by Elizabeth Odom, MD MPH
EMS MEd editor: Maia Dorsett MD PhD (@maiadorsett)
Case Scenario
It’s a hot summer day and EMS is dispatched to an old farmhouse on the edge of the town for a patient who has been ”generally weak” and now unable to get out of bed. Upon arrival, paramedics find a previously healthy 65 year old female who has had a productive cough for a week. She has had little oral intake for 3 days and her urine has been dark and low in volume. Her husband called EMS because she has become progressively more confused over the course of the day. Her vital signs are T 38.1 HR 96 BP 115/80 RR 23 O2 Sat 91%.
The patient is quickly loaded into the ambulance. An IV is placed and fluid bolus is initiated. Fingerstick blood sugar is within normal limits and an ECG demonstrates sinus rhythm. Given the semi-rural location, transport to the hospital will exceed 30 minutes.
The paramedic suspects sepsis. What is the role of EMS in sepsis screening and treatment? How should we best screen for sepsis in the prehospital environment? Beyond IV fluids, should EMS administer antibiotics?
Literature Review
Sepsis is a Time-Critical Diagnosis
Advancements in protocols for STEMI and trauma patients have drastically improved early identification and treatment [1,2]. Like STEMI and Trauma, sepsis is a time-critical diagnosis where early screening and intervention can impact outcome [3-6]. With a mortality rate of 18-50% depending on other risk factors, severe sepsis should be acted on as quickly as possible [7]. Septic patients who are transported by EMS are sicker and have a higher mortality than those who arrive via other means, so the effect of any delay in antibiotic administration in this population may be amplified [8]. Delays in care of even 1 hour after first medical contact have been shown to increase mortality in patients with severe sepsis [9-12] while antibiotic therapy within the first hour of severe sepsis recognition contributed to an 80% survival [13]. The rapid administration of broad spectrum IV antibiotics may save more lives than the administration of aspirin in acute MI and epinephrine in anaphylaxis [14].
Current literature suggests that sepsis is both underrecognized and undertreated in the prehospital setting [15-16]. The reasons are likely multi-factorial, but include knowledge gaps as well as poor prehospital performance of sepsis screening tools. A recently published survey study from Atlanta found that 24% of paramedics were unaware of evidence supporting early sepsis treatment [17]. Moreover, 73% of participating Emergency Physicians reported caring for patients with sepsis almost every shift, while 62% of EMS providers reported caring for patients with sepsis no more than occasionally. While there are multiple sets of criteria for diagnosing sepsis, sepsis screening tools have variable performance in the prehospital setting. MEWS (Modified Early Warning Score) and BAS 90-30-90 scores were 74% and 62% sensitive, while the Robson score has been found to be 75-90% sensitive [18-21]. The PRESS (prehospital severe sepsis) score to identify severe sepsis also has a sensitivity near 90%, but is rather complicated for prehospital use [22]. qSOFA was developed as a simple tool to prompt clinicians to consider sepsis and escalate therapy as appropriate [23,24]. However, recent studies have demonstrated that although very specific, it has extremely poor sensitivity for severe sepsis in the prehospital setting, predominantly due to absence of hypotension until after ED admission [25,26]. SIRS itself lacks specificity in the prehospital setting. Moreover, in the hospital, 12.1% of patients with documented severe infection causing end-organ dysfunction are SIRS-negative [27].
Some services have successfully introduced lactate meters to detect occult hypoperfusion to enable hospital notification of a need for early, aggressive intervention [6]. As lactate meters are cost-prohibitive for many services, an important alternative to is end-tidal capnography, which is more widely available and has increasing applications in the prehospital setting. More recently, end-tidal CO2 levels were found to correlate with lactate levels and mortality in the ED setting [28]. Incorporation of end-tidal capnography into a SIRS-based prehospital sepsis alert protocol had a sensitivity of 90% (95% CI 81-95%), a specificity of 58% (95% CI 52-65%), and a negative predictive value of 93% (95% CI 87-97%) for sepsis and severe sepsis [29] .
EMS Interventions and Antibiotic Administration
Although decreased time to from first medical contact to antibiotic administration has the potential to impact mortality for patients with severe sepsis and septic shock, few EMS systems have initiated the administration of antibiotics to septic patients in the prehospital setting. This is due to a number of complexities. First, as discussed above, sepsis may be difficult to diagnose, despite the numerous algorithms that have been presented. Second, blood cultures allow for targeted antimicrobial therapy and these should typically be drawn prior to antibiotic administration, which may be subject to contamination or be difficult to obtain in the prehospital setting. Third, logistics and costs behind carrying and administering antibiotic agents on ambulances limits feasibility without substantial evidence behind the routine administration of antibiotics in the field.
