Recognition and Awareness of Sepsis by First-Aid Providers in Adults With Suspected Infection: A Scoping Review

Sepsis accounts for a significant proportion of preventable deaths worldwide and early treatment has been found to be a mainstay of decreasing mortality. Early identification of sepsis in the first-aid setting is critical as this results in a shorter time to hospital presentation and management with antibiotics and initial resuscitation. Our aim was to explore the existing literature related to either sepsis recognition or awareness of sepsis by first-aid providers who are evaluating an adult suspected of an acute infection. Our scoping review was performed as part of the International Liaison Committee on Resuscitation's (ILCOR) continuous evidence evaluation process to update the 2024 ILCOR Consensus on Science with Treatment Recommendations. We searched Embase, Medline, and Cochrane databases from their inception to January 17, 2023, with updated searches performed on November 21, 2023, and December 2, 2023. The gray literature search was conducted on August 29, 2023. The population included adults presenting with an acute illness exhibiting signs and symptoms of a severe infection. Outcomes included sepsis recognition or awareness of sepsis by a lay first-aid provider. After reviewing 4380 potential sources, four reviews (three systematic reviews and one scoping review), 11 observational studies, and 27 websites met the inclusion criteria. No study directly addressed our PICOST (Population, Intervention, Comparator, Outcomes, Study Design, and Timeframe) question as none were performed in the first-aid setting. Three systematic reviews and nine observational studies that assessed the ability of early warning scores to detect sepsis and predict adverse outcomes secondary to sepsis had inconsistent results, but many found the screening tools to be useful. One scoping review and one observational study found public knowledge and awareness of sepsis to be variable and dependent upon healthcare employment, location, education level, ethnicity, sex, and age. Signs and symptoms associated with sepsis as listed by gray literature sources fell primarily under nine general categories as a means of educating the public on sepsis recognition. Although this scoping review did not identify any studies that directly addressed our outcomes, it highlights the need for future research to better understand the recognition of sepsis in first-aid settings.


Introduction And Background
Sepsis is a critical medical condition characterized by a dysregulated host response to infection, leading to organ dysfunction and potential mortality [1].With its potential for rapid progression and poor outcomes, frequently requiring admission to the medical wards or an intensive care unit (ICU), sepsis poses a significant burden to healthcare systems worldwide [2].While the precise global incidence of sepsis is difficult to ascertain, estimates suggest that millions of cases occur annually and it is a major public health issue [3].Hospital mortality rates have been reported as ranging between 15% and 30% in high-income countries (HICs), increasing to 50% or more in low-to middle-income countries (LMICs) [4,5].
Sepsis presents with a diverse array of signs and symptoms that can vary depending on the underlying infection, the patient's age, and comorbidities.Common clinical manifestations include fever, lethargy, tachycardia, tachypnea, altered mental status, and subjectively feeling unwell, although these may or may not be present.The non-specific nature of these features often results in sepsis mimicking other conditions and diagnostic uncertainty [6].
Prompt recognition and early intervention are paramount in managing sepsis effectively.Early administration of appropriate antibiotics and resuscitative measures have been shown to improve outcomes, including reducing mortality rates [7][8][9].Identifying sepsis in its early stages has proven to be challenging, even for healthcare providers with access to advanced testing.Screening tools have been developed to assist with the identification of sepsis, examples of which include vital signs, Systemic Inflammatory Response Syndrome (SIRS) criteria, quick Sequential Organ Failure Score (qSOFA) criteria, or Sequential Organ Failure Assessment (SOFA) criteria, National Early Warning Score (NEWS), NEWS2, Modified Early Warning Score (MEWS), and Phoenix Sepsis Score [10][11][12][13].However, the utility of these scores has been limited to the healthcare setting.A major limitation to these tools is that they cannot be universally applied by those assessing an acutely ill person for possible sepsis, specifically the lay provider who is often the initial contact and lacks the ability to obtain some of the required variables.Consequently, first-aid providers are limited to more basic means of evaluating someone suspected of sepsis, relying solely on subjective and objective signs of infection and hypoperfusion.
Despite the critical importance of early recognition and intervention, there is limited research evaluating a first-aid provider's ability to identify sepsis.We sought to explore the existing literature that was related to either sepsis recognition or awareness of sepsis by first-aid providers who are evaluating an adult suspected of an acute infection.

