grade D: Case series or expert opinion
Factors that may decrease the strength of the evidence:
1. Poor quality of planning and implementation of available RCTs suggesting high likelihood of bias
2. Inconsistency of results (including problems with subgroup analyses)
3. Indirectness of evidence (differing population, intervention, control, outcomes, comparison)
4. Imprecision of results
5. High likelihood of reporting bias
Main factors that may increase the strength of evidence
1. Large magnitude of effect (direct evidence, relative risk [RR] >2 with no plausible confounders)
2. Very large magnitude of effect with RR >5 and no threats to validity (by two levels)
3. Dose response gradient
Methods Used to Analyze the Evidence
Review of Published Meta-Analyses
Systematic Review
Description of the Methods Used to Analyze the Evidence
Quality of evidence was judged by pre-defined Grades of Recommendation, Assessment, Development and Evaluation
(GRADE) criteria (see the "Rating Scheme for the Strength of the Evidence" field in this summary). Significant education
of committee members on the GRADE approach was performed via email prior to the first committee meeting and at
the first meeting. Rules were distributed concerning assessing the body of evidence and GRADE experts were available
for questions throughout the process.
The Surviving Sepsis Campaign (SSC) Steering Committee and individual authors collaborated with GRADE
representatives to apply the GRADE system to the SSC guidelines revision process. The members of GRADE group were
directly involved, either in person or via e-mail, in all discussions and deliberations amongst the guidelines committee
members as to grading decisions. Subsequently, the SSC authors used written material prepared by the GRADE group
and conferred with GRADE group members who were available at the first committee meeting and subsequent nominal
group meetings. GRADE representatives were also used as a resource throughout subgroup deliberation.
Methods Used to Formulate the Recommendations
Expert Consensus (Consensus Development Conference)
Expert Consensus (Delphi)
Expert Consensus (Nominal Group Technique)
Description of Methods Used to Formulate the Recommendations
In 2004, an international group of experts in the diagnosis and management of infection and sepsis, representing 11
organizations, published the first internationally accepted guidelines that the bedside clinician could use to improve
outcomes in severe sepsis and septic shock. These guidelines represented Phase II of the Surviving Sepsis Campaign
(SSC), an international effort to increase awareness and improve outcomes in severe sepsis. Joined by additional
organizations, the group met again in 2006 and 2007 to update the guidelines document using a new evidence-based
methodology system for assessing quality of evidence and strength of recommendations.
The guideline process included a modified Delphi method, a consensus conference, several subsequent meetings of
subgroups and key individuals, teleconferences and electronically based discussions among subgroups and members of
the entire committee and two follow-up nominal group meetings in 2007.
Subgroups agreed electronically on draft proposals that were presented to committee meetings for general discussion.
In January 2006, the entire group met during the 35th Society of Critical Care Medicine (SCCM) Critical Care Congress in
San Francisco, California, USA. The results of that discussion were incorporated into the next version of
recommendations and again discussed using electronic mail. Recommendations were finalized during nominal group
meetings (composed of a subset of the committee members) at the 2007 SCCM (Orlando) and 2007 International
Symposium on Intensive Care and Emergency Medicine (Brussels) meetings with recirculation of deliberations and
decisions to the entire group for comment or approval. At the discretion of the chair and following adequate discussion,
competing proposals for wording of recommendations or assigning strength of evidence were resolved by formal voting.
On occasions, voting was performed to give the committee a sense of distribution of opinions to facilitate additional
discussion. The manuscript was edited for style and form by the writing committee with final approval by section leads
for their respective group assignment and then by the entire committee.
Differences of opinion among committee members about interpretation of evidence, wording of proposals, or strength
of recommendations were resolved using a specifically developed set of rules. In summary, the main approach for
converting diverse opinions into a recommendation was: 1. to give a recommendation a direction (for or against the
given action), a majority of votes were to be in favor of that direction, with no more than 20% preferring the opposite
direction (there was a neutral vote allowed as well); 2. to call a given recommendation "strong" rather than "weak" at
least 70% "strong" votes were required; 3. if fewer than 70% of votes indicated "strong" preference, the
recommendation was assigned a "weak" category of strength. The guideline developers used a combination of modified
Delphi Process and Nominal (Expert) Group techniques to ensure both depth and breadth of review. The entire review
group (together with their parent organizations as required) participated in the larger, iterative, modified Delphi
process. The smaller working group meetings which took place in person functioned as the Nominal Groups. If a clear
consensus could not be obtained by polling within the Nominal Group meetings, the larger group was specifically asked
to use the polling process. This was only required for corticosteroids and glycemic control. The larger group had the
opportunity to review all outputs. In this way the entire review combined intense focused discussion (Nominal Group)
with broader review and monitoring using the Delphi process.
converting diverse opinions into a recommendation was: 1. to give a recommendation a direction (for or against the
given action), a majority of votes were to be in favor of that direction, with no more than 20% preferring the opposite
direction (there was a neutral vote allowed as well); 2. to call a given recommendation "strong" rather than "weak" at
least 70% "strong" votes were required; 3. if fewer than 70% of votes indicated "strong" preference, the
recommendation was assigned a "weak" category of strength. The guideline developers used a combination of modified
Delphi Process and Nominal (Expert) Group techniques to ensure both depth and breadth of review. The entire review
group (together with their parent organizations as required) participated in the larger, iterative, modified Delphi
process. The smaller working group meetings which took place in person functioned as the Nominal Groups. If a clear
consensus could not be obtained by polling within the Nominal Group meetings, the larger group was specifically asked
to use the polling process. This was only required for corticosteroids and glycemic control. The larger group had the
opportunity to review all outputs. In this way the entire review combined intense focused discussion (Nominal Group)
with broader review and monitoring using the Delphi process.
Rating Scheme for the Strength of the Recommendations
Grade 1 (Strong): A recommendation in favor of an intervention reflects that the desirable effects of adherence to a
recommendation (beneficial health outcomes, less burden on staff and patients, and costs savings) will clearly
outweigh the undesirable effects (harms, more burden and greater costs).
Grade 2 (Weak): A recommendation in favor of an intervention indicates that the desirable effects of adherence to a
recommendation probably will outweigh the undesirable effects, but the panel is not confident about these tradeoffseither
because some of the evidence is low-quality (and thus there remains uncertainty regarding the benefits and
risks) or the benefits and downsides are closely balanced.
Cost Analysis
Guideline developers reviewed published cost analyses.
