IDENTIFYING SEPSIS IN THE PREHOSPITAL SETTING Christopher Hunter, MD, PhD, FACEP Director, Health Services Department Associate Medical Director, Orange County EMS System Medical Director, Orlando Health Air Care Team
Conflict of interest Disclosure None
Topics Prehospital Sepsis Screening: Why does it matter? Sepsis screening tools and outcome predictors Lactate ETCO2 qsofa Future steps
Sepsis End result of an overwhelming infection Hypoperfusion leads to end-organ damage multi-organ system failure Early identification and targeted therapy has been shown to improve outcomes Surviving Sepsis Campaign guidelines for best practice
Sepsis and the Index of Suspicion: Traditional Approach
Organ Failure Sepsis and the Index of Suspicion: New Definition
Development of Sepsis Infection Maladaptive response (Vitals) Hypoperfusion Organ Failure (Acidosis) Sepsis Severe Sepsis Shock (Hypotension)
The Keys To Treating Sepsis Early Recognition, Fluid Resuscitation, and Antibiotics
The Keys to Treating Sepsis Early initiation 0f antibiotics improves survival Kumar et al 2006
The Keys to Treating Sepsis Initiation of IV Fluids within 30 minutes decreased length of stay Leisman et al., 2016
Sepsis in EMS: More common than you think EMS incidence of sepsis estimated at 3.3 per 100 Mortality rates similar to STEMI, worse than stroke
Sepsis in EMS: More common than you think Over 30% of all ED infection patients will arrive by ambulance (Wang 2009) 50-60% of all ED sepsis patients arrive by ambulance (Studnek 2012, Wang 2009) The majority of patients admitted to ICU with sepsis arrived at the ED via EMS (Femling 2012)
EMS transport decreases time to EGDT and antibiotics (Studnek et al., 2012) Prospective study of 311 patients (160 transported by EMS) SOFA score 7.0 vs 6.1; P =.02 Time to first antibiotics (111 vs 146 minutes, P =.001) Time from triage to EGDT initiation (119 vs 160 minutes, P =.005) If EMS provider indicated a written impression of sepsis, there was a shorter time to antibiotics (70 vs 122 minutes, P =.003) and a shorter time to EGDT initiation (69 vs 131 minutes, P =.001) compared to those without an impression of sepsis
Prehospital IV and fluid resuscitation improves outcomes Seymour et al., 2014 Prospective, observational study on patients with severe sepsis transported by EMS over a two year period Analyzed outcomes of those receiving venous catheter alone, catheter plus IV fluids (LR), and no access Prehospital intravenous catheter placement alone (Odds ratio =0.3; 95% CI: 0.17 to 0.57; P <0.01) and administration of intravenous fluids (Odds ratio =0.46; 95% CI: 0.23, 0.88; P =0.02) was associated with reduced hospital mortality
Prehospital Sepsis Care Frequent, high-mortality encounters Early identification and prehospital interventions such as initiation of fluids may improve outcomes Can we identify septic patients in the field?
Prehospital Screening Tools
Robson screening tool 2 criteria to for a positive screen Temperature > 38.3 C or < 36.0 C Heart Rate > 90 beats/min Respiratory Rate > 20 breaths/min Acutely altered mental status Serum glucose < 120 mg/dl or 6.6 mmol/l
BAS 90-30-90 tool 1 criteria to for a positive screen Systolic blood pressure < 90 mmhg Respiratory Rate > 30 breaths/min Oxygen Saturation < 90%
PRESS Score PRESS score of 2 had sensitivity of 86% and specificity of 47% for severe sepsis
PRESEP Score Cutoff value for a possible existing septic disease was 4 Temperature > 38 C = 4 Temperature < 36 C = 1 HR > 90 beats/min = 2 RR > 22 breaths/min = 1 SaO2 < 92% = 2 Systolic BP < 90 mm Hg = 2 More sensitive than Modified Early Warning System (MEWS) and more specific than Robson tool
Prehospital outcome predictors
The role of serum lactate Lactate levels predict mortality (Ranzani et al., 2013) It is feasible to monitor serum lactate levels in the prehospital environment (Jensen et all., 2008) Increased prehospital lactate levels correlate with mortality (Jansen et al., 2008) Septic patients have elevated prehospital lactate levels (Wang et al., 2009) Cryptic shock may be identified by prehospital lactate levels (Shiuh et al., 2011;Hanudel et al., 2008)
Prehospital screening with lactate Prospective cohort study using a Sepsis Alert Protocol that incorporated point-of-care venous lactate meters 67 severe sepsis patients (32 of the 67 severe sepsis patients identified correctly (47.8%) Mortality was improved for those identified by EMS Crude odds ratio for survival until discharge was 3.19 (95% CI 1.14-8.88; p = 0.040)
Challenges with prehospital lactate Cost (equipment plus training) ALS skill Poor Correlation Hokanson et al., 2012 found poor correlation between EMS and hospital lactate levels (r=0.6 suggesting 9%- 36% variance) Is there another way?
