Abstract
Introduction:
Sepsis is the leading cause of mortality, and various scoring systems have been developed for its early identification and treatment. The objective was to test the ability of quick sequential organ failure assessment (qSOFA) score to identify sepsis and predict sepsis-related mortality in the emergency department (ED).
Methods:
We conducted a prospective study from July 2018 to April 2020. Consecutive patients with age ≥18 years who presented to the ED with a clinical suspicion of infection were included. Sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV), and odds ratio (OR) for sepsis related mortality on day 7 and 28 were measured.
Results:
A total of 1200 patients were recruited; of which 48 patients were excluded and 17 patients were lost to follow-up. 54 (45.4%) of 119 patients with positive qSOFA (qSOFA >2) died at 7 days and 76 (63.9%) died at 28 days. A total of 103 (10.1%) of 1016 patients with negative qSOFA (qSOFA score <2) died at 7 days and 207 (20.4%) died at 28 days. Patients with positive qSOFA score were at higher odds of dying at 7 days (OR: 3.9, 95% confidence interval [CI]: 3.1–5.2, P < 0.001) and 28 days (OR: 6.9, 95% CI: 4.6–10.3, P < 0.001). The PPV and NPV with positive qSOFA score to predict 7- and 28-day mortality were 45.4%, 89.9% and 63.9%, 79.6%, respectively.
Conclusion:
The qSOFA score can be used as a risk stratification tool in a resource-limited setting to identify infected patients at an increased risk of death.
Keywords: Emergency department, infection, mortality, quick sequential organ failure assessment, sepsis
INTRODUCTION
Sepsis is one of the leading causes of mortality worldwide.[1] Various scoring systems have been developed for the early identification of sepsis and its related adverse clinical outcome, including death.[2] Some sepsis scoring systems are the quick Sequential Organ Failure Assessment score (qSOFA), Sequential Organ Failure Assessment score (SOFA), Modified Early Warning Score, National Early Warning Score (NEWS), and NEWS-2.[3] The qSOFA scoring system was introduced by a panel of experts at the third international consensus for sepsis and septic shock in 2016 as a screening tool.[2] A few prospective studies have been reported from the emergency department (ED) to validate qSOFA as a screening tool for the early identification of patients with suspected infection. qSOFA also predicts an increased risk of sepsis-related adverse outcome.[4,5,6,7,8]
To the best of our knowledge, this is one among the few prospective studies conducted till date to test the utility of qSOFA score in sepsis identification and related mortality prediction in a resource-limited setting of low- and middle-income countries (LMICS), which represents 87% of the world population.
METHODS
It is a single-center prospective observational study of 1200 consecutive patients aged 18 years or above who presented to the ED between July 2018 and April 2020. This is the high-volume ED of a tertiary care hospital and handles over 220 thousand patients annually. Pregnant women and patients with conditions such as dementia, mental illness, and poisoning, with time-sensitive conditions such as suspected acute myocardial infarction, acute stroke, and ongoing seizures, were excluded from our study.
Patients arriving at the ED were identified by the treating emergency physician as having a suspected infection based on an infectious source (identified on radiology or microbiology studies) or due to an equivocal presentation (like fever without a clear source). Patients who fulfilled the inclusion criteria were recruited by the emergency physician at the triage, and the qSOFA score was calculated based on clinical criteria: respiratory rate (RR) >22/min, systolic blood pressure <100 mmHg, and Glasgow Coma Scale (GCS) <13. Patients were allotted one point for the fulfillment of each criterion. If patients fulfilled two of the three criteria, they were identified as qSOFA positive (qSOFA >2), and when they fulfilled <2 criteria, they were identified as qSOFA negative (qSOFA <2). All patients were followed at 7 and 28 days. The study’s goal was to predict mortality at the 7th and 28th day after the initial presentation to ED.
Statistical analysis
Counts and percentages were used to summarize the categorical data. The mean and standard deviation (SD) were used to summarize normally distributed data, whereas median, range, and interquartile range (IQR) were used to summarize nonnormal continuous data. The primary outcome was to find out the diagnostic utility of qSOFA in sepsis, for which measures used were sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios, with area under a receiver operating characteristic curve (AUROC). For the secondary outcome, logistic regression was utilized for examining the predictive ability (odds ratio [OR]) of qSOFA for 7- and 28-day mortality. All information was collected and collated in a Microsoft Excel spreadsheet (MS office-365). All the above analyses were performed, and graphs were prepared with IBM SPSS statistics for Windows, version 23.0. Armonk, NY, USA: IBM Corp. All tests of significance used a two-sided P < 0.05.
