The TIMES Project: (Time to Initiation of Antibiotic Therapy in Medical Patients Presenting to the Emergency Department with Sepsis) - Preliminary Findings Andrea Blotsky MDCM FRCPC General Internal Medicine, McGill University Thursday, October 15, 2015
Disclosures No conflicts of interest to disclose.
Background Delays in initiation of appropriate antimicrobial therapy play a substantial role in determining the mortality of patients with sepsis and septic shock. Kumar et al. (2006): The delay to initial administration of effective antimicrobial therapy is the single strongest predictor of survival, with significant decreases in projected patient survival for every hour of antibiotic delay. 1 1 Kumar et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock.crit Care Med. 2006 Jun;34(6):1589-96.
A New Golden Hour
Implications of Sepsis in the ED Literature pertaining to Sepsis management in the Critical Care Environment is robust Fewer studies addressing sepsis management in the ED Two studies demonstrate that delays in initiation of appropriate antibiotic therapy of > 6-8 hours, after triage, has led to increased mortality 2-3 2 Meehan et al. Quality of care, process, and outcomes in elderly patients with pneumonia. JAMA. 1997 Dec 17;278(23):2080-4 3 Puscharich et al. Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol. Crit Care Med. 2011 Sep;39(9):2066-71.
TIMES Study Rationale We hypothesized that there are substantial delays between patient presentation, medical evaluation, and effective antimicrobial administration in patients presenting to the Emergency Department of our institution.
TIMES Project: 2 Step Process Step I: Medical Audit Purpose: To examine the time to initiation of appropriate antimicrobial therapy in medical patients presenting to the Emergency Department (ED) with sepsis. Step II: Intervention Purpose: Implementation of an early sepsisidentification/antibiotic-delivery protocol in order to : Facilitate the recognition of deteriorating ED patients with sepsis Expedite the delivery of appropriate broad-spectrum antimicrobial therapy.
TIMES AUDIT
Part 1: TIMES Audit A retrospective chart review of medical patients presenting to the ED with sepsis. Location: Montreal General Hospital Dates: July 1, 2013 and June 30, 2014
Defining Sepsis: SIRS Criteria (2/4): Temp >38 C (100.4 F) or < 36 C (96.8 F) HR > 90 RR > 20 or PaCO 2 <32 mmhg WBC > 12,000/mm> 3, < 4,000/mm> 3, or > 10% bands *** with documented or presumed infection. 4. "American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis" (PDF). Crit. Care Med. 20(6): 864 74.
Audit Structure Patient Selection Total Admissions from ED to Medical CTU (Direct) Total Admissions where Antibiotics were Initiated in the ED for presumed Infection Total Medical Admissions from ED to ICU Total Admissions meeting criteria for Sepsis
Study Objectives Primary outcomes: Time to first dose of appropriate antibiotic In-hospital mortality Secondary outcomes: Length of hospitalization 30-Day Mortality Rate of subsequent ICU Admission For patients admitted to CTU directly from the ED
Appropriate Antibiotic Selection We also reviewed the appropriateness of initial antibiotic selection by reviewing culture results and/or chart-review of the working diagnosis at the time of antibiotic administration. Appropriateness criteria were extracted from IDSA Guidelines/Recommendations and McGill University Health Centre Antibiotic Guidelines.
