Improving Outcomes in Sepsis

Standardizing the prehospital approach to sepsis patients may benefit the overall system of care, the authors write.

Recommendations for Regionalization of Sepsis Care

Standardizing the prehospital approach to sepsis patients may benefit the overall system of care, the authors write.

Introduction

Sepsis is a condition in which infection, often complicated by comorbid conditions, overwhelms the body’s compensatory physiological processes. Failure to identify sepsis early risks progression to severe sepsis or septic shock, for which mortality rates can reach 40%.1 Emergency medical services (EMS) systems have historically offered early recognition and management for patients with other emergent and life-threatening conditions. Moreover, the evolution of EMS systems has closely paralleled the development of clinical care evaluation and management within hospital emergency medicine. Examples of these close alliances include the evaluation and management of victims of acute traumatic injury, acute coronary syndrome, stroke and burns. To date, however, EMS systems have yet to widely adopt a uniform protocol for sepsis identification and treatment.

Prehospital Versus Hospital Care for Sepsis

Prehospital care focuses on medical evaluation and response both in the field and in transit to the hospital. This includes the initiation of management strategies and guidelines authorized by the EMS system medical director, as governed by state-specific laws and regulations. EMS medical directors provide general guidance in creating protocols and guidelines, but uniform standards generally do not exist unless mandated by governing bodies at the regional and/or state level. By contrast, hospital systems are generally monitored by the Joint Commission or similar regulatory bodies for various nationally standardized metrics. Despite this apparent disconnect between prehospital and hospital domains, coordinated care for several emergency conditions already exists.

Related

One such protocol is time to activation of cardiac intervention teams for the treatment of ST elevation myocardial infarction (STEMI) with percutaneous coronary intervention (PCI). Prehospital systems commonly communicate closely with hospital systems to optimize their response to time-sensitive conditions such as STEMI, including the facilitation of early PCI laboratory activation to improve time to re-vascularization. 

The benefit of early activation of hospital facilities for patients with known or suspected sepsis identified in the prehospital arena remains unclear. The purpose of this study is to explore both the published science and the efforts of various EMS agencies to determine if a clinical benefit might result from early sepsis intervention. Specifically, this paper examines selected examples from the scientific literature for evidence of benefit to early identification of sepsis patients in the field, the effects of various management strategies, and the potential value of field activation of hospital sepsis teams. Outcome parameters are measured through the reduction of morbidity, mortality and response times. Finally, this paper examines the benefits of various management strategies, including fluid administration and the potential role of antibiotics in the field.

Status of the Prehospital Sepsis Evaluation and Management in the North Texas Region

In 2019, the North Central Texas Trauma Regional Advisory Council (NCTTRAC) surveyed regional EMS systems to determine for the use of sepsis protocols or clinical practice guidelines and the components thereof. The survey was sent to 220 recipients of which 43 responded for a response rate of 20%. Their responses are summarized in Table 1.

  EAGLES SurveyNorth Texas Survey
Survey QuestionsNo. of Respondents2943
Have a specific sepsis protocol 68.9%97.7%
Activate a sepsis alert 58.6%81.4%
Sepsis team activated at receiving hospital 17.0%N/A
Parameters used to assess sepsis   
     Tachycardia N/A100%
     Temperature 79.3%69.8%
     EtCO2 58.6%69.8%
     Tachypnea 34.5%74.4%
     Blood Pressure 44.8%83.7%
     Lactate 6.9%4.7%
Administered antibiotics in the field 13.8%16.3%
Table 1

The survey questions consisted of:

  1. Identification of sepsis patients, including the use of Systemic Inflammatory Response Syndrome (SIRS) criteria (Figure 1), if any
  2. Fluid management
  3. Vasopressor management
  4. Dopamine, norepinephrine, epinephrine, other
  5. Use of antibiotics in the field
  6. Sepsis team activation at destination facilities
Systemic Inflammatory Response Syndrome (SIRS)qSOFA Criteria
Two or more of the following:Two or more of the following:
Temperature: <36°C or >38°CRespiratory Rate: >22 breaths per minute
Heart Rate: >90 beats per minuteSystolic Blood Pressure: <100 mmHg
Respiratory Rate: >20 breaths per minute or PaCO2 <32 mmHgAltered Mental Status (GCS<14)
White Blood Cell Count: >12,000 or <4,000 or >10% immature forms
Figure 1

Ninety-seven percent of respondents reported specific criteria for the identification of sepsis patients, 97% initiated a fluid bolus intravenously, and 16% administered antibiotics in the field to patients meeting their sepsis criteria. Fifty-six percent of agencies included options for vasopressor administration, including norepinephrine (34.9%), dopamine (11.6%), epinephrine (9.3%) and/or other (16.3%).

