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Updates in Sepsis 2016

Raymundo F. Resurreccion, MD
From the PCS-MMC 34th Post Grad Course on Surgical Infections
August 16 – 19, 2016

Objectives
• Review key concepts in sepsis
• Discuss new definitions in sepsis
• Highlight changes in the sepsis diagnostic criteria
• Summarize findings of recent EGDT trials and their
implications in sepsis resuscitation
• Demonstrate the impact of sepsis pathway in local
clinical practice

Sepsis
• “Harmful systemic reaction to infection”
• Infectious etiology + response that results in
hypofunction of uninfected organs
• Incomplete understanding of pathobiology

Sepsis: what do we know
Crude estimates Mortalit
y
Sepsis
22 – 240/100,000
30%
Severe sepsis 13 to 300/100,000
50%
Septic shock
11/100,000
80%

Sepsis: What do we know
• Contributing factor in > 200,000 deaths per year in the
US
• Annual cases > 750,000 (~3 per 1000 population)

and anti-inflammatory responses Major modifications in non-immunologic pathways .Sepsis: what do we know Age Underlying comorbidities Concurrent injuries Medications Mechanical devices Early activation of both pro.

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causing nearly half of all deaths in the ICU. but little can be done t treat or prevent it today.Massive inflammation leads to organ failure. Organ failure occurs when vital organs stop working. .

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Issues with the 1991 and 2001 definitions • Poor discriminant validity • Poor convergent validity • Variability with different scoring systems • Variability with different clinical variables .

SIRS is an appropriate response to infection – or any other stimulus that activates inflammation .

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315 (8).10.0287 .801810.doi.1001/jama. 2016.JAMA.2016.

Sepsis-3: Issues addressed • Increased understanding of sepsis pathobiology • • • • More than just rampant inflammation Key role of immunosuppression Contribution of non-immune mechanisms Possible adaptive nature of organ dysfunction-hibernation .

Sepsis-3: Definition Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection So… “sepsis” now = the old “severe sepsis” .

Sepsis-3: Definition Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection As opposed to the “regulated host response” that characterizes the non-septic response to infection .

Sepsis-3 Consensus SEPSIS .

Sepsis-3 definition Septic shock is a subset of sepsis in which underlying circulatory. and metabolic abnormalities re associated with a greater risk of mortality than sepsis alone . cellular.

Sepsis-3 consensus: clinical criteria • No current clinical measure reflect the concept of a dysregulated host response • Bedside examination + routine laboratory test results indicative of inflammation or organ dysfunction .

The host response is of key importance 3. Sepsis represents bad infection where bad = infection leading to organ dysfunction 4. “Severe sepsis” is not helpful and should be eliminated .Task force decisions 1. Sepsis is not simply infection + two or more SIRS criteria 2.

Who is septic? .

How to define really sick? • There is no gold standard for sepsis • “Really sick” is a proxy • More common among infected patients who are septic than those who are not .

How to define really sick? • Clinical review committees • Death in the hospital • Prolonged stay in the ICU • Discharge diagnosis of sepsis • Positive microbiological cultures .

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81.82) similar to full SOFA score outside the ICU .Assessment of clinical criteria: qSOFA • 2 or 3 qSOFA points accounted for 70% of deaths or ICU stays of >/+ 3 days • Predictive validity (AUROC= 0. 0.80-0. 95% CI.

• Should prompt: • Further investigation for organ dysfunction • Initiation or escalation of therapy • Referral to critical care • Increase frequency in monitoring .

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EGDT: landmark study Timeframe Setting Population Treatment Control Outcome Rivers March 1997 – March 2000 Single-center Adult with SIRS + SBP < 90 after fluid challenge OR lactate > 4 EGDT x >/= 6 hours Standard care 60-day in-hospital mortality .

Protocoliz ed Managem ent in Sepsis (ProMISe) (April 2015) Protocoliz ed Care for Early Septic Shock (ProCESS) (May 2014) Resuscita tion in Sepsis Evaluatio n (ARISE) .