Method of Guideline Validation
Peer Review
Description of Method of Guideline Validation
Recommendations were finalized during nominal group meetings (composed of a subset of the committee members) at
the 2007 Society of Critical Care Medicine (Orlando) and 2007 International Symposium on Intensive Care and
Emergency Medicine (Brussels) meetings with recirculation of deliberations and decisions to the entire group for
comment or approval. At the discretion of the chair and following adequate discussion, competing proposals for wording
of recommendations or assigning strength of evidence were resolved by formal voting. On occasions, voting was
performed to give the committee a sense of distribution of opinions to facilitate additional discussion. The manuscript
was edited for style and form by the writing committee with final approval by section leads for their respective group
assignment and then by the entire committee.
Recommendations
Major Recommendations
The grades of evidence (A-D) and levels of recommendations (1-2) are defined at the end of the Major
Recommendations.
Management of Severe Sepsis
A. Initial Resuscitation
1. The guideline committee recommends the protocolized resuscitation of a patient with sepsis-induced shock,
defined as tissue hypoperfusion (hypotension persisting after initial fluid challenge or blood lactate
concentration equal to or greater than 4 mmol/L). This protocol should be initiated as soon as hypoperfusion is
recognized and should not be delayed pending intensive care unit (ICU) admission. During the first 6 hours of
resuscitation, the goals of initial resuscitation of sepsis-induced hypoperfusion should include all of the
following as one part of a treatment protocol:
l Central venous pressure (CVP): 8–12 mm Hg
l Mean arterial pressure (MAP) >65 mm Hg
l Urine output >0.5 mL/kg/hour
l Central venous (superior vena cava) or mixed venous oxygen saturation >70% or >65%, respectively
(Grade 1C)
2. The guideline committee suggests that during the first 6 hours of resuscitation of severe sepsis or septic
shock, if central venous oxygen saturation (SCVO2) or mixed venous saturation (SvO2) of 70% or 65%
respectively is not achieved with fluid resuscitation to the CVP target, then transfusion of packed red blood cells
to achieve a hematocrit of >30% and/or administration of a dobutamine infusion (up to a maximum of 20
micrograms/kg/min) be utilized to achieve this goal. (Grade 2C)
B. Diagnosis
1. The guideline committee recommends obtaining appropriate cultures before antimicrobial therapy is initiated
if such cultures do not cause significant delay in antibiotic administration. To optimize identification of
causative organisms, the committee recommends at least two blood cultures be obtained prior to antibiotics
with at least one drawn percutaneously and one drawn through each vascular access device, unless the device
was recently (less than 48 hours) inserted. Cultures of other sites (preferably quantitative where appropriate)
such as urine, cerebrospinal fluid, wounds, respiratory secretions, or other body fluids that may be the source of
infection should also be obtained before antibiotic therapy if not associated with significant delay in antibiotic
administration. (Grade 1C)
2. The guideline committee recommends that imaging studies be performed promptly in attempts to confirm a
potential source of infection. Sampling of potential sources of infection should occur as they are identified;
however, some patients may be too unstable to warrant certain invasive procedures or transport outside of the
ICU. Bedside studies, such as ultrasound, are useful in these circumstances. (Grade 1C)
C. Antibiotic Therapy
1. The guideline committee recommends that intravenous antibiotic therapy be started as early as possible and
within the first hour of recognition of septic shock (Grade 1B) and severe sepsis without septic shock (Grade 1D).
Appropriate cultures should be obtained before initiating antibiotic therapy, but should not prevent prompt
administration of antimicrobial therapy. (Grade 1D)
2a. The guideline committee recommends that initial empirical anti-infective therapy include one or more drugs that
2. The guideline committee recommends that imaging studies be performed promptly in attempts to confirm a
potential source of infection. Sampling of potential sources of infection should occur as they are identified;
however, some patients may be too unstable to warrant certain invasive procedures or transport outside of the
ICU. Bedside studies, such as ultrasound, are useful in these circumstances. (Grade 1C)
C. Antibiotic Therapy
1. The guideline committee recommends that intravenous antibiotic therapy be started as early as possible and
within the first hour of recognition of septic shock (Grade 1B) and severe sepsis without septic shock (Grade 1D).
Appropriate cultures should be obtained before initiating antibiotic therapy, but should not prevent prompt
administration of antimicrobial therapy. (Grade 1D)
2a. The guideline committee recommends that initial empirical anti-infective therapy include one or more drugs that
have activity against all likely pathogens (bacterial and/or fungal) and that penetrate in adequate concentrations
into the presumed source of sepsis. (Grade 1B)
2b. The guideline committee recommends that the antimicrobial regimen be reassessed daily to optimize activity,
to prevent the development of resistance, to reduce toxicity, and to reduce costs. (Grade 1C)
2c. The guideline committee suggests combination therapy for patients with known or suspected Pseudomonas
infections as a cause of severe sepsis. (Grade 2D)
2d. The guideline committee suggests combination empiric therapy for neutropenic patients with severe sepsis.
(Grade 2D)
2e. When used empirically in patients with severe sepsis, the guideline committee suggests that combination
therapy should not be administered for more than 3 to 5 days. De-escalation to the most appropriate single therapy
should be performed as soon as the susceptibility profile is known. (Grade 2D)
3. The guideline committee recommends that the duration of therapy typically be 7 to 10 days; longer courses may
be appropriate in patients who have a slow clinical response, undrainable foci of infection, or who have immunologic
deficiencies including neutropenia. (Grade 1D)
4. If the presenting clinical syndrome is determined to be due to a noninfectious cause, the guideline committee
recommends antimicrobial therapy be stopped promptly to minimize the likelihood that the patient will become
infected with an antibiotic resistant pathogen or will develop a drug related adverse effect. (Grade 1D)
Source Control
1a. The guideline committee recommends that a specific anatomic diagnosis of infection requiring consideration for
emergent source control- for example necrotizing fasciitis, diffuse peritonitis, cholangitis, intestinal infarction – be
sought and diagnosed or excluded as rapidly as possible (Grade 1C) and within the first 6 hours following
presentation (Grade 1D).
1b. The guideline committee further recommends that all patients presenting with severe sepsis be evaluated for
the presence of a focus of infection amenable to source control measures, specifically the drainage of an abscess or
local focus of infection, the debridement of infected necrotic tissue, the removal of a potentially infected device, or
the definitive control of a source of ongoing microbial contamination (Grade 1C) (see Appendix A in the original
guideline document for examples of potential sites needing source control).