Some EMS systems have standardized sepsis protocols based on one or a combination of scales references above. The mainstay of these protocols is fluid resuscitation and prehospital notification [6]. A small number of EMS systems have begun to introduce antibiotic administration into their protocols for patients with severe sepsis. This has reduced time to antibiotic from an average of 131 minutes after first contact to 69 minutes [30]. Even with short transport times, antibiotics may be initiated prior to arrival, eliminating the wait time for a bed, to see a physician, to receive the drug from pharmacy, and for a nurse to administer it. In South Carolina, EMS has treated 650 septic patients according to this protocol and 59% have received antibiotics [31]. Patients with > 2 SIRS criteria and a Point of Care Lactate >2.2mmol/L were treated with IV or interosseous ceftriaxone 1 g is in cases of suspected pneumonia or piperacillin/tazobactam 4.5 g following obtainment of blood cultures. Contamination rate for EMS-obtained blood cultures was <6%. Preliminary data showing a reduction from 25.6% mortality vs 9.3% mortality for patients with sepsis within the hospital system. In Australia and New Zealand, the PASS (Paramedic Antibiotics for Severe Sepsis) study, a randomized trial in which paramedics following a similar protocol is underway [32].
One of the most commonly cited fears regarding prehospital antibiotic administration is that it will cause an in antibiotic resistance. Inappropriately prescribed antibiotics do indeed increase resistance [33]. “Inappropriate” antibiotic use in an undifferentiated patient is not straightforward to define. Programs will have to fairly be compared to ED-administered antibiotics (rather than hospital final-diagnosis) and the impact on patient-centered outcomes measured prospectively. Empiric antibiotics provided are consistent with those recommended by local agencies for bacterial sensitivity resistance patterns for each area [34]. Ideally, a randomized-controlled trial will be conducted as the true risks-benefits of EMS-initiated antibiotics is unclear.
Take Home
Sepsis is a time-critical diagnosis and EMS can play a key role in reducing time to intervention and impacting patient-centered outcomes. Currently, sepsis remains underrecognized and undertreated in the prehospital setting, largely due to knowledge gaps and poor performance of screening methods. Recently, end-tidal capnography has emerged as a tool to enhance prehospital sepsis screening. Some EMS agencies have introduced paramedic-initiated antibiotics with some success. Further research is needed to fully understand the risks and benefits of this approach, which may vary regionally due to transport times and subsequent hospital-based patient management.
References
1. Mehta RH, Montoye CK, Gallogly M, et al., for the GAP Steering Committee of the American College of Cardiology. Improving quality of care for acute myocardial infarction: The Guidelines Applied in Practice (GAP) Initiative. JAMA. 2002; 287: 1269–1276.
2. Demetriades D, Martin M, Salim A, Rhee P, Brown C, Chan L. The Effect of Trauma Center Designation and Trauma Volume on Outcome in Specific Severe Injuries. Annals of Surgery. 2005;242(4):512-519.
3. McPherson D, Griffiths C, Williams M, et al. Sepsis-associated mortality in England: an analysis of multiple cause of death data from 2001 to 2010. BMJ Open. 2013;3(8).
4. Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369(21):2063.
5. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580–637.
6. Guerra, W. F., Mayfield, T. R., Meyers, M. S., Clouatre, A. E., & Riccio, J. C. (2013). Early detection and treatment of patients with severe sepsis by prehospital personnel. The Journal of emergency medicine, 44(6), 1116-1125.
7. 7. Linde-Zwirble WT, Angus DC. Severe sepsis epidemiology: sampling, selection, and society. Crit Care 2004;8(4):222–226
8. Angus, Derek C.; Seymour, Christopher W.; Coopersmith, Craig M.; Deutschman, Clifford S.; Klompas, Michael; Levy, Mitchell M.; Martin, Gregory S.; Osborn, Tiffany M.; Rhee, Chanu. “A Framework for the Development and Interpretation of Different Sepsis Definitions and Clinical Criteria”. Critical Care Medicine. 44 (3): e113–e121.
9. Cannon CM et al. The GENESIS Project (GENeralized Early Sepsis Intervention Strategies): A multicenter quality improvement collaborative. J Intensive Care Med 2012 Aug 17; [e-pub ahead of print].
10. Seymour, CW, Gesten F Prescott H, et. al. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med 2017; 376:2235-2244
11. Kumar A, Roberts D, Wood KE, 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;34(6):1589–1596.
12. Seymour, C. W., Kahn, J. M., Martin-Gill, C., Callaway, C. W., Yealy, D. M., Scales, D., & Angus, D. C. (2017). Delays From First Medical Contact to Antibiotic Administration for Sepsis. Critical care medicine, 45(5), 759-765.
13. Gaieski DF, Mikkelsen ME, Band RA, et al. Impact of time to antibiotics on survival in patients with severe sepsis or septic shock in whom early goal-directed therapy was initiated in the emergency department. Crit Care Med. 2010;38(4):1045–1053.
14. van Ruler O, Schultz MJ, Reitsma JB, et al. Has mortality from sepsis improved and what to expect from new treatment modalities: Review of current insights. Surg Infect (Larchmt). 2009;10(4):339–348.
15. Seymour CW, Carlbom D, Engelberg RA, et al. Understanding of sepsis among emergency medical services: a survey study. J Emerg Med. 2012;42(6):666–77.
