LITHUANIAN UNIVERSITY OF HEALTH SCIENCES MEDICAL ACADEMY
FACULTY OF MEDICINE
DEPARTMENT OF EMERGENCY MEDICINE
The role of the National Early Warning Score in
early identification of sepsis and septic shock at
the emergency department
Author/Student: Debora Studer Supervisor: Prof. Kęstutis Stašaitis Consultant: assist. Artūras Kačiulis
TABLE OF CONTENTS
SUMMARY /ABSTRACT 3 RESEARCH AIM 3 OBJECTIVES 3 METHODOLOGY 3 RESEARCH RESULTS 3 CONCLUSIONS 3 ACKNOWLEDGMENT 4 CONFLICTS OF INTEREST 4 ABBREVIATIONS LIST 5 TERMS 5 INTRODUCTION 6AIM AND OBJECTIVES 7
LITERATURE REVIEW 7
RESEARCH METHODOLOGY 11
LITERATURE SEARCH STRATEGY 11
ELIGIBILITY CRITERIA 12 DATA EXTRACTION 12 RESULTS 12 STUDY CHARACTERISTICS 13 STUDY SET UP 14 STUDY FINDINGS 22
IDENTIFICATION VALUE OF NEWS FOR SEPSIS,SS/SS 22
PREDICTION VALUE FOR CLINICAL OUTCOMES 22
DISCUSSION OF THE RESULTS 23
CONCLUSION 25
SUMMARY /ABSTRACT
D.S - The role of the National Early Warning Score (NEWS) in early identification of sepsis and septic shock at the emergency department
Research aim
Early identification of sepsis or septic shock in an emergency department can have a critical impact on the outcome of a patient’s wellbeing. To identify early signs of sepsis or septic shock medical institutions use early warning score systems which are based on either exclusively monitoring the vital signs or in other cases including pre-existing comorbidities of a patient. This was a literature review performed to search two different databases, for publications, that used NEWS to identify sepsis or septic shock and additionally calculated its prediction for mortality or ICU transfer.
Objectives
The aim of this literature review was, to collect information on how many studies have been conducted to investigate the performance of the national early warning score related to sepsis, at the emergency department.
Methodology
A bibliographical research of two medical libraries was conducted using medical subject headings, to identify studies that included the use of NEWS at the emergency department and its performance in detecting infection or deterioration for patients at risk for sepsis. The time-frame from 2012 to 2020 was chosen to screen for papers that were published after NEWS had been officially implemented into the clinical practice.
Research results
Our literature review identified 10 relevant articles out of an initial dataset of 1738 publications. Each study included the evaluation of performance for NEWS at the emergency department for either identification of sepsis or for prediction of risk stratification. All the articles used the receiver operating characteristic curves to plot the diagnostic ability of the track and trigger systems. There were only 3 papers that evaluated the performance of NEWS specifically at identifying early signs of sepsis at the emergency department and the results showed a good performance in discrimination of patients at risk for sepsis. ICU admission or in – hospital mortality was found to be predicted with high accuracy by the national early warning score compared to other track and trigger systems suggested by the Surviving Sepsis Campaign.
Conclusions
ACKNOWLEDGMENT
I want to extend my sincere gratitude to my supervisor, Prof. Kęstutis Stašaitis and consultant assist. Artūras Kačiulis for their support.
CONFLICTS OF INTERESTS
ABBREVIATIONS LIST
AMU – Acute medical unit
AUC / AUROC – Area Under the Curve / Area under receiver operating characteristic curve AVPU – Alert Verbal Pain Unresponsive
CI – Confidence interval
COPD – Chronic Obstructive Pulmonary Disease ED – Emergency department
EWS – Early Warning Score H – Hour
ICU – Intensive care Unit IV – Intravenous
MCU – Medium Care Unit
MEWS – Modified Early Warning Score NEWS – National Early Warning Score
PIRO – Predisposition, Infection, Response, Organ failure SOFA – Sequential Organ Failure Assessment
qSOFA – Quick Sepsis-related Organ Failure Assessment SIRS - Systemic inflammatory response syndrome
SS/SS – Severe Sepsis or Septic Shock ROC – Receiver Operator Characteristics RCPL – Royal College of Physicians, London SD – Standard Deviation
TERMS
Track and Trigger Systems (TTS): Warning systems that track physiological parameters of
the hospitalized or emergency department patients and trigger a clinical response if a significant deviation from the norm has been noted
Bedside prompt: a simple guidance for the clinical practitioner to allow a general impression
INTRODUCTION
Early identification of sepsis is crucial to the outcome of a patient’s well-being. According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) in 2016, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.[1]
The initial definitions for sepsis in 1991 was set by a consensus conference which defined sepsis as the identification of two or more systemic inflammatory response syndrome (SIRS) criteria, in addition to known or suspected infection.[2]
In the following years studies showed that SIRS can be caused by non-infectious courses of diseases and that the criteria for SIRS was too sensitive. As a result the majority of patients admitted to the ICU met the criteria for sepsis, without the evidence of an infection.[3, 4] An attempt in 2001 to revise the sepsis definitions of 1991 resulted in unspecific criteria and failed to introduce simple variables to define sepsis, which consequently lead to the continuance of the use of SIRS.[5, 6]
In 2016 the international consensus definitions of sepsis were changed and quick SOFA (qSOFA) was introduced as an early identification tool for sepsis. The rapid bedside prompt should determine patients at the emergency departments or hospital wards who were likely to develop sepsis. The aim was to detect sepsis-related organ dysfunction outside the ICU at an early stage and to start adequate timely treatment.[7]
The latest Surviving Sepsis Campaign (SSC) guidelines recommend specific treatment steps for patients at risk for sepsis or septic shock. Initial resuscitation with IV crystalloid fluid for patients with sepsis-induced hypoperfusion, is the first step of the guidelines. The following steps consist of screening for sepsis, diagnosis and initiation of antimicrobial therapy. The SSC guidelines recommend administration of IV antimicrobials be initiated as soon as possible after recognition, preferably within one hour, for both sepsis and septic shock.[8] A retrospective cohort study presented evidence that an effective antimicrobial administration within the first hour of documented hypotension was associated with increased survival to hospital discharge in adult patients with septic shock.[9]
While the treatment for sepsis and septic shock seems more distinct the diagnosis and foremost screening for sepsis or septic shock confronts more challenges. The lack of a “gold standard” diagnostic test for sepsis can cause delays in the adequate response for a patient suffering of sepsis or septic shock.
