The Surviving Sepsis Campaign Guidelines Committee Members of the SSC Guidelines .. key committee members was held to finalize the draft doc-. Guidelines for Management of Severe Sepsis and Septic Shock: , condensed from Dellinger RP, Levy MM, Rhodes A, et al: Surviving Sepsis Campaign. Objective: To provide an update to the “Surviving Sepsis Cam- Members of the SSC Guidelines Committee and Pediatric Sub- group are listed in tions appear in the printed text and are provided in the HTML and PDF ver- sions of.
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The Surviving Sepsis Campaign recently developed and published an updated version in of the international guidelines for the assessment and. OBJECTIVE: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in The Surviving Sepsis Campaign recently developed and published an updated version in of the international guidelines for the.
The entire guidelines process was groups: A stand-alone general care of the critically ill patient and considered high priority inmeeting was held for all subgroup heads, co- and vice-chairs, severe sepsis; and 3 pediatric considerations. Teleconferences and electronic-based Results: Key recommendations and suggestions, listed by cat-discussion among subgroups and among the entire committee egory, include: Supplemental digital content is available for this article.
Louis, Missouri. Digital Content 1 http: For additional information regarding this article, contact R. Dellinger16 University of Pittsburgh, Pittsburgh, Pennsylvania. Dellinger-Phil CooperHealth.
Recommendations specific to pediatric severeto decrease norepinephrine dose but should not be used as sepsis include: Strong agreement existed among a large cohortcoronary artery disease, or acute hemorrhage 1B ; low tidal of international experts regarding many level 1 recommenda-volume 1A and limitation of inspiratory plateau pressure 1B tions for the best care of patients with severe sepsis.
Althoughfor acute respiratory distress syndrome ARDS ; application of a significant number of aspects of care have relatively weakat least a minimal amount of positive end-expiratory pressure support, evidence-based recommendations regarding the PEEP in ARDS 1B ; higher rather than lower level of PEEP acute management of sepsis and septic shock are the founda-for patients with sepsis-induced moderate or severe ARDS tion of improved outcomes for this important group of critically 2C ; recruitment maneuvers in sepsis patients with severe ill patients.
Crit Care Med ; Participation and endorsement: Critical Care Medicine www. Dellinger et alDr. Dellinger consulted for Biotest immunoglobulin concentrate available in Dr. Rhodes consulted for Eli Lilly with monetary compensation paid to him- ; he has a pending patent for a bed backrest elevation monitor. Jaeschke has disclosed that he has no potential conflicts of interest.
Her institutionsuch as data monitoring boards, statistical analysis from Orion, and for Eli receives grant support from the National Institutes of Health Research,Lilly; he is an author on manuscripts describing early goal-directed therapy, Health Technology Assessment Programme-United Kingdom trial doc-and believes in the concept of minimally invasive hemodynamic monitoring.
Salary paid through the NIHR government funded nonindustry grant. Grant awarded to chief investigator fromDr. She is a trial clinician for ProMISe.
His nonfinancial disclosures include being the princi-pal investigator of a completed investigator-led multicenter randomized con- Dr. Nunnally received a stipend for a chapter on diabetes mellitus; he is antrolled trial assessing the early guided benefit to risk of NIRS tissue oxygen author of editorials contesting classic tight glucose control. Townsend is an advocate for healthcare quality improvement. He received hono-Dr. Critical Care Nurses one night hotel coverage at national conference.
Sevransky received grant support to his institution from Sirius Genom- for sepsis-induced tissue hypoperfusion. He maintains that protocols serve as useful Dr. Machado reports unrestricted grant support paid to her institution forreminders to busy clinicians to consider certain therapies in patients with Surviving Sepsis Campaign implementation in Brazil Eli Lilly do Brasil ;sepsis or other life-threatening illness. Sprung received grants paid to his institution from Artisan Pharma Dr.