16. Wang HE, Weaver MD, Shapiro NI, Yealy DM. Opportunities for Emergency Medical Services care of sepsis. Resuscitation. 2010;81(2):193–7.
17. Polito, C. C., Bloom, I., Yancey, A. H., Lairet, J. R., Isakov, A. P., Martin, G. S., … & Sevransky, J. E. (2017). Prehospital sepsis care: Understanding provider knowledge, behaviors, and attitudes. The American journal of emergency medicine, 35(2), 362-365.
18. Bayer O, Schwarzkopf D, Stumme C, Stacke A, Hartog CS, Hohenstein C, Kabisch, B, Reichel J, Reinhart K, Winning J. An Early Warning Scoring System to Identify Septic Patients in the Prehospital Setting: The PRESEP Score. Acad Emerg Med. 2015 Jul;22(7):868-71.
19. Adkins E, Koser S, Allion A, et al. White paper for early recognition and prehospital management of the adult septic patient [white paper]. Central Ohio Trauma System: Ohio, 2013.
20. Baez AA, Hanudel P, Wilcox SR. The prehospital sepsis project: Out-of-hospital physiologic predictors of sepsis outcomes. Prehosp Disaster Med. 2013;28(6):632–635.
21. Wallgren UM, Castrén M, Svensson AE, et al. Identification of adult septic patients in the prehospital setting: A comparison of two screening tools and clinical judgment. Eur J Emerg Med. Sept. 30, 2013. [Epub ahead of print.]22. Polito CC, Isakov A, Yancey AH 2nd, Wilson DK, Anderson BA, Bloom I, Martin GS, Sevransky JE. Prehospital recognition of severe sepsis: development and validation of a novel EMS screening tool. Am J Emerg Med. 2015 Sep;33(9):1119-25. doi: 10.1016/j.ajem.2015.04.024. Epub 2015 Apr 22. PubMed PMID: 26070235; PubMed Central PMCID: PMC4562872.
23. Singer, M., Deutschman, C. S., Seymour, C. W., Shankar-Hari, M., Annane, D., Bauer, M., … & Hotchkiss, R. S. (2016). The third international consensus definitions for sepsis and septic shock (sepsis-3). Jama, 315(8), 801-810.
24. Seymour, C. W., Liu, V. X., Iwashyna, T. J., Brunkhorst, F. M., Rea, T. D., Scherag, A., … & Deutschman, C. S. (2016). Assessment of clinical criteria for sepsis: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). Jama, 315(8), 762-774.
25. Dorsett M, Kroll M, Smith CS, Asaro P, Liang SY, Moy HP. qSOFA Has Poor Sensitivity for Prehospital Identification of Severe Sepsis and Septic Shock. Prehosp Emerg Care. 2017 Jul-Aug;21(4):489-497. doi: 10.1080/10903127.2016.1274348. Epub 2017 Jan 25.
26. AlQahtani, S., Menzies, P., Bigham, B., & Welsford, M. (2017). P007: A comparative analysis of qSOFA, SIRS and Early Warning Scores Criteria to identify sepsis in the prehospital setting. CJEM, 19(S1), S79-S80. doi:10.1017/cem.2017.209
27. Kaukonen, K. M., Bailey, M., Pilcher, D., Cooper, D. J., & Bellomo, R. (2015). Systemic inflammatory response syndrome criteria in defining severe sepsis. New England Journal of Medicine, 372(17), 1629-1638.
28. Hunter, C. L., Silvestri, S., Dean, M., Falk, J. L., & Papa, L. (2013). End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. The American journal of emergency medicine, 31(1), 64-71.
29. Hunter, C. L., Silvestri, S., Ralls, G., Stone, A., Walker, A., & Papa, L. (2016). A prehospital screening tool utilizing end-tidal carbon dioxide predicts sepsis and severe sepsis. The American journal of emergency medicine, 34(5), 813-819.
30. Studnek JR, Artho MR, Garner CL Jr, et al. The impact of emergency medical services on the ED care of severe sepsis. Am J Emerg Med. 2012;30(1):51–56.
31. Walchok, J. G., Pirrallo, R. G., Furmanek, D., Lutz, M., Shope, C., Giles, B., … & Dix, A. (2017). Paramedic-initiated CMS sepsis core measure bundle prior to hospital arrival: a stepwise approach. Prehospital Emergency Care, 21(3), 291-300.
32. Mayfield, TR, Meyers, M. Mackie, J, Incidence of Adverse Reactions to Initial Antibiotic Administration in Severe Sepsis Patients, poster presentation, EMSToday 2015 Baltimore, MD February 26, 2015
33. Centers for Disease Control and Prevention, Office of Infectious Disease Antibiotic resistance threats in the United States, 2013. Apr, 2013. Available at: http://www.cdc.gov/drugresistance/threat-report-2013. Accessed January 28, 2015.
34. Pradipta IS, Sodik DC, Lestari K, et al. Antibiotic Resistance in Sepsis Patients: Evaluation and Recommendation of Antibiotic Use. North American Journal of Medical Sciences. 2013;5(6):344-352.