Audit Structure Patient Selection Total Admissions from ED to Medical CTU (Direct) n=1520 Total Admissions where Antibiotics were Initiated in the ED for presumed Infection n=712 n=326 Total Medical Admissions from ED to ICU Total Admissions meeting criteria for Sepsis n=272
Table 1: Baseline Characteristics for Patients while in the ED (1) CHARACTERISTIC (n = 272) AGE 73.1±17.4 SEX % Female Male 54.4 45.6
Table 1: Baseline Characteristics (2) VARIABLES (n = 272) HEART RATE (beats/min) 114±27 SYSTOLIC BLOOD PRESSURES (mmhg) 106±31 RESPIRATORY RATE (breaths/min) 23±4 TEMPERATURE (Degree Centrigrade) 37.4±2.1 WBC (per mm2) 13.6±8.3 Lactate (mmol/l) 2.6±1.9 Creatinine (mmol/l) 194±24 Sodium (mmol/l) 135±3.8 Potassium (mmol/l) 4.8±0.6 Glucose (mmol/l) 8.3±4.2 Hematocrit 0.336±0.102
TIMES Audit: Working Diagnoses WORKING DIAGNOSIS % Pneumonia Urosepsis/UTI Cellulitis/Nec Fasc Septic Arthritis Peritonitis Meningitis/Encephalitis Other OR Uncertain Primary Source n=272 36.8 26.2 14.6 7.2 2.6 2.5 10.1
TIMES Audit: Antibiotics Utilized Antibiotic Usage 3rd and 4th Generation Cephalosporins 11% Other 39% 8% 5% 5% 5% Quinolones Carbapenems 27% Macrolides 2 Antibiotics 3 or More Antibiotics
TIMES Audit: Antibiotic Appropriateness Antibiotic Appropriateness 22% 78% * Cultures were drawn prior to ABX initiation for 74 % of patients Percent Appropriate Percent Inappropriate
RESULTS PRIMARY OUTCOMES Median delay from presentation to initiation of antibiotics was 4.2 hours (IQR 1.2h 12.4h). In-hospital mortality was 6.8%. For the ICU Cohort: In-hospital mortality was 12.8% Increased mortality was observed with each additional hour of antibiotic delay Odds ratio for mortality for >3 hour delay in appropriate antibiotic administration was 3.21 (95% CI 1.25-9.28). SECONDARY OUTCOMES Average length of stay was 9.1 days 30-Day Mortality was 7.6% Subsequent ICU Admission for patients originally admitted to CTU: 5.9% (IQR 5.1%-7.0%).
TIMES INTERVENTION
Step 2: TIMES Intervention Purpose: Implementation of an early sepsisidentification/antibiotic-delivery protocol in our Emergency Department.
Intervention Planning: Education Educational POD sessions were organized between members of our team and stake-holders (ED staff physicians and nurses, pharmacists, and Internal Medicine (IM) physicians working in the Emergency Department in a gate-keeping capacity) during the three months prior to the implementation date of our protocol. Go Live: May 2015
Sample Protocol (Page 1)
Sample Protocol (Page 2)
RESULTS (1) A prospective observational study to assess outcomes after protocol initiation is presently underway For data collected over a ~ 3 month period: CHARCTERISTICS/VARIABLES (n=48) Intervention (n = 272) Control AGE 74.1±15.2 73.1±17.4 SEX % Female Male 52.2 47.8 54.4 45.6 HEART RATE (beats/min) 112±17 114±27 SYSTOLIC BLOOD PRESSURES (mmhg) 114±26 106±31 RESPIRATORY RATE (breaths/min) 21±3 23±4 TEMPERATURE (Degree Centrigrade) 37.2±1.8 37.4±2.1
RESULTS (2) Appropriate Initial Antibiotic Usage increased from 78% to 86%. Preliminary results suggest a reduction in the time to appropriate antibiotic initiation of 1.8 hours (IQR 0.4h-2.3h) post-intervention. In-hospital mortality decreased from 6.8% to 5.5%.
More Work on the Horizon Continuation of Project in ED (Medicine + Primary ED Team) Introduction of Protocol to CTU Sub-Analyses of times based on hour of presentation to the ED (AM vs. PM) and ED occupancy
Conclusions The delay to initial administration of effective antimicrobial therapy is the single strongest predictor of survival. Our work suggests the benefit of instituting a rapid, low-cost, protocol-based system to improve empiric management of sepsis. Such a protocol has potential for subsequent implementation on other units (ie: Medical and Surgical Clinical Teaching Units), which could further improve outcomes.
ACKNOWLEDGEMENTS Thanks to: Christina Weisstock and Maxime Billick MED 3, McGill University Ling Kong, MDCM, Infectious Disease Fellow, McGill University Dev Jayaraman, MDCM, FRCPC, MPH, Associate Professor, General Internal Medicine and Critical Care, McGill University McGill GIM Residency Program Scholarly Activity Enrichment Fund