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Sepsis Incidence: A Population-Based Study

Sepsis Incidence: A Population-Based Study Open Forum Infectious Diseases MAJOR ARTICLE 1 1 2 1 1 1 Lisa Mellhammar, Sven Wullt, Åsa Lindberg, Peter Lanbeck, Bertil Christensson, and Adam Linder 1 2 Department of Clinical Sciences, Division of Infection Medicine, University of Lund, Sweden; Hallands Hospital Halmstad, Sweden Background. Although sepsis is a major health problem, data on sepsis epidemiology are scarce. The aim of this study was to assess the incidence of sepsis, based on clinical findings in all adult patients treated with intravenous antibiotic in all parts of all hospitals in an entire population. Methods. This is a retrospective chart review of patients ≥18 years, living in 2 regions in Sweden, who were started on an intrave- nous antibiotic therapy on 4 dates, evenly distributed over the year of 2015. The main outcome was the incidence of sepsis with organ dysfunction. The mean population ≥18 years at 2015 in the regions was 1 275 753. Five hundred sixty-three patients living in the regions were started on intravenous antibiotic treatment on the dates of the survey. Patients who had ongoing intravenous antibiotic therapy preceding the inclusion dates were excluded, if sepsis was already present. Results. Four hundred eighty-two patients were included in the study; 339 had a diagnosed infection, of those, 96 had severe sepsis according to the 1991/2001 sepsis definitions, and 109 had sepsis according to the sepsis-3. This is equivalent to an annual incidence of traditional severe sepsis of 687/100 000 persons (95% confidence interval [CI], 549–824) or according to the sepsis-3 definition of 780/100 000 persons (95% CI, 633–926). Seventy-four patients had sepsis according to both definitions. Conclusions. e in Th cidence of sepsis with organ dysfunction is higher than most previous estimates independent of definition. e in Th clusion of all inpatients started on intravenous antibiotic treatment of sepsis in a population makes an accurate assessment of sepsis incidence possible. Keywords. incidence; qSOFA; sepsis; SIRS. e co Th mplexity of sepsis and its interactions with other diseases for sepsis definitions [1, 2]. The Sepsis Definitions Task Force contribute to the difficulty to diagnose sepsis and to estimate also launches a tool to recognize patients who should be further the incidence. examined to discover sepsis, known as quick SOFA (qSOFA), er Th e is no gold standard for diagnosing sepsis. The diag- based on ≥2 of altered mental status, hypotension (systolic nostic criteria for sepsis, which have been applied since 1991, blood pressure ≤100 mmHg), and tachypnea (respiratory rate with additions in 2001, are insufficient to discriminate between ≥22 breaths/minute) [5]. uncomplicated infection and severe disease and have proven a e a Th nnual incidence of sepsis varies in studies. The most cited lack of sensitivity [1–4]. studies on incidence of traditional severe sepsis are based on e S Th epsis Definitions Task Force, endorsed by the European International Classic fi ation of Diseases, Ninth and Tenth Revision Society of Intensive Care and the Society of Critical Care codes (ICD-9 and ICD-10) in hospital discharge databases and Medicine, recommends sepsis to be defined as organ dysfunc- vary between 132 and 300/100 000 [6–8]. Depending on which tion, characterized by a rise in Sequential (Sepsis-Related) code abstraction method is used, the incidence varies by 3- to Organ Failure Assessment (SOFA) score ≥2, due to a dysregu- 3.5-fold within a cohort and with poor accuracy. The incidence lated host response to infection. The discrimination between estimates have risen over the years to 300–1031/100 000 (2004– sepsis and severe sepsis is not advocated. 2009), but these estimates are remarkably lower from Swedish e n Th ew sepsis definition is designated sepsis-3, which it will databases [9, 10]. Comparisons between ICD code abstractions be called throughout this paper [5]. We use the term traditional and medical record review for identification of traditional severe severe sepsis in accordance with the 1991 and 2001 conferences sepsis have shown good specificity but poor sensitivity [11]. Prospective collection of sepsis incidence data is labor intensive; however, Henriksen et al [12] collected data and recognized an Received 13 July 2016; editorial decision 23 September 2016; accepted 2 October 2016. incidence of traditional severe sepsis of 457/100 000 (95% confi- Correspondence: Lisa Mellhammar, MD, Department of Clinical Sciences, Division of dence interval [CI], 430–485). e Th study was restricted to patients Infection Medicine, University of Lund, S-221 84 Lund, Sweden ([email protected]). presenting at a medical emergency department (ED) with com- Open Forum Infectious Diseases © The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases munity-acquired sepsis and excluded large patient groups such as Society of America. This is an Open Access article distributed under the terms of the Creative surgery and dialysis patients and nosocomial sepsis [12]. Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any Although sepsis is a major challenge for clinicians, healthcare medium, provided the original work is not altered or transformed in any way, and that the work systems, and researchers, comprehensive data on the epidemi- is properly cited. For commercial re-use, please contact [email protected]. DOI: 10.1093/ofid/ofw207 ology of sepsis are scarce. Because the criteria for sepsis were Sepsis Incidence: A Population-Based Study • OFID • 1 recently changed, a comparison of incidence based on both ear- prescribed, most abnormal physiological parameters ±12 hours, lier and forthcoming criteria is valuable in understanding how and diagnostic and microbiological data for the sepsis- caus- this change of definitions will ae ff ct epidemiological estimates. ing infection. Two experienced physicians (L. M.  and Å. L.) e Th ability of qSOFA to predict poor outcome in patients reviewed the medical records. To validate the review, 2.5% of with suspected infection has thus far only been evaluated with the included patients were randomly selected and also reviewed inhospital mortality and/or prolonged intensive care unit (ICU) by a second physician (A. L.  or L.  