Oxygenation and Ventilation Oxygen -> lungs -> alveoli -> blood breath Oxygen CO 2 lungs muscles + organs Oxygen CO 2 blood CO 2 energy cells Oxygen + Glucose
ETCO2 provides a non-invasive mechanism to detect metabolic acidosis ETCO2 correlates with serum bicarbonate and PH levels in children and adults with Diabetic Ketoacidosis Fearon et al., 2002, Soleimanpour et al., 2013 ETCO2 correlates with serum bicarbonate in children with gastroenteritis Nagler et al., 2006 ETCO2 correlates with serum bicarbonate and lactate levels in patient with undifferentiated shock and metabolic disorders Kehng and Rahman 2012, Kartel et al., 2006 ETCO2 correlates with lactic acidosis and poor outcomes in patient with severe trauma Deacon 2004, Caputo et al., 2012
End tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis Hunter et al., 2013 Correlation Coefficient P-Value ETCO2-Lactate Sepsis -0.421 <0.001 Severe Sepsis -0.597 <0.001 Septic Shock -0.482 0.011
End tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis Hunter et al., 2013
The role of ETCO2 in sepsis ETCO2 is a non-invasive outcome predictor in suspected sepsis ETCO2 performs as well as serum lactate predicting mortality in septic patients ETCO2 may provide a method for earlier identification and intervention in patients with suspected sepsis
Severe Sepsis: Hospital Approach Suspect Infection SIRS Criteria ( 2) Temp > 100.4 OR < 96.8 HR > 90 bpm RR > 20 bpm OR PaCO2 < 32 mmhg WBC > 12,000 OR < 4,000 OR > 10% Bands Identify Hypoperfusion Lactate > 4 mm OR SBP < 90 mmhg
Severe Sepsis: Prehospital Approach Suspect Infection SIRS Criteria ( 2) Temp > 100.4 OR < 96.8 HR > 90 bpm RR > 20 bpm OR PaCO2 < 32 mmhg WBC > 12,000 OR < 4,000 OR > 10% Bands Identify Hypoperfusion Lactate > 4 mm OR SBP < 90 mmhg OR ETCO2
Orange County EMS System Sepsis Protocol
Prehospital sepsis alert protocol using ETCO2 Prospective Evaluation of 330 consecutive sepsis alerts activated 183 met all protocol criteria and 147 did not ICD-9 codes, lab values, disposition Those patients whereby EMS personnel followed all diagnostic criteria of the protocol formed our protocol compliant group Protocol Driven Process - In 100% of these patients, EMS personnel suspected infection, patients had 2 of the above SIRS criteria, and initial ETCO2 values were 25 mmhg. Those patients whereby EMS personnel activated a sepsis alert but did not follow all diagnostic criteria of the protocol defined our control or protocol noncompliant group Paramedic Discretionary Process - In the protocol noncompliant group, EMS personnel suspected infection in all patients, but they either did not have 2 SIRS criteria (5% of the cases), or ETCO2 values were > 25 mmhg (95% of the cases)
