Assessing Treatment of Severe Sepsis and Septic Shock: How Are We Performing? A Case-Comparison Study to Evaluate the Treatment of Severe Sepsis and Septic Shock in Critical Care Patients at Sisters of Charity Hospital in Buffalo, NY Erik Diringer, DO Mentor: Thomas Brewer, DO

Background Severe sepsis and septic shock are complex disease states that carry high rates of mortality. – 28.6% overall and 38.4% in those >85 yrs. old 1 International efforts, such as the Surviving Sepsis Campaign, have been made to define, diagnose and treat sepsis in attempts to improve morbidity and mortality 2.

Background Evidence suggests that early goal-directed therapy (EGDT) contributes to a significant improvement in morality in severe sepsis and septic shock 3. On December 1, 2008, the Catholic Health System released a new clinical standards order set for the septic patient. This order set is designed to utilize recommendations from the Surviving Sepsis Campaign.

Introduction Definitions 4 : – Systemic inflammatory response syndrome (SIRS) – Sepsis is comprised of SIRS with a known source of infection. – Severe sepsis involves dysfunction in one or more vital organs with hypotension that is responsive to adequate fluid resuscitation. – Septic shock is comprised of the same criteria, however, it is not responsive to fluid resuscitation.

Introduction As a result of global tissue hypoxia, these conditions can quickly progress to multiorgan dysfunction syndrome (MODS), multiorgan failure (MOF) and death 5. – Global tissue hypoxia is difficult to evaluate using traditional hemodynamic measurements, such as physical findings, vital signs, central venous pressure (CVP), and urinary output.

Introduction The Cost of Sepsis – Despite major advances in medicine and technology, mortality rates remain high. – In the United States, treatment of sepsis costs $16.7 billion annually and is projected to increase by 1.5% per year 1.

Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock Emanuel Rivers, M.D., M.P.H., Bryant Nguyen, M.D., Suzanne Havstad, M.A., Julie Ressler, B.S., Alexandria Muzzin, B.S., Bernhard Knoblich, M.D., Edward Peterson, Ph.D., Michael Tomlanovich, M.D., for the Early Goal- Directed Therapy Collaborative Group November 8, 2001

S CV O 2 Monitoring 6 Surrogate of global tissue hypoxia – Sepsis results in increased metabolic stress at the tissue level – Response is to increase cardiac output and/or O 2 utilization – When O 2 supply is overwhelmed by the disease, S CV O 2 continues to decrease (O 2 demand > supply) – Thus, S CV O 2 is proposed to be a marker of adequate O 2 utilization at the tissue level as a response to metabolic stress

EGDT Treatment

EGDT Results Significant (P=0.009) decrease in in-hospital mortality from 46.5 to 30.5% when EGDT was used over of standard therapy – significant decrease in 28-day mortality Rapid identification and treatment – These results were seen when therapy was initiated immediately and continued for at least six hours.

12/01/08 – CHS Sepsis Order Set 3 page admission order set Provides option to initiate EGDT – Access: CVC, arterial line – Monitoring: CVP/MAP monitoring, I/O – Treatment: fluids, transfusions, vasopressors, inotropic therapy

Study Objective The goal of this study is compare set outcomes in patients at Sisters of Charity Hospital (SOCH) in Buffalo, NY diagnosed with severe sepsis and/or septic shock prior to and following the release of the new sepsis order set.

Study Design A case-comparison study of 100 ICU patients with the diagnosis of severe sepsis and/or septic shock prior to and following the release of the sepsis standardized order set.

Methods Approved by SOCH Institutional Review Board Using December 1, 2008 as a reference, a chart review of SOCH ICU patients with the diagnosis of severe sepsis and/or septic shock was performed until 100 charts that met inclusion criteria were reviewed prior to and following the release of the CHS sepsis order set

Methods Inclusion criteria: similar to EGDT – fulfillment of two of four criteria for SIRS – systolic blood pressure no higher than 90 mm Hg (after a crystalloid-fluid challenge) or a blood lactate concentration 36 mg/dL

Methods Exclusion criteria: – age <18 years – pregnancy – CVA – ACS – Acute pulm. edema – Cardiac dysrhythmias (as a primary diagnosis) – active gastrointestinal hemorrhage – seizure/drug overdose – contraindication to CVC – burn injury/trauma – requirement for immediate surgery – uncured cancer (during chemotherapy) – immunosuppression – do-not-resuscitate status