The National Institute for Health and Clinical Excellence recommends early warning scores to detect early clinical deterioration for acutely ill patients in the hospital.[10] In 2012 the Royal College of Physicians along with the help of the National Early Warning Score Development and Implementation Group (NEWSDIG), introduced the National Early Warning Score as a bedside prompt, with the remit to develop a model that could be adopted across the NHS to provide a standardized track-and-trigger system for acute illness in people presenting to, or within hospitals.[11]
AIM AND OBJECTIVES
Due to several recommendation for early identification of early signs of sepsis or septic shock in the emergency department, this qualitative review was performed. Various reviews have investigated the effect of early warning scores on patient’s clinical outcome. However, there is no literature review which focuses specifically on the role of NEWS in the detection of early signs of sepsis or septic shock at the emergency department and its prediction for adverse outcomes.
The introduction of NEWS was not primarily aimed for the identification of sepsis but rather as a screening tool for clinical aggravation of hospitalized patients. A study that collected patient data over a time period of approximately 8 years, found that commonly used EWS are more accurate than the qSOFA score for predicting death and ICU transfer in non-ICU patients. In the same study, NEWS was established to be the most accurate tool for predicting outcomes in both ED and medical ward.[12]
With that being said, the NEWS is a widely used EWS in various European countries and it has already been properly implemented into the clinical routine. This is the reason why there is an interest to discover its capability to help with identifying sepsis because it would save time and demand less administrative ability to expand the use of an already existing EWS instead of enforcing a new one.
The aim was to conduct a literature review to summarize the publications that examine the role of NEWS in detecting sepsis or septic shock in the ED.
Our defined research questions were:
• What is the accuracy of the National Early Earning Score in the early detection of sepsis or septic shock in the emergency department?
• What is the predictive value for mortality or ICU Admission of NEWS in the ED? • What is the role of comorbidities or age on the performance of the NEWS?
LITERATURE REVIEW
of sepsis based on HICs data will not be accurate because 85% of all sepsis cases are expected to occur in LMICs. The reason for that is, that there are 140 countries with a population of 6’248 billion inhabitants which comprise the LMICs and only 78 economies with 119 billion inhabitants that belong to the HICs.[14]
Generally, those low – or middle – income countries lack sufficient means to prevent community and nosocomial acquired sepsis and therefore are at higher risk for increasing mortality rates related to sepsis. The use of an adequate sepsis alerting bedside prompt could be a useful tool to discriminate high risk patients.[16] Better understanding of the pathobiology of sepsis has emphasized the heterogeneity of sepsis manifestation and this challenges the health care system around the globe to develop a norm for the diagnosis of sepsis.[17] For example do 20 – 40% of patients suffering from sepsis not produce positive culture results.[16]
The Quick Sequential Organ Failure Assessment (qSOFA) is the latest proposed track and trigger system to be used to identify patients with suspected infection, and to indicate consideration of possible infection, in patients previously not recognized as infected.[1] The qSOFA is composed of 3 elements that can be assessed without laboratory data. Altered mental status (Glasgow Coma Scale ≤13), respiratory rate (≥ 22 breaths/min) and systolic blood pressure (≤ 100 mmHg) is being measured and if 2 or 3 of these elements are present, the patient is considered to be at risk for clinical deterioration.
