ABSTRACT
Objective:
To compare the clinical characteristics and outcomes of patients with community-acquired and hospital-acquired sepsis.
Methods:
This is a retrospective cohort study that included all patients with a diagnosis of sepsis detected between January 2010 and December 2015 at a private hospital in southern Brazil. Outcomes (mortality, intensive care unit and hospital lengths of stay) were measured by analyzing electronic records.
Results:
There were 543 hospitalized patients with a diagnosis of sepsis, with a frequency of 90.5 (85 to 105) cases/year. Of these, 319 (58%) cases were classified as hospital-acquired sepsis. This group exhibited more severe disease and had a larger number of organ dysfunctions, with higher hospital [8 (8 - 10) versus 23 (20 - 27) days; p < 0.001] and intensive care unit [5 (4 - 7) versus 8.5 (7 - 10); p < 0.001] lengths of stay and higher in-hospital mortality (30.7% versus 15.6%; p < 0.001) than those with community-acquired sepsis. After adjusting for age, APACHE II scores, and hemodynamic and respiratory dysfunction, hospital-acquired sepsis remained associated with increased mortality (OR 1.96; 95%CI 1.15 - 3.32, p = 0.013).
Conclusion:
The present results contribute to the definition of the epidemiological profile of sepsis in the sample studied, in which hospital-acquired sepsis was more severe and was associated with higher mortality.
Keywords:
Sepsis; Iatrogenic disease; Community-acquired infections; Mortality; Brazil
RESUMO
Objetivo:
Comparar as características clínicas e os desfechos de pacientes com sepse adquirida na comunidade ou no hospital.
Métodos:
Trata-se de estudo retrospectivo de coorte, que incluiu todos os pacientes com diagnóstico de sepse detectada entre janeiro de 2010 e dezembro de 2015 em um hospital privado localizado na Região Sul do Brasil. Os desfechos (mortalidade, tempo de permanência na unidade de terapia intensiva e no hospital) foram avaliados por meio da análise dos registros eletrônicos.
Resultados:
Foram hospitalizados, no total, 543 pacientes com diagnóstico de sepse, com frequência de 90,5 (85 a 105) casos por ano. Destes, 319 (58%) casos foram classificados como sepse adquirida no hospital. Este grupo apresentava doença mais grave e tinha um maior número de disfunções de órgãos, assim como teve um tempo maior de permanência no hospital [8 (8 - 10) versus 23 (20 - 27) dias; p < 0,001] e na unidade de terapia intensiva [5 (4 - 7) versus 8,5 (7 - 10); p < 0,001] do aqueles que apresentavam sepse adquirida na comunidade. Após ajustar quanto à idade, escore APACHE II e disfunção hemodinâmica e respiratória, a sepse adquirida no hospital persistiu associada com maior mortalidade (OR 1,96; IC95% 1,15 - 3,32, p = 0,013).
Conclusão:
Nossos resultados contribuem para a definição do perfil epidemiológico da sepse na amostra estudada, na qual a sepse adquirida no hospital foi mais grave e associada com mortalidade mais alta.
Descritores:
Sepse; Doença iatrogênica; Infecções comunitárias adquiridas; Mortalidade; Brasil
INTRODUCTION
Sepsis, which is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, is an important public health problem.(11 Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-10.) Based on population studies conducted in the United States that showed an annual sepsis incidence of 300 cases per 100,000 inhabitants, the estimated incidence in Brazil is 600,000 cases per year, generating massive costs for the healthcare system.(22 Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303-10.,33 Sogayar AM, Machado FR, Rea-Neto A, Dornas A, Grion CM, Lobo SM, Tura BR, Silva CL, Cal RG, Beer I, Michels V, Safi J, Kayath M, Silva E; Costs StudyGroup - Latin American Sepsis Institute. A multicentre, prospective study to evaluate costs of septic patients in Brazilian intensive care units. Pharmacoeconomics. 2008;26(5):425-34.) In addition to its high incidence, sepsis is a leading cause of death in intensive care units (ICUs) worldwide.(44 Liu V, Escobar GJ, Greene JD, Soule J, Whippy A, Angus DC, et al. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014;312(1):90-2.) Despite advances in diagnosis and management, sepsis-related mortality continues to be high, especially in developing countries.