M.), regarding presence of stay as outcome [13]. The aim of this study was to estimate the infection, focus, and sepsis-induced organ dysfunction and incidence of sepsis based on clinical findings in all patients organ failure. The reviewers were blinded to the others’ result. treated with intravenous (IV) antibiotics in all parts of all hos- Definitions pitals in 2 entire regions. We estimated the incidence based on Traditional severe sepsis and traditional septic shock were both earlier and forthcoming criteria, and we assessed systemic defined based on the 1991 and 2001 conferences for sepsis defi- inflammatory response syndrome (SIRS)’s and qSOFA’s ability nitions and Surviving Sepsis Campaign [1, 2, 16], and sepsis-3 to identify traditional severe sepsis and sepsis-3. and septic shock were defined according to the sepsis-3 [5] for separate estimations of incidence. Traditional severe sepsis was METHODS defined as hypotension, hypoperfusion, or organ dysfunction Study Design, Population, and Setting induced by sepsis (see Supplementary Data for details) [1, 2, We conducted a retrospective chart review of patients ≥18 years 16]. The requirement of fulfilling 2 SIRS criteria was not applied living in the regions of Skåne and Halland in southern Sweden. We due to its lack of sensitivity [3]. Septic shock was defined as tra- reviewed medical records for all patients who were started on an IV ditional severe sepsis with hypotension refractory to ≥2000 mL antibiotic therapy at hospitals on 4 dates evenly distributed over the fluid resuscitation or the need for vasopressors [1, 2]. Sepsis-3 year of 2015: January 12, April 13, July 13, and October 12. was defined as organ dysfunction characterized by a rise in total e R Th egions of Skåne and Halland are geographic regions SOFA ≥2 due to a dysregulated host response to infection, and with self-governing local authorities with responsibility for septic shock as, despite adequate fluid resuscitation, a lactate providing healthcare. The mean population in the regions >2 mmol/L and vasopressors needed for mean arterial pressure was 1 275 753  ≥18  years at 2015: 146 401 were 18–24  years, ≥65 mmHg [5, 17]. 208 282 were 25–34  years, 208 483 were 35–44  years, 212 104 Partial pressure of oxygen in arterial blood (PaO ) was pref- were 45–54  years, 183 976 were 55–64  years, 178 073 were erably used. When not available, we used the oxygen saturation 65–74 years, 96 749 were 75–84 years, 38 478 were 85–94 years, by pulse oximetry (SpO ) for values <96% and calculated PaO 2 2 and 3207 were ≥95 years [14]. The regions are served by 11 hos- by the Ellis equation. This substitution correlates with PaO , but pitals, 2 of which are tertiary, academic hospitals. it has a tendency to overestimate it [18–20]. Reaction level scale Patients were identified by a national database, the anti-infec- (RLS 85)  was used because it is applied in clinical practice in tion tool, which registers all out- and inpatients who are started Sweden, although its association with Glasgow Coma Scale has on antibiotic therapy at the hospitals [15]. It is impossible to only been evaluated for APACHE II [21]. prescribe antibiotics and circumvent the registration in the For assessment of sepsis incidence, infections were defined anti-infection tool, which is aimed for surveillance of antibiotic as described by Calandra et  al [22]. The definitions are aimed use and healthcare-associated infections. For a few departments for trials in ICU. To adapt the definitions to patients on the (8 of 56) at hospitals in the regions that are not affiliated to this ward, the following modifications were permitted. The criteria database, medical records were reviewed manually to identify for pneumonia were changed regarding possible pneumonia, patients who received antibiotics. where high clinical suspicion without an abnormal chest radio- Data Collection graph was included. Patients were included in the study if they fulfilled at least 1 In urinary tract infections, 2 of the following were required: of the 4 SIRS criteria or had experienced fever or chills, blood symptoms, urine culture with ≥10 colony-forming unit/L pressure ≤110, or had an altered mental status within ±12 hours uropathogens or radiographic evidence of infection. Because from the initiation of antibiotic therapy. Patients under palli- bone and joint, central nervous system, ear-nose-throat, repro- ation and hospice care at home were excluded. Patients who ductive tract infections and gastroenteritis are not included in had another IV antibiotic therapy preceding the inclusion dates the definitions, we used the Centers for Disease Control and were not included when calculating incidence if traditional Prevention/National Healthcare Safety Network Surveillance severe sepsis, sepsis-3, or septic shock (traditional sepsis or sep- Definitions for Specific Types of Infections [23]. For evaluation sis-3 criteria) was already present. of SIRS’s and qSOFA’s ability to identify traditional severe sep- Data were collected regarding basic demography including sis and sepsis-3, clinical suspicion was the only requirement for mortality, the department at which the antibiotic therapy was infection. 2 • OFID • Mellhammar et al prescribed, most abnormal physiological parameters ±12 hours, e p Th resence of the following comorbid conditions was reg- This is equivalent to an annual incidence of patients receiving and diagnostic and microbiological data for the sepsis- caus- istered: congestive heart failure (New York Heart Association IV antibiotics for a diagnosed infection of 2425/100 000 persons ing infection. Two experienced physicians (L. M.  and Å. L.) class  III–IV), history of acute myocardial infarction, liver cir- (95% CI, 2167–2683). reviewed the medical records. To validate the review, 2.5% of rhosis, cerebrovascular disease, chronic obstructive pulmonary e a Th nnual incidence of traditional severe sepsis was the included patients were randomly selected and also reviewed disease or asthma, diabetes mellitus with ongoing treatment 687/100 000 persons (95% CI, 549–824), and according to the by a second physician (A. L.  or L.  M.), regarding presence of for glucose control, chronic renal failure (serum creatinine new sepsis-3 definition the annual incidence was 780/100 000 infection, focus, and sepsis-induced organ dysfunction and >177 μmol/L), malignancy diagnosed in the last 5 years, auto- persons (95% CI, 633–926). The incidences of traditional severe organ failure. The reviewers were blinded to the others’ result. immune disease, and immunodeficiency including human sepsis and sepsis-3 for different 10-year age strata increased immunodeficiency virus. with increasing age; however, the actual numbers were small Definitions e I Th CD-10 codes for sepsis at hospital discharge were reg- (Table 1). Traditional severe sepsis and traditional septic shock were istered. The ICD-10 codes for sepsis were as follows: R65.1, Among the 96 patients with traditional severe sepsis, 51 defined based on the 1991 and 2001 conferences for sepsis defi- R57.2, A02.1, A22.7, A26.7, A32.7, A40.0–A40.3, A40.8–A409, (53.1%) were female, 23 (24.0%) had bacteraemia, 15 (15.6%) nitions and Surviving Sepsis Campaign [1, 2, 16], and sepsis-3 A41.0–A41.5, A41.8–A419, and B37.7. The study protocol had any sepsis diagnose code (ICD-10) at hospital discharge, and septic shock were defined according to the sepsis-3 [5] for was approved by the local ethics committee (decision number and the inhospital mortality