Review
This scoping review was developed as part of the International Liaison Committee on Resuscitation's (ILCOR) continuous evidence evaluation process, conducted by the ILCOR First Aid Task Force [14] and was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) [15].

Questions and objectives
We sought to answer the following PICOST (Population, Intervention, Comparator, Outcome, Study Designs and Timeframe) question, which was defined as: Population: Adults who are being evaluated by a first-aid provider for an acute illness.
Intervention: The identification of any specific signs or symptoms (e.g., pale, blue, or mottled skin, lips or tongue, gums, nails; non-blanching rash; difficulty in breathing or rapid respiratory rates; rigors/shivering; lack of urination in a day; muscle pain; confusion or slurred speech).
Outcome: 1. Recognition of a seriously ill person requiring hospitalization or evaluation by a physician for sepsis, 2. Increased awareness of sepsis.
Study designs: Randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies) are eligible for

Gray Literature
One reviewer (AK) screened the first 100 titles of each search for relevance, and after removal for redundancy, a total of 27 were selected for inclusion in the review.

Data extraction and analysis
Data from included data sources were extracted into an extraction matrix that was developed a priori.Data were subjected to simple descriptive analysis and organized into major topic domains and presented narratively.As is permitted in a scoping review, no formal risk of bias assessments were undertaken.

Study Characteristics
We identified three systematic reviews [17][18][19], one scoping review [20], and 11 observational studies [21][22][23][24][25][26][27][28][29][30][31] for inclusion, all of which were conducted in HICs; none were performed in the first-aid setting.No published studies directly addressed a first-aid provider's recognition of sepsis through the presence of specific signs or symptoms in a seriously ill person with the subsequent need to seek further medical attention.Given the lack of any direct evidence, we included studies that were performed in either the prehospital or in-hospital settings, or by emergency medical service (EMS) providers, and extrapolated the data to suggest relevance to the first-aid setting.Studies evaluating physiologic variables that a lay provider could obtain in a first-aid setting, such as temperature, heart rate, and respiratory rate, either in isolation or when assessing using clinical scoring tools, were selected for inclusion.Seven studies assessed screening score performance in the prehospital or in-hospital setting to identify sepsis [17][18][19][22][23][24][25].One study explored the clinical signs and field assessments by emergency medical service providers of patients with and without a suspicion of sepsis [29].Five studies evaluated prehospital and emergency triage screening score prediction for adverse in-hospital outcomes (ICU admission or mortality) [21,26,28,30,31].Two studies evaluated the awareness and knowledge of sepsis by various members of the population and identified potential contributing factors affecting the results [20,27].The characteristics of the included studies are provided in Tables 1, 2      One prospective, ambulance-based, cohort study analyzed the performance of qSOFA, NEWS2, and modified SOFA (mSOFA) as sepsis predictors in the prehospital setting among patients with a suspected infection and did not find any statistically significant differences between the scores [24].Barbara et al. performed a retrospective chart review of patients that met all the three qSOFA criteria by EMS and found a sepsis diagnosis in the ED to have a positive predictive value of 66.67% (95% CI 55.8-77.6)[22].The ED septic patients demonstrated a statistically significant difference of higher average temperature by >2 °F (>1 °C) (p=0.001),mean maximum heart rate by a difference of >10 beats per minute (p=0.019), and mean maximum respiratory rate of >4 breaths per minute (p=0.0001)compared with the non-septic patients.A retrospective diagnostic cohort study evaluated the accuracy of 21 prehospital early warning scores in combination with parametric diagnostic impression for identifying sepsis and found NEWS2 to be superior to all other scores [23].A retrospective analysis by Nualprasert et al. evaluated the ability of two early warning scores, Prehospital Early Sepsis Detection (PRESEP) score and Miami Sepsis Score, to detect septic patients in the prehospital setting and found both to be potential screening tool options for EMS given the relatively high sensitivities at the given cutoff values, 0.83 (0.73-0.90) and 0.81 (0.71-0.89), respectively [25].

