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CRITICAL PATIENT ENCOUNTERS: USING ET TO RECOGNIZE SEVERE SEPSIS IN THE PREHOSPITAL SETTING Christopher Hunter, MD, PhD Director, Health Services Department Associate Medical Director, EMS System Orange County, FL Conflict of interest Disclosure Authors Conflicts of Interest: C. Hunter, No Conflict of interest 1

Topics Sepsis and acid/base physiology Prehospital sepsis care ETCO2 as a diagnostic tool in sepsis Orange County EMS System Sepsis Alert Protocol Preliminary Findings Sepsis End result of an overwhelming infection Hypoperfusion leads to end organ damage and lactic acidosis The severity of lactic acidosis predicts outcomes Early Goal Directed Therapy early identification and aggressive therapy has been shown to improve outcomes Surviving Sepsis Campaign guidelines for best practice 2

Prehospital Sepsis Care Frequent, high mortality encounters Seymour et al (2012) identified EMS transported more patients diagnosed with sepsis than STEMIs or CVSs, and there was a 19.7% mortality rate Prehospital interventions can make a difference EMS transport decreased time to antibiotics and initiation of EGDT Studnek et al., 2012 Prehospital IV access and fluid administration improved survival Seymour et al., 2014 Prehospital sepsis protocol decreased mortality Guerra et al., 2013 Early recognition and fluid resuscitation may be most important Development of Sepsis Infection Internal response (Vitals) SIRS Hypoperfusion (Acidosis) Sepsis Shock (Hypotension) 3

Respiratory Cycle > lungs > alveoli > blood breath lungs blood energy muscles + organs cells + Glucose ation and Ventilation > lungs > alveoli > blood breath lungs blood energy muscles + organs cells + Glucose 4

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 ETCO2 predicts mortality in Emergency Room patients with suspected sepsis Correlation Coefficient P-Value ETCO2-Lactate Sepsis -0.421 <0.001 Severe Sepsis -0.597 <0.001 Septic Shock -0.482 0.011 5

ETCO2 predicts mortality in Emergency Room patients with suspected sepsis ROC Curve performance of ETCO2 and Lactate in predicting mortality ETCO2 AUC (95%CI) Lactate AUC (95%CI) Sepsis Categories Suspected Sepsis 0.60 (0.37-0.83) 0.61 (0.36-0.87) Severe Sepsis 0.67 (0.46-0.88) 0.69 (0.48-0.89) Septic Shock 0.78 (0.59-0.96) 0.74 (0.55-0.93) Intubation Intubated 0.77 (0.60-0.94) 0.82 (0.68-0.96) Not Intubated 0.72 (0.56-0.88) 0.64 (0.46-0.82) 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 6

A role for ETCO2 in the out of hospital diagnosis of sepsis Infection without Sepsis N=55 (95%CI) Infection with Sepsis N=31 (95%CI) Total N=86 (95%CI) P-Value ETCO2 35 (33-37) 28 (22-33) 32 (30-35) 0.013 Respiratory Rate 28 (25-31) 29 (25-32) 28 (26-30) 0.763 Systolic BP 143 (136-151) 73 (66-81) 81 (77-85) <0.001 Diastolic BP 85 (80-90) 74 (56-91) 86 (84-88) 0.006 Pulse 101 (93-109) 111 (101-121) 104 (98-110) 0.123 Saturation 92 (90-94) 88 (83-92) 91 (88-94) 0.072 Shock Index 0.74 (0.66-0.82) 1.02 (0.88-1.15) 0.84 (0.76-0.91) <0.001 AUC (95% CI) P-Value ETCO2 0.74 (0.62-0.87) <0.001 Respiratory Rate 0.50 (0.37-0.64) 0.982 Systolic BP 0.76 (0.65-0.86) <0.001 Diastolic BP 0.68 (0.55-0.80) 0.007 Pulse 0.61 (0.49-0.74) 0.090 Saturation 0.62 (0.49-0.74) 0.069 Shock Index 0.73 (0.62-0.85) <0.001 Prehospital ETCO2 predicts mortality in patients with SIRS Survivors N=371 (95% CI) Non-Survivors N=14 (95% CI) Total N=385 (95% CI) P-Value ETCO2 34 (33-35) 23 (19-26) 33 (32-34) <0.001 Respiratory Rate 29 (28-30) 31 (26-36) 29 (28-30) 0.519 Systolic BP 142 (139-145) 113 (88-138) 141 (138-144) 0.001 Diastolic BP 86 (84-88) 74 (56-91) 86 (84-88) 0.131 Pulse 114 (112-117) 111 (100-123) 114 (112-117) 0.617 Saturation 94 (93-95) 85 (79-90) 93 (93-94) <0.001 AUC (95% CI) P-Value ETCO2 0.84 (0.77-0.92) <0.001 Respiratory Rate 0.55 (0.38-0.71) 0.563 Systolic BP 0.69 (0.54-0.85) 0.014 Diastolic BP 0.60 (0.43-0.77) 0.226 Pulse 0.46 (0.30-0.62) 0.604 Saturation 0.79 (0.66-0.92) <0.001 Shock Index 0.57 (0.40-0.73) 0.411 7