and mortality <90  days were 19 separate estimations of incidence. Traditional severe sepsis was 2015/285). (19.8%) and 30 (31.3%), respectively. Among the 106 patients defined as hypotension, hypoperfusion, or organ dysfunction with sepsis-3, 59 (54.1%) were female, 21 (19.3%) had bacte- induced by sepsis (see Supplementary Data for details) [1, 2, Statistical Analysis raemia, 17 (15.6%) had any sepsis diagnose code (ICD-10) at 16]. The requirement of fulfilling 2 SIRS criteria was not applied Incidence rates of patients starting antibiotic therapy and ful- hospital discharge, and the inhospital mortality and mortality due to its lack of sensitivity [3]. Septic shock was defined as tra- filling sepsis definitions were calculated, and their 95% CIs <90  days were 19 (17.4%) and 28 (25.7%), respectively. There ditional severe sepsis with hypotension refractory to ≥2000 mL from the incidence ±1.96 times the square root of the incidence were no significant differences between the groups in these fluid resuscitation or the need for vasopressors [1, 2]. Sepsis-3 divided by person years at risk (i ± 1.96 √I⁄T). Person-years at regards. Enterobacteriaceae were most frequently found in was defined as organ dysfunction characterized by a rise in total risk were calculated from the regions population by dividing blood cultures, followed by Staphylococcus aureus and strepto- SOFA ≥2 due to a dysregulated host response to infection, and it by 365 days and multiplied by 4 days. All missing data were cocci in both groups. septic shock as, despite adequate fluid resuscitation, a lactate regarded as within the normal range for calculation of incidence. er Th e were no significant seasonal variations in when the >2 mmol/L and vasopressors needed for mean arterial pressure For continuous variables, medians are shown. Categorical val- patients were observed with sepsis, neither in the patients ≥65 mmHg [5, 17]. ues are expressed as percentages. Comparisons are made by who fulfilled the traditional severe sepsis criteria (January 23 Partial pressure of oxygen in arterial blood (PaO ) was pref- McNemar’s test for incidence between different sepsis defini- [24.0%], April 24 [25.0%], July 18 [18.8%], October 31 [32.3%]) erably used. When not available, we used the oxygen saturation tions. For demographic differences between the patients identi- nor in those who fulfilled the sepsis-3 criteria (January 29 by pulse oximetry (SpO ) for values <96% and calculated PaO fied with the different sepsis definitions, P values are calculated 2 2 [26.6%], April 26 [23.9%], July 18 [16.5%], October 36 [33.0%]). by the Ellis equation. This substitution correlates with PaO , but by χ or Fishers exact test. P values are shown when significant. For details on demography, distribution of organ failure/dys- it has a tendency to overestimate it [18–20]. Reaction level scale Sensitivity, specificity, positive predictive values, and negative function, and infection, see Table 1. e Th interrater agreement (RLS 85)  was used because it is applied in clinical practice in predictive values with 95% CIs were calculated using Wilson’s for the reviewers was 87% (κ = 0.82; 95% CI, 0.73–0.95). Sweden, although its association with Glasgow Coma Scale has score interval. Patients with missing SIRS or qSOFA parameters To evaluate the SIRS’s and qSOFA’s ability to identify tradi- only been evaluated for APACHE II [21]. were excluded when comparing SIRS’s and qSOFA’s ability to tional severe sepsis and sepsis-3, 339 patients with a diagnosed For assessment of sepsis incidence, infections were defined identify sepsis. infection and 99 patients with clinically suspected infection as described by Calandra et  al [22]. The definitions are aimed Cohen’s κ statistics were used to measure the interrater agree- were judged to be eligible. Sixty-six patients were excluded due for trials in ICU. To adapt the definitions to patients on the ment regarding presence of infection and whether organ fail- to missing data, rendering 372 patients with diagnosed or sus- ward, the following modifications were permitted. The criteria ure/organ dysfunction was due to sepsis. pected infection for evaluation of qSOFA and SIRS. for pneumonia were changed regarding possible pneumonia, IBM SPSS statistics 23.0 and Graph-Pad Prism 6.0 were used For distribution of SIRS and qSOFA in relation to traditional where high clinical suspicion without an abnormal chest radio- for the calculations. severe sepsis and sepsis-3, see Table  2. For SIRS’ and qSOFA’s graph was included. sensitivity, specificity, positive predictive value, and negative In urinary tract infections, 2 of the following were required: RESULTS predictive value, see Table  3. Of the 66 patients with missing symptoms, urine culture with ≥10 colony-forming unit/L SIRS or qSOFA parameters, 13 had traditional severe sepsis and Five hundred sixty-three patients living in the regions started uropathogens or radiographic evidence of infection. Because 21 had sepsis-3. IV antibiotic treatment on the dates of the survey. Four hun- bone and joint, central nervous system, ear-nose-throat, repro- dred eighty-two patients were included in the study, and 44 ductive tract infections and gastroenteritis are not included in DISCUSSION of those patients had no infection diagnosis. An additional 99 the definitions, we used the Centers for Disease Control and patients had a suspected infection, but they did not fulfill the Our study suggests a high incidence of traditional severe sep- Prevention/National Healthcare Safety Network Surveillance criteria for infection diagnosis and were excluded. This left 339 sis (687/100 000), and the incidence was even somewhat higher Definitions for Specific Types of Infections [23]. For evaluation patients with a diagnosed infection: 96 (28.3%) of these patients using the newly proposed sepsis-3 definitions (780/10 000) of SIRS’s and qSOFA’s ability to identify traditional severe sep- had traditional severe sepsis, and 109 patients (32.3%) had sep- but without a significant difference. A  substantial portion of sis and sepsis-3, clinical suspicion was the only requirement for sis-3 (see Figure 1 for details). Seventy-four (21.8%) of these patients with sepsis fulfilled only 1 of the sepsis definitions infection. patients fulfilled both traditional severe sepsis and sepsis-3. (traditional severe sepsis or sepsis-3). The qSOFA showed poor Sepsis Incidence: A Population-Based Study • OFID • 3 Table  1. Demography and Distribution of Organ Failure, Organ Dysfunction, and Infection in Patients With Traditional Severe Sepsis and Sepsis-3. Patients Can Be Represented in Both Columns Variables Traditional Severe Sepsis Sepsis-3 PValue N = 131 96 109 Age, median 78 80 18–24 1 (1.0%) 1 (0.9%) 25–34 1 (1.0%) 0 35–44 3 (3.1%) 1 (0.9%) 45–54 3 (3.1%) 1 (0.9%) 55–64 6 (6.3%) 10 (9.2%) 65–74 22 (22.9%) 25 (22.9%) 75–84 29 (30.2%) 32 (29.4%) 85–94 29 (30.2%) 36 (33.0%) ≥95 