In Brazil, the mortality rate is 55.7% according the SPREAD study and 57.4% according to the PROGRESS study,(55 Machado FR, Cavalcanti AB, Bozza FA, Ferreira EM, Angotti Carrara FS, Sousa JL, Caixeta N, Salomao R, Angus DC, Pontes Azevedo LC; SPREAD Investigators; Latin American Sepsis Institute Network. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study. Lancet Infect Dis. 2017;17(11):1180-9.,66 Beale R, Reinhart K, Brunkhorst FM, Dobb G, Levy M, Martin G, Martin C, Ramsey G, Silva E, Vallet B, Vincent JL, Janes JM, Sarwat S, Williams MD; PROGRESS Advisory Board. Promoting Global Research Excellence in Severe Sepsis (PROGRESS): lessons from an international sepsis registry. Infection. 2009;37(3):222-32.) which is in contrast with 45% observed in other developing countries and 38.2% in developed countries.(77 Westphal GA, Koenig A, Caldeira Filho M, Feijó J, de Oliveira LT, Nunes F, et al. Reduced mortality after the implementation of a protocol for the early detection of severe sepsis. J Crit Care. 2011;26(1):76-81.,88 Sales Júnior JA, David CM, Hatum R, Souza PC, Japiassú A, Pinheiro CT, Friedman G, Silva OB, Dias MD, Koterba E, Dias FS, Piras C, Luiz RR; Grupo de Estudo de Sepse do Fundo AMIB. An epidemiological study of sepsis in intensive care units: Sepsis Brazil study. Rev Bras Ter Intensiva, 2006;18(1):9-17. Portuguese.)
Strategies to reduce sepsis-related mortality are widely disseminated through the Surviving Sepsis Campaign (SSC)(99 Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2): 580-637.) and include fluid resuscitation, lactate measurement and obtaining blood cultures before the administration of antibiotics, as well as the administration of broad-spectrum antibiotics within the first hour of diagnosis. Several studies published over the last 15 years have confirmed that interventions that contribute to a reduction in sepsis-related mortality are early detection, resuscitation and antibiotic therapy.(1010 Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-77.
11 Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM; ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-11.
12 ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683-93.-1313 ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371(16):1496-506.) However, these studies mainly evaluated patients seen at emergency departments, which primarily correspond to cases of community-acquired sepsis. A recent study conducted by the Instituto Latino Americano de Sepse (ILAS) in Brazilian adult ICUs showed that for patients with hospital-acquired sepsis, the time to diagnosis is longer, adherence to treatment is lower, and mortality is higher.(55 Machado FR, Cavalcanti AB, Bozza FA, Ferreira EM, Angotti Carrara FS, Sousa JL, Caixeta N, Salomao R, Angus DC, Pontes Azevedo LC; SPREAD Investigators; Latin American Sepsis Institute Network. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study. Lancet Infect Dis. 2017;17(11):1180-9.)
Few studies, however, have compared the characteristics, evolution and mortality of patients with community-acquired and hospital-acquired sepsis.(1414 Page DB, Donnelly JP, Wang HE. Community-, healthcare-, and hospital-acquired severe sepsis hospitalizations in the University Health System Consortium. Crit Care Med. 2015;43(9):1945-51.)
Within this context, the objective of this study was to compare the clinical characteristics and outcomes of patients with community-acquired and hospital-acquired sepsis.
METHODS
This was a retrospective cohort study that analyzed the records of septic patients from a private hospital in southern Brazil identified between January 2010 and December 2015.
All patients older than 18 years diagnosed with sepsis between January 2010 and December 2015 were included. The diagnosis of sepsis was established based on the recognition of a suspicious or confirmed source of infection associated with at least one organ dysfunction. Patients at risk of infection and sepsis were screened based on signs suggestive of infection and clinically detectable organ dysfunction (Table 1).
Expanded clinical signs of infection, including clinically detectable signs of organ dysfunction
The patients were divided into two groups according to the origin of sepsis identified in the medical records: community-acquired sepsis and hospital-acquired sepsis. Cases of sepsis diagnosed on hospital admission or up to 48 hours thereafter were classified as community-acquired and cases diagnosed 48 hours after hospital admission were classified as hospital-acquired. Patients transferred from another hospital, with incomplete records and with end-stage disease according to the judgment of the assisting medical team were not included in the study.