2. The guideline committee suggests that when infected peripancreatic necrosis is identified as a potential source
of infection, definitive intervention is best delayed until adequate demarcation of viable and non-viable tissues has
occurred. (Grade 2B)
3. The guideline committee recommends that when source control is required, the effective intervention associated
with the least physiologic insult be employed, for example, percutaneous rather than surgical drainage of an
abscess. (Grade 1D)
4. The guideline committee recommends that when intravascular access devices are a possible source of severe
sepsis or septic shock, they be promptly removed after establishing other vascular access. (Grade 1C)
D. Fluid Therapy
1. The guideline committee recommends fluid resuscitation with either natural/artificial colloids or crystalloids.
There is no evidence-based support for one type of fluid over another. (Grade 1B)
2. The guideline committee recommends fluid resuscitation initially target a CVP of at least 8 mm Hg (12 mm Hg in
mechanically ventilated patients). Further fluid therapy is often required. (Grade 1C)
3a. The guideline committee recommends that a fluid challenge technique be applied, wherein fluid administration
is continued as long as the hemodynamic improvement (for example, arterial pressure, heart rate, urine output)
continues. (Grade 1D)
3b. The guideline committee recommends fluid challenge in patients with suspected hypovolemia be started with at
least 1000 mL of crystalloids or 300 to 500 mL of colloids over 30 minutes. More rapid administration and greater
amounts of fluid may be needed in patients with sepsis induced tissue hypoperfusion (see initial resuscitation
recommendations). (Grade 1D)
3c. The guideline committee recommends the rate of fluid administration be reduced substantially when cardiac
filling pressures (CVP or pulmonary artery balloon-occluded pressure) increase without concurrent hemodynamic
improvement. (Grade 1D)
E. Vasopressors
1. The guideline committee recommends mean arterial pressure (MAP) be maintained >65 mm Hg. (Grade 1C)
The guideline committee recommends either norepinephrine or dopamine as the first choice vasopressor agent to
correct hypotension in septic shock (administered through a central catheter as soon as one is available). (Grade
1C)
3a. The guideline committee suggests that epinephrine, phenylephrine, or vasopressin should not be administered
as the initial vasopressor in septic shock. (Grade 2C) Vasopressin .03 units/min may be subsequently added to
norepinephrine with anticipation of an effect equivalent to norepinephrine alone.
3b. The guideline committee suggests that epinephrine be the first chosen alternative agent in septic shock that is
poorly responsive to norepinephrine or dopamine. (Grade 2B)
5. The guideline committee recommends that low dose dopamine not be used for renal protection. (Grade 1A)
6. The guideline committee recommends that all patients requiring vasopressors have an arterial line placed as
soon as practical if resources are available. (Grade 1D)
F. Inotropic Therapy
1. The guideline committee recommends a dobutamine infusion be administered in the presence of myocardial
3a. The guideline committee suggests that epinephrine, phenylephrine, or vasopressin should not be administered
as the initial vasopressor in septic shock. (Grade 2C) Vasopressin .03 units/min may be subsequently added to
norepinephrine with anticipation of an effect equivalent to norepinephrine alone.
3b. The guideline committee suggests that epinephrine be the first chosen alternative agent in septic shock that is
poorly responsive to norepinephrine or dopamine. (Grade 2B)
5. The guideline committee recommends that low dose dopamine not be used for renal protection. (Grade 1A)
6. The guideline committee recommends that all patients requiring vasopressors have an arterial line placed as
soon as practical if resources are available. (Grade 1D)
F. Inotropic Therapy
1. The guideline committee recommends a dobutamine infusion be administered in the presence of myocardial
dysfunction as suggested by elevated cardiac filling pressures and low cardiac output. (Grade 1C)
2. The guideline committee recommends against the use of a strategy to increase cardiac index to
predetermined supranormal levels. (Grade 1B)
G. Corticosteroids
1. The guideline committee suggests intravenous hydrocortisone be given only to adult septic shock patients
after blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor therapy. (Grade
2C)
2. The guideline committee suggests the adrenocorticotropic hormone (ACTH) stimulation test not be used to
identify the subset of adults with septic shock who should receive hydrocortisone. (Grade 2B)
3. The guideline committee suggests that patients with septic shock should not receive dexamethasone if
hydrocortisone is available. (Grade 2B)
4. The guideline committee suggests the daily addition of oral fludrocortisone (50 micrograms) if hydrocortisone
is not available and the steroid that is substituted has no significant mineralocorticoid activity. Fludrocortisone
is considered optional if hydrocortisone is used. (Grade 2C)
5. The guideline committee suggests clinicians wean the patient from steroid therapy when vasopressors are
no longer required. (Grade 2D)
6. The guideline committee recommends doses of corticosteroids comparable to >300 mg hydrocortisone daily
not be used in severe sepsis or septic shock for the purpose of treating septic shock. (Grade 1A)
7. The guideline committee recommends corticosteroids not be administered for the treatment of sepsis in the
absence of shock. There is, however, no contraindication to continuing maintenance steroid therapy or to using
stress-dose steroids if the patient's endocrine or corticosteroid administration history warrants. (Grade 1D)
H. Recombinant Human Activated Protein C (rhAPC)
1. The guideline committee suggests that adult patients with sepsis induced organ dysfunction associated with
a clinical assessment of high risk of death, most of whom will have Acute Physiology and Chronic Health
Evaluation II (APACHE II) >25 or multiple organ failure, receive recombinant human activated protein C (rhAPC)
if there are no contraindications (Grade 2B except for patients within 30 days of surgery where it is Grade
2C). Relative contraindications should also be considered in decision making.
2. The guideline committee recommends that adult patients with severe sepsis and low risk of death, most of
whom will have APACHE II <20 1a="1a" do="do" failure="failure" not="not" one="one" or="or" organ="organ" p="p" rade="rade" receive="receive" rhapc.="rhapc.">I. Blood Product Administration
1. Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, such as
myocardial ischemia, severe hypoxemia, acute hemorrhage, cyanotic heart disease, or lactic acidosis (see
recommendations for initial resuscitation), the guideline committee recommends that red blood cell transfusion
occur when hemoglobin decreases to <7 .0=".0" 7.0="7.0" 9.0="9.0" 90="90" a="a" dl="dl" g="g" hemoglobin="hemoglobin" of="of" p="p" target="target" to="to">g/L) in adults. (Grade 1B)
2. The guideline committee recommends that erythropoietin not be used as a specific treatment of anemia
associated with severe sepsis, but may be used when septic patients have other accepted reasons for
administration of erythropoietin such as renal failure-induced compromise of red blood cell production. (Grade
1B)
3. The guideline committee suggests that fresh frozen plasma not be used to correct laboratory clotting
abnormalities in the absence of bleeding or planned invasive procedures. (Grade 2D)
4. The guideline committee recommends against antithrombin administration for the treatment of severe sepsis
and septic shock. (Grade 1B)
5. In patients with severe sepsis, the guideline committee suggests that platelets should be administered
when counts are <5000 109="109" apparent="apparent" be="be" bleeding.="bleeding." may="may" mm3="mm3" of="of" p="p" platelet="platelet" regardless="regardless" transfusion="transfusion">considered when counts are 5,000 to 30,000/mm3 (5 to 30 × 109/L) and there is a significant risk of bleeding.