RESULTS
Among the 1200 patients recruited for the study, 48 patients met the exclusion criteria, and 17 were lost to follow-up, leaving 1135 patients for analysis [Figure 1]. The median age was 37 years (IQR: 25–55), and 35.2% (400) were male patients and 64.7% (735) were female. The clinical characteristics of the included participants are described in Table 1. Of 1135 patients, 157 (13.8%) patients died at 7 days and 283 (24.9%) patients died at 28 days. Patients with a positive qSOFA score (qSOFA >2) were 119 (10.5% of the total included patients) and 45.4% (54) of these patients died at 7 days, and 63.9% (76) of patients died at 28 days [Table 2]. Based on the qSOFA score of 0, 1, 2, and 3, the mortality at 7 days was 4.4%, 19.7%, 40.3%, and 80%, respectively [Table 3]. Similarly, the mortality at 28 days was 11.2%, 35.8%, 59.6%, and 93.3% as qSOFA score increased from 0 to 3 [Table 3]. The sensitivity and specificity of the qSOFA score to predict 7-day mortality were 34.4% and 93.4%. The sensitivity and specificity of the qSOFA score to predict 28-day mortality were 26.9% and 94.6% [Table 4] Logistic regression model was used to see how the qSOFA score predicts 7- and 28-day mortality. The AUROC of qSOFA for 7-day mortality was 85.2% (75.3–92.1) and for 28-day mortality was 77.9% (65.6–89.2). Patients with positive qSOFA scores were at higher odds of dying at 7 days (OR: 3.9, 95% confidence interval [CI]: 3.1–5.2, P < 0.001) and at 28 days (OR: 6.9, 95% CI: 4.6–10.3, P < 0.001).
Figure 1.
Flow diagram of our prospective observational study
Table 1.
Demography and clinical profile of the study participants
| Number of patients | Total (n=1135), n (%) |
|---|---|
| Age (years), median (IQR) | 37 (25-55) |
| Gender | |
| Female | 400 (35.2) |
| Male | 735 (64.7) |
| Comorbidities | |
| Hypertension | 80 (7) |
| Diabetes mellitus | 98 (8.6) |
| Chronic liver disease | 86 (7.5) |
| Chronic kidney disease | 56 (4.9) |
| Chronic obstructive pulmonary disease | 28 (2.4) |
| Pulmonary tuberculosis | 44 (3.8) |
| Malignancy | 98 (8.6) |
| Presenting clinical symptoms | |
| Fever | 966 (85) |
| Cough | 666 (58) |
| Pain in abdomen | 654 (57) |
| Vomiting | 506 (44) |
| Diarrhea | 382 (33) |
| Shortness of breath | 348 (30) |
| Altered mental status | 303 (26) |
| Dysuria | 31 (3) |
| Headache | 18 (1.5) |
| Clinical signs on presentation | |
| Systolic blood pressure (<100 mmHg) | 231 (20.35) |
| Respiratory rate (>22/min) | 363 (31.98) |
| GCS (<13) | 112 (9.86) |
| qSOFA score | |
| qSOFA score 0 | 636 (56) |
| qSOFA score 1 | 380 (33.5) |
| qSOFA score 2 | 104 (9.1) |
| qSOFA score 3 | 15 (1.4) |
| Positive qSOFA (score >2) | 119 (10.5) |
| Negative qSOFA (score <2) | 1016 (89.5) |
n: Number of participants, IQR: Interquartile range, qSOFA: Quick sequential organ failure assessment, GCS: Glasgow Coma Scale
Table 2.
Mortality at day 7 and day 28 based on quick sequential organ failure assessment category
| qSOFA category | Outcomes at 7 days (%) | Outcomes at 28 days (%) | ||
|---|---|---|---|---|
|
|
|
|||
| Died (n=157) | Alive (n=978) | Died (n=283) | Alive (n=852) | |
| Positive qSOFA (n=119) | 54 (45.4, 36.2-54.8) | 65 (54.6, 45.2-63.8) | 76 (63.9, 54.6-72.5) | 43 (36.1, 27.5-45.5) |
| Negative qSOFA (n=1016) | 103 (10.1, 8.4-12.1) | 913 (89.7, 87.8-91.7) | 207 (20.4, 17.9-22.9) | 809 (79.6, 77.0-82.1) |
Positive qSOFA: qSOFA score is ≥2, negative qSOFA; qSOFA score is <2), proportions provided in each cell are calculated with taking total number of positives or negatives as denominator and 95% confidence of proportions are provided with it in parenthesis. qSOFA: Quick sequential organ failure assessment
Table 3.