Study terminated before patients enrolled. He hasnational Sepsis Forum as of Oct. He received grant support www. His nonfinancial dis- closures include authorship of the position statement on fluid resuscitationDr. Beale received compensation for his participation as board member for from the ESICM task force on colloids yet to be finalized. Moreno consulted for bioMerieux expert meeting. He is the authorHearing , Eisai eritoran through leader touch plan in Brussels , Eli Lilly of several manuscripts defining sepsis and stratification of the patient with Lunchtime Symposium, Vienna , Covidien adult monitoring advisory board sepsis.
Severe sepsis and septic shock are major health- infection together with systemic manifestations of infection. Similar to polytrauma, acute myocardial Throughout this manuscript and the performance improve-infarction, or stroke, the speed and appropriateness of therapy ment bundles, which are included, a distinction is madeadministered in the initial hours after severe sepsis develops between definitions and therapeutic targets or thresholds.
Sep-are likely to influence outcome. Most of these recommendations are appro- bundles for the use of vasopressors. The use of definition vs.
In fact, the committee believes that the greatest outcome be evident throughout this article. Septic shock is defined asimprovement can be made through education and process sepsis-induced hypotension persisting despite adequate fluidchange for those caring for severe sepsis patients in the non- resuscitation.
Sepsis-induced tissue hypoperfusion is definedICU setting and across the spectrum of acute care. Resource as infection-induced hypotension, elevated lactate, or oliguria. History of the GuidelinesThus, these recommendations are intended to be best practice These clinical practice guidelines are a revision of the the committee considers this a goal for clinical practice and SSC guidelines for the management of severe sepsis and septicnot created to represent standard of care.
The Surviving Sepsis shock 7. The initial SSC guidelines were published in Campaign SSC Guidelines Committee hopes that over time, 8 and incorporated the evidence available through the endparticularly through education programs and formal audit of The publication analyzed evidence availableand feedback performance improvement initiatives, the guide- through the end of The most current iteration is basedlines will influence bedside healthcare practitioner behavior on updated literature search incorporated into the evolvingthat will reduce the burden of sepsis worldwide.
Dellinger et alSelection and Organization of Committee Members Grading of RecommendationsThe selection of committee members was based on inter- We advised the authors to follow the principles of the Gradingest and expertise in specific aspects of sepsis. Each sponsoring organiza- strength of recommendations Tables 3 and 4. Thetion appointed a representative who had sepsis expertise. Addi- SSC Steering Committee and individual authors collaboratedtional committee members were appointed by the co-chairs with GRADE representatives to apply the system during theand executive committee to create continuity with the previous SSC guidelines revision process.
Four clinicians with experience all discussions and deliberations among the guidelines com-in the GRADE process application referred to in this docu- mittee members as to grading decisions. Each group was Keeping the rating of quality of evidence and strength ofresponsible for drafting the initial update to the edition recommendation explicitly separate constitutes a crucial andin their assigned area with major additional elements of infor- defining feature of the GRADE approach.
This system classifiesmation incorporated into the evolving manuscript through quality of evidence as high grade A , moderate grade B , lowyear-end and early Randomized trials begin With input from the EBM group, an initial group meet- as high-quality evidence but may be downgraded due toing was held to establish procedures for literature review and limitations in implementation, inconsistency, or imprecision ofdevelopment of tables for evidence analysis. Committees and the results, indirectness of the evidence, and possible reportingtheir subgroups continued work via phone and the Internet.
Examples of indirectness of the evidenceSeveral subsequent meetings of subgroups and key indi- include population studied, interventions used, outcomesviduals occurred at major international meetings nominal measured, and how these relate to the question of interest. Ultimately, a meeting of all group the basis of a large magnitude of effect. An example of this isheads, executive committee members, and other key commit- the quality of evidence for early administration of antibiotics.