ETCO2 in Emergency Department Sepsis Protocol ORMC ED began an internal sepsis screening protocol for those with suspected infection and 2 SIRS criteria (hold ICU beds, contact pharmacy) ETCO2 and serum lactate levels were collected in triage Of 54 activations 87% were diagnosed with sepsis Mean lactate levels were 3.4 (95%CI 2.6 4.2) vs 2.1 (95%CI 0.5 3.7; p=0.169 Mean ETCO2 levels were 31 (95%CI 27 34) vs 47 (95%CI 33 66; p=0.001) The AUC for ETCO2 predicting sepsis was 0.87 (95%CI 0.75 0.98) and for lactate was 0.68 (95%CI 0.42 0.93) Low ETCO2 predicted sepsis in a triage screening tool Orange County EMS System Sepsis Protocol 8

Accuracy of a prehospital sepsis alert protocol utilizing ETCO2 Preliminary pilot study to determine the accuracy of the protocol Poor protocol compliance created a study group 38 sepsis alert called by single agency to single ED 14 (37% appropriately called based on ETCO2 25mmHg, 24 (63%) had 2 SIRS criteria but ETCO2 > 25mmHg Mean ETCO2 in appropriate alerts was 18 (95%CI 15 20) vs 32 ((95%CI 29 35; p=0.001). Mean lactate levels in the ED were 5.3 (95%CI 2.5 8.2) vs 2.1 (95%CI 1.7 2.6; p=0.003) The correlation between ETCO2 and lactate was 0.50, p=0.008 The AUC for ETCO2 predicting appropriate activation of sepsis alert was 0.97 (95%CI 0.91 1.0) Using the ETCO2 25mmHg cut off yielded a sensitivity of 100% and a specificity of 95% When appropriately used, the Orange County EMS System sepsis alert was highly sensitive and specific Effectiveness of a prehospital sepsis alert protocol utilizing ETCO2 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%) Preliminary data, but 9

Take Home Points Early identification and resuscitation by prehospital providers may improve outcomes for patients with sepsis 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 ETCO2 may be used as a non invasive, real time adjunct screening tool to create protocols for prehospital sepsis identification Works Cited McGillicuddy, D, Tang, A, Cataldo, L, Gusev, J, Shapiro, N. Evaluation of end tidal carbon dioxide role in predicitng elevated SOFA scores and lactic acidosis. Intern Emerg Med. 2010 Nagler, J, Wright, R, Krauss, B. End tidal carbon dioxide as a measure of acidosis among children with gastroenteritis. Pediatrics 118:1 2008 Deakin, CD, Sado, DM, Coats, TJ, Davies, G (2004) Prehospital end tidal carbon dioxide concentration and outcome in major trauma. J Trauma 57(1):65 68 Hunter, Cl, Silvestri, S, Dean, M, Falk, JL, Papa, L End tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emergg Med 2013 Jan;31(1):64 71 Fearon, DM, Steele, DW (2002) End tidal carbon dioxide predicts the presence and severity of acidosis in children with diabetes. Acad Emerg Med 9(12): 1373 1378. Kartal, M, Oktay, E, Rinnert, S, Goksu, E, Bektas, F, Eken, C. ETCO2: a precitive tool for excluding metabolic disturbances in nonintubated patients. Am J Emerg Med. 2011;29:65 69. Kheng, CP, Rahman, NH. The use of end tidal carbon dioxide monitoring in patients with hypotension in the emergency department. Inter J Emerg Med. 2012;5:31 38. Silvestri S, Ralls GA, Krauss B, et al. The effectiveness of out of hospital use of continuous end tidal carbon dioxide monitoring on the rate of unrecognized misplaced intubation within a regional emergency medical services system. Ann Emerg Med 2005; 45:497. Ward, KR, Yealy, DM. End tidal carbon dioxide monitoring in emergency medicine, part 1: Basic principles. Acad Emerg Med. 1997; 5:628 636. Caputo, ND, Fraser, RM, Paliga, A, Matarlo, J, Kanter, M, Hosford, K, Madlinger, R. Nasal cannula end tidal CO2 correlates with serum lactate levels and odss of operative intervention in penetrating trauma patients: a prospective cohort study. J Tramua Acute Care Surg. 2012;73(5):1202 7. Nagler, J, Wright, RO, Krauss, B (2006) End tidal carbon dioxide as a measure of acidosis among children with gastroenteritis. Pediatrics 118(1): 260 267. Santos, LJ, Varon, J, Pic Aluas, L, Combs, AH (1994) Practical uses of end tidal carbon dioxide monitoring in the emergency department. J Emerg Med 12(5):633 644 Soleimanpour H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE Esfanjani RM. Predictive value of capnography for suspected diabetic ketoacidosis in the emergency department West J Emerg Med 2013 14(6):590 4 10