2 (2.1%) 3 (2.8%) Comorbidities None 23 (24.0%) 20 (18.3%) Heart disease 30 (31.3%) 40 (36.7%) Malignancy 23 (24.0%) 26 (23.9%) Asthma, COPD 22 (22.9%) 19 (17.4%) Diabetes mellitus 18 (18.8%) 22 (20.2%) Cerebrovascular disease 17 (17.7%) 22 (20.2%) Chronic renal failure 10 (10.4%) 11 (10.1%) Cirrhosis 2 (2.1%) 1 (0.9%) Immunodeficiency 0 0 Connective tissue disorder 9 (9.4%) 11 (10.1%) Ward at Initiation of Antibiotis Emergency Department 65 (67.7%) 67 (61.5%) Nonsurgical ward 19 (19.8%) 31 (28.4%) Surgical ward 10 (10.4%) 8 (7.3%) Intensive care unit 2 (2.1%) 3 (2.8%) Organ Dysfunction Cardiovascular 50 (52.1%) 41 (37.6%) .037 CNS 30 (31.3%) 28 (25.7%) Hepatic 0 7 (6.4%) .015 Renal 29 (30.2%) 37 (33.9%) Respiratory 27 (28.1%) 87 (79.8%) <.01 Hematologic 7 (7.3%) 11 (10.1%) Hypoperfusion 24 (25.0%) Chock 7 (7.3%) 4 (3.7%) Number of Organs Dysfunction 1 49 (51.0%) 40 (36.7%) .038 >1 47 (49.0%) 69 (63.3%) Site of Infection Respiratory tract 40 (41.7%) 55 (50.5%) Urinary tract 17 (17.7%) 19 (17.4%) Abdominal 14 (14.6%) 12 (11.0%) Skin or soft tissue 7 (7.3%) 5 (4.6%) Other 18 (18.8%) 18 (16.5%) Abbreviations: COPD, chronic obstructive pulmonary disease; CNS, central nervous system. sensitivity but good specificity in predicting traditional severe fail to register many episodes [11]. Our study also differs from sepsis and sepsis-3. other studies in that the study cohort was older; however, a recent study from Prescott et al [24] shows similar results. Comparison to Similar Studies e in Th cidence found in the present study was also higher The incidence of traditional severe sepsis was higher than in than in studies based on clinical findings [12]. This is probably most preceding studies, which is not surprising because many partly due to different definitions; for example, we did not apply studies are based on discharge diagnoses and have proven to the requirement of fulfilling 2 SIRS criteria, which probably 4 • OFID • Mellhammar et al Table  2. Contingency Table of SIRS, qSOFA, and Traditional Severe Sepsis and Sepsis-3 (N = 372) Traditional Severe Sepsis Sepsis-3 Variables Yes No Yes No <2 SIRS 11 60 10 61 ≥2 SIRS 98 203 106 195 <2 qSOFA 49 246 67 228 ≥2 qSOFA 60 17 49 28 Abbreviations: qSOFA, quick Sequential (Sepsis-Related) Organ Failure Assessment; SIRS, systemic inflammatory response syndrome. increased the incidence. In addition, earlier studies have been restricted to certain wards or EDs [12, 25]. In this study, we screened all adult patients who were started on IV antibiotic treatment in all parts of all hospitals in 2 entire regions; therefore, we identified both community-acquired and nosocomial sepsis cases. Even if our study includes a smaller number of patients, the CIs are well above the previously pro- posed incidences. e m Th agnitude of our data is illustrated by our recorded incidence of 2425/100 000 adults receiving IV antibiotics for a diagnosed infection, which corresponds to more than 200 000 Swedish patients each year. Approximately 1 of 4 of these patients receiving IV antibiotics had or developed organ dysfunction. The burden of antibiotic resistance is still relatively low in Sweden, indicating that the incidence of traditional severe sepsis and sep- sis-3 may be higher in other parts of the world, and with a grow- ing antimicrobial resistance it will likely increase [26]. Strengths and Limitations We applied restrictive criteria of infection, demanding both clin- ical and objective signs of infection except for pneumonia where high clinical suspicion was sufficient for inclusion. The defini- tions for traditional severe sepsis are based on interpretations of consensus criteria, and the definitions can therefore vary from other studies. We believe that the incidence of patients with sep- sis-related organ dysfunction is not overestimated, and we sus- pect that it might be underestimated. It is probable that several patients with sepsis were unobserved due to a lack of clinical suspicion and diagnostic measures or oral antibiotic treatment, avoidance of treatment, or sudden death. Organ dysfunction may have occurred before or after the infection is suspected and treatment initiated, and outside of the time window we screened for organ dysfunction. Other limitations to this study are the small size, only adults included, and the retrospective design. e s Th trengths of this study are the comprehensive inclu- sion of all patients with IV antibiotic therapy in a well defined population, the manual chart reviews, and the use of 2 different definitions. The outcomes and the features of the patients with only traditional severe sepsis or sepsis-3 would be interesting to characterize further, but the numbers are too small in the present study. Sepsis Incidence: A Population-Based Study • OFID • 5 Table 3. Sensitivity, Specificity, Positive Predictive Value, and Negative Predictive Value of SIRS and qSOFA for Predicting Traditional Severe Sepsis and Sepsis-3 Parameters Sensitivity Specificity Positive Predictive Value Negative Predictive Value Variables Traditional Sepsis-3 Traditional Sepsis-3 Traditional Sepsis-3 Traditional Sepsis-3 Severe Sepsis Severe Sepsis Severe Sepsis Severe Sepsis 2 SIRS 89.9 (82.7–94.9) 91.4 (84.7–95.8) 22.8 (17.9–28.4) 23.8 (18.7–29.5) 32.6 (27.3–38.2) 35.2 (29.8–40.9) 84.5 (74.0–92.0) 85.9 (75.6–93.0) 2 qSOFA 55.0 (45.2–64.6) 42.2 (33.1–51.8) 93.5 (89.9–96.2) 89.1 (84.6–92.6) 77.9 (67.0–86.6) 63.6 (51.9–74.3) 83.4 (78.6–87.5) 77.3 (72.1–81.9) Abbreviations: qSOFA, quick Sequential (Sepsis-Related) Organ Failure Assessment; SIRS, systemic inflammatory response syndrome. Figure 1. Flow chart of patient recruitment and sepsis groups. Financial support. This work was supported by Swedish Government e qSO Th FA has been validated against inhospital mortality and Research Grant, Skåne University Hospital Foundations, Southern Health ICU stay, among patients receiving treatment. However, a large Care Region Grant, Svenska Läkaresällskapet, Grochinsky Foundation, proportion of patients with sepsis and multiorgan dysfunctions Lundgrens Foundation, and Österlunds Foundation. never reach the ICU and are hence treated in the wards [27, 28]. Potential coni fl cts of interest. All authors report no conflicts of inter - ests that the editors consider relevant to the content of this manuscript. In our study, in patients with clinically suspected infection All authors have submitted the ICMJE Form for Disclosure of Potential with traditional severe sepsis and sepsis-3 as outcomes, the sen- Conflicts of Interest. sitivity and the negative predictive value were unsatisfactory. 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Sepsis Incidence: A Population-Based Study • OFID • 7 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Open Forum Infectious Diseases Pubmed Central

Sepsis Incidence: A Population-Based Study

Mellhammar, Lisa; Wullt, Sven; Lindberg, Åsa; Lanbeck, Peter; Christensson, Bertil; Linder, Adam