Search Techniques The GRADE system classifies recommendations as strongA separate literature search was performed for each clearly grade 1 or weak grade 2. The factors influencing this deter-defined question. The committee chairs worked with subgroup mination are presented in Table 4. The assignment of strongheads to identify pertinent search terms that were to include, or weak is considered of greater clinical importance than aat a minimum, sepsis, severe sepsis, septic shock, and sepsis syn- difference in letter level of quality of evidence.
Thus, a strong recommendation in favor oferal topic-related searches or recent trials. The potential drawbacks of making strong recommenda-Other databases were optional ACP Journal Club, Evidence- tions in the presence of low-quality evidence were taken intoBased Medicine Journal, Cochrane Registry of Controlled account.
A weak recommendation in favor of an interventionClinical Trials, International Standard Randomized Controlled indicates the judgment that the desirable effects of adherenceTrial Registry [http: Where appropriate, available evidence was either because some of the evidence is low quality and thussummarized in the form of evidence tables. Special ArticleTable 1. Diagnostic Criteria for Sepsis Infection, documented or suspected, and some of the following: General variables Fever Diagnostic criteria for sepsis in the pediatric population are signs and symptoms of inflammation plus infection with hyper- or hypothermia rectal temperature In the opinion of the committee, characteristics that make the recommendation less applica-these recommendations were not conducive for the GRADE ble.
A strong recommendation does not automatically implyprocess.
For example, the strong recommendationCritical Care Medicine www. Dellinger et alTable 2. Theverified by practice data.
Draft recommendationsefforts. Several members of the committee were trained in were distributed to the entire committee and finalized duringthe use of GRADEpro software, allowing more formal use of an additional nominal group meeting in Berlin in Octoberthe GRADE system Rules were distributed concerning Deliberations and decisions were then recirculated to theassessing the body of evidence, and GRADE representatives entire committee for approval.
At the discretion of the chairsTable 3. 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 2 with no plausible confounders 2. Very large magnitude of effect with relative risk 5 and no threats to validity by two levels 3. Special ArticleTable 4.
Factors Determining Strong vs. Weak Recommendation What Should be Considered Recommended Process High or moderate evidence The higher the quality of evidence, the more likely a strong recommendation.
Is there high or moderate quality evidence? Certainty about the balance of benefits vs. The larger the difference between the desirable and undesirable consequences and harms and burdens Is there certainty? The smaller the net benefit and the lower the certainty for that benefit, the more likely a weak recommendation. Certainty in or similar values The more certainty or similarity in values and preferences, the more likely a strong Is there certainty or similarity?
Resource implications The lower the cost of an intervention compared to the alternative and other costs related to Are resources worth expected benefits? They were required to work withinof recommendations or assigning strength of evidence were their group with full disclosure when a topic for which theyresolved by formal voting within subgroups and at nominal had relevant COI was discussed, and they were not allowedgroup meetings. The manuscript was edited for style and form to serve as group head.
At the time of final approval of theby the writing committee with final approval by subgroup document, an update of the COI statement was required. Noheads and then by the entire committee. To satisfy peer review additional COI issues were reported that required furtherduring the final stages of manuscript approval for publication, adjudication.
We recommend the protocolized, quantitative resuscitation ofof the committee represented industry; there was no industry patients with sepsis- induced tissue hypoperfusion defined ininput into guidelines development; and no industry represen- this document as hypotension persisting after initial fluid chal-tatives were present at any of the meetings.
This proto-or comment on the recommendations was not allowed. No col should be initiated as soon as hypoperfusion is recognizedmember of the guidelines committee received honoraria for and should not be delayed pending ICU admission.
During theany role in the , , or guidelines process. We suggest targeting resuscitation to normalize lactate in On initial review, 68 financial conflict of interest COI patients with elevated lactate levels as a marker of tissuedisclosures and 54 nonfinancial disclosures were submitted hypoperfusion grade 2C.
In a randomized, controlled, single-center study,not relevant to the guidelines content process. Nine who early quantitative resuscitation improved survival for emer-were determined to have COI financial and nonfinancial gency department patients presenting with septic shock COI was discussed.