Since the introduction of qSOFA the use and role in the clinical practice to detect sepsis has led to considerable debates. A large analysis of clinical and administrative patient data from 85 hospitals was performed to identify the ability of qSOFA to detect or give an accurate prognosis for sepsis or another clinical outcome related to infection.[18] The findings were, that qSOFA had a poor screening performance for suspected infection and sepsis. One-third of patients with a positive qSOFA score had suspected infection and only one in six patients had eventually sepsis. The early warning score suggested by the Sepsis-3 Task Force missed one-third of patients with sepsis.[18] The strength of this study compared to the validation studies for qSOFA, was that it did not only include patients with suspected infection but also patients without suspicion of infection or sepsis.[19]
The controversy surrounding the use of the suggested early warning scores by the SSC guidelines over the past decades, caused hospitals worldwide to introduce their own early warning score. With the introduction of the National Early Warning Score, the NHS attempted to embed a culture of training and education in the assessment and response to acute illness for all grades of health care professionals across their health care system.[11]
NEWS is solely based on six physiological parameters which can be routinely measured at the emergency department.
i) Respiratoy rate ii) Oxygen saturations iii) Temperature
iv) Systolic blood pressure v) Pulse rate
vi) Level of consciousness
Every parameter is scored according to what degree the elements are shifting from the norms. All the scores for each vital sign are summed up to determine the final score. In addition, the score is elevated if a patient requires supplemental oxygen. The following chart gives an overview of the NEWS and its evaluation.
Table 1 National Early Warning Score and its weighting [11]
Physiologic parameter 3 2 1 0 1 2 3 RRi (breaths/min) ≤ 8 9 – 11 12 – 20 21 – 24 ≥25 SpO2ii, % ≤ 91 92 – 93 94 – 95 ≥ 96 Supplemental O2? Yes No Temp.iii, °C ≤ 35.0 35.1 – 36.0 36.1 – 38.0 38.1 – 39.0 ≥ 39.1 Syst. BPiv, mmHg ≤ 90 91 – 100 101 – 110 111 – 219 ≥ 220 PR, bpmv ≤ 40 41 – 50 51 – 90 91 – 110 111 – 130 ≥ 131 Level of consciousness, AVPUvi A V, P, or U i RR = Respiratory rate,
ii SpO2 = peripheral capillary oxygen saturation
iii Temp.= Temperature
iv Syst. BP = systolic Blood pressure
v PR = Pulse/Heart rate, bpm = beats per minute
The NEWSDIG suggested trigger levels for the calculated scores, to provide an alert system for clinical response to the care takers. Understandably those different levels had to be in an adequate equilibrium between specificity and sensitivity for clinical escalation of care, to not cause unnecessary frequent clinical review of patients that are not at high – risk for clinical deterioration but also to avoid to oversee patients that would benefit of early clinical intervention that could improve their clinical outcome.
Table 2 NEWS Thresholds and Trigger-levels [11]
NEW Score Clinical risk
0
Low Aggregate 1-4
RED Score (individual parameter
scoring 3) Medium
Aggregate 5-6
Aggregate 7 or more High
The Red score was a novel construct to use as an alert indicator. An extreme deviation from the norm values of a single physiological parameter, is being marked as a red score and should indicate urgent clinical attention and evaluation.
NEWS has been recommended to be used as a clinical assessment for every patient above the age of 16 years. It was emphasized that the score should be considered to be a tool to support clinical assessment and not replace competent clinical judgement. Furthermore, the score is not indicated for a pediatric as well as a pregnant patient, because of the possible modified physiological response in children or pregnancy. In addition, patients with chronic obstructive pulmonary disease (COPD), suffer of a chronically disturbed physiology which may influence the sensitivity of NEWS and therefore should be recognized with anticipation to provide adequate interpretation.
Apart from the parameters included in the NEW score, the NEWSDIG also considered parameters that were important to acknowledge in the examination of a patient at risk of clinical aggravation, but were not included in the NEWS calculation chart.
While urine output and pain can be indicators for physiological response to worsening of disease, those two parameters are difficult to implement as regular criteria into the NEWS, because urine output might not be available at the first assessment of the patient and pain is difficult to assess objectively, because it might not always cause physiological disturbances. However, both parameters should be monitored closely if possible.
developed score, additionally to the fact that chronological age is not necessarily a good indicator of biological age.
The existence of comorbidities including immunosuppression is highly important to the outcome of a patient. In spite of that, does the NEW score not specifically include comorbidities variables into the calculation chart, for the reason that the NEWS aims to be a universal warning screening tool and should reflect physiological derivations associated with numerous comorbidities.
Lastly, the NEWS has also been endorsed to be used in the prehospital setting to evaluate acutely ill patients and enhance the communication of acute – disease aggravation to the receiving institutions.
And at this point we wanted to investigate the National Early Warning Score. An early warning score that could identify patients at risk for sepsis or septic shock at the emergency department can have a significant impact on the outcome of those patients’ well – being.
Smith GB et al. in 2013 undertook an evaluation of the NEWS compared to other existing EWS, to investigate the clinical outcomes and unanticipated ICU admission. NEWS showed to be a better discriminative tool for patients at risk of the combined outcome of cardiac arrest, unanticipated ICU admission or death within 24 hours, than the other 33 EWS included in that study.[20]
A later study published in 2017 by Churpek et al. examined the prediction value of SIRS, qSOFA and other commonly used early warning score, such as the Modified Early Warning Score (MEWS) and NEWS. They found evidence that commonly used early warning scores have better prediction for adverse outcomes compared to qSOFA, including patients at the emergency department and in the medical ward.[12]
Lastly a narrative review by Nannan et al. proved that no EWS can infallibly detect all patients at risk for adverse clinical outcome, which present to the emergency department or the acute medical ward. Nonetheless, it is advisable to conduct further study to find a simple but accurate early warning system for the entire acute health chain, which might lead to improved care in high – income as well as low – or middle – income countries. Moreover, do they recommend to conduct those studies with the NEWS in the general population, as they found that NEWS has a good prognostic performance in their study.[21]
RESEARCH METHODOLOGY
Literature search strategy
A bibliographic search of the electronic databases PubMed and ScienceDirect by Elsevier for papers published between January 2012 and January 2020 was performed in January 2020. In the literature search on PubMed only papers published within that period including only adults and humans were considered. To allow a more specific literature search on PubMed, Medical Subject Headings (MESH) were used for following terms:
A structured search strategy on Science Direct by Elsevier using the Key words “Early Warning Score” AND “Sepsis OR Septic Shock” AND “Emergency Department” helped to identify more relevant studies. Additionally, a manual search was performed to identify theme – related articles that included the National Early Warning Score specifically. The same timeframe was chosen and only research articles were included into the systematical search.