The Eagles Survey

In February 2021, the authors polled the Metropolitan EMS Medical Directors Global Alliance “Eagles” regarding their sepsis protocols. Our survey contained similar components to that of NCTTRAC, but applied to a much wider geographical range, including international EMS agencies. Out of a total of 96 agencies, 29 responded for a response rate of 30%. Of the 29 responses, 69% (20/29) of agencies reported use of an EMS sepsis protocol, and 58% (17/29) reported activating a sepsis alert in the field. Common metrics used to identify sepsis in the field include temperature, EtCO2, blood pressure, heart rate, respiration rate, and SIRS or qSOFA criteria.2

Literature Review

Our review of the prehospital literature on sepsis identification and management reveals two important findings: 1) EMS clinicians demonstrate difficulty identifying sepsis in the field, and 2) sepsis patients transported by EMS clinicians typically exhibit more severe symptoms compared to their counterparts who arrived at the emergency department (ED) by means other than EMS.3-5 The difficulty of out-of-hospital sepsis identification and severity of presentation, in turn, delay appropriate treatment, and potentially leads to increased incidence of adverse outcomes.

Identification of sepsis in the field is a critical step in initiating management and often times the most difficult part. One study by Sjösten et al. retrospectively compared the final diagnosis of sepsis in the hospital with initial identification in the field by EMS clinicians.3

Their patient population included 353 individuals with a final hospital diagnosis of sepsis who were transported to the hospital by EMS. They found that EMS clinicians correctly identified sepsis patients in only 36% of the cases.Similarly, Smyth et al. conducted a meta-analysis to analyze the success rate of sepsis screening by EMS.4 They reported a diagnostic variance ranging from 48% to 78% for the correct identification of sepsis in patients prior to arrival in the ED (4). Methods used to identify sepsis relied significantly on a patient history suggestive of infection, oxygen saturation, temperature and respiratory rate. Among these populations, EMS- transported sepsis patients were more likely to present with comorbidities, end organ damage, and septic shock.5

Implementation of a sepsis alert in the field has been useful in promoting early downstream treatment administration times. Measurements by Hunter et al. included fluid resuscitation, blood cultures, serum lactate and time to antibiotic administration. Data showed that time to completion for all measured metrics improved for those patients transported to hospitals that received a sepsis alert from the field. Of note, patients for whom the hospitals received a field sepsis alert experienced higher hospital admission rates and lower ICU admission.5 However, no significant difference in mortality was observed between the sepsis alert group and the non-sepsis alert group (11% vs 14%, p=0.565).6

Alam et al. report that focused training for EMS personnel improved the ability to diagnose sepsis in the field and enhanced overall the access to timely patient care.7 In this study, EMS clinicians were enrolled in a curriculum focused on identifying and managing sepsis. The efficacy of their training was assessed using time to antibiotics between the cohort of patients treated by EMS clinicians who participated in the curriculum and those who had not. This study also assessed the efficacy of early antibiotic administration in sepsis patients for all-cause mortality at 28 days after treatment. The authors divided the patients into two cohorts: those receiving early antibiotic administration (200 mg ceftriaxone intravenously) versus those receiving basic care and management with oxygen supplementation and fluid resuscitation. The mortality rate difference between the intervention group (7.8%) and the basic care and management group (8.2%) was not statistically significantly different, with a relative risk of 0.95 (95% CI 0.74 – 1.24). The rate of hospital readmission was, however, significantly lower in the intervention group (6.6% vs. 10.5%) than in the basic care management group (p=0.0004).8

A Proposed Strategy for Sepsis Evaluation and Hospital Notification

Early identification of sepsis in the field remains challenging for EMS clinicians. Lack of standardization in sepsis patient identification across EMS agencies and systems may result in a potential delay in definitive medical treatment. Focused education and training among EMS clinicians to better identify sepsis in the field, as well as standardized sepsis screening tools (along with early receiving hospital notification) may be needed to improve clinical outcomes among sepsis patients.

An example of such a screening tool is a composite, standardized sepsis checklist developed for the North Central Texas region to facilitate the identification of sepsis (Figure 2). It is derived from established, evidence-based metrics used to screen for sepsis including established criteria (e.g., SIRS and qSOFA criteria), vital signs (including temperature) and mental status, excluding criteria that may not be available to EMS (such as point-of-care lactate measurement). A key checklist feature is the pre-arrival notification of the receiving hospital to facilitate expedited care. The receiving hospitals’ responses to the EMS sepsis alerts will be at their discretion, and widespread implementation of this sepsis screening tool would require collaborative education and training for both EMS and hospital healthcare professionals.

Figure 2

Discussion

Vigorous crystalloid fluid resuscitation, supplemental oxygen, and vasopressors remain the mainstays of prehospital sepsis treatment.

On the other hand, the potential benefits of early prehospital antibiotic administration for potential sepsis are not well established. Early antibiotic treatment in this sense is defined as administration in the field by EMS prior to arrival at the ED. At least one ED study reported improved mortality inpatient who received antibiotics earlier, as measured by time to antibiotics after arrival in the ED as seen in the work conducted by Ferrer et al.9 Similar studies of early antibiotic administration in the field for sepsis patients failed to demonstrate a statistically significant difference in mortality. This may be because transport times are not long enough to factor significantly into patient survival with regards to antibiotic treatment. 