EMS Use of Clinical Signs and Assessments in Suspected Sepsis
Sjösten et al. performed a retrospective observational analysis of EMS field assessments of patients with a prehospital suspicion of sepsis during which symptoms and vital signs were recorded in the research protocol [29].Prehospital signs and symptoms that were identified in patients with sepsis included: respiratory difficulties, gastrointestinal symptoms, altered mental status, skin rash, rigors or shivering, temperature abnormalities, and tachycardia.The most common symptoms were dyspnea, rigors or shivering, and confusion, and elevated respiratory and heart rate as well as temperature abnormalities were the most common abnormal vital signs observed in patients with a prehospital suspicion of sepsis.

Prediction of Adverse Outcomes
One systematic review [17] and four observational studies [24,28,30,31] evaluated the prognostic ability of sepsis screening tests performed in the prehospital or emergency setting to predict adverse in-hospital outcomes, such as progression to septic shock, mortality, critical care intervention, or ICU requirement.The qSOFA score was universally evaluated in all the studies but with variable results.
Based on the 18 articles included in the review conducted by De Silva et al., the authors concluded that qSOFA most successfully predicted mortality in at-risk patients compared to 31 other screening tools [17].A retrospective observational study that evaluated patients presenting to the ED with community-acquired pneumonia also found the qSOFA score to be useful in predicting ED mortality and identifying septic patients requiring critical care support [30].Usul  A comparison of qSOFA, NEWS2, and mSOFA in a prospective, multicenter cohort study showed that the mSOFA score performed consistently better in two-day mortality prediction and diagnosis of septic shock than both NEWS2 and qSOFA [24].However, the unique variables of mSOFA differentiating it from NEWS2 and qSOFA are derived from blood work.Perman et al. calculated qSOFA scores obtained at triage and during the ED stay derived from the worst vital signs to predict in-hospital mortality and compared these results with triage SIRS criteria of patients admitted with severe sepsis [28].Sensitivities for the prediction of inhospital mortality of triage qSOFA, maximum qSOFA, and triage SIRS were 33%, 69%, and 82%, respectively, suggesting that triage qSOFA is not reliable at identifying septic patients at a high risk of death.
Two observational studies [21,26] assessed prehospital characteristics of patients who were admitted to the hospital with diagnosed or suspected sepsis for association with adverse outcomes.One retrospective, crosssectional descriptive study found that rapid respiratory rate had high predictability for ICU admission (OR 4.81 (CI, 1.16-21.01;P = .0116))but no physiologic variables were predictive of mortality [21].Among the 327 patients who were admitted for suspected sepsis and initiation of treatment with antibiotics in a retrospective observational study by Olander et al., it was noted that the presence of prehospital altered mental status and low temperature may be related to poorer prognosis and adverse outcomes with need for ICU level of care and mortality [26].

Awareness and Knowledge of Sepsis
A review of 80 articles related to sepsis awareness and knowledge among healthcare professionals, patients.and the general public found that both knowledge and awareness varied significantly across the groups and geographically [20].Patients and the public, most of whom obtained information from the Internet, had less awareness and knowledge of sepsis than healthcare professionals.One cross-sectional survey evaluating public awareness and knowledge of sepsis in Canada found significant regional variation in self-reported awareness (p<0.001) and significant association with the respondents' education, ethnicity, sex, and age [27].The most recognized sign or symptom of sepsis was "fever" (55.7%) and others being "infection" (52.9%), "feeling extremely ill (like you are going to die)" (39.3%), "extreme shivering or muscle pain" (27.6%), "fast heart rate" (26.4%), "fast breathing/severe breathlessness" (21.2%), "skin blotchy or discolored" (20.7%), "slurred speech or confusion" (12.5%), and "passing no urine all day" (8.0%).

