Abstract
Background:
High in-hospital mortality in sepsis patients remains challenging for clinicians worldwide. Early recognition, prognostication, and aggressive management are essential for treating septic patients. Many scores have been formulated to guide clinicians to predict the early deterioration of such patients. Our objective was to compare predictive values of quick Sequential Organ Failure Assessment (qSOFA) and National Early Warning Score 2 (NEWS2) with respect to in-hospital mortality.
Methods:
This prospective observational study was conducted in a tertiary care center in India. Adults with suspected infection with at least two Systemic Inflammatory Response Syndrome criteria presenting to the emergency department (ED) were enrolled. NEWS2 and qSOFA scores were calculated, and patients were followed until their primary outcome of mortality or hospital discharge. The diagnostic accuracy of qSOFA and NEWS2 for predicting mortality was analyzed.
Results:
Three hundred and seventy-three patients were enrolled. Overall mortality was 35.12%. A majority of patients had LOS between 2 and 6 days (43.70%). NEWS2 had higher area under curve at 0.781 (95% confidence interval [CI] (0.59, 0.97)) than qSOFA at 0.729 (95% CI [0.51, 0.94]), with P < 0.001. Sensitivity, specificity, and diagnostic efficiency to predict mortality by NEWS2 were 83.21% (95% CI [83.17%, 83.24%]); 57.44% (95% CI [57.39%, 57.49%]); and 66.48% (95% CI [66.43%, 66.53%]), respectively. qSOFA score had sensitivity, specificity, and diagnostic efficiency to predict mortality of 77.10% (95% CI [77.06%, 77.14%]); 42.98% (95% CI [42.92%, 43.03%]); and 54.95% (95% CI [54.90%, 55.00%]), respectively.
Conclusion:
NEWS2 is superior to qSOFA in predicting in-hospital mortality for sepsis patients presenting to the ED in India.
Keywords: Mortality, National Early Warning Score 2, quick Sequential Organ Failure Assessment, sepsis
INTRODUCTION
Sepsis has around the globe in the last two decades been recognized as a medical emergency that carries high mortality and morbidity.[1] Despite multiple recent advances in the care of sepsis, in-hospital mortality remains high at 25%–30%.[2] Septic shock patients may have mortality rates between 45% and 58%.[3] Key strategies in the management of sepsis patients are early recognition, quick prognostication, and aggressive management. Identification of patients at high risk for early deterioration will help clinicians customize treatment plans accordingly. Many scoring strategies have been developed to prognosticate sepsis patients and thus guide physicians. The quick Sequential Organ Failure Assessment (qSOFA) score was a new tool suggested by the Third International Consensus (Sepsis-3) guidelines to identify patients at risk of death.[4] The National Early Warning Score (NEWS) was established in 2012 and was revised in 2017 under the name NEWS2. NEWS2 was developed and implemented in the National Health Service (United Kingdom) for aiding clinicians to assess the severity of clinical illness and detection of deterioration and thus help with the initiation of timely clinical interventions.[5] There have been attempts to externally validate qSOFA as a predictor of mortality in sepsis patients since it was published in the Sepsis-3 guidelines. Hwang et al. found the diagnostic performance of a positive qSOFA to be low in predicting 28-day mortality in critical sepsis patients.[6] Modified Early Warning Score (MEWS) and NEWS were found to be more reliable in predicting death than qSOFA in sepsis patients.[7] The NEWS2 has been found to be superior to the qSOFA in detecting sepsis with organ dysfunction.[8] However, there is still a lack of published data on the comparison of the two (NEWS2 and qSOFA) scoring systems as predictors of mortality in septic patients, especially in India. This study, therefore, seeks to bridge the knowledge gap by comparing the performance of qSOFA and NEWS2 on the prediction of mortality in patients with suspected sepsis.
METHODS
Study design and setting
This was a prospective observational study approved by the institutional ethics review committee. The study was conducted in the emergency department (ED) of a tertiary care hospital in New Delhi, India. All emergency physicians and nurses were briefed regarding the study and they contributed toward data collection. Adult patients presenting to the ED between July 2021 and December 2021 were recruited if they had a suspected infection along with at least two Systemic Inflammatory Response Syndrome (SIRS) criteria. Patients were followed using electronic health records (EHRs), and the patients in whom sepsis was not the final diagnosis were removed from the study. COVID patients were not included in the study. On recruitment, demographics and vital signs were recorded. Informed consent from the patient or next of kin was taken for inclusion in the study. Parameters of qSOFA and NEWS2 of patients who had a final diagnosis of sepsis were recorded. All patients were treated as per the Surviving Sepsis Guidelines. Patients enrolled for the study underwent calculation and interpretation of their qSOFA and NEWS2 scores and were followed to the determination of primary and secondary outcomes using the EHR-VistA Computerized Patient Record System (U.S. Department of Veteran Affairs, United States of America).