Higher platelet counts (>50,000/mm3 (50 × 109/L) are typically required for surgery or invasive procedures.
(Grade 2D)
Supportive Therapy of Severe Sepsis
A. Mechanical Ventilation of Sepsis-Induced Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome
(ARDS)
1. The guideline committee recommends that clinicians target a tidal volume of 6 mL/kg (predicted) body weight in
patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). (Grade 1B)
2. The guideline committee recommends that plateau pressures be measured in patients with ALI/ARDS and that
the initial upper limit goal for plateau pressures in a passively inflated patient be <30 chest="chest" cm="cm" h2o.="h2o." p="p" wall="wall">compliance should be considered in the assessment of plateau pressure. (Grade 1C)
3. The guideline committee recommends that hypercapnia (allowing partial pressure of arterial carbon dioxide
[PaCO2] to increase above its pre-morbid baseline, so-called permissive hypercapnia) be allowed in patients with
ALI/ARDS if needed to minimize plateau pressures and tidal volumes. (Grade 1C)
4. The guideline committee recommends that positive end-expiratory pressure (PEEP) be set so as to avoid
extensive lung collapse at end-expiration. (Grade 1C)
5. The guideline committee suggests prone positioning in ARDS patients requiring potentially injurious levels of
fraction of inspired oxygen (FIO2) or plateau pressure who are not at high risk for adverse consequences of
positional changes in those facilities who have experience with such practices. (Grade 2C)
6a. Unless contraindicated, the guideline committee recommends mechanically ventilated patients be maintained
with the head of the bed elevated to limit aspiration risk and to prevent the development of ventilator-associated
pneumonia. (Grade 1B)
3. The guideline committee recommends that hypercapnia (allowing partial pressure of arterial carbon dioxide
[PaCO2] to increase above its pre-morbid baseline, so-called permissive hypercapnia) be allowed in patients with
ALI/ARDS if needed to minimize plateau pressures and tidal volumes. (Grade 1C)
4. The guideline committee recommends that positive end-expiratory pressure (PEEP) be set so as to avoid
extensive lung collapse at end-expiration. (Grade 1C)
5. The guideline committee suggests prone positioning in ARDS patients requiring potentially injurious levels of
fraction of inspired oxygen (FIO2) or plateau pressure who are not at high risk for adverse consequences of
positional changes in those facilities who have experience with such practices. (Grade 2C)
6a. Unless contraindicated, the guideline committee recommends mechanically ventilated patients be maintained
with the head of the bed elevated to limit aspiration risk and to prevent the development of ventilator-associated
pneumonia. (Grade 1B)
6b. The guideline committee suggests that the head of bed is elevated approximately 30 to 45 degrees. (Grade
2C)
7. The guideline committee suggests that noninvasive mask ventilation (NIV) only be considered in that minority of
ALI/ARDS patients with mild-moderate hypoxemic respiratory failure (responsive to relatively low levels of pressure
support and PEEP) with stable hemodynamics who can be made comfortable and easily arousable, who are able to
protect the airway, spontaneously clear the airway of secretions, and are anticipated to recover rapidly from the
precipitating insult. A low threshold for airway intubation should be maintained. (Grade 2B)
8. The guideline committee recommends that a weaning protocol be in place, and mechanically ventilated patients
with severe sepsis undergo spontaneous breathing trials on a regular basis to evaluate the ability to discontinue
mechanical ventilation when they satisfy the following criteria: a) arousable; b) hemodynamically stable (without
vasopressor agents); c) no new potentially serious conditions; d) low ventilatory and end-expiratory pressure
requirements; and e) FIO2 requirements that could be safely delivered with a face mask or nasal cannula. If the
spontaneous breathing trial is successful, consideration should be given for extubation (see Appendix E in the
original guideline document). Spontaneous breathing trial options include a low level of pressure support,
continuous positive airway pressure (approximately 5 cm H2O) or a T-piece. (Grade 1A)
9. The guideline committee recommends against the routine use of the pulmonary artery catheter for patients with
ALI/ARDS. (Grade 1A)
10. To decrease days of mechanical ventilation and ICU length of stay the guideline committee recommends a
conservative fluid strategy for patients with established acute lung injury who do not have evidence of tissue
hypoperfusion. (Grade 1C)
B. Sedation, Analgesia, and Neuromuscular Blockade in Sepsis
1. The guideline committee recommends sedation protocols with a sedation goal when sedation of critically ill
mechanically ventilated patients with sepsis is required. (Grade 1B)
2. The guideline committee recommends intermittent bolus sedation or continuous infusion sedation to
predetermined end points (e.g., sedation scales) with daily interruption/lightening of continuous infusion
sedation with awakening and retitration if necessary for sedation administration to septic mechanically
ventilated patients. (Grade 1B)
3. The guideline committee recommends that neuromuscular blocking agents (NMBAs) be avoided if possible in
the septic patient due to the risk of prolonged neuromuscular blockade following discontinuation. If NMBAs must
be maintained, either intermittent bolus as required or continuous infusion with monitoring the depth of
blockade with train-of-four monitoring should be used. (Grade 1B)
C. Glucose Control
1. The guideline committee recommends that, following initial stabilization, patients with severe sepsis and
hyperglycemia who are admitted to the ICU receive intravenous (IV) insulin therapy to reduce blood glucose
levels. (Grade 1B)
2. The guideline committee suggests use of a validated protocol for insulin dose adjustments and targeting
glucose levels to the <150 2c="2c" dl="dl" mg="mg" p="p" rade="rade" range.="range.">3. The guideline committee recommends that all patients receiving intravenous insulin receive a glucose calorie
source and that blood glucose values be monitored every 1 to 2 hours until glucose values and insulin infusion
rates are stable and then every 4 hours thereafter. (Grade 1C)
4. The guideline committee recommends that low glucose levels obtained with point-of-care testing of capillary
blood be interpreted with caution, as such measurements may overestimate arterial blood or plasma glucose
values. (Grade 1B)
D. Renal Replacement
1. The guideline committee suggests that continuous renal replacement therapies and intermittent
hemodialysis are equivalent in patients with severe sepsis and acute renal failure. (Grade 2B)
2. The guideline committee suggests the use of continuous therapies to facilitate management of fluid balance