Discussion
This topic was selected by the ILCOR First Aid Task Force as a significant proportion of preventable deaths are caused by sepsis worldwide, and there are known benefits of early detection and treatment.No prior review has been undertaken, and in 2022, the Task Force elected by consensus to undertake a scoping review on the recognition and awareness of sepsis by first-aid providers evaluating adults with an acute illness.There were insufficient studies identified to support a systematic review.
Sepsis initiatives have increasingly focused on early sepsis recognition by the lay provider as a means to decrease time to hospital presentation and management with antibiotics and initial resuscitation.Despite the utilization of early warning scoring tools by trained clinicians in the healthcare setting to assist in the detection of sepsis, sepsis recognition remains a challenge due to the variable reliability of the scoring tools.
Based on evidence from the EMS and in-hospital settings, no specific sign or symptom or compilation of signs and symptoms has demonstrated a clear association with sepsis.Therefore, it is unreasonable to expect a lay provider to recognize and subsequently diagnose an acute illness as sepsis using only the signs and symptoms exhibited by an ill person.A more feasible request of a lay provider is to, at a minimum, consider an infection in a person being evaluated with an acute illness.
It was noted that online resources providing education to the public on sepsis recognition listed presenting signs and symptoms of sepsis under nine general categories (Table 4): temperature (fever or hypothermia), neurologic (change in mental state, dizziness, slurred speech), musculoskeletal (severe muscle pain, extreme shivering), urologic (poor urine output), respiratory (rapid breathing or breathlessness), skin (clammy/sweaty, new rash, mottled or discolored), cardiac (elevated heart rate), gastrointestinal (nausea, vomiting, diarrhea), and subjective (feeling very unwell or impending sense of doom).However, it was variable as to which signs or symptoms were highlighted by each campaign or organization.For instance, only five of the 27 websites included from the gray literature search mentioned "infection" when describing presenting signs and symptoms of sepsis.Additionally, the presence of a fever (≥ 38°C) was noted to be inconsistently listed as a sign of sepsis and highlights that an elevated temperature is not a prerequisite for this diagnosis.It is noteworthy that no literature originating from LMICs was included in this scoping review.Owing to a greater burden of infectious diseases and delayed presentations due to poor access to healthcare, the LMIC contexts may have much higher incidences of sepsis, resulting in higher mortality [4,5].It is also unclear to what extent the signs and symptoms reported in the HIC literature are transferable to LMICs, where diarrheal illnesses or vector-borne diseases (such as malaria) predominate.In LMICs that feature developing or do not have emergency care systems and services, the integration of community-based first-aid providers offers a prime opportunity to increase sepsis recognition and initiate healthcare-seeking behavior [59], ultimately resulting in decreased mortality.Given a higher sepsis incidence and the critical role that a firstaid provider might play in such nascent systems, it is necessary that research in LMIC contexts should be advanced.

Limitations
There are several limitations to this review.Although this scoping review has not identified sufficient evidence to prompt a further systematic review, it highlights important gaps in research, specifically in the first-aid setting.Retrospective diagnostic studies are needed to evaluate the accuracy of criteria used in specific sepsis awareness campaigns for lay providers.The effectiveness of sepsis awareness campaigns in helping lay responders identify sepsis should be studied to determine if any one campaign is more helpful than the other.Additionally, none of the included studies were conducted in LMICs where access of the disadvantaged to sepsis care or education may have led to alternative results.