Mortality at 7 days and 28 days based on quick sequential organ failure assessment score
| qSOFA score | Number of patients (n=1135) | Mortality at 7 days (n=157) (%) | Mortality at 28 days (n=283) (%) |
|---|---|---|---|
| 0 | 636 | 28 (4.4, 2.9-6.3) | 71 (11.2, 8.8-13.9) |
| 1 | 380 | 75 (19.7, 16.1-24.2) | 136 (35.8, 30.9-40.8) |
| 2 | 104 | 42 (40.3, 30.8-50.5) | 62 (59.6, 49.5-69.1) |
| 3 | 15 | 12 (80, 51.9-95.7) | 14 (93.3, 68.1-99.8) |
| Total | 1135 | 157 (13.8) | 283 (24.9) |
Table 4.
Diagnostic performance of quick sequential organ failure assessment for the prediction of 7- and 28-day mortality
| Statistical tools | 7-day mortality (%) | 28-day mortality (%) |
|---|---|---|
| Sensitivity | 34.4 | 26.9 |
| Specificity | 93.4 | 94.6 |
| PPV | 45.4 | 63.9 |
| NPV | 89.9 | 79.6 |
| PLR | 5.18 | 5.32 |
| NLR | 0.70 | 0.77 |
| Accuracy (AUROC) | 85.2 (75.3-92.1) | 77.9 (65.6-89.2) |
AUROC: Area under a receiver operating characteristic curve, PPV: Positive predictive value, NPV: Negative predictive value, PLR: Positive likelihood ratio, NLR: Negative likelihood ratio
DISCUSSION
Sepsis is one of the leading causes of mortality, and early identification is the key for a good outcome. Multiple scoring systems are available to identify those with infection and at risk for adverse clinical outcome and death; however, their utility is limited in the ED of a resource-limited setting. In such a scenario, qSOFA would be of immense utility as it can be performed quickly on the bedside without requiring any laboratory value.
A multicentric prospective cohort study was done by Freund et al. at 30 participating ED in France, Spain, Belgium, and Switzerland involving 879 patients with suspected infection treated at ED. For the prediction of inhospital mortality, qSOFA had a sensitivity of 70% (95% CI, 59%–80%) and specificity of 79% (95% CI, 76%–82%) with PPV and NPVs of 24 and 97. The positive and negative likelihood ratios were 3.40 and 0.37. This study concluded that the qSOFA score was better at predicting inhospital mortality with the Area under receiver operating Curve (AUROC) of 0.80.[4]
In our study, for patients with a positive qSOFA (qSOFA >2), the 7-day mortality was almost four times compared to patients with negative qSOFA (qSOFA <2), and their 28-day mortality was almost four times the mortality for negative qSOFA. The sensitivity and specificity of positive qSOFA to predict 7-day mortality were 34.4% and 93.4%, and to predict 28-day mortality, it was 26.9% and 94.6%, respectively.
Askim et al. performed a single-center observational study and found that the sensitivity and specificity of positive qSOFA to predict 7-day mortality were 16% and 96%, respectively. A similar study was done by Hwang et al. and found that the sensitivity and specificity of positive qSOFA to predict 28-day mortality were 39% and 77% with AUROC 0.58. These two studies did show that the qSOFA score has a poor sensitivity but a higher specificity to predict 7- and 28-day mortality in patients with suspected infection.[5,9]
An observational study was conducted by Abdullah et al. including 434 patients with sepsis of any severity. A total of 73 patients had a positive qSOFA score and were more frequently transferred to the intensive care unit (ICU) care (26% vs. 6.7%, 95% CI of the difference 8.9%–29.7%) and had increased 30-day mortality (32.9% vs. 9.1%, 95% CI of the difference 12.6%–35.0%) compared to patients with a negative qSOFA score. A positive qSOFA score was independently associated with 30-day mortality (OR 4.83, 95% CI 2.11–11.02). This study indicated that positive qSOFA score provides useful prognostic information for sepsis patients defined by the systemic inflammatory response syndrome criteria.[8]
Singer et al. conducted a single-center retrospective study of adult ED patients between January 2014 and March 2015 including 22,530 patients. The mean age was 54 years (SD-21 years), 53% were women, 45% were admitted, and the mortality rate was 1.6%. qSOFA scores were associated with mortality (0 [0.6%], 1 [2.8%], 2 [12.8%], and 3 [25.0%]), ICU admission (0 [5.1%], 1 [10.5%], 2 [20.8%], and 3 [27.4%]), and hospital length of stay (0 [123 h], 1 [163 h], 2 [225 h], and 3 [237 h]).[10]