Characteristics Protocol Noncompliant N=147 Protocol Compliant N=183 Total N=330 P-Value Age 67 (SD18) [Range 16-96] 72 (SD16) [Range 24-99] 70 (SD17) [Range 16-99] Gender (% male) 79 (54%) 90 (49%) 169 (51%) 0.439 Admitted to Hospital (n=295) 124 (93%) 162 (99%) 286 (97%) 0.014 Admitted to ICU (n=295) 33 (25%) 67 (41%) 100 (34%) 0.006 Diagnostic Category (n=297) Abdominal/GI Altered Mental Status Cardiac Respiratory Infectious Neurological Metabolic/Endocrine Trauma Alcohol/Drugs Urinary/Renal Other 9 (7%) 13 (10%) 4 (3) 20 (15%) 58 (44%) 2 (2%) 3 (2%) 0 (0) 0 (0) 15 (11%) 8 (6%) 8 (5%) 13 (8%) 1 (1%) 24 (15%) 90 (55%) 1 (1%) 8 (5%) 0 (0) 0 (0) 15 (9%) 5 (3%) 17 (6%) 26 (9%) 5 (2%) 44 (15%) 148 (50%) 3 (1%) 11 (4%) 0 (0) 0 (0) 30 (10%) 13 (4%) 0.014 0.352 Mortality (n=298) 6 (5%) 19 (11%) 25 (8%) 0.036 Developed Sepsis (n=298) 58 (43%) 129 (78%) 187 (63%) <0.001 Developed Severe Sepsis 9 (7%) 78 (47%) 87 (29%) <0.001
Vital Signs Protocol Noncompliant N=147 (95%CI) Protocol Compliant N=183 (95%CI) Total N=330 (95%CI) P-Value Temperature (n=264) Range 101.9 (101.7-102.2) [96.6-106.3] 100.9 (100.6-101.3) [91.5-104.3] 101.4 (101.1-101.6) [91.5-106.3] <0.001 Pulse 115 (111-119) 120 (117-124) 118 (115-120) 0.043 Respiratory Rate 28 (27-30) 31 (30-32) 30 (29-31) 0.007 Systolic BP 132 (127-137) 125 (121-129) 128 (125-131) 0.031 Diastolic BP 77 (74-81) 79 (68-91) 78 (72-85) 0.784 Oxygen Saturation (n=318) 94 (92-95) 92 (91-93) 93 (92-93) 0.043 ETCO2 (n=320) 33 (32-34) 20 (19-20) 25 (25-26) <0.001
Predictive Value for Sepsis EMS VITAL SIGNS AUC (95% CI) P-Value ETCO2 0.99 (0.99-1.00) <0.001 Temperature 0.64 (0.57-0.71) <0.001 Pulse 0.44 (0.36-0.51) 0.081 Respiratory Rate 0.47 (0.40-0.54) 0.417 Systolic BP 0.44 (0.37-0.51) 0.114 Diastolic BP 0.45 (0.38-0.52) 0.163 Oxygen Saturation 0.45 (0.38-0.52) 0.165
Predictive Value for Severe Sepsis EMS VITAL SIGNS AUC (95% CI) P-Value ETCO2 0.80 (0.73-0.86) <0.001 Temperature 0.41 (0.33-0.49) 0.029 Pulse 0.54 (0.46-0.63) 0.309 Respiratory Rate 0.52 (0.43-0.60) 0.690 Systolic BP 0.65 (0.57-0.73) <0.001 Diastolic BP 0.64 (0.55-0.72) 0.001 Oxygen Saturation 0.59 (0.52-0.68) 0.024
Predictive Value for Mortality EMS VITAL SIGNS AUC (95% CI) P-Value ETCO2 0.70 (0.57-0.83) 0.005 Temperature 0.31 (0.18-0.48) 0.018 Pulse 0.55 (0.38-0.72) 0.478 Respiratory Rate 0.45 (0.30-0.60) 0.490 Systolic BP 0.62 (0.48-0.76) 0.089 Diastolic BP 0.59 (0.44-0.74) 0.217 Oxygen Saturation 0.55 (0.40-0.70) 0.497
Correlation with Lactate Correlation Coefficient P-Value ETCO2-Lactate -0.394 <0.001