“In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation. hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome.” .

” .“In a multicenter trial conducted in the tertiary care setting. protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes.

EGDT did not reduce all-cause mortality at 90 days.“In critically ill patients presenting to the emergency department with early septic shock.” .

specifically antibiotics and intravenous fluids. perhaps contributed most to the survival rates observed.Is EGDT obsolete? • Conclusion: • In-hospital survival with usual care = EGDT • Continuous ScvO2 monitoring and strict protocolization do not improve outcomes • The “usual care” comparator in theses trials are of high quality • Front-end interventions. .

. the SSC Executive Committee has revised the improvement bundles as follows: • To be completed within 3 hours of time of presentation: • • • • Measure lactate level Obtain blood cultures prior to administration of antibiotics Administer broad spectrum antibiotics Administer 30 ml/kg crystalloid for hypotension or lactate >/= 4 mmol/L * Time of presentation is defined as the time of triage in the emergency department or. if presenting from another care venue.Updated Bundles in Response to New Evidence • With publication of 3 trials (2. 4) that do not demonstrate superiority of required use of a central venous catheter (CVC) to monitor central venous pressure (CVP) and central venous oxygen saturation (ScvO2) in all patients with septic shock who have received timely antibiotics and fluid resuscitation compared with controls or in all patients with lactate > 4 mmol/L. 3. from the earliest chart annotation consistent with all elements of severe sepsis or septic shock entertained through chart review.

Updated Bundles in Response to New Evidence • With publication of 3 trials (2. re-assess volume status and tissue perfusion and document findings according to Table 1. • Re-measure lactate if initial lactate elevated. 4) that do not demonstrate superiority of required use of a central venous catheter (CVC) to monitor central venous pressure (CVP) and central venous oxygen saturation (ScvO2) in all patients with septic shock who have received timely antibiotics and fluid resuscitation compared with controls or in all patients with lactate > 4 mmol/L. . the SSC Executive Committee has revised the improvement bundles as follows: • To be completed within 6 hours of time of presentation: • Apply vasopressors (for hypotension that does not respond to initial fluid resuscitation) to maintain a mean arterial pressure (MAP) >/= 65 mmHg • In the event of persistent hypotension after initial fluid resuscitation (MAP < 65 mmHg) or if initial lactate was >/= 4 mmol/L. 3.

non-localized presentations • Feeling very unwell • May not have a high temperature • Pay particular attention to concerns expressed by the person and their family or caregivers • Changes from usual behavior .When should you suspect sepsis? • Think: “could this be sepsis?” • If a person presents with signs or symptoms that indicate possible infection • Take into account that people with sepsis may have nonspecific.

International Guidelines for Management of Severe Sepsis and Septic Shock: 2012 .

Fluid therapy • Initial fluid challenge in sepsis-induced hypoperfusion with hypovolemia to achieve a minimum of 30 ml/kg of crystalloid [1C] • More rapid administration and greater amounts of fluid may be needed in some patients [1C] .

[1C] • Perform imaging studies promptly in order to confirm and sample any source of infection.Diagnosis • Obtain appropriate cultures before starting antibiotics. [UG] .

Antibiotic therapy • Administer IV antibiotics within the first hour of recognizing severe shock [1B] and severe sepsis without shock [1C]. and with good penetration into presumed source. • Broad spectrum: one or more agents active against likely bacterial/fungal pathogens.[1B] .

[1C] • Formally evaluate patient for a focus of infection amenable to emergent source control measures [1C] • Undertake intervention for source control within the first 12 hours after diagnosis is made.Source control • A specific anatomical diagnosis of infection should be established as rapidly as possible. [1C] . if feasible.

Its recognition mandates urgent attention. .Key concepts of sepsis • Sepsis is the primary cause of death from infection. especially if not recognized and treated promptly.

comorbidities. race. and other genetic determinants. Sex. • What differentiates sepsis from infection is an aberrant or dysregulated host response and the presence of organ dysfunction.Key concepts of sepsis • Sepsis is a syndrome shaped by pathogen factors and host factors 9eg. . environment) with characteristics that evolve over time.

therefore. . • An unexplained organ dysfunction should thus raise the possibility of underlying infection. unrecognized infection may be the cause of new-onset organ dysfunction. its presence should be considered in any patient presenting with infection. • Conversely.Key concepts of sepsis • Sepsis-induced organ dysfunction may be occult.