A meta-analysis was performed by Maitra et al. including 406802 patients from 45 observational studies. Pooled sensitivity (95% CI) and specificity (95% CI) of qSOFA score ≥2 for predicting mortality in patients who were not in the ICU were 0.48 (0.41–0.55) and 0.83 (0.78–0.87), respectively. Pooled sensitivity (95% CI) of qSOFA ≥2 for predicting mortality in patients (both ICU and non-ICU setting) with suspected infection was 0.56 (0.47–0.65) and pooled specificity (95% CI) was 0.78 (0.71–0.83).[11]
Rudd et al. performed a retrospective secondary analysis of eight cohort studies and one randomized clinical trial including 6569 hospitalized adults with suspected infection in ED. Among 6218 patients with nonmissing outcome status in the combined cohort, 643 (10%) died. A high qSOFA score (>2) was associated with an increased risk of death (19% vs. 6%; difference, 13% (95% CI, 11%–14%); OR, 3.6 (95% CI, 3.0–4.2) and across cohorts (P < 0.05 for eight of nine cohorts). Compared with a low qSOFA score (0), a moderate qSOFA score (1) was also associated with an increased risk of death (8% vs. 3%; difference, 5% [95% CI, 4%–6%]; OR, 2.8 [95% CI, 2.0–3.9]), but the results were not consistent in every cohort (P < 0.05 in 2 of 7 cohorts).[12]
Our study suggests that there is a significant increased risk of death among patients with positive qSOFA on presentation to the ED. Since the sensitivity of qSOFA is poor, it has a propensity to miss the patients at a higher risk of death on presentation to ED. Hence, we suggest that due to the high specificity of qSOFA score, it should be used as a risk stratification tool rather than a screening tool to initiate early therapy, escalate the standard of care, and proper allocation of resources for patients with positive qSOFA score to reduce the risk of death. The GCS score (<13) in inclusion criteria makes this study unique from other studies validating qSOFA score. A clinical model which was developed with multivariable logistic regression identified that any two of three clinical variables – GCS of ≤13, systolic blood pressure of ≤100 mmHg, and RR ≥22/min, offered predictive validity (AUROC = 0.81; 95% CI, 0.80–0.82) which was similar to the full SOFA score outside the ICU settings.[13] The predictive validity of qSOFA was not significantly different when using more simple measures like any altered mentation (GCS score <15 [P = 0.56] compared with the model with GCS score ≤13).[13] Further studies may be needed to comparatively assess the predictive validity of qSOFA score with GCS <15 and GCS ≤13.
The presence of a positive qSOFA should alert the emergency physician to the possibility of sepsis; the sensitivity of the qSOFA was consistently poor in various studies in sepsis identification, but it is very useful in risk stratification of patients who are more likely to die due to sepsis.[14,15] The Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021 has issued a strong recommendation against its use as a single screening tool to detect sepsis, but its use as a risk stratification tool to identify sepsis-related death will remain useful mainly in lower- and middle-income countries.[16]
Limitations
The major limitations are being a single-center study, it lacks external validation; many of our patients were lost to follow-up (5.41%). The GCS score was estimated by the emergency physicians; hence, there may exist an interobserver variability in the calculation of the GCS score. Furthermore, qSOFA may not capture all aspects of organ dysfunction (i.e., elevated creatinine, which would require laboratory testing).
CONCLUSION
In this prospective observational study, the qSOFA score failed as a screening tool to identify sepsis on presentation to the ED with suspected infection. However, it can be used as a risk stratification tool which may help in escalating the standard of care for such patients on priority to prevent adverse outcome and death. Moreover, qSOFA does not include any laboratory parameter, which makes it a better bedside risk stratification tool in the ED of resource-limited LMICS.
Research quality and ethics statement
Our study was approved by the Institute’s Ethics Committee, All India Institute of Medical Sciences, New Delhi, having IEC no– 228 dated June 28, 2018, The authors followed applicable EQUATOR Network (https://www.equator-network.org/) guidelines during the conduct of this research project.
Declaration
We certify that Dr. Praveen Aggarwal and Dr. Sanjeev Bhoi are members of the editorial board of the Journal of Emergencies, Trauma and Shock.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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