The screening of sepsis consisted of actively looking for signs suggestive of infection and clinically detectable organ dysfunction at the first examination in all patients seen on the wards and in the emergency department. Nurse technicians were trained to identify and communicate the manifestation of two or more signs suggestive of infection to the department nurse. After recording signs suggestive of infection, the electronic medical record was programmed to send electronic alerts to mobile devices carried by the nurses. After initial assessment by the nurse, the medical team was notified to evaluate the patient, to confirm the diagnosis of sepsis, to look for other organ dysfunctions not evaluated in the screening protocol and to initiate treatment.(55 Machado FR, Cavalcanti AB, Bozza FA, Ferreira EM, Angotti Carrara FS, Sousa JL, Caixeta N, Salomao R, Angus DC, Pontes Azevedo LC; SPREAD Investigators; Latin American Sepsis Institute Network. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study. Lancet Infect Dis. 2017;17(11):1180-9.,77 Westphal GA, Koenig A, Caldeira Filho M, Feijó J, de Oliveira LT, Nunes F, et al. Reduced mortality after the implementation of a protocol for the early detection of severe sepsis. J Crit Care. 2011;26(1):76-81.,99 Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2): 580-637.
10 Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-77.
11 Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM; ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-11.
12 ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683-93.
13 ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371(16):1496-506.
14 Page DB, Donnelly JP, Wang HE. Community-, healthcare-, and hospital-acquired severe sepsis hospitalizations in the University Health System Consortium. Crit Care Med. 2015;43(9):1945-51.-1515 Westphal GA, Lino AS. Systematic screening is essential for early diagnosis of severe sepsis and septic shock. Rev Bras Ter Intensiva. 2015;27(2):96-101.) The diagnosis of sepsis (formerly called severe sepsis) was defined in the presence of a presumed infection plus any organ dysfunction. Septic shock was identified by the vasopressor requirement to maintain a mean arterial pressure (MAP) of 65mmHg.(11 Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-10.)
Clinical management was based on the recommendations proposed by the SSC, which included obtaining blood cultures before the administration of antibiotics, antibiotic therapy in the first hour after the diagnosis of sepsis, an initial lactate measurement, adequate volume expansion (defined as the administration of at least 30mL/kg of crystalloid fluid when hypotension or lactate level > 4mmol/L), and the use of vasopressors in the case of persistent hypotension (MAP < 65mmHg). The complete resuscitation bundle was characterized as the accomplishment of all these steps.
The variables studied were sex, age, Acute Physiology and Chronic Health Disease Classification System II (APACHE II) score, type of hospitalization (surgical or medical), Charlson's comorbidity index,(1616 Oltean S, Tatulescu D, Bondor C, Slavcovici A, Cismaru C, Lupse M, et al. Charlson's weighted index of comorbidities is useful in assessing the risk of death in septic patients. J Crit Care. 2012;27(4):370-5.) infection source, number and type of organ dysfunction (respiratory, renal, platelet, hepatic, hemodynamic and neurological), and the need for hemodialysis.
Organ dysfunction was characterized as defined by the SSC:(99 Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2): 580-637.) respiratory dysfunction: arterial hypoxemia (partial pressure arterial oxygen/fraction of inspired oxygen - PaO2/FiO2 < 300); renal dysfunction: acute oliguria (urine output < 0.5mL/kg/h for at least 2 hours) or an increase in creatinine levels > 0.5mg/dL; platelet dysfunction: platelet count < 100.000µ/L; hepatic dysfunction: total bilirubin > 4mg/dL; hemodynamic dysfunction: MAP < 70mmHg or systolic blood pressure < 90mmHg or systolic blood pressure decrease > 40mmHg; and neurological dysfunction: any alteration in the level of consciousness.
The primary outcomes were in-hospital mortality. The mortality at 30 days, length of ICU stay and length of hospital stay were considered secondary outcomes.