Eligibility criteria
Eligible papers had to assess the performance of the National early warning score in identifying sepsis or septic shock in the emergency department setting. The time frame for this study was set from January 2012 to January 2020 for the reason that the Royal College of Physicians introduced the NEWS in 2012 as a track and trigger tool to detect early deterioration of patients.[11] Similar criteria used in a previous study to evaluate the prognostic value of early warning scores in the emergency department and acute medical unit were used for this literature review but with a specific focus on the performance of the National Early Warning Score and the identification of sepsis.[21]
Therefore, studies were selected if they met our predefined inclusion criteria:
i) retrospective or prospective study in the format of a cohort or observational study ii) study population were adults (≥16 years old) admitted to the ED or an AMU
iii) predictive value related to mortality, ICU admission or a composite outcome of these for NEWS, was either evaluated as the primary or secondary outcome
iv) identification value of NEWS for sepsis or septic shock
All papers including pediatric patients (≤ 16 years old) or pregnant women were excluded. Publications which reviewed Pediatric Early Warning Scores or calculated the Early Warning Scores in combination with other additional clinical signs or laboratory data incoherent to the original score were excluded. In addition, studies performed outside the ED involving the general ward, ICU or prehospital setting were excluded for this research. All types of reviews, guidelines and case reports were removed, along with duplications.
Data Extraction
Multiple steps helped with the selection of publications. In the first place the publications were screened for title match then the abstracts were reviewed to assess the publications eligible for full text review. The full text review was done by DS. And in an independent approach AK verified the selected articles.
RESULTS
The Prisma Flow Chart should visualize our selection strategy and final results.
Study characteristics
Characteristics of the studies are shown in the following table. Most of the studies we identified were retrospective observational studies [22 – 24, 26 -28, 31] with one study being a prospective cohort study [25] and another 2 prospective observational studies [29,30]. 3 of the studies included in our review assessed the performance of NEWS exclusively. [22 – 24] The other studies focused on a comparison of different early warning scores and assessed their validity against each other.
From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal.pmed1000097
For more information, visitwww.prisma-statement.org. Records identified through
database searching Pubmed/Elsevier (n = 1704 ) Sc re ening Inc lude d El igi bi lity Ide ntif ic ation
Additional records identified through manual search
(n = 36)
Records after duplicates removed (n = 1738)
Records screened after Filter Application and
Title match (n = 85)
Records excluded after Abstract evaluation
(n = 60)
Full-text articles assessed for eligibility
(n = 25)
Full-text articles excluded, with reasons
(n = 15)
• Sepsis screening tool other than NEWS = 13
• Study setting not exclusively ED = 2 Studies included in
qualitative synthesis (n = 10)
Despite the variety of study settings, a great homogeneity in the results among the papers was noticed. In general, the Early Warning Scores suggested by the Surviving Sepsis Campaign Guidelines for adults (qSOFA and SIRS) throughout the years were assessed and compared to the performance of other commonly used early warning scores.