in hemodynamically unstable septic patients. (Grade 2D)
E. Bicarbonate Therapy
1. The guideline committee recommends against the use of sodium bicarbonate therapy for the purpose of
improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic
acidemia with pH >7.15. (Grade 1B)
F. Deep Vein Thrombosis Prophylaxis
1. The guideline committee recommends that severe sepsis patients receive deep vein thrombosis (DVT)
prophylaxis with either (a) low-dose unfractionated heparin (UFH) administered twice daily or three times daily
or (b) daily low-molecular weight heparin (LMWH) unless there are contraindications (i.e., thrombocytopenia,
severe coagulopathy, active bleeding, recent intracerebral hemorrhage). (Grade 1A)
2. The guideline committee recommends that septic patients who have a contraindication for heparin use
receive mechanical prophylactic device such as graduated compression stockings (GCS) or intermittent
compression devices (ICD) unless contraindicated. (Grade 1A)
3. The guideline committee suggests that in very high-risk patients such as those who have severe sepsis and
history of DVT, trauma, or orthopedic surgery, a combination of pharmacologic and mechanical therapy be used
unless contraindicated or not practical. (Grade 2C)
4. The guideline committee suggests that in patients at very high risk, LMWH be used rather than UFH as
LMWH is proven superior in other high-risk patients. (Grade 2C)
G. Stress Ulcer Prophylaxis (SUP)
1. The guideline committee recommends that stress ulcer prophylaxis (SUP) using H2 blocker (Grade 1A) or
proton pump inhibitor (Grade 1B) be given to patients with severe sepsis to prevent upper gastrointestinal
(GI) bleed. Benefit of prevention of upper GI bleed must be weighed against potential effect of an increased
2. The guideline committee recommends that septic patients who have a contraindication for heparin use
receive mechanical prophylactic device such as graduated compression stockings (GCS) or intermittent
compression devices (ICD) unless contraindicated. (Grade 1A)
3. The guideline committee suggests that in very high-risk patients such as those who have severe sepsis and
history of DVT, trauma, or orthopedic surgery, a combination of pharmacologic and mechanical therapy be used
unless contraindicated or not practical. (Grade 2C)
4. The guideline committee suggests that in patients at very high risk, LMWH be used rather than UFH as
LMWH is proven superior in other high-risk patients. (Grade 2C)
G. Stress Ulcer Prophylaxis (SUP)
1. The guideline committee recommends that stress ulcer prophylaxis (SUP) using H2 blocker (Grade 1A) or
proton pump inhibitor (Grade 1B) be given to patients with severe sepsis to prevent upper gastrointestinal
(GI) bleed. Benefit of prevention of upper GI bleed must be weighed against potential effect of an increased
stomach pH on development of ventilator-associated pneumonia.
H. Selective Digestive Tract Decontamination (SDD)
1. The guideline committee was evenly split on the issue of selective digestive tract decontamination (SDD),
with equal numbers weakly in favor and against recommending the use of SDD (see Appendix H of the original
guideline document). The committee therefore chose not to make a recommendation for the use of SDD
specifically in severe sepsis at this time. The final consensus on use of SDD in severe sepsis was achieved at
the last nominal committee meeting and subsequently approved by the entire committee.
I. Consideration for Limitation of Support
1. The guideline committee recommends that advance care planning, including the communication of likely
outcomes and realistic goals of treatment, be discussed with patients and families. (Grade 1D)
Pediatric Considerations in Severe Sepsis
A. Antibiotics
1. The guideline committee recommends antibiotics be administered within one hour of the identification of
severe sepsis, after appropriate cultures have been obtained. (Grade 1D)
B. Mechanical Ventilation
The guideline committee has no graded recommendations.
C. Fluid Resuscitation
1. The guideline committee suggests initial resuscitation begin with infusion of crystalloids with boluses of 20
mL/kg over 5 to 10 minutes, titrated to clinical monitors of cardiac output, including heart rate, urine output,
capillary refill, and level of consciousness. (Grade 2C)
D. Vasopressors/Inotropes (should be used in volume loaded patients with fluid refractory shock)
1. The guideline committee suggests dopamine as the first choice of support for the pediatric patient with
hypotension refractory to fluid resuscitation. (Grade 2C)
2. The guideline committee suggests that patients with low cardiac output and elevated systemic vascular
resistance states (cool extremities, prolonged capillary refill, decreased urine output but normal blood pressure
following fluid resuscitation) be given dobutamine. (Grade 2C)
E. Therapeutic End Points
1. The guideline committee suggests that the therapeutic end points of resuscitation of septic shock be
normalization of the heart rate, capillary refill of <2 between="between" differential="differential" no="no" normal="normal" p="p" pulses="pulses" seconds="seconds" with="with">peripheral and central pulses, warm extremities, urine output >1 mL/kg/hour, and normal mental status.
(Grade 2C)
F. Approach to Pediatric Septic Shock
Figure 1 in the original guideline document shows a flow diagram summarizing an approach to pediatric septic
shock.
G. Steroids
1. The guideline committee suggests that hydrocortisone therapy be reserved for use in children with
catecholamine resistance and suspected or proven adrenal insufficiency. (Grade 2C)
H. Protein C and Activated Protein C
1. The guideline committee recommends against the use rhAPC in children. (Grade 1B)
I. DVT Prophylaxis
1. The guideline committee suggests the use of DVT prophylaxis in post-pubertal children with severe sepsis.
(Grade 2C)
J. Stress Ulcer Prophylaxis
The guideline committee has no graded recommendations.
K. Renal Replacement Therapy
The guideline committee has no graded recommendations.
L. Glycemic Control
The guideline committee has no graded recommendations.
M. Sedation/Analgesia
1. The guideline committee recommends sedation protocols with a sedation goal when sedation of critically ill
mechanically ventilated patients with sepsis is required. (Grade 1D)
N. Blood Products
The guideline committee has no graded recommendations.
O. Intravenous Immunoglobulin
1. The guideline committee suggests that immunoglobulin may be considered in children with severe sepsis.
(Grade 2C)
P. Extracorporeal Membrane Oxygenation (ECMO)
1. The guideline committee suggests that use of extracorporeal membrane oxygenation (ECMO) be limited to
refractory pediatric septic shock and/or respiratory failure that cannot be supported by conventional therapies.
(Grade 2C)
Definitions:
The guideline committee has no graded recommendations.