Open Forum Infectious Diseases , Volume 3 (4) – Dec 8, 2016
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Abstract

Open Forum Infectious Diseases MAJOR ARTICLE 1 1 2 1 1 1 Lisa Mellhammar, Sven Wullt, Åsa Lindberg, Peter Lanbeck, Bertil Christensson, and Adam Linder 1 2 Department of Clinical Sciences, Division of Infection Medicine, University of Lund, Sweden; Hallands Hospital Halmstad, Sweden Background. Although sepsis is a major health problem, data on sepsis epidemiology are scarce. The aim of this study was to assess the incidence of sepsis, based on clinical findings in all adult patients treated with intravenous antibiotic in all parts of all hospitals in an entire population. Methods. This is a retrospective chart review of patients ≥18 years, living in 2 regions in Sweden, who were started on an intrave- nous antibiotic therapy on 4 dates, evenly distributed over the year of 2015. The main outcome was the incidence of sepsis with organ dysfunction. The mean population ≥18 years at 2015 in the regions was 1 275 753. Five hundred sixty-three patients living in the regions were started on intravenous antibiotic treatment on the dates of the survey. Patients who had ongoing intravenous antibiotic therapy preceding the inclusion dates were excluded, if sepsis was already present. Results. Four hundred eighty-two patients were included in the study; 339 had a diagnosed infection, of those, 96 had severe sepsis according to the 1991/2001 sepsis definitions, and 109 had sepsis according to the sepsis-3. This is equivalent to an annual incidence of traditional severe sepsis of 687/100 000 persons (95% confidence interval [CI], 549–824) or according to the sepsis-3 definition of 780/100 000 persons (95% CI, 633–926). Seventy-four patients had sepsis according to both definitions. Conclusions. e in Th cidence of sepsis with organ dysfunction is higher than most previous estimates independent of definition. e in Th clusion of all inpatients started on intravenous antibiotic treatment of sepsis in a population makes an accurate assessment of sepsis incidence possible. Keywords. incidence; qSOFA; sepsis; SIRS. e co Th mplexity of sepsis and its interactions with other diseases for sepsis definitions [1, 2]. The Sepsis Definitions Task Force contribute to the difficulty to diagnose sepsis and to estimate also launches a tool to recognize patients who should be further the incidence. examined to discover sepsis, known as quick SOFA (qSOFA), er Th e is no gold standard for diagnosing sepsis. The diag- based on ≥2 of altered mental status, hypotension (systolic nostic criteria for sepsis, which have been applied since 1991, blood pressure ≤100 mmHg), and tachypnea (respiratory rate with additions in 2001, are insufficient to discriminate between ≥22 breaths/minute) [5]. uncomplicated infection and severe disease and have proven a e a Th nnual incidence of sepsis varies in studies. The most cited lack of sensitivity [1–4]. studies on incidence of traditional severe sepsis are based on e S Th epsis Definitions Task Force, endorsed by the European International Classic fi ation of Diseases, Ninth and Tenth Revision Society of Intensive Care and the Society of Critical Care codes (ICD-9 and ICD-10) in hospital discharge databases and Medicine, recommends sepsis to be defined as organ dysfunc- vary between 132 and 300/100 000 [6–8]. Depending on which tion, characterized by a rise in Sequential (Sepsis-Related) code abstraction method is used, the incidence varies by 3- to Organ Failure Assessment (SOFA) score ≥2, due to a dysregu- 3.5-fold within a cohort and with poor accuracy. The incidence lated host response to infection. The discrimination between estimates have risen over the years to 300–1031/100 000 (2004– sepsis and severe sepsis is not advocated. 2009), but these estimates are remarkably lower from Swedish e n Th ew sepsis definition is designated sepsis-3, which it will databases [9, 10]. Comparisons between ICD code abstractions be called throughout this paper [5]. We use the term traditional and medical record review for identification of traditional severe severe sepsis in accordance with the 1991 and 2001 conferences sepsis have shown good specificity but poor sensitivity [11]. Prospective collection of sepsis incidence data is labor intensive; however, Henriksen et al [12] collected data and recognized an Received 13 July 2016; editorial decision 23 September 2016; accepted 2 October 2016. incidence of traditional severe sepsis of 457/100 000 (95% confi- Correspondence: Lisa Mellhammar, MD, Department of Clinical Sciences, Division of dence interval [CI], 430–485). e Th study was restricted to patients Infection Medicine, University of Lund, S-221 84 Lund, Sweden ([email protected]). presenting at a medical emergency department (ED) with com- Open Forum Infectious Diseases © The Author 2016. Published by Oxford University Press on behalf of the Infectious Diseases munity-acquired sepsis and excluded large patient groups such as Society of America. This is an Open Access article distributed under the terms of the Creative surgery and dialysis patients and nosocomial sepsis [12]. Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/ by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any Although sepsis is a major challenge for clinicians, healthcare medium, provided the original work is not altered or transformed in any way, and that the work systems, and researchers, comprehensive data on the epidemi- is properly cited. For commercial re-use, please contact [email protected]. DOI: 10.1093/ofid/ofw207 ology of sepsis are scarce. Because the criteria for sepsis were Sepsis Incidence: A Population-Based Study • OFID • 1 recently changed, a comparison of incidence based on both ear- prescribed, most abnormal physiological parameters ±12 hours, lier and forthcoming criteria is valuable in understanding how and diagnostic and microbiological data for the sepsis- caus- this change of definitions will ae ff ct epidemiological estimates. ing infection. Two experienced physicians (L. M.  and Å. L.) e Th ability of qSOFA to predict poor outcome in patients reviewed the medical records. To validate the review, 2.5% of with suspected infection has thus far only been evaluated with the included patients were randomly selected and also reviewed inhospital mortality and/or prolonged intensive care unit (ICU) by a second physician (A. L.  or L.  