The selection of population determined different inclusion criteria for the patients. 4 publications include patients above the age of 18 years old, [23 ,26, 28 ,31] while another 4 publications did not specify the exact age of participants apart from expressing the criteria of only “adults”.[25, 27, 29] One paper included participants above the age of 17 years old [30] and only 2 studies chose the age range that has been recommended by the RCPL. [22, 24] Additionally, nearly each study used a separate definition of sepsis for their population sample. Two studies based the definition of infection or suspicion of sepsis on the SIRS criteria. [24, 26] Early administration of antibiotics at the emergency department was the inclusion criteria for another two studies. [28, 30] Keep et al. based the definition of sepsis on the SSC guidelines of 2012 [22], while Lim et al. identified their patients through the primary discharge diagnosis based on the international Classification of Diseases, the 10th revision (ICD-10). [23] The newly revised sepsis definitions in 2016 were the base for patient classification in the study conducted through Nieves et al. (Nieves). Different definitions were likewise used in the studies of Camm et al., Delahanty et al. and Goulden et al. [29, 31, 27] The latter organized a clinical team that reviewed the patients for suspected infection and included each patient that had a sepsis form filled out at the admission to the emergency department. These forms were composed of the SIRS, qSOFA and NEWS scores. [27] Delahanty et al. used the Rhee clinical surveillance criteria as standard definition of sepsis to develop their ROS score. [31] And finally, Camm et al. defined suspected sepsis according to the NICE Guideline-51(NG51). [29]
Study set up
The identified studies varied greatly in regards to their study setting. The size of population ranged from 500 to 2’759’529 patients. [22, 31] Most of the publications were single – center studies, conducted in only one country. [22, 23, 25 – 29] The remaining 3 studies were multi – center studies conducted in one country, where de Groot et al. included 3 different medical centers in the Netherlands for its study, Corfield et al. 20 mainland district general and teaching hospital emergency departments and finally, Delahanty et al. collected data from 49 urban community hospitals in 39 different cities in the United States. [30, 24, 31]
Table 3 Study characteristics Study / Year Design ED or AMU/ Country No. of Patients Population EWS assessed Outcome Keep JW et al. (2015) [22] retrospective observational study ED Urban university Hospital, London, UK
500 All patients (age ≥ 16yr) with final diagnosis taken from ED medical records or hospital discharge summary as SIRS, Sepsis and Severe Sepsis According to 2012 Surviving Sepsis Campaign guidelines and the 2001 International Sepsis Definitions Conference
NEWS Ability of the NEWS to
identify severely septic patients and overall performance of NEWS Lim WT et al. (2019) [23] retrospective cohort study ED Singapore General Hospital, Singapore
11’300 All admissions (age ≥ 18yr) to acute medical unit
Subgroups: primary discharge diagnosis based on the
International Classification of Diseases, 10th revision (ICD-10)
NEWS Composite of deterioration
in vital signs over 24H after AMU admission and
unexpected transfer to Intermediate care area (ICA), ICU or death
Corfield AR et al. (2014) [24] retrospective observational study 20 mainland district general and teaching hospital EDs, Scotland, UK 2003 of 2489 available patients Inclusion of patients
(age ≥ 16yr) with positive SIRS criteria
According to the 2008 Surviving sepsis campaign
NEWS Primary endpoint: ICU
Nieves Ortega R et al. (2019) [25] prospective all-comer cohort study ED Swiss academic tertiary hospital, Switzerland
2523 All adult patients presented to the ED during a period of 3 weeks qSOFA, NEWS, SIRS, Emergency severity index (ESI)
Primary outcome: sepsisvii Secondary Outcome: admission to ward, ICU, in-hospital mortality and 30-day mortality
Usman OA et al (2019) [26]
retrospective
data analysis ED Urban tertiary-care academic centre, USA 130’595 ED visits; 64,995 unique patients
All ED (age ≥ 18yr) encounters with ICD- 9 or ICD-10viii codes related to sepsis and selective patients with blood culture, urine cultures or antibiotics orders within 12H of ED arrival
SIRS, qSOFA, NEWS
Primary endpoint: diagnosis of SS/SS within 8H of ED arrival
Secondary endpoints: SS/SS, and sepsis-related
(in-hospital) mortality Goulden R et al. (2018) [27] retrospective cohort study ED/MAU Royal Liverpool University Hospital (RLUH), tertiary centre, UK 1818 (94% of 1942 patients)
All patients with sepsis – form completedix in their electronic medical record (EMR) (qSOFA, SIRS, NEWS scores on arrival and suspected source of infection with other aspects of patient care) during the study period, based on a referral made from the ED or medical admission unit (MAU)
SIRS, qSOFA, NEWS
Primary outcome: in-hospital mortality
Brink A et al. (2019) [28] retrospective cohort study Erasmus University Medical Centre, Rotterdam, the Netherlands
8’204 All patients (age ≥18 yr) with suspected sepsis; defined as initiation of IV antibiotics (non-prophylactic) or collection of any culture or viral diagnostics during the index visit in the ED
quick SOFA (≥ 2), SIRS (≥2), NEWS (≥7)
Primary outcome: 10-day and 30-day all-cause
mortality after ED admission
Camm CF et al. (2018) [29] prospective observational study Abingdon Hospital EMU, Oxfordshire, UK
533 Patient included if residing within Oxfordshire (to obtain appropriate follow-up details) and clinical phenotype
suggesting possible infection (NICE Guideline 51-Sepsis)
SIRS, qSOFA, NEWS, NICE-HR and NICE-MR
Processes of care: Need for IV antibiotics, IV fluids and pathway of care (ambulatory vs hospital) and readmission within 30 days;
Clinical outcome: 30-day all-cause mortality de Groot B et al. (2017) [30] prospective observational multi - center study
3 Dutch Eds, the Netherlands
2280 All consecutive ED patients (age ≥17 yr) with suspected infection and Manchester triage system (MTS) yellow, orange or red and IV antibiotics in the ED and subsequently
admission to the hospital
PIRO, qSOFA, MEDS, MEWS, NEWS
Primary outcome: in-hospital mortality
Delahanty RJ et al. (2019) [31] retrospective cohort study 49 urban community hospitals, USA
2’759’529 All adult (age ≥ 18 yr) patients admitted to ED during study period Ros Scorex, SIRS, SOFA, qSOFA, NEWS, MEWS
Primary outcome: Patient meeting clinical surveillance criteria for sepsis7
Secondary outcome: in – hospital mortality
vii According to the 2016 Definitions as a confirmed or suspected infection and an increase of ≥ 2 points in the SOFA score
viii ICD- 9 (prior to October 1, 2015) or ICD-10 (on and after October 1, 2015) codes
ix All adults in which sepsis was suspected or treated by clinical team. First identified through sepsis nurse at ED arrival then in agreement with clinical team sepsis form was
completed
x For developing ROS Score the Rhee clinical surveillance criteria (according to Rhee C, Dantes R, Epstein L, et al. Incidence and trends of sepsis in US hospitals using clinical
vs claims data, 2009-2014. JAMA. 2017;318:1241-1249.) was used as standard definition of sepsis
Table 4 Study setup and findings
Study Study setup Findings
Keep JW et al. (2015) [22]
This was a single – center study where all adults presenting to the ED with MTS of 1 – 3 were included until a total population of 500 patients was reached during the time period of 21st of July 2013 until the 26 July 2013. NEWS was evaluated using receiver operating
characteristic (ROC) curves and the overall performance with Area under the curve (AUC).