Methods Data collection – Hemodynamic parameters at 0, 4, 8, 12, 16, 20, 24h Temp, HR, input, output (when available), systolic pressure, diastolic pressure, MAP (calculated) – Age, sex, weight, APACHE II score – Sepsis order set used? – LOS in ED, ICU – Mortality (all-cause, in-hospital)

Methods Statistical analysis – Unpaired, two-tailed t-test – Chi-square test

Results 213 charts reviewed (12/24/07- 10/10/09) 50 charts prior to 12/01/08 50 charts on or after 12/01/ charts met inclusion criteria

Baseline Characteristics SOS = sepsis order set APACHE II = Acute Physiologic and Chronic Health Evaluation II, scale range from 0 to 71, with higher values indicating more severe disease. CVP = central venous pressure *Average time to CVP placement 10.17h

Results SOS = sepsis order set

Results SOS = sepsis order set *Urine output available 0-4h in 24% of patients

Results SOS = sepsis order set MAP = mean arterial pressure

Results SOS = Sepsis order set LOS = Length of stay *Lactate available within 24h in 50% of patients pre-SOS and 68% post-SOS

Discussion No significant difference in hemodynamic parameters SOCH mortality rate similar to those reported nationally 1 CVP lines placed in 21% of pts – Average time to line was 10.17h Average IVF in 1324ml in first 4h; 2467ml in first 8h – EGDT averaged 4981ml in first 6h 3 Urine output only available in 24% of pts in first 4h Sepsis order set only used in 14% of pts

Can EGDT be done in real-world clinical practice?

Discussion A 1-Year Experience With Implementing Early Goal-Directed Therapy for Septic Shock in the Emergency Department 7 – Academic center in Camden, NJ – 22 pts treated with EGDT protocol in ED Executed by ED/ICU physicians and nurses as part of regular duties – ED physicians identify and initiate – ICU physicians ensure outcomes are achieved – Required no extra staffing or modification to physical plant

Discussion Future consideration – Early identification of severe sepsis and septic shock Hemodynamic parameters, lab values “Door-to-EGDT” <60min in original trial 3 – In-hospital mortality in STEMI 3% with door-to-balloon time <90min 8 – Collaboration between ED and ICU teams – Modification of sepsis order set “Sepsis bundles” 9 – Modification of EGDT?

Discussion Role of the resident – Diagnosis of severe sepsis and septic shock – EGDT – Procedural competency

References 1.Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. CritCare Med. 2001; 29: Surviving Sepsis Campaign® Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345: 1368– Marino P. The ICU Book, Third Edition. Philadelphia: Lippincott Williams & Wilkins, Beal AL, Cerra FB. Multiple organ failure syndrome in the 1990s: systemic inflammatory response and organ dysfunction. JAMA 1994; 271: Pinsky R, Brochard L, Mancebo J. Applied Physiology in Intensive Care Medicine. Springer-Verlag Berlin Heidelberg Trzeciak JES, Dellinger RP, Abate NL, Cowan RM, Stauss M, Kilgannon JH, Zanotti S. A 1-Year Experience With Implementing Early Goal-Directed Therapy for Septic Shock in the Emergency Department. Chest. 2006; 129: McNamara RL, Wang Y, Herrin J, Curtis JP, Bradley EH, Magid DJ, Peterson ED, Blaney M, Frederick PD, Krumholz HM. Effect of door-to-balloon time on mortality in patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol Jun 6;47 (11): Institute for Health Care Improvement. Accessed May 2010.

ProCESS Study Protocolized Care for Early Septic Shock Funded by NIH, coordinated by UPMC 24 US sites 3-pronged – Clinical efficacy Do we need S CV O 2, blood transfusions? – Mechanism of action Trend markers of cellular hypoxia, oxidative stress, inflammation, and coagulation/thrombosis – Costs and cost-effectiveness

Baseline Characteristics SOS = sepsis order set APACHE II = Acute Physiologic and Chronic Health Evaluation II, scale range from 0 to 71, with higher values indicating more severe disease. CVP = central venous pressure *Average time to CVP placement 10.17h

Results SOS = sepsis order set

Results SOS = sepsis order set

Results SOS = sepsis order set MAP = mean arterial pressure

Results SOS = Sepsis order set LOS = Length of stay *Lactate available within 24h in 50% of patients pre-SOS and 68% post-SOS