M.), regarding presence of stay as outcome [13]. The aim of this study was to estimate the infection, focus, and sepsis-induced organ dysfunction and incidence of sepsis based on clinical findings in all patients organ failure. The reviewers were blinded to the others’ result. treated with intravenous (IV) antibiotics in all parts of all hos- Definitions pitals in 2 entire regions. We estimated the incidence based on Traditional severe sepsis and traditional septic shock were both earlier and forthcoming criteria, and we assessed systemic defined based on the 1991 and 2001 conferences for sepsis defi- inflammatory response syndrome (SIRS)’s and qSOFA’s ability nitions and Surviving Sepsis Campaign [1, 2, 16], and sepsis-3 to identify traditional severe sepsis and sepsis-3. and septic shock were defined according to the sepsis-3 [5] for separate estimations of incidence. Traditional severe sepsis was METHODS defined as hypotension, hypoperfusion, or organ dysfunction Study Design, Population, and Setting induced by sepsis (see Supplementary Data for details) [1, 2, We conducted a retrospective chart review of patients ≥18 years 16]. The requirement of fulfilling 2 SIRS criteria was not applied living in the regions of Skåne and Halland in southern Sweden. We due to its lack of sensitivity [3]. Septic shock was defined as tra- reviewed medical records for all patients who were started on an IV ditional severe sepsis with hypotension refractory to ≥2000 mL antibiotic therapy at hospitals on 4 dates evenly distributed over the fluid resuscitation or the need for vasopressors [1, 2]. Sepsis-3 year of 2015: January 12, April 13, July 13, and October 12. was defined as organ dysfunction characterized by a rise in total e R Th egions of Skåne and Halland are geographic regions SOFA ≥2 due to a dysregulated host response to infection, and with self-governing local authorities with responsibility for septic shock as, despite adequate fluid resuscitation, a lactate providing healthcare. The mean population in the regions >2 mmol/L and vasopressors needed for mean arterial pressure was 1 275 753  ≥18  years at 2015: 146 401 were 18–24  years, ≥65 mmHg [5, 17]. 208 282 were 25–34  years, 208 483 were 35–44  years, 212 104 Partial pressure of oxygen in arterial blood (PaO ) was pref- were 45–54  years, 183 976 were 55–64  years, 178 073 were erably used. When not available, we used the oxygen saturation 65–74 years, 96 749 were 75–84 years, 38 478 were 85–94 years, by pulse oximetry (SpO ) for values <96% and calculated PaO 2 2 and 3207 were ≥95 years [14]. The regions are served by 11 hos- by the Ellis equation. This substitution correlates with PaO , but pitals, 2 of which are tertiary, academic hospitals. it has a tendency to overestimate it [18–20]. Reaction level scale Patients were identified by a national database, the anti-infec- (RLS 85)  was used because it is applied in clinical practice in tion tool, which registers all out- and inpatients who are started Sweden, although its association with Glasgow Coma Scale has on antibiotic therapy at the hospitals [15]. It is impossible to only been evaluated for APACHE II [21]. prescribe antibiotics and circumvent the registration in the For assessment of sepsis incidence, infections were defined anti-infection tool, which is aimed for surveillance of antibiotic as described by Calandra et  al [22]. The definitions are aimed use and healthcare-associated infections. For a few departments for trials in ICU. To adapt the definitions to patients on the (8 of 56) at hospitals in the regions that are not affiliated to this ward, the following modifications were permitted. The criteria database, medical records were reviewed manually to identify for pneumonia were changed regarding possible pneumonia, patients who received antibiotics. where high clinical suspicion without an abnormal chest radio- Data Collection graph was included. Patients were included in the study if they fulfilled at least 1 In urinary tract infections, 2 of the following were required: of the 4 SIRS criteria or had experienced fever or chills, blood symptoms, urine culture with ≥10 colony-forming unit/L pressure ≤110, or had an altered mental status within ±12 hours uropathogens or radiographic evidence of infection. Because from the initiation of antibiotic therapy. Patients under palli- bone and joint, central nervous system, ear-nose-throat, repro- ation and hospice care at home were excluded. Patients who ductive tract infections and gastroenteritis are not included in had another IV antibiotic therapy preceding the inclusion dates the definitions, we used the Centers for Disease Control and were not included when calculating incidence if traditional Prevention/National Healthcare Safety Network Surveillance severe sepsis, sepsis-3, or septic shock (traditional sepsis or sep- Definitions for Specific Types of Infections [23]. For evaluation sis-3 criteria) was already present. of SIRS’s and qSOFA’s ability to identify traditional severe sep- Data were collected regarding basic demography including sis and sepsis-3, clinical suspicion was the only requirement for mortality, the department at which the antibiotic therapy was infection. 2 • OFID • Mellhammar et al prescribed, most abnormal physiological parameters ±12 hours, e p Th resence of the following comorbid conditions was reg- This is equivalent to an annual incidence of patients receiving and diagnostic and microbiological data for the sepsis- caus- istered: congestive heart failure (New York Heart Association IV antibiotics for a diagnosed infection of 2425/100 000 persons ing infection. Two experienced physicians (L. M.  and Å. L.) class  III–IV), history of acute myocardial infarction, liver cir- (95% CI, 2167–2683). reviewed the medical records. To validate the review, 2.5% of rhosis, cerebrovascular disease, chronic obstructive pulmonary e a Th nnual incidence of traditional severe sepsis was the included patients were randomly selected and also reviewed disease or asthma, diabetes mellitus with ongoing treatment 687/100 000 persons (95% CI, 549–824), and according to the by a second physician (A. L.  or L.  M.), regarding presence of for glucose control, chronic renal failure (serum creatinine new sepsis-3 definition the annual incidence was 780/100 000 infection, focus, and sepsis-induced organ dysfunction and >177 μmol/L), malignancy diagnosed in the last 5 years, auto- persons (95% CI, 633–926). The incidences of traditional severe organ failure. The reviewers were blinded to the others’ result. immune disease, and immunodeficiency including human sepsis and sepsis-3 for different 10-year age strata increased immunodeficiency virus. with increasing age; however, the actual numbers were small Definitions e I Th CD-10 codes for sepsis at hospital discharge were reg- (Table 1). Traditional severe sepsis and traditional septic shock were istered. The ICD-10 codes for sepsis were as follows: R65.1, Among the 96 patients with traditional severe sepsis, 51 defined based on the 1991 and 2001 conferences for sepsis defi- R57.2, A02.1, A22.7, A26.7, A32.7, A40.0–A40.3, A40.8–A409, (53.1%) were female, 23 (24.0%) had bacteraemia, 15 (15.6%) nitions and Surviving Sepsis Campaign [1, 2, 16], and sepsis-3 A41.0–A41.5, A41.8–A419, and B37.7. The study protocol had any sepsis diagnose code (ICD-10) at hospital discharge, and septic shock were defined according to the sepsis-3 [5] for was approved by the