Statistical analysis
Data on risk factors associated with the main outcome were tabulated and analyzed using descriptive statistics methods including proportions, means and standard deviations. The association of the continuous variables with the main outcome and exposure factor was performed by Student's t-test and categorical variables by the chi-square test. Mantel-Haenszel estimates were used to define possible confounding variables and odds ratio homogeneity tests were used to define possible effect-modifying variables considering a significance level of 5%. Variables that altered the crude effect of the exposure variable on the main outcome by more than 20% were considered as possible effect confounders and were included in the logistic regression, as well as those that presented nonhomogeneous odds ratios. The likelihood ratio test was used for inclusion and maintenance of the variable in the logistic regression model considering a significance level of 5%.
The study protocol was approved by the Ethics Committee of Hospital Municipal São José de Joinville under registration number CAAE 51661515.3.0000.5362.
RESULTS
A total of 543 hospitalized patients diagnosed with sepsis between 2010 and 2015 were included. The mean frequency was 90.5 (85 to 105) cases/year. Of these, 319 (58.8%) patients had hospital-acquired sepsis.
Table 2 shows the characteristics of the groups. There was no difference in time between changes in vital signs and diagnosis (0:55 minutes versus 1:25 hours between community and hospital sepsis, respectively, p = 0.06). The most prevalent sources of infection were the lungs, urinary tract and abdomen. Patients with hospital-acquired sepsis had a higher frequency of abdominal (p = 0.02) and bloodstream infections (p < 0.001). This group also exhibited more severe disease according to the APACHE II score (p < 0.001), had a greater need for hemodialysis (p = 0.02), and had a larger number of organ dysfunctions, particularly respiratory (p < 0.001) and neurological dysfunctions (p < 0.001).
Adherence to the different resuscitation guidelines is shown in table 3. As seen in the table, adherence to the complete resuscitation bundle was present in 34.8% of patients with community-acquired sepsis and in 41.4% with hospital-acquired sepsis (p = 0.12). No differences were observed for the other components of the resuscitation bundle.
Frequency of application of resuscitation bundle items in patients with sepsis of community and hospital origin
The outcomes of the patients are shown in table 4. The overall in-hospital mortality was 24.4% (n = 133) and was higher in patients with hospital-acquired sepsis compared to those with community-acquired sepsis (30.7% versus 15.6%; p < 0.001). The group with hospital-acquired sepsis had longer hospital [8 (8 - 10) versus 23 (20 - 27) days; p < 0.001] and ICU lengths of stay [5 (4 - 7) versus 8.5 (7 - 10); p < 0.001]. The time of hospitalization after diagnosis of sepsis was also higher in patients with hospital-acquired sepsis [8 (8 - 10) versus 13 (7 - 24) days; p < 0.001].
Logistic regression was performed to evaluate the association between clinically significant variables (community/hospital sepsis, hemodialysis, respiratory dysfunction, hemodynamic instability, length of stay in the ICU, age, APACHE II score, and neurological dysfunction) and the risk of death (Table 1S - Supplementary material). After adjusting for age, APACHE II score, and hemodynamic and respiratory dysfunction, hospital-acquired sepsis remained associated with increased mortality (OR 1.96; 95%CI 1.15 - 3.32; p = 0.013).
DISCUSSION
Our results show that hospital-acquired sepsis is associated with higher mortality and longer ICU and hospital stays compared to community-acquired sepsis. These results corroborate the few studies comparing community-acquired and hospital-acquired sepsis, showing that the latter is associated with poorer outcomes.(1414 Page DB, Donnelly JP, Wang HE. Community-, healthcare-, and hospital-acquired severe sepsis hospitalizations in the University Health System Consortium. Crit Care Med. 2015;43(9):1945-51.,1717 Adrie C, Alberti C, Chaix-Couturier C, Azoulay E, De Lassence A, Cohen Y, et al. Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost. J Crit Care. 2005;20(1):46-58.
18 Tsertsvadze A, Royle P, McCarthy N. Community-onset sepsis and its public health burden: protocol of a systematic review. Syst Rev. 2015;4:119.-1919 Hoenigl M, Wagner J, Raggam RB, Prueller F, Prattes J, Eigl S, et al. Characteristics of hospital-acquired and community-onset blood stream infections, South-East Austria. PLoS One 2014;9(8):e104702.)