Nine were judged as having conflicts This strategy, termed early goal-directed therapy, was evalu-that could not be resolved solely by reassignment. One of ated in a multicenter trial of patients with severe sepsis inthese individuals was asked to step down from the commit- eight Chinese centers This trial reported a The other eight were assigned to the groups in which reduction in day mortality survival rates, A large number of other observational studies using generally can be relied upon as supporting positive response tosimilar forms of early quantitative resuscitation in comparable fluid loading.
Either intermittent or continuous measurementspatient populations have shown significant mortality reduction of oxygen saturation were judged to be acceptable. As part of performance improvement programs, attempts to achieve the Scvo2 or Svo2 goal are options.
The publicationto be recommended physiologic targets for resuscitation. Table 5. Initial Resuscitation and Infection Issues A. Initial Resuscitation 1.
Goals during the first 6 hrs of resuscitation: In patients with elevated lactate levels targeting resuscitation to normalize lactate grade 2C. Screening for Sepsis and Performance Improvement 1. Hospital—based performance improvement efforts in severe sepsis UG. Diagnosis 1. Imaging studies performed promptly to confirm a potential source of infection UG.
Antimicrobial Therapy 1. Antimicrobial regimen should be reassessed daily for potential deescalation grade 1B. Combination empirical therapy for neutropenic patients with severe sepsis grade 2B and for patients with difficult-to-treat, multidrug- resistant bacterial pathogens such as Acinetobacter and Pseudomonas spp. For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for P.
A combination of beta-lactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniae infections grade 2B. Continued www. Special ArticleTable 5. Continued Recommendations: Initial Resuscitation and Infection Issues 4b. De-escalation to the most appropriate single E therapy should be performed as soon as the susceptibility profile is known grade 2B.
Duration of therapy typically 7—10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, bacteremia with S.
Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin grade 2C.
Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause UG. Source Control 1. A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 hr after the diagnosis is made, if feasible grade 1C. When infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred grade 2B.
When source control in a severely septic patient is required, the effective intervention associated with the least physiologic insult should be used eg, percutaneous rather than surgical drainage of an abscess UG. Infection Prevention 1a. Norepinephrine is preferred over other vasopressors because it's a potent vasoconstrictor without the adverse side effects of tachycardia and other dysrhythmias.
Current evidence suggests dopamine should only be used in select patients with a low risk of dysrhythmias or with bradycardia. If Mr. L's BP doesn't improve on norepinephrine, or if he requires additional BP support, the guidelines recommend vasopressin as an alternative, or added therapy.
L shows signs of low cardiac output despite adequate fluid resuscitation and MAP, the guidelines recommend the addition of dobutamine as first-choice inotrope to improve cardiac output and tissue perfusion.
L is started on norepinephrine administered through his CVC. His nurse carefully titrates the infusion with the goal to maintain his MAP at 65 mm Hg or more. The attending physician inserts a radial artery catheter to continuously monitor the patient's BP.
V hydrocortisone isn't recommended if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability; I. V hydrocortisone is suggested only if fluid resuscitation and vasopressor therapy are insufficient. L is in septic shock, he likely has developed relative adrenal insufficiency an inadequate stress response.
In addition, the guidelines suggest administering hydrocortisone in a continuous infusion instead of intermittent bolus doses. Following the new guidelines, Mr. L's attending physician orders a continuous infusion of hydrocortisone over a hour period.
L begins to have difficulty breathing and his nurse determines that he's agitated and confused. The nurse auscultates bibasilar crackles. Arterial blood gases are drawn and reveal he's acidotic and hypoxic. His nurse suspects he's developing ARDS. In ARDS, diffuse, inflammatory lung injury leads to increased pulmonary vascular permeability.