• Specific infections may result in local organ dysfunction without generating a dysregulated systemic host response. . medication and interventions. long-standing comorbidities.Key concepts of sepsis • The clinical and biological phenotype of sepsis can be modified by pre-existing acute illness.

Resuscitation with intravenous fluids and vasoactive drugs . Early recognition 2.Fundamental principles of sepsis management 1. Appropriate and timely administration of antibiotics 4. Control of the source of infection 3.

qSOFA implications • Patients with suspected infection who are likely to have a prolonged ICU stay or to die in the hospital can be promptly identified at the bedside with qSOFA (‘HAT”) • Hypotension: SBP less than or equal to 100 mmHg • Altered mental status (any GCS less than 15) • Tachypnea: RR >/= 22 .

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International study of the prevalence and outcomes of infection in intensive care units. Deutschman CS. Martin GS. Early goal-directed therapy in the treatment of severe sepsis and septic shock. Severe sepsis and septic shock. Tomlanovich M. Bailey M. NEJM 370 (18): 1683-1693 • Mouncey PR. Society of critical care Medicine. Vincent JL. Bellomo R. 2012. Shankar-Hari M. NEJM 369 (9): 841-851 • Kaukonen KM. Liu VX. Power S.2016. A randomized trial of protocol-based care for early septic shock. Peterson E. NEJM 371 (16): 1496-1506 • ProCESS Investigators. Martin CD. Coats TJ. NEJM 372 (14)1301-1311 • Deutschman CS. Angus D. Singer M. Scherag A. 2009. NEJM 372 (17): 1629-1638 • Surviving Sepsis campaign. Angus DC. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Shankar-Hari M. Pilcher D. 2015. • Singer M. Angus DC. Osborn TM. JAMA 2016 315: 801-10. Deutschman CS. JAMA 2016 315 (8): 8101-810 • Angus DC. Opal SM. 2003. Bellomo R. Muzzin A. Assessment of clinical criteria for sepsis for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Abraham E. Marshall J. Escobar GJ. Anzueto A. Young D. Bauer M. Sadique Z. international Guidelines for Management of Severe Sepsis and septic Shock 2012. Rello J. Moreno R. 302 (21): 2323-2329 • Rivers E. Brunkhorst FM. Kahn JM. Van der Poll T. goal-directed resuscitation for septic shock. Fink MP. Opal SM. 2001. Annane D. 315(8): 762-774 • Vincent JL. Gomersall c.References • Levy MM. Iwashyna TJ. Goal-directed resuscitation for patients with early septic shock. Jahan R. Intensive Care Med (2003) 29:530-538 • Seymour CW. Harvey SE. Cooper J. Harrison DA. Silva E. Havstad S. Bernard GR. Lipman J. Knoblich B. The Third International Consensus definitions for Sepsis and Septic Shock (Sepsis-3). Van der Poll T. Coopersmith CM. Rubenfeld G. Rubenfeld GD. Rowan KM. Marshall JC. Cook D. Seymour CW. Sakr Y. Reinhart K. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). 2014. Nguyen B. Cohen J. 2013. Levy MM. Vincent JL. Trial of early. JAMA 2016. 2015. 2016. 2014. JAMA 2009. Seymour CW. Ressler J. Shankar-Hari M. 2016. Rea TD. Ramsay G. Critical care Med 2013 41 (2): 580-637 . Singer M. Chiche JD. Hotchkiss RS. Grieve RD. NEJM 345 (19): 1368-1377 • ARISE Investigators and the ANZICS clinical trials group. Systemic inflammatory response syndrome criteria in defining severe sepsis. Bell D. Bion JF. Singer M.

Thank you! .