In our survey, we found that few EMS agencies administer antibiotics, and those that do have not reported their data on this treatment’s impact on patient mortality or other patient-centered outcomes.

This preliminary report has limitations. One limitation is the use of convenience sampling to survey our agencies. We sought to mitigate the potential regional bias of the NCTTRAC’s survey via our Eagles survey by introducing geographical diversity amongst our respondents. It is important to note, however, that this is a preliminary study of existing literature, and our initial sample size lacks statistical power. Many studies on this topic likewise report small sample sizes with low statistical power to detect a true effect of intervention.

Moving forward, our goal is to explore quantifiable results for patient outcomes using prospective cohort studies. Such studies would compare patient mortality before and after implementation of a regional, prehospital-and-ED sepsis alert initiative to assess the feasibility and efficacy of early prehospital sepsis notifications and interventions.

Conclusion

Sepsis is a potentially life-threatening condition requiring prompt identification and intervention to enhance outcome. The literature suggests that incorporation of a prehospital sepsis alert leads to earlier treatment. While our review indicates that the administration of antibiotics in the field at this time is of unclear value in improving outcome, robust observational data support timely use of other well-established treatment modalities and benchmarks. Specifically, patients for whom a sepsis alert was activated during prehospital care were more likely to have faster door-to-antibiotic times, earlier blood cultures, and earlier targeted supportive therapy. Thus, standardizing the prehospital approach to sepsis patients may benefit the overall system of care for these patients.

References

1. Vincent JL, Jones G, David S, Olariu E, Cadwell KK. Frequency and mortality of septic shock in Europe and North America: a systematic review and meta-analysis. Crit Care. 2019 May 31;23(1):196. doi: 10.1186/s13054-019-2478-6. PMID: 31151462; PMCID: PMC6545004.

2. Gaddis ML, Gaddis GM. Detecting Sepsis in an Emergency Department: SIRS vs. qSOFA. Mo Med. 2021 May-Jun;118(3):253-258. PMID: 34149086; PMCID: PMC8210984.

3. Sjösten O, Nilsson J, Herlitz J, Axelsson C, Jiménez-Herrera M, Andersson Hagiwara M. The prehospital assessment of patients with a final hospital diagnosis of sepsis: Results of an observational study. Australas Emerg Care. 2019 Sep;22(3):187-192. doi: 10.1016/j.auec.2019.02.002. Epub 2019 Mar 14. PMID: 31042522.

4. Smyth MA, Brace-McDonnell SJ, Perkins GD. Identification of adults with sepsis in the prehospital environment: a systematic review. BMJ Open. 2016 Aug 5;6(8):e011218. doi: 10.1136/bmjopen-2016-011218. PMID: 27496231; PMCID: PMC4985978.

5. Wang HE, Weaver MD, Shapiro NI, Yealy DM. Opportunities for Emergency Medical Services care of sepsis. Resuscitation. 2010 Feb;81(2):193-7. doi: 10.1016/j.resuscitation.2009.11.008. Epub 2009 Dec 16. PMID: 20006419; PMCID: PMC4028958.

6. Hunter CL, Silvestri S, Stone A, Shaughnessy A, Miller S, Rodriguez A, Papa L. Prehospital sepsis alert notification decreases time to initiation of CMS sepsis core measures. Am J Emerg Med. 2019 Jan;37(1):114-117. doi: 10.1016/j.ajem.2018.09.034. Epub 2018 Sep 22. PMID: 30269999.

7. Alam N, Oskam E, Stassen PM, Exter PV, van de Ven PM, Haak HR, Holleman F, Zanten AV, Leeuwen-Nguyen HV, Bon V, Duineveld BAM, Nannan Panday RS, Kramer MHH, Nanayakkara PWB; PHANTASi Trial Investigators and the ORCA (Onderzoeks Consortium Acute Geneeskunde) Research Consortium the Netherlands. Prehospital antibiotics in the ambulance for sepsis: a multicentre, open label, randomised trial. Lancet Respir Med. 2018 Jan;6(1):40-50. doi: 10.1016/S2213-2600(17)30469-1. Epub 2017 Nov 28. PMID: 29196046.

8. Seymour CW, Kahn JM, Martin-Gill C, Callaway CW, Yealy DM, Scales D, Angus DC. Delays From First Medical Contact to Antibiotic Administration for Sepsis. Crit Care Med. 2017 May;45(5):759-765. doi: 10.1097/CCM.0000000000002264. PMID: 28234754; PMCID: PMC6065262.

9. Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP, Artigas A, Schorr C, Levy MM. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014 Aug;42(8):1749-55. doi: 10.1097/CCM.0000000000000330. PMID: 24717459.

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