Prehospital sepsis alert protocol using ETCO2 Sepsis with appropriate activation Sensitivity 69% (95% CI 62-75%) Specificity 67% (95%CI 57-75%) Positive predictive value 78% (95%CI 70-84%) Negative predicative value 99% (95%CI 92-100%) Severe Sepsis with appropriate activation Sensitivity 90% (95% CI 81-95%) Specificity 58% (95%CI 52-65%) Positive predictive value 47% (95%CI 39-97%) Negative predicative value 93% (95%CI 87-97%) Mortality with appropriate activation Sensitivity 76% (95% CI 54-90%) Specificity 46% (95%CI 40-52%) Positive predictive value 11% (95%CI 7-18%) Negative predicative value 95% (95%CI 90-98%)
Effectiveness of a prehospital sepsis alert protocol utilizing ETCO2 Preliminary data Prospective pilot pre/post intervention study to assess impact of patient care in single ED 137 cases (110 pre, 27 post) Initiation of prehospital sepsis alert decreased: Time to blood culture 27 (95%CI 18-36) vs 14 (95%CI 9-19) Time to antibiotics 56 (95%CI 39-74) vs 40 (95%CI 24-55) Time to fluids 34 (95%CI 17-52) vs 10 (95%CI 4-16) Length of Stay 13 (95%CI 11-16) vs 9 (95%CI 6-12) ICU Admission 53% (95%CI 43-62%) vs 33% (95%CI 14-52%) Mortality 14% (95%CI 7-20%) vs 7% (95%CI 0-18%)
Do Sepsis-3 Definitions Change the approach? Quick Sequential Organ Failure Assessment (qsofa) score RR 22/min, Altered Mental Status, SBP 100 mmhg Immediate requires no bloodwork Mortality predictor not a screen for sepsis OR suspected infection Developed by intensivists without emergency medicine input Not prospectively validated
ETCO2 and qsofa as outcome predictors in suspected sepsis Severe Sepsis AUROC P-Value qsofa (0-3) 0.69 (0.62-0.75) <0.001 EMS ETCO2 0.78 (0.72-0.84) <0.001 qsofa and ETCO2 0.81 (0.75-0.86) <0.001 Mortality AUROC P-Value qsofa (0-3) 0.57 (0.44-0.69) 0.277 EMS ETCO2 0.69 (0.59-0.80) 0.001 qsofa and ETCO2 0.70 (0.59-0.82) 0.001
ETCO2 and qsofa as outcome predictors in suspected sepsis ETCO2 25 mmhg Measure (95%CI) Sensitivity 80 (59-92) Specificity 42 (36-48) PPV 12 (7-18) NPV 96 (90-98) ETCO2 25 mmhg AND qsofa 2 Measure (95%CI) Sensitivity 60 (39-78) Specificity 62 (55-67) PPV 13 (8-21) NPV 94 (89-97) qsofa 2 Measure (95%CI) Sensitivity 68 (46-84) Specificity 40 (34-46) PPV 10 (6-15) NPV 93 (86-97) ETCO2 25 mmhg OR qsofa 2 Measure (95%CI) Sensitivity 88 (68-97) Specificity 20 (16-26) PPV 9 (6-14) NPV 95 (84-99)
Take Home Points Early identification and resuscitation by prehospital providers may improve outcomes for patients with sepsis A System of Care Low ETCO2 is correlated with an acidotic state, and in the setting of suspected sepsis it serves as a similar outcome predictor to serum lactate levels It is feasible to develop screening tools to identify potentially septic patients in the field ETCO2 and/or qsofa may be useful as noninvasive, real time predictors of mortality in these patients
IDENTIFYING SEPSIS IN THE PREHOSPITAL SETTING Christopher Hunter, MD, PhD, FACEP Director, Health Services Department Associate Medical Director, Orange County EMS System Medical Director, Orlando Health Air Care Team