local ethics committee (decision number and the inhospital mortality and mortality <90  days were 19 separate estimations of incidence. Traditional severe sepsis was 2015/285). (19.8%) and 30 (31.3%), respectively. Among the 106 patients defined as hypotension, hypoperfusion, or organ dysfunction with sepsis-3, 59 (54.1%) were female, 21 (19.3%) had bacte- induced by sepsis (see Supplementary Data for details) [1, 2, Statistical Analysis raemia, 17 (15.6%) had any sepsis diagnose code (ICD-10) at 16]. The requirement of fulfilling 2 SIRS criteria was not applied Incidence rates of patients starting antibiotic therapy and ful- hospital discharge, and the inhospital mortality and mortality due to its lack of sensitivity [3]. Septic shock was defined as tra- filling sepsis definitions were calculated, and their 95% CIs <90  days were 19 (17.4%) and 28 (25.7%), respectively. There ditional severe sepsis with hypotension refractory to ≥2000 mL from the incidence ±1.96 times the square root of the incidence were no significant differences between the groups in these fluid resuscitation or the need for vasopressors [1, 2]. Sepsis-3 divided by person years at risk (i ± 1.96 √I⁄T). Person-years at regards. Enterobacteriaceae were most frequently found in was defined as organ dysfunction characterized by a rise in total risk were calculated from the regions population by dividing blood cultures, followed by Staphylococcus aureus and strepto- SOFA ≥2 due to a dysregulated host response to infection, and it by 365 days and multiplied by 4 days. All missing data were cocci in both groups. septic shock as, despite adequate fluid resuscitation, a lactate regarded as within the normal range for calculation of incidence. er Th e were no significant seasonal variations in when the >2 mmol/L and vasopressors needed for mean arterial pressure For continuous variables, medians are shown. Categorical val- patients were observed with sepsis, neither in the patients ≥65 mmHg [5, 17]. ues are expressed as percentages. Comparisons are made by who fulfilled the traditional severe sepsis criteria (January 23 Partial pressure of oxygen in arterial blood (PaO ) was pref- McNemar’s test for incidence between different sepsis defini- [24.0%], April 24 [25.0%], July 18 [18.8%], October 31 [32.3%]) erably used. When not available, we used the oxygen saturation tions. For demographic differences between the patients identi- nor in those who fulfilled the sepsis-3 criteria (January 29 by pulse oximetry (SpO ) for values <96% and calculated PaO fied with the different sepsis definitions, P values are calculated 2 2 [26.6%], April 26 [23.9%], July 18 [16.5%], October 36 [33.0%]). by the Ellis equation. This substitution correlates with PaO , but by χ or Fishers exact test. P values are shown when significant. For details on demography, distribution of organ failure/dys- it has a tendency to overestimate it [18–20]. Reaction level scale Sensitivity, specificity, positive predictive values, and negative function, and infection, see Table 1. e Th interrater agreement (RLS 85)  was used because it is applied in clinical practice in predictive values with 95% CIs were calculated using Wilson’s for the reviewers was 87% (κ = 0.82; 95% CI, 0.73–0.95). Sweden, although its association with Glasgow Coma Scale has score interval. Patients with missing SIRS or qSOFA parameters To evaluate the SIRS’s and qSOFA’s ability to identify tradi- only been evaluated for APACHE II [21]. were excluded when comparing SIRS’s and qSOFA’s ability to tional severe sepsis and sepsis-3, 339 patients with a diagnosed For assessment of sepsis incidence, infections were defined identify sepsis. infection and 99 patients with clinically suspected infection as described by Calandra et  al [22]. The definitions are aimed Cohen’s κ statistics were used to measure the interrater agree- were judged to be eligible. Sixty-six patients were excluded due for trials in ICU. To adapt the definitions to patients on the ment regarding presence of infection and whether organ fail- to missing data, rendering 372 patients with diagnosed or sus- ward, the following modifications were permitted. The criteria ure/organ dysfunction was due to sepsis. pected infection for evaluation of qSOFA and SIRS. for pneumonia were changed regarding possible pneumonia, IBM SPSS statistics 23.0 and Graph-Pad Prism 6.0 were used For distribution of SIRS and qSOFA in relation to traditional where high clinical suspicion without an abnormal chest radio- for the calculations. severe sepsis and sepsis-3, see Table  2. For SIRS’ and qSOFA’s graph was included. sensitivity, specificity, positive predictive value, and negative In urinary tract infections, 2 of the following were required: RESULTS predictive value, see Table  3. Of the 66 patients with missing symptoms, urine culture with ≥10 colony-forming unit/L SIRS or qSOFA parameters, 13 had traditional severe sepsis and Five hundred sixty-three patients living in the regions started uropathogens or radiographic evidence of infection. Because 21 had sepsis-3. IV antibiotic treatment on the dates of the survey. Four hun- bone and joint, central nervous system, ear-nose-throat, repro- dred eighty-two patients were included in the study, and 44 ductive tract infections and gastroenteritis are not included in DISCUSSION of those patients had no infection diagnosis. An additional 99 the definitions, we used the Centers for Disease Control and patients had a suspected infection, but they did not fulfill the Our study suggests a high incidence of traditional severe sep- Prevention/National Healthcare Safety Network Surveillance criteria for infection diagnosis and were excluded. This left 339 sis (687/100 000), and the incidence was even somewhat higher Definitions for Specific Types of Infections [23]. For evaluation patients with a diagnosed infection: 96 (28.3%) of these patients using the newly proposed sepsis-3 definitions (780/10 000) of SIRS’s and qSOFA’s ability to identify traditional severe sep- had traditional severe sepsis, and 109 patients (32.3%) had sep- but without a significant difference. A  substantial portion of sis and sepsis-3, clinical suspicion was the only requirement for sis-3 (see Figure 1 for details). Seventy-four (21.8%) of these patients with sepsis fulfilled only 1 of the sepsis definitions infection. patients fulfilled both traditional severe sepsis and sepsis-3. (traditional severe sepsis or sepsis-3). The qSOFA showed poor Sepsis Incidence: A Population-Based Study • OFID • 3 Table  1. Demography and Distribution of Organ Failure, Organ Dysfunction, and Infection in Patients With Traditional Severe Sepsis and Sepsis-3. Patients Can Be Represented in Both Columns Variables Traditional Severe Sepsis Sepsis-3 PValue N = 131 96 109 Age, median 78 80 18–24 1 (1.0%) 1 (0.9%) 25–34 1 (1.0%) 0 35–44 3 (3.1%) 1 (0.9%) 45–54 3 (3.1%) 1 (0.9%) 55–64 6 (6.3%) 10 (9.2%) 65–74 22 (22.9%) 25 (22.9%) 75–84 29 (30.2%) 32 (29.4%) 85–94 29 (30.2%) 36 (33.0%) ≥95 2 (2.1%) 3 (2.8%) Comorbidities None 23 (24.0%) 20 (18.3%) Heart disease 30 (31.3%) 40 (36.7%) Malignancy 23 (24.0%) 26 (23.9%) Asthma, COPD 22 (22.9%) 19 (17.4%) Diabetes mellitus 18 (18.8%) 22 (20.2%) Cerebrovascular disease 17 (17.7%) 22 (20.2%) Chronic renal failure 10 (10.4%) 11 (10.1%) Cirrhosis 2 (2.1%) 1 (0.9%) Immunodeficiency 0 0 Connective tissue disorder 9 (9.4%) 11 (10.1%) Ward at Initiation of Antibiotis Emergency Department 65 (67.7%) 67 (61.5%) Nonsurgical ward 19 (19.8%) 31 (28.4%) Surgical ward 10 (10.4%) 8 (7.3%) Intensive care unit 2 (2.1%) 3 (2.8%) Organ Dysfunction Cardiovascular 50 (52.1%) 41 (37.6%) .037 CNS 30 (31.3%) 28 (25.7%) Hepatic 0 7 (6.4%) .015 Renal 29 (30.2%) 37 (33.9%) Respiratory 27 (28.1%) 87 (79.8%) <.01 Hematologic 7 (7.3%) 11 (10.1%) Hypoperfusion 24 (25.0%) Chock 7 (7.3%) 4 (3.7%) Number of Organs Dysfunction 1 49 (51.0%) 40 (36.7%) .038 >1 47 (49.0%) 69 (63.3%) Site of Infection Respiratory tract 40 (41.7%) 55 (50.5%) Urinary tract 17 (17.7%) 19 (17.4%) Abdominal 14 (14.6%) 12 (11.0%) Skin or soft tissue 7 (7.3%) 5 (4.6%) Other 18 (18.8%) 18 (16.5%) Abbreviations: COPD, chronic obstructive pulmonary disease; CNS, central nervous system. sensitivity but good specificity in predicting traditional severe fail to register many episodes [11]. Our study also differs from sepsis and sepsis-3. other studies in that the study cohort was older; however, a recent study from Prescott et al [24] shows similar results. Comparison to Similar Studies e in Th cidence found in the present study was also higher The incidence of traditional severe sepsis was higher than in than in studies based on clinical findings [12]. This is probably most preceding studies, which is not surprising because many partly due to different definitions; for example, we did not apply studies are based on discharge diagnoses and have proven to the requirement of fulfilling 2 SIRS criteria, which probably 4 • OFID • Mellhammar et al Table  2. Contingency Table of SIRS, qSOFA, and Traditional Severe Sepsis and Sepsis-3 (N = 372) Traditional Severe Sepsis Sepsis-3 Variables Yes No Yes No <2 SIRS 11 60 10 61 ≥2 SIRS 98 203 106 195 <2 qSOFA 49 246 67 228 ≥2 qSOFA 60 17 49 28 Abbreviations: qSOFA, quick Sequential (Sepsis-Related) Organ Failure Assessment; SIRS, systemic inflammatory response syndrome. increased the incidence. In addition, earlier studies have been restricted to certain wards or EDs [12, 25]. In this study, we screened all adult patients who were started on IV antibiotic treatment in all parts of all hospitals in 2 entire regions; therefore, we identified both community-acquired and nosocomial sepsis cases. Even if our study includes a smaller number of patients, the CIs are well above the previously pro- posed incidences. e m Th agnitude of our data is illustrated by our recorded incidence of 2425/100 000 adults receiving IV antibiotics for a diagnosed infection, which corresponds to more than 200 000 Swedish patients each year. Approximately 1 of 4 of these patients receiving IV antibiotics had or developed organ dysfunction. The burden of antibiotic resistance is still relatively low in Sweden, indicating that the incidence of traditional severe sepsis and sep- sis-3 may be higher in other parts of the world, and with a grow- ing antimicrobial resistance it will likely increase [26]. Strengths and Limitations We applied restrictive criteria of infection, demanding both clin- ical and objective signs of infection except for pneumonia where high clinical suspicion was sufficient for inclusion. The defini- tions for traditional severe sepsis are based on interpretations of consensus criteria, and the definitions can therefore vary from other studies. We believe that the incidence of patients with sep- sis-related organ dysfunction is not overestimated, and we sus- pect that it might be underestimated. It is probable that several patients with sepsis were unobserved due to a lack of clinical suspicion and diagnostic measures or oral antibiotic treatment, avoidance of treatment, or sudden death. Organ dysfunction may have occurred before or after the infection is suspected and treatment initiated, and outside of the time window we screened for organ dysfunction. Other limitations to this study are the small size, only adults included, and the retrospective design. e s Th trengths of this study are the comprehensive inclu- sion of all patients with IV antibiotic therapy in a well defined population, the manual chart reviews, and the use of 2 different definitions. The outcomes and the features of the patients with only traditional severe sepsis or sepsis-3 would be interesting to characterize further, but the numbers are too small in the present study. Sepsis Incidence: A Population-Based Study • OFID • 5 Table 3. Sensitivity, Specificity, Positive Predictive Value, and Negative Predictive Value of SIRS and qSOFA for Predicting Traditional Severe Sepsis and Sepsis-3 Parameters Sensitivity Specificity Positive Predictive Value Negative Predictive Value Variables Traditional Sepsis-3 Traditional Sepsis-3 Traditional Sepsis-3 Traditional Sepsis-3 Severe Sepsis Severe Sepsis Severe Sepsis Severe Sepsis 2 SIRS 89.9 (82.7–94.9) 91.4 (84.7–95.8) 22.8 (17.9–28.4) 23.8 (18.7–29.5) 32.6 (27.3–38.2) 35.2 (29.8–40.9) 84.5 (74.0–92.0) 85.9 (75.6–93.0) 2 qSOFA 55.0 (45.2–64.6) 42.2 (33.1–51.8) 93.5 (89.9–96.2) 89.1 (84.6–92.6) 77.9 (67.0–86.6) 63.6 (51.9–74.3) 83.4 (78.6–87.5) 77.3 (72.1–81.9) Abbreviations: qSOFA, quick Sequential (Sepsis-Related) Organ Failure Assessment; SIRS, systemic inflammatory response syndrome. Figure 1. Flow chart of patient recruitment and sepsis groups. Financial support. This work was supported by Swedish Government e qSO Th FA has been validated against inhospital mortality and Research Grant, Skåne University Hospital Foundations, Southern Health ICU stay, among patients receiving treatment. However, a large Care Region Grant, Svenska Läkaresällskapet, Grochinsky Foundation, proportion of patients with sepsis and multiorgan dysfunctions Lundgrens Foundation, and Österlunds Foundation. never reach the ICU and are hence treated in the wards [27, 28]. Potential coni fl cts of interest. All authors report no conflicts of inter - ests that the editors consider relevant to the content of this manuscript. In our study, in patients with clinically suspected infection All authors have submitted the ICMJE Form for Disclosure of Potential with traditional severe sepsis and sepsis-3 as outcomes, the sen- Conflicts of Interest. sitivity and the negative predictive value were unsatisfactory. 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Sepsis Incidence: A Population-Based Study • OFID • 7

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Open Forum Infectious Diseases – Pubmed Central

Published: Dec 8, 2016

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