As a result, fluid leaks from the capillaries into the alveoli, which interferes with gas exchange. To reduce the work of breathing and improve oxygenation, Mr. L is endotracheally intubated and placed on mechanical ventilation. PEEP is used to help prevent end-expiratory alveolar collapse and optimize gas exchange. To keep him comfortable, Mr. L is maintained on continuous I. Daily sedation interruptions and awakenings help decrease the amount of time Mr. L is mechanically ventilated.
The new guidelines offer additional support for mechanically ventilated patients with sepsis. Implementation of the ventilator bundle to prevent the development of VAP includes the following components: In addition, routine oral care with chlorhexidine is recommended to reduce the risk of VAP. Maintaining tight glycemic control is important and has been shown to decrease mortality in surgical patients. Because of his hyperglycemia, Mr. L is started on a continuous insulin infusion and his glucose levels are closely monitored.
Use of recombinant human-activated protein C rhAPC. The guidelines no longer support the use of rhAPC due to recent studies that have found it ineffective in less severely ill patients with severe sepsis.
One of the most significant changes in the guidelines is the removal of drotrecogin alfa activated Xigris , an rhAPC indicated for adult patients with severe sepsis and acute organ dysfunction. A review of the current evidence failed to support a benefit from administration of this medication.
Substantial controversy regarding its benefit, safety, and cost led to the removal of this drug from the market. Other supportive therapies for severe sepsis not recommended by the guidelines include the use of I. After several days of intensive medical and nursing care, Mr. L's clinical status begins to improve. His lactate is 1.
His urine output is adequate and his BP remains stable as his nurse weans him off the norepinephrine. He's extubated and on his way to recovery.
L's story has a positive outcome due to an early diagnosis and treatment by the rapid response team. The ICU nurses supported and managed Mr. L's condition using evidence-based sepsis guidelines that have been shown to reduce mortality in patients with severe sepsis and septic shock.
L's physicians and nurses were aware of the most current Surviving Sepsis Campaign guidelines, he received the best possible care for his life-threatening condition. Sepsis is a complex condition that progresses rapidly as the infectious organism releases endotoxins into the bloodstream.
In reaction to these endotoxins, the body initiates an exaggerated immune response that causes significant vasodilatation, resulting in hypotension and decreased tissue perfusion.
If left untreated, sepsis will progress to severe sepsis or septic shock, leading to multiple organ failure. Sepsis is defined as the presence of documented or suspected infection in addition to some of the following systemic manifestations of infection. Severe sepsis is sepsis-induced tissue hypoperfusion or organ dysfunction any of the following believed to be a result of the infection Adapted and updated from: Sepsis and the systemic inflammatory response syndrome: Definitions, epidemiology, and prognosis.
In the updated guidelines, the previous management bundle was dropped and the resuscitation bundle was broken into two parts. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: Crit Care Med.
Procalcitonin PCT is a precursor of the hormone calcitonin, which along with parathyroid hormone helps regulate the body's calcium and phosphate balance.
In healthy individuals, PCT is produced by specialized cells in the thyroid, lung, and intestine. PCT isn't normally detected in the blood; however, in response to systemic inflammation, serum levels will rise significantly if the source of the infection is bacterial.
Levels won't rise significantly with viral or noninfectious causes of inflammation surgery, trauma, burns. Serum PCT is used as a biomarker to detect sepsis and severe sepsis caused by a bacterial organism. It should be drawn as soon as there's a suspected infection.
Used in conjunction with other lab findings and clinical assessment, it can help confirm the diagnosis of sepsis, severe sepsis, or septic shock.
PCT levels can also guide antibiotic therapy. Decreasing PCT levels in a patient treated for a severe bacterial infection indicate a response to therapy. PCT levels should be repeated every 24 to 48 hours to help determine effectiveness of treatment and patient prognosis. In response to a bacterial infection, PCT levels rise within 3 to 6 hours, peaking at 12 hours, with a half-life of 24 hours.
PCT levels 1.