We observed a frequency of community-acquired sepsis of 42%, in contrast to the findings of two other studies that reported a predominance of community-acquired sepsis cases (57.0% and 55.8%).(1717 Adrie C, Alberti C, Chaix-Couturier C, Azoulay E, De Lassence A, Cohen Y, et al. Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost. J Crit Care. 2005;20(1):46-58.,2020 Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A, et al. Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med. 2002;28(2):108-21.) These differences can be explained by the epidemiological particularities of each institution, such as patient age, severity, and presence of comorbidities. Regardless of the agreement of the findings between studies, epidemiological knowledge is of clinical importance and has implications for the development of early identification strategies for patients with sepsis. On the other hand, there is agreement between our findings and the other studies regarding mortality and length of hospital and ICU stay, which were higher among patients with hospital-acquired sepsis.(1414 Page DB, Donnelly JP, Wang HE. Community-, healthcare-, and hospital-acquired severe sepsis hospitalizations in the University Health System Consortium. Crit Care Med. 2015;43(9):1945-51.,1717 Adrie C, Alberti C, Chaix-Couturier C, Azoulay E, De Lassence A, Cohen Y, et al. Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost. J Crit Care. 2005;20(1):46-58.
18 Tsertsvadze A, Royle P, McCarthy N. Community-onset sepsis and its public health burden: protocol of a systematic review. Syst Rev. 2015;4:119.
19 Hoenigl M, Wagner J, Raggam RB, Prueller F, Prattes J, Eigl S, et al. Characteristics of hospital-acquired and community-onset blood stream infections, South-East Austria. PLoS One 2014;9(8):e104702.-2020 Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A, et al. Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med. 2002;28(2):108-21.) In addition, the sites of infection were similar among the different studies, with a prevalence of pulmonary and abdominal infections.(1717 Adrie C, Alberti C, Chaix-Couturier C, Azoulay E, De Lassence A, Cohen Y, et al. Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost. J Crit Care. 2005;20(1):46-58.,2020 Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A, et al. Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med. 2002;28(2):108-21.) Corroborating the findings of Page et al.,(1414 Page DB, Donnelly JP, Wang HE. Community-, healthcare-, and hospital-acquired severe sepsis hospitalizations in the University Health System Consortium. Crit Care Med. 2015;43(9):1945-51.) we observed a clear predominance of abdominal infections and infections resulting from surgical procedures among the cases of hospital-acquired sepsis, a fact that can help define specific strategies for the detection of a characteristic phenotype of nosocomial sepsis.(1414 Page DB, Donnelly JP, Wang HE. Community-, healthcare-, and hospital-acquired severe sepsis hospitalizations in the University Health System Consortium. Crit Care Med. 2015;43(9):1945-51.) In this respect, the present results suggest that surgical patients with a clinical suspicion of abdominal infection should be monitored closely since they are more likely to develop sepsis, at least at our institution.
Mortality was significantly higher among patients with hospital-acquired sepsis than among those with community-acquired sepsis (30.7% versus 15.6%; p < 0.001). Page et al.(1414 Page DB, Donnelly JP, Wang HE. Community-, healthcare-, and hospital-acquired severe sepsis hospitalizations in the University Health System Consortium. Crit Care Med. 2015;43(9):1945-51.) suggested that, in contrast to emergency departments, wards often do not have the necessary resources for the frequent monitoring of vital data and laboratory test results. If this is the case, specific strategies need to be implemented so that sepsis can also be detected early on the wards. In our hospital, we have an electronic warning system coupled to the electronic chart that allows the rapid detection of patients with sepsis both in the emergency room and in the ward (1:22 ± 3:28 hours versus 1:58 ± 3:41 hours; p = 0.06). Despite the strong tendency towards a mathematical difference in the time of detection between the two groups, the average difference of 36 minutes does not seem to be clinically relevant. Although sepsis is detected within less than 2 hours both on the wards and in the emergency room, mortality from hospital-acquired sepsis was higher than that associated with community-acquired sepsis, supporting the view that hospital-acquired sepsis occurs in intrinsically more severe patients. In addition, even after adjusting for confounding factors, such