O. Intravenous Immunoglobulin
1. The guideline committee suggests that immunoglobulin may be considered in children with severe sepsis.
(Grade 2C)
P. Extracorporeal Membrane Oxygenation (ECMO)
1. The guideline committee suggests that use of extracorporeal membrane oxygenation (ECMO) be limited to
refractory pediatric septic shock and/or respiratory failure that cannot be supported by conventional therapies.
(Grade 2C)
Definitions:
Grades of Evidence
Grade A: Randomized controlled trial (RCT)
Grade B: Downgraded RCT or upgraded observational studies
Grade C: Well-done observational studies
Grade D: Case series or expert opinion
Levels of Recommendations
Grade 1 (Strong): A recommendation in favor of an intervention reflects that the desirable effects of adherence to a
recommendation (beneficial health outcomes, less burden on staff and patients, and cost savings) will clearly outweigh
the undesirable effects (harms, more burden and greater costs).
Grade 2 (Weak): A recommendation in favor of an intervention indicates that the desirable effects of adherence to a
recommendation probably will outweigh the undesirable effects, but the panel is not confident about these tradeoffs –
either because some of the evidence is low-quality (and thus there remains uncertainty regarding the benefits and
risks) or the benefits and downsides are closely balanced.
Clinical Algorithm(s)
An algorithm is provided in the original guideline for the "Approach to Pediatric Shock."
Evidence Supporting the Recommendations
Type of Evidence Supporting the Recommendations
The type of supporting evidence is identified and graded for each recommendation (see Major Recommendations).
Benefits/Harms of Implementing the Guideline Recommendations
Potential Benefits
Appropriate management of patients with severe sepsis and septic shock
Potential Harms
l There is a certain increased risk of bleeding with administration of recombinant human activated protein C (rhAPC)
which may be higher in surgical patients and in the context of invasive procedures.
l Heparin increases the risk of bleeding.
l Side effects of steroids include increased risk of infection and myopathy.
l Administration of hydroxyethyl starch may increase the risk of acute renal failure in patients with sepsis.
l Source control interventions may cause further complications such as bleeding, fistulas, or inadvertent organ
injury.
Contraindications
Contraindications
Recombinant human activated protein C (rhAPC) is contraindicated in patients with the following clinical situations in
which bleeding could be associated with a high risk of death or significant morbidity.
l Active internal bleeding
l Recent (within 3 months) hemorrhagic stroke
l Recent (within 2 months) intracranial or intraspinal surgery, or severe head trauma
l Trauma with an increased risk of life-threatening bleeding
l Presence of an epidural catheter
l Intracranial neoplasm or mass lesion or evidence of cerebral herniation
l Known hypersensitivity to rhAPC or any component of the product
See labeling instructions for relative contraindications. The committee recommends that platelet count be maintained
at >30,000 or greater during infusion of rhAPC.
The use of hypercapnia is limited in patients with preexisting metabolic acidosis and is contraindicated in patients with
increased intracranial pressure.
Thrombocytopenia, severe coagulopathy, active bleeding, and recent intracerebral hemorrhage are contraindications to
the use of heparin.
Qualifying Statements
Qualifying Statements
See labeling instructions for relative contraindications. The committee recommends that platelet count be maintained
at >30,000 or greater during infusion of rhAPC.
The use of hypercapnia is limited in patients with preexisting metabolic acidosis and is contraindicated in patients with
increased intracranial pressure.
Thrombocytopenia, severe coagulopathy, active bleeding, and recent intracerebral hemorrhage are contraindications to
the use of heparin.
Qualifying Statements
Qualifying Statements
These recommendations are intended to provide guidance for the clinician caring for a patient with severe sepsis or
septic shock. Recommendations from these guidelines cannot replace the clinician's decision-making capability when he
or she is provided with a patient's unique set of clinical variables. Most of these recommendations are appropriate for
the severe sepsis patient in both the intensive care unit (ICU) and non-ICU settings. In fact the committee believes
that, currently, the greatest outcome improvement can be made through education and process change for those caring
for severe sepsis patients in the non-ICU setting and across the spectrum of acute care. It should also be noted that
resource limitations in some institutions and countries may prevent physicians from accomplishing particular
recommendations.
Implementation of the Guideline
Description of Implementation Strategy
An implementation strategy was not provided.
Implementation Tools
Audit Criteria/Indicators
Chart Documentation/Checklists/Forms
Clinical Algorithm
Foreign Language Translations
Patient Resources
Personal Digital Assistant (PDA) Downloads
Pocket Guide/Reference Cards
Resources
Wall Poster
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.
Institute of Medicine (IOM) National Healthcare Quality Report Categories
IOM Care Need
Getting Better
IOM Domain
Effectiveness
Timeliness
Identifying Information and Availability
Bibliographic Source(s)
Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R,
Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT,
Townsend S, Vender JS, Zimmerman JL, Vincent JL. Surviving Sepsis Campaign: International guidelines for
management of severe sepsis and septic shock: 2008. Intensive Care Med 2008 Jan;34(1):17-60. [341 references]
PubMed
Adaptation
Not applicable: The guideline was not adapted from another source.
Date Released
2004 (revised 2008 Jan)
Guideline Developer(s)
Society of Critical Care Medicine - Professional Association
Source(s) of Funding
The Surviving Sepsis Campaign (SSC) is partially funded by unrestricted educational industry grants, including those
from Edwards LifeSciences, Eli Lilly and Company, and Philips Medical Systems. SSC also received funding from the
Coalition for Critical Care Excellence of the Society of Critical Care Medicine. The great majority of industry funding has
come from Eli Lilly and Company.
Current industry funding for the Surviving Sepsis Campaign is directed to the performance improvement initiative. No
industry funding was used for committee meetings. No honoraria were provided to committee members. The revision
process was funded primarily by the Society of Critical Care Medicine, with the sponsoring professional organizations
providing travel expenses for their designated delegate to the guidelines revision meeting where needed.
Guideline Developer(s)
Society of Critical Care Medicine - Professional Association
Source(s) of Funding
The Surviving Sepsis Campaign (SSC) is partially funded by unrestricted educational industry grants, including those
from Edwards LifeSciences, Eli Lilly and Company, and Philips Medical Systems. SSC also received funding from the
Coalition for Critical Care Excellence of the Society of Critical Care Medicine. The great majority of industry funding has
come from Eli Lilly and Company.
Current industry funding for the Surviving Sepsis Campaign is directed to the performance improvement initiative. No
industry funding was used for committee meetings. No honoraria were provided to committee members. The revision
process was funded primarily by the Society of Critical Care Medicine, with the sponsoring professional organizations
providing travel expenses for their designated delegate to the guidelines revision meeting where needed.
Guideline Committee
2008 Surviving Sepsis Campaign (SSC) Guidelines Committee
Composition of Group That Authored the Guideline
Authors: R. Phillip Dellinger; Mitchell M. Levy; Jean M. Carlet; Julian Bion; Margaret M. Parker; Roman Jaeschke; Konrad
Reinhart; Derek C. Angus; Christian Brun-Buisson; Richard Beale; Thierry Calandra; Jean-Francois Dhainaut; Herwig
Gerlach; Maurene Harvey; John J. Marini; John Marshall; Marco Ranieri; Graham Ramsay; Jonathan Sevransky; B. Taylor
Thompson; Sean Townsend; Jeffrey S. Vender; Janice L. Zimmerman; Jean-Louis Vincent
Committee Members: R. Phillip Dellinger (Chair), Tom Ahrens, American Association of Critical-Care Nurses; Naoki
Aikawa, Japanese Association for Acute Medicine; Derek Angus; Djillali Annane; Richard Beale; Gordon R. Bernard;
Julian Bion, European Society of Intensive Care Medicine; Christian Brun-Buisson; Thierry Calandra; Joseph Carcillo;
Jean Carlet, European Society of Intensive Care Medicine; Terry Clemmer; Jonathan Cohen; Edwin A. Deitch, Surgical
Infection Society; Jean-Francois Dhainaut; Mitchell Fink; Satoshi Gando, Japanese Association for Acute Medicine;
Herwig Gerlach, European Society of Intensive Care Medicine; Gordon Guyatt, Grades of Recommendation, Assessment,
Development and Evaluation (GRADE) Group; Maurene Harvey; Jan Hazelzet; Hiroyuki Hirasawa, Japanese Society of
Intensive Care Medicine; Steven M. Hollenberg; Michael Howell; Roman Jaeschke, Grades of Recommendation,
Assessment, Development and Evaluation (GRADE) Group; Robert Kacmarek; Didier Keh; Mitchell M. Levy, Society of
Critical Care Medicine; Jeffrey Lipman; John J. Marini; John Marshall; Claude Martin, European Society of Intensive Care
Medicine; Henry Masur; Steven Opal; Tiffany M Osborn, American College of Emergency Physicians; Giuseppe
Pagliarello, Canadian Critical Care Society; Margaret Parker; Joseph Parrillo; Graham Ramsay, European Society of
Intensive Care Medicine; Adrienne Randolph; Marco Ranieri, European Society of Intensive Care Medicine; Robert C.
Read, European Society of Clinical Microbiology and Infectious Diseases; Konrad Reinhart, German Sepsis Society;
Andrew Rhodes, European Society of Intensive Care Medicine; Emmanuel Rivers, American College of Emergency
Physicians; Gordon Rubenfeld; Jonathan Sevransky; Eliezer Silva, Latin American Sepsis Institute; Charles L. Sprung,
European Society of Intensive Care Medicine; B. Taylor Thompson; Sean R. Townsend; Jeffery Vender, American College
of Chest Physicians; Jean-Louis Vincent, International Sepsis Forum; Tobias Welte, European Respiratory Society;
Janice Zimmerman
Financial Disclosures/Conflicts of Interest
For both the 2004 and the 2006/2007 efforts there were no members of the committee from industry, no industry input
into guidelines development, and no industry presence at any of the meetings. Industry awareness or comment on the
recommendations was not allowed. No member of the guideline committee received any honoraria for any role in the
2004 or 2006/2007 guidelines process. The committee considered the issue of recusement of individual committee
members during deliberation and decision making in areas where committee members had either financial or academic
competing interests; however, consensus as to threshold for exclusion could not be reached. Alternatively, the
committee agreed to ensure full disclosure and transparency of all committee members' potential conflicts at time of
publication (see following):
Dr. Dellinger has consulted for AstraZeneca, Talecris, and B Braun. He has received honoraria from Eli Lilly (2), Brahms
(2), INO Therapeutics (1), Pulsion (1), and bioMerieux (1). He has also received grant support from AstraZeneca and
Artisan.
Dr. Levy has received honoraria from Eli Lilly and Edwards Lifesciences. He has also received grant support from Phillips
Medical Systems, Edwards Lifesciences, Phillips Medical Systems, Novartis, Biosite, and Eisai.
Dr. Carlet has consulted for Forrest, Wyeth, Chiron, bioMerieux, and GlaxoSmithKline. He has also received honoraria
from Eli Lilly, Becton Dickinson, Jansen, Cook, AstraZeneca, Hutchinson, Bayer, Gilead, MSD, and Targanta.
Dr. Bion has not disclosed any potential conflicts of interest.
Dr. Parker has consulted for Johnson & Johnson.
Dr. Jaeschke has received honoraria from AstraZeneca, Boehringer, Eli Lilly, GlaxoSmithKline, and MSD.
Dr. Reinhart has consulted for Eli Lilly and Edwards Lifesciences. He has also received honoraria from B Braun and
royalties from Edwards Lifesciences.
Dr. Angus has consulted for or received speaking fees from AstraZeneca, Brahms Diagnostica, Eisai, Eli Lilly,
GlaxoSmithKline, OrthoBiotech, Takeda, and Wyeth-Ayerst. He has also received grant support from GlaxoSmithKline,
OrthoBiotech, and Amgen.
Dr. Brun-Buisson has not disclosed any potential conflicts of interest.
Dr. Beale has received honoraria from Eisai and speaking fees (paid to university) from Lilly UK, Philips, Lidco, and
Chiron.
Dr. Calandra has consulted for Baxter, received honoraria from Roche Diagnostics, and grant support from Baxter and
Roche Diagnostics. He also served on the advisory board for Biosite.
Dr. Dhainaut has consulted for Eli Lilly and Novartis. He has also received honoraria from Eli Lilly.
Dr. Gerlach has not disclosed any potential conflicts of interest.
Ms. Harvey has not disclosed any potential conflicts of interest.
Dr. Marini has consulted for KCI and received honoraria from Maquet.
Dr. Marshall has consulted for Becton-Dickinson, Takeda, Pfizer, Spectral Diagnostics, Eisai, and Leo-Pharma. He has
also received honoraria from Spectral Diagnostics.
Dr. Ranieri has served on the advisory board for Maquet and received support for a sponsored trial from Eli Lilly. He has
also received grant support from Tyco, Draeger, and Hamilton.
Roche Diagnostics. He also served on the advisory board for Biosite.
Dr. Dhainaut has consulted for Eli Lilly and Novartis. He has also received honoraria from Eli Lilly.
Dr. Gerlach has not disclosed any potential conflicts of interest.
Ms. Harvey has not disclosed any potential conflicts of interest.
Dr. Marini has consulted for KCI and received honoraria from Maquet.
Dr. Marshall has consulted for Becton-Dickinson, Takeda, Pfizer, Spectral Diagnostics, Eisai, and Leo-Pharma. He has
also received honoraria from Spectral Diagnostics.
Dr. Ranieri has served on the advisory board for Maquet and received support for a sponsored trial from Eli Lilly. He has
also received grant support from Tyco, Draeger, and Hamilton.
Dr. Ramsay has consulted for Edwards Lifesciences and Respironics.
Dr. Sevransky has not disclosed any potential conflicts of interest.
Dr. Thompson has consulted for Eli Lilly, Abbott, and AstraZeneca. He has also received grant support from the NIH for
a study on computerized glucose control.
Dr. Townsend has not disclosed any potential conflicts of interest.
Dr. Vender has consulted and received honoraria from Eli Lilly.
Dr. Zimmerman has not disclosed any potential conflicts of interest.
Dr. Vincent has consulted for AstraZeneca, Biosite, bioMerieux, Edwards Lifesciences, Eli Lilly Eisai, Ferring,
GlaxoSmithKline, Intercell, Merck, Novartis, NovoNordisk, Organon, Pfizer, Phillips Medical Systems, Roche Diagnostics,
Spectral Diagnostics, Takeda, and WyethLederle. He has also received honoraria from Eli Lilly, Edwards Lifesciences,
Eisai, GlaxoSmithKline, Novartis, NovoNordisk, and Pfizer.
Guideline Endorser(s)
German Sepsis Society - Disease Specific Society
Latin American Sepsis Institute - Disease Specific Society
Guideline Status
This is the current release of the guideline.
This guideline updates a previous version: Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-
Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM. Surviving sepsis
campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004 Mar;32(3):858-73.
Guideline Availability
Electronic copies: Available in Portable Document Format (PDF) from the Society of Critical Care Medicine (SCCM) Web
site .
Print copies: Available from the Society of Critical Care Medicine, 701 Lee Street, Suite 200, Des Plaines, IL 60016;
Phone: (847) 827-6869; Fax: (847) 827-6886; on-line through the SCCM Bookstore .
Availability of Companion Documents
The following is available:
l Dorman T, Angood PB, Angus DC, Clemmer TP, Cohen NH, Durbin CG Jr, Falk JL, Helfaer MA, Haupt MT, Horst HM,
Ivy ME, Ognibene FP, Sladen RN, Grenvik AN, Napolitano LM. Guidelines for critical care medicine training and
continuing medical education. Crit Care Med 2004 Jan;32(1):263-72.
Electronic copies: Available in Portable Document Format (PDF) from the Society of Critical Care Medicine (SCCM) Web
site .
Print copies: Available from the Society of Critical Care Medicine, 701 Lee Street, Suite 200, Des Plaines, IL 60016;
Phone: (847) 827-6869; Fax: (847) 827-6886; on-line through the SCCM Bookstore
The following are also available:
l Guidelines for management of severe sepsis and septic shock. Pocket guide. 2008 Jan. Electronic copies: Available
in Portable Document Format (PDF) from the Surviving Sepsis Campaign Web site .
l Guidelines for management of severe sepsis and septic shock. Wall poster. 2008 Jan. Electronic copies: Available
in Portable Document Format (PDF) from the Surviving Sepsis Campaign Web site .
Additional implementation tools, including quality indicators, measures, screening tools, a tool for Personal Digital
Assistants (PDAs), and a chart review database, are available from the Surviving Sepsis Campaign Web site .
Several of the tools are available in Chinese, as well as English.
Patient Resources
The following is available:
l Sepsis: what you should know. Information about sepsis for individuals and families. Available from the Surviving
Sepsis Campaign Web site .
Please note: This patient information is intended to provide health professionals with information to share with their patients to help them
better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC
to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then
to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to
their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals
included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether
The following is available:
l Sepsis: what you should know. Information about sepsis for individuals and families. Available from the Surviving
Sepsis Campaign Web site .
Please note: This patient information is intended to provide health professionals with information to share with their patients to help them
better understand their health and their diagnosed disorders. By providing access to this patient information, it is not the intention of NGC
to provide specific medical advice for particular patients. Rather we urge patients and their representatives to review this material and then
to consult with a licensed health professional for evaluation of treatment options suitable for them as well as for diagnosis and answers to
their personal medical questions. This patient information has been derived and prepared from a guideline for health care professionals
included on NGC by the authors or publishers of that original guideline. The patient information is not reviewed by NGC to establish whether
or not it accurately reflects the original guideline's content.
NGC Status
This NGC summary was completed by ECRI on June 22, 2004. The information was verified by the guideline developer
on August 9, 2004. This summary was updated by ECRI on November 14, 2006, following the U.S. Food and Drug
Administration (FDA) advisory on Xigris. This summary was updated by ECRI on January 29, 2007, following the U.S.
Food and Drug Administration advisory on erythropoiesis stimulating agents. This summary was updated by ECRI
Institute on June 22, 2007 following the U.S. Food and Drug Administration (FDA) advisory on heparin sodium injection.
This summary was updated by ECRI Institute on July 9, 2007, following the FDA advisory on erythropoiesis stimulating
agents. This summary was updated by ECRI Institute on February 26, 2008 following the U.S. Food and Drug
Administration advisory/voluntary market withdrawal of the liquid formulation of Leukine (sargramostim). This summary
was updated by ECRI Institute on March 13, 2008 following the updated FDA advisory on heparin sodium injection. This
summary was updated by ECRI Institute on March 21, 2008 following the FDA advisory on Erythropoiesis Stimulating
Agents. This summary was updated by ECRI Institute on August 15, 2008 following the U.S. Food and Drug
Administration advisory on Erythropoiesis Stimulating Agents (ESAs). This NGC summary was updated by ECRI Institute
on June 11, 2008. The updated information was verified by the guideline developer on August 15, 2008. This summary
was updated by ECRI Institute on December 26, 2008 following the FDA advisory on Innohep (tinzaparin). This
summary was updated by ECRI Institute on April 1, 2010 following the U.S. Food and Drug Administration advisory on
Erythropoiesis-Stimulating Agents (ESAs). This summary was updated by ECRI Institute on July 26, 2010 following the
U.S. Food and Drug Administration (FDA) advisory on Proton Pump Inhibitors (PPI). This summary was updated by ECRI
Institute on July 27, 2010 following the FDA drug safety communication on Heparin.
Copyright Statement
This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright
restrictions.
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