27 patients (5.4%) had criteria for SS. AUC for NEWS was 0.89 (95% CI 0.84 - 0.94) and the cut-off ≥3 for NEWS at ED triage had a sensitivity of 92.6% (95% CI 74.2% to 98.7%) and a specificity of 77% (95% CI 72.8% to 80.6%) to detect patients at risk for SS/SS at ED triage.
A score of ≥3 for NEWS in the ED showed good performance in the early screening for SS/SS.
Lim WT et al. (2019) [23]
This was a single – center study where the NEWS records for all patients admitted to the AWS over the time period of 2 years between August 1, 2015 and July 30, 2017 were screened.
The data was extracted using Singhealth-IHIS Electronic Health Intelligence System. NEWS was evaluated by ROC curves and the overall performance with AUC.
AUROC for the 3 outcomes over 24H – period was 0.896 (95% CI, 0.890 - 0.901). Even rate with NEWS Score >9 was high (> 0.250) and in the medium – risk group (score of 5 or 6) event rate was <0.125. AUROC for any of the 3 outcomes was 0.896 (95% CI, 0.890-0.901).
This speaks for an accurate likelihood for adverse outcomes with increased NEWS values.
Corfield AR et al. (2014) [24]
This was a multi – center study where all patients admitted for at least 2 days or who died within 2 days were screened for sepsis criteria, during a time period of 3 months.
NEWS was evaluated using ROC curves and the overall performance with AUC.
Higher values in NEWS category was associated with an increased risk of mortality when compared to the lowest category (5-6: OR 1.95, 95% CI 1.21 to 3.14), (7-8: OR 2.26, 95% CI 1.42 to 3.61), (9-20: OR 5.64, 95% CI 3.70 to 8.60).
Nieves Ortega R et al. (2019) [25]
This was a single – center study where all patients
consecutively presenting to the ED during a time period of 3-weeks between January 30 to February 19, 2017 were screened.
The Scores were evaluated using receiver operating characteristic curves.
39 patients (1.6%) had the primary outcome of sepsis. The AUC for NEWS was 0.85 (95% CI 0.77–0.92) and differed significantly from the AUC of qSOFA (p= 0.03).
The cut-off ≥4 showed the highest combination of sensitivity (71.8% (95% CI 56.4–84.6%) and specificity 90.2% (95% CI 89.1– 91.3%) compared to the other cut-offs for NEWS and compared to SIRS and qSOFA. NEWS had good prediction of adverse
outcomes and while screening for sepsis it outperformed qSOFA in this study.
Usman OA et al (2019) [26]
This was a single – center study where all ED patients presenting during 2 time periods were screened. First timeframe was from January 1, 2014 to April 30, 2015 and the second from February 1, 2016 to December 31, 2016. The scores were assed for their predictive ability using AUROC curves.
NEWS outperformed SIRS and qSOFA for detection of SS/SS as well as for the secondary outcomes of predicting septic shock, sepsis – related mortality and all – cause mortality.
Goulden R et al. (2018) [27]
This was a single – center study where all adults with suspected sepsis and completed sepsis form were screened during a time period between April 2016 and May 2017. The scores were assed for their predictive ability using AUROC curves.
Among 1818 patients, 53 were admitted to ICU (3%) and 265 died in hospital (15%). NEWS had a similar or superior performance compared to the SIRS and qSOFA in predicting mortality as well as for the secondary outcome of ICU admission.
Brink A et al. (2019) [28]
This was a single – center study where all adults presenting to the ED during a time period from June 1st 2012 to May 31st 2016 with suspected sepsis were screened. The scores were assed for their predictive ability using AUROC curves.
3.5% of the patients died within 10 days and 6.0% within 30 days after presentation. NEWS outperformed qSOFA and SIRS in predicting 10-days and 30-days mortality. qSOFA lacked
Camm CF et al. (2018) [29]
This was a single – center study where all patients presenting to the ED over a time period of 4 months between August 12 2015 and December 18 2015 were screened. PPV, NPV, sensitivity and specificity with 95% CI were the parameters which assessed the diagnostic accuracy of each sepsis predictive tool.
316 patients of the initial study population had suspected infection and 120 patients needed escalated care.
NEWS and SIRS showed better predictive value for escalated care compared to qSOFA and NICE criteria in patients with supsected infection. 23.7% of the older (≥ 85 years old) patients had new – onset of confusion without evidence of infection.
de Groot B et al. (2017) [30]
This was a multi – center study where all patients presenting to the ED in different time periods were screened for suspicion of infection. In LUMC from April 1st 2011 to February 1st 2016, in RH from March 1st 2012 to November 1st 2012 and in ASZ from September 1st 2015 to November 1st 2015. The patients were grouped by age into an older (≥ 70 years old) and younger (<70 years old) group. The scores were assessed using ROC curves and AUC analysis.
9.5% was the in-hospital mortality in the 783 older patients, and 4.6% in the 1497 included younger patients. In younger patients
the higher disease severity scores associated better with the prediction of mortality compared to the older patients. That was shown by the low AUCs (0.56 to 0.64) of all disease severity scores in older patients, which were significantly lower than the good AUC range (0.72 to 0.86) in younger patients. ICU and MCU admission was predicted best with NEWS in the total cohort and younger patients, with AUCs of 0.75 and 0.80, respectively.
Delahanty RJ et al. (2019) [31]
This was a multi – center study where all patients presenting to the EDs in the time period from January 1, 2016 and October 31, 2017 were assessed for suspected infection. The performance of a new machine learning model created by the authors was assessed to existing benchmarks. The scores were assessed using AUROC, alert rate, sensitivity, specificity and precision (PPV).
Study findings
According to our findings the performance of qSOFA as well as SIRS in early identification of sepsis was challenged by other early warning scores. 3 studies in our review focused on the identification of sepsis [22, 25, 26], while the remaining papers studied the prediction value of various EWS including NEWS.[23, 24, 27-31]
Identification value of NEWS for sepsis, SS/SS
The area under the curve (AUC) for NEWS to identify patients at risk for sepsis was 0.89 (95% CI 0.84 to 0.94) according to a British retrospective single – center observational study of 500 patients.[22] Furthermore the AUC for the diagnosis of sepsis in the publication of a Swiss prospective single – center all-comer cohort study was 0.85 (95% CI 0.77–0.92).[25] The AUROC for NEWS in detection of SS/SS had an excellent performance of 0.91 (95% CI 0.903– 0.926) in an American retrospective single – center data analysis.[26]
Sensitivity and specificity in identifying sepsis and septic shock for NEWS altered with increasing cut-offs. The British group with Keep J. found that a cut-off of ≥3 for NEWS at the ED admission had a sensitivity of 92.6% (95% CI 74.2% to 98.7%) and a specificity of 77% (95% CI 72.8% to 80.6%) to detect patients at risk for septic shock at ED admission.[22] Highest sum of sensitivity and specificity for NEWS in the study of the swiss team with Nieves Ortega R., was measured at a cut-off of ≥4 and resulted in the highest results compared to the SIRS, qSOFA and ESI, with values of 71.8% (95% CI 56.4–84.6%) and 90.2% (95% CI 89.1– 91.3%) for sensitivity and specificity, respectively.[25] The same cut-off of ≥ 4 for NEWS demonstrated similar results for the study by the American group with Usman OA with values of 84.2% sensitivity for severe sepsis and 88.1% for septic shock and specificity of 85% and 84.8% for both, respectively. [26]
Prediction value for clinical outcomes
All studies except one, stated process of care, ICU or ward admission, in – hospital mortality, 30 – day mortality, death or a composite of those, as either a primary or secondary outcome. [23-31]
There were 5 studies that evaluated the prediction of ICU admission.[23-25, 27, 30] 30 – day mortality was included in 4 studies [24, 25, 28, 29] and in – hospital mortality in 5 papers [25-27, 30, 31], while Camm et al. examined the process of care for patients at risk of infection.[29] A Singaporean single – center retrospective cohort study identified a mean NEWS score of 6.52 for all the patients having had a composite outcome of death or unplanned transfer to a higher acuity care area, as for example the intermediate care area (ICA) or ICU.[23] The performance of NEWS was similar, if not better, in a cohort of patients with infectious conditions and can differentiate those at risk of a combined clinical outcome of transfer to ICA, ICU or death within 24 hours of NEW score calculations at the acute medical ward. [23]
And NEWS showed the most agreeable performance comparing the expected and the observed clinical outcomes.[28]
The British multi – center study conducted by Corfield et al. illustrated that 27% of patients with a NEW score cut-off of ≥ 7 were transferred to the ICU within 2 days and/or died within thirty days. This predictive value rose to 35% with an increased cut-off of NEWS ≥9. [24] The prospective observational study by Camm et al. support the use of NEWS in discriminating patients in need of care, in a community setting. It showed that in his study the early warning systems recommended by NICE and the Sepsis-3 taskforce tend to have a high false – positive rate when compared to NEWS, and this could potentially lead to substantial overtreatment. It is to be noted that in that study NEWS was evaluated at a cut-off of > 4. [29]
Regarding the age of patients, there was only one study that differentiated between older patients (≥70 years old) and younger (< 70 years old) ones. It found that younger patients benefited more from the use of EWS than older patients and that the most commonly used disease severity scores are less useful for risk stratification of older ED patients at risk for sepsis.[30]
DISCUSSION OF THE RESULTS
To appraise the role of the NEWS in the early identification of sepsis at the emergency department, the various results from these 10 studies were compared to examine the identification as well as the predictive value of the National Early Warning Score.
The results of the mentioned studies that specifically investigating the identification value for infection, indicated a good performance of NEWS in the detection of sepsis or septic shock at the emergency department, in three different study settings.
While the report of the Royal College of Physicians suggests different trigger levels for clinical response, they also suggest, that the threshold for urgency of response be agreed upon locally. [11] Therefore the fact, that three studies found that a NEWS cut-off of ≥3 or ≥4 has a good performance in identifying patients at risk for sepsis at the emergency department, is an essential finding to weigh the validity of an early warning score in detecting early signs of sepsis.
On the other hand, the study setting as well as the choice of population differs considerably between each publication. While the British group only included 500 patients with a triage category between 1-3 MTS (Manchester Triage system), the Swiss group included all patients presenting to the ED consecutively during a time-period of 3 weeks and the American one included all adults presenting to the ED during two separate time periods. [22, 25, 26] Therefore, the sample size is not comparable and in addition the population selection varies significantly. Despite those facts, the results for the performance of NEWS demonstrate similar results, which might lead to a conclusion that NEWS is a good tool for early identification of sepsis in various populations.
has to be considered that almost each of these studies have been performed in a specific population with suspicion of sepsis or infection and therefore lacks substantial assertion for the performance of NEWS in a heterogeneous ED population.
Furthermore, did the authors chose various approaches to handle missing data in their studies. While two authors decided to exclude all the patients with missing data required to calculate the EWS in their medical records,[22, 24] others assumed the missing data to be normal.[25, 27, 30] The intend to favor the missing data as normal might reflect a more realistic approach in the clinical practice for an early warning system in the emergency department, due to the fact that the patients might arrive in a critical state and the particular circumstances might lead to neglection of measurement for a vital sign. The external factors are not to be forgotten, as for example lack of communication or material, might influence the performance of the care giver who records the vital parameters. Brink et al. used another approach to include the patients with missing data. The missing parameters were replaced using the multiple imputation technique, which was previously validated to be considered in large sets of missing data.[28, 32]
Due to the fact that each study had a separate study setting, different definitions for sepsis as well as inhomogeneous selection of population, it is impossible to conclude that the NEWS is the best leading warning score for the detection and outcome of patients at risk of acute infection or sepsis. Yet, it accentuates that NEWS has a better discrimination value compared to the previously recommended scores by the Sepsis Task Force, SIRS and qSOFA.
Comorbidities and age as mentioned earlier, do not particularly influence the calculation of NEWS. Nonetheless, we found four studies in our review that collected data about the preexisting comorbidities in their study population. COPD, chronic heart failure, liver disease, renal disease and dementia were among the most common clinical conditions found in the evaluated patients of these four studies. [30, 31] Despite those preexisting conditions, the performance of NEWS was not detected to be significantly worse. This finding provides evidence that the recommendation by the RCPL to evaluate comorbidities as a separate parameter apart the EWS, is a reasonable suggestion. On the other hand, did the study by de Groot et al. proof unsatisfying results for EWS in detecting risk stratification for elderly patient.[30] According to this data, the use of NEWS in elderly patient is controversial and the use of EWS in geriatric patients should be further investigated. Precisely, in older patients suffering of dementia, the EWS might be misinterpret. Patients suffering of dementia have an altered state of mind and the difficulty lies in the detection of a new onset of altered consciousness compared to a preexisting mental deficit.
Comprehensive implementation of a universal early warning system, as for example the NEWS, could create a common language in the detection and management of sepsis. The uncertainty in defining sepsis has once again raised difficulties in comparing various studies to each other. The major strength of this study, was that it included papers that examined the NEWS score exclusively in an emergency department setting and not as previous validation studies, in the hospital ward or ICU. We tried to screen the library data bases for studies which focused primarily on the identification value of NEWS and not only on the prediction value for in-hospital mortality. The studies evaluating the NEW score ability to identify sepsis, had homogenously found good results, and support the use of NEWS in the ED for early identification of sepsis or septic shock.
published before 2012. The thought was to only include papers that have been published since the official introduction of NEWS in 2012, to observe the performance of the EWS in the clinical practice. Secondly, the use of Mesh Terms in the bibliographical search can result in omission of relevant papers. Therefore, we conducted another manual search to identify additional important publications. Lastly, the lack of a common target across the studies made it impractical to compare the papers to each other. Each study had different selection criteria for their study population and on top of that did once again the discrepancy in sepsis definitions, cause considerable disparity among the objectives of the articles. Most of the studies we found were retrospective single – center studies, which in this case lack generalizability.
All of the identified papers were conducted in high – income countries which highlights the problematic that was addressed at the beginning. Early warning scores identifying sepsis at the emergency department can be a significant life-saving tool for middle - or low – income countries. The NEWS is an early warning score not requiring laboratory data and can therefore be calculated using simple vital parameters, which are usually measure in all hospitals throughout each social class.
Therefore, it is recommended to attempt validation studies for the National Early Warning Score in those communities, to identify potential variations between the social classes and eventually cause a decrease of mortality related to sepsis in the future.
CONCLUSION
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