Conclusions
Given the diagnostic challenge faced in the first-aid setting and time-sensitive nature of sepsis, increasing sensitivity for the detection of sepsis can be achieved by screening people with an infection and any correlating signs or symptoms that may fall along the spectrum of a less severe presentation.Although the criteria for sepsis may not be fulfilled, at that time or anytime in the future, they are likely to still benefit from an evaluation by a medical professional.Therefore, a first-aid provider should consider an infection in a person who presents with an acute illness, and if associated with any abnormal signs or symptoms, recommend seeking further medical evaluation.This scoping review found no studies directly addressing our outcomes.However, we identified studies that evaluated patients in the prehospital and in-hospital settings for potential sepsis, as well as awareness and knowledge of sepsis by various members of the community.

TABLE 2 : Characteristics of and Findings in the Included Observational Studies
[19][23][24][25] reviews[17][18][19]and four observational studies[22][23][24][25]evaluated the performance of sepsis screening scores to identify adult patients with sepsis in both the prehospital and in-hospital settings and found the accuracy of sepsis recognition by EMS providers to be variable.De Silva et al. identified 18 studies that compared the sensitivity and specificity of qSOFA to 31 other screening tools for the diagnosis of sepsis and determined that qSOFA produced high specificity and low sensitivity for the emergency diagnosis of sepsis among people with suspected or confirmed sepsis in either the prehospital setting or Emergency Department (ED)[17].Lane et al. described in a narrative review of 17 articles that the accuracy of prehospital sepsis identification of septic patients by EMS using SIRS criteria or a combination of vital signs was heterogeneous[18].The most common vital signs taken into consideration in seven studies were temperature, heart rate, and respiratory rate.Smyth et al. discussed very low quality of evidence in six studies that addressed the recognition of sepsis by EMS with the majority of screening tools relying on SIRS criteria[19].

Appendix 1 No. Search String Query (January 17, 2023) Results
The limited literature identified in this scoping review does not support the development of a systematic review but highlights the need for future research 2024 Kule et al.Cureus 16(6): e61612.DOI 10.7759/cureus.616129 of 14 to institute measures for the recognition of sepsis in first-aid settings.

TABLE 5 : Initial Search Query in and Results from Embase and Medline databases (January 17, 2023) No. Search String Query (January 17, 2023) Results #
1("emergency care" OR "emergency health service" OR "emergency medical service" OR "medical emergency service" OR "emergency health services" OR "emergency medical services" OR emergicenter* OR "medical emergency service" OR "medical emergency services" OR "prehospital emergency care" OR emergicentre* OR emergi-center* OR emergi-centre* OR "pre-hospital emergency care" OR EMT* OR "emergency medical technician" OR "first responder" OR "emergency medical technicians" OR "first responders" OR "first aid" OR "critical care"):ti,ab,kw #15 #12 NOT #13 in Cochrane Reviews, Trials (15 Cochrane Reviews, 405 Trials) 420

TABLE 8 : Follow-Up Search Query in and Results from Medline database (November 21, 2023) Appendix 3
Cochrane Follow-Up Search String(November 21, 2023)("emergency care" OR "emergency health service" OR "emergency medical service" OR "medical emergency service" OR "emergency health services" OR "emergency medical services" OR emergicenter* OR "medical emergency service" OR "medical emergency services" OR "prehospital emergency care" OR emergicentre* OR emergi-center* OR emergi-centre* OR "pre-hospital emergency care" OR EMT* OR "emergency medical technician" OR "first responder" OR "emergency medical technicians" OR "first responders" OR "first aid" OR "critical care") in Title Abstract Keyword AND (sepsis OR sepses OR septic OR "bloodstream infection" OR "bloodstream infections" OR pyemi* OR pyohemi* OR pyaemi* OR septicemi* OR septicaemi* OR "blood poisoning" OR "blood poisonings" OR bacteremi* OR fungemi* OR candidemi*) in Title Abstract Keyword AND (evaluat* OR assess*) in Title Abstract Keyword -(Word variations have been searched).