Selection of participants
All adult (≥18 years) patients who presented to the ED with suspected or confirmed infection with at least two SIRS criteria were enrolled in the study.
Measurements
Demographic information of patients who were included in the study was collected at the time of enrollment by the treating emergency physician or emergency nurse. Sepsis in patients was defined as the presence of at least two SIRS criteria with a confirmed or suspected infection (bacterial, fungal, or viral).[9] SIRS criteria include: Heart rate >90 beats/min, respiratory rate >20 breaths/min, temperature >38°C or <36°C, and white blood cells >12,000/mm3, <4000/mm3, or bandemia ≥10%. Parameters of qSOFA included the respiratory rate, systolic blood pressure, and change in mental status. The NEWS2 parameters include respiratory rate, oxygen saturation scales, use of air/oxygen, systolic blood pressure, pulse rate, consciousness, and temperature. Parameters for qSOFA and NEWS2 and their interpretations are tabulated in Tables 1 and 2.
Table 1.
Quick Sequential Organ Failure Assessment parameters and interpretation
| qSOFA parameters | Score | Interpretation |
|---|---|---|
| Respiratory rate ≥22/min | 1 | 0-1: Not high risk for in-hospital mortality |
| Systolic BP ≤100 mmHg | 1 | 2-3: High risk for in-hospital mortality |
| Change in mental status | 1 |
qSOFA: quick Sequential Organ Failure Assessment, BP: Blood pressure
Table 2.
National Early Warning Score 2 parameters and interpretation
| Physiological parameter | NEWS2 calculation | ||||||
|---|---|---|---|---|---|---|---|
|
| |||||||
| 3 | 2 | 1 | 0 | 1 | 2 | 3 | |
| Respiration rate (per min) | ≤8 | 9-11 | 12-20 | 21-24 | ≥25 | ||
| SpO2 Scale 1 (%) | ≤91 | 92-93 | 94-95 | ≥96 | |||
| SpO2 Scale 2 (%) | ≤83 | 84-85 | 86-87 | 88-92≥93 on air | 93-94 on oxygen | 95-96 on oxygen | 97 on oxygen |
| Air or oxygen# | Oxygen | Air | |||||
| Systolic BP (mmHg) | ≤90 | 91-100 | 101-110 | 111-219 | ≥220 | ||
| Pulse (per min) | ≤40 | 41-50 | 51-90 | 91-110 | 111-130 | ≥131 | |
| Consciousness | Alert | CVPU | |||||
| Temperature (°C) | ≤35.0 | 35.1-36.0 | 36.1-38.0 | 38.1-39.0 | ≥39.1 | ||
|
| |||||||
| NEWS2 score | NEWS2 interpretation | ||||||
|
| |||||||
| 0-4 | Low clinical risk for deterioration and in-hospital mortality | ||||||
| 5-6 | Medium clinical risk for deterioration and in-hospital mortality | ||||||
| 7-20 | High clinical risk for deterioration and in-hospital mortality | ||||||
SpO2 scoring Scale 2 should only be used in patients confirmed to have a hypercapnic respiratory failure on blood gas analysis on either a prior, or their current, hospital admission (Source: Additional guidance file at https://www.rcplondon.ac.uk/projects/outputs/news2-additional-implementation-guidance). If one of the physiological measures cannot be obtained because of no equipment, the score should still be calculated and documented as incomplete. BP: Blood pressure, NEWS2: National Early Warning Score 2, SpO2: Oxygen saturation, CVPU: Confusion, voice, pain, unresponsive
Outcomes
In-hospital mortality and length of stay (LOS) were, respectively, the primary and secondary outcomes studied.
Primary data analysis
Data were collected and organized in MS Excel, followed by the use of IBM® SPSS® version 22 (IBM Corp., Armonk, USA) for analysis and visualization. Continuous variables have been presented as measures of central tendencies, mean ± standard deviation, and categorical variables have been measured as proportions and frequencies. Chi-square test and Mann–Whitney U-test have been used to calculate P values, i.e., probability values at a 95% confidence interval (CI). Area under the receiver operating characteristic curve (AUROC) was used for analyzing mortality with respect to NEWS2 and qSOFA. Diagnostic accuracy measures sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic efficiency for NEWS2 and qSOFA have also been calculated. Demographic characteristics of the sample along with crosstabs between variables such as LOS and probability of mortality have also been calculated. Listwise, deletion was the priori plan for any missing data.
RESULTS
Three hundred and seventy-three patients were included in this study. Figure 1 illustrates the recruitment process of the patients. The distribution of patients between men (54%) and women (46%) was fairly even. The majority of patients had a LOS between 2 and 6 days (43.70%). Gender distribution, age, class interval, and LOS class interval are mentioned in Table 3. Overall mortality was 35.12% [95% CI (30.45%, 40.09%)]. The most common source of infection was respiratory (214/373). The distribution of the source of infection is presented in Table 4. The distribution of NEWS2 and qSOFA scores has been found to be a normal distribution. The same has been shown in Figure 2. The higher LOS did not result in a higher NEWS2 score, the correlation (−0.081) between the two variables was rather negative. Higher NEWS2 score was concentrated more toward the left of the scatter plot [Figure 3], i.e., suggesting in the lower LOS range. A similar negative correlation was established between LOS and qSOFA with a correlation coefficient measuring-0.15. NEWS2 had a marginally higher area under curve (AUC) at 0.781 [95% CI (0.59, 0.97)] than qSOFA at 0.729 [95% CI (0.51, 0.94)], with P < 0.001 [Figures 4 and 5]. Only marginally high, the output provides precedence for NEWS2 to be the better measure than qSOFA. Sensitivity, specificity, PPV, NPV, and diagnostic efficiency are presented in Table 5. The sensitivity to predict mortality was greater for NEWS2 in comparison to qSOFA (83.21% vs. 77.10%). Strong statistical significance has also been established between mortality outcome and probability of mortality using both NEWS2 and qSOFA at P < 0.001 and 0.001, respectively. qSOFA was found to have less sensitivity and AUC when compared to NEWS2. The measures have been found to have strong statistical significance.
Figure 1.
Flowchart depicting patient recruitment
Table 3.
Patient characteristics
| Characteristics (n=373) | Age | LOS |
|---|---|---|
| Measures | ||
| Mean±SD | 62.42±14.85 | 8.6±7.21 |
| Median | 63 | 6 |
| Mode | 70 | 3 |
| Range | 16-91 | 1-40 |
| Gender, n (%) | ||
| Female | 172 (46.11) | |
| Male | 201 (53.89) | |
SD: Standard deviation, LOS: Length of stay
Table 4.
Source of infection
| Source (n=373) | n (%), 95% CI |
|---|---|
| Respiratory | 214 (57.37), 52.30-62.29 |
| Endocrinology | 13 (3.49), 2.05-5.87 |
| Hepatic and gastrointestinal | 17 (4.56), 2.86-7.18 |
| Multi-organ involvement | 62 (16.61), 13.19-20.74 |
| Cardiology | 25 (6.70), 4.85-9.71 |
| Neurology | 11 (2.95), 1.65-5.20 |
| Nephrology and urology | 24 (6.43), 4.36-9.40 |
| Dengue | 7 (1.88), 0.91-3.82 |
CI: Confidence interval
Figure 2.
Normal distribution of NEWS2 and qSOFA. NEWS2: National Early Warning Score 2, qSOFA: quick Sequential Organ Failure Assessment
Figure 3.
NEWS2 score versus hospital length of stay. NEWS2: National Early Warning Score 2
Figure 4.
AUROC of NEWS2. NEWS2: National Early Warning Score 2, AUROC: Area under the receiver operating characteristic curve
Figure 5.
AUROC of qSOFA. qSOFA: quick Sequential Organ Failure Assessment, AUROC: Area under the receiver operating characteristic curve
Table 5.
Measures of diagnostic accuracy
| Diagnostic accuracy | 95% CI | |
|---|---|---|
|
| ||
| NEWS2 | Positive (score >1) qSOFA | |
| Sensitivity | 83.21 (83.17-83.24) | 77.10 (77.06-77.14) |
| Specificity | 57.44 (57.39-57.49) | 42.98 (42.92-43.03) |
| PPV | 51.42 (51.36-51.47) | 42.26 (42.21-42.31) |
| Diagnostic efficiency | 66.48 (66.43-66.53) | 54.95 (54.90-55.00) |
PPV: Positive predictive value, NEWS2: National Early Warning Score 2, qSOFA: quick Sequential Organ Failure Assessment, CI: Confidence interval
DISCUSSION
This is the first study conducted in India to compare the predictive strength of qSOFA and NEWS2 scores for in-hospital mortality in sepsis patients presenting to the ED. In our study, we found NEWS2 to be a better predictor of in-hospital mortality than qSOFA, with higher sensitivity and diagnostic efficiency. In 1992, Bone et al. first described the consensus definitions for sepsis which focused on the SIRS criteria. SIRS helped identify an inflammatory response which in the presence of an “infection” was termed “sepsis.”[10] For almost three decades now, the focus on sepsis, its early detection, early management, and prognostication has only become more thorough and protocol based. It, however, still remains one of the most common causes of in-hospital death. Sepsis definitions were redefined in 2016 and published by the Third International Consensus Definitions Task Force (SEP-3).[4] The severity of illness scores is applicable for population-based prognostication and identification of similar risk cohorts.[11] The qSOFA was defined as a tool to provide aid to clinicians in identifying septic patients at a higher risk of short-term in-hospital mortality. qSOFA has since then been externally validated and compared to SIRS with regard to the prediction of in-hospital mortality. George et al., in their multicentric study, found SIRS to have 89% sensitivity for death and qSOFA to have an 80% sensitivity.[12] Henning et al., in their secondary analysis, found SIRS to have a sensitivity of 83% for predicting death as compared to 52% for qSOFA.[13] A prospective study of 664 patients found the modified Sequential Organ Failure Assessment (mSOFA) (AUROC – 0.923; 99% CI [0.896, 0.950]) and qSOFA (AUROC – 0.947, 99% CI 0.885–0.965) had equal sensitivity and specificity in predicting death in nontraumatic critically ill patients, but qSOFA was found to be a better predictor of mortality.[14] A retrospective study evaluating qSOFA had sensitivities of 39%, 68%, 82%, and 91% for in-hospital death at 28 days, within 3 h, within 6 h, and within 24 h, respectively.[6] The NEWS was developed by the Royal College of Physicians of London (RCPL) in 2012 to predict clinical deterioration in sepsis patients.[15] The RCPL revised the NEWS to NEWS2 in 2017 which added modifications to the vital sign weightings.[5] Mellhammar et al. concluded in their study that NEWS2 was superior to qSOFA in screening for sepsis with organ dysfunction, infection-related mortality, or intensive care due to infection. They found that the NEWS2 had a significantly higher AUROC as compared to qSOFA.[8] Our study result was similar in that the AUROC for NEWS2 was higher than that of a positive qSOFA. Churpek et al., when comparing different severity of illness tools, found the AUC of qSOFA to be 0.69 [95% CI (0.67, 0.70)]. This was lower as compared to NEWS (AUROC 0.77) and MEWS (AUROC 0.73).[7] In their retrospective cohort study, Brink et al. concluded that NEWS had the best performance, followed by SIRS and qSOFA in predicting 10- and 30-day mortality in sepsis patients presenting to the ED.[16]
Limitations
The major limitation of our study was that it was a single-center study. It was conducted in an academic department of an Indian hospital, and hence, the results may not be generalizable to other settings. The relatively smaller sample size of our study may result in decreased precision of the scores. There could have been a potential selection bias for the recruitment of patients on behalf of the emergency physicians, which could have led to patients not being recruited. This may contribute toward the skewing of the data and results.
CONCLUSION
No studies comparing the accuracy for the prediction of in-hospital mortality of NEWS2 and qSOFA have been done in an Indian ED. In our study, we compared the ability of NEWS2 and qSOFA to predict in-hospital mortality in sepsis patients presenting to our ED. The findings are similar to studies conducted on different populations across the world. This was a single-center study, but the results were favorable toward the use of NEWS2 as a superior tool than qSOFA for prognosticating a poor outcome in sepsis patients. Larger multicentric studies would be required to validate the results in the Indian populace.
Research quality and ethics statement
This study was approved by the Institutional Review Board/Ethics Committee at Max Super Specialty Hospital, Patparganj, New Delhi, India (Approval # TS/MSSH/BMDRC/IEC/EM/20-28; Approval date 07/07/2021). The authors followed the applicable EQUATOR Network (http://www.equator-network.org/) guidelines, specifically the STROBE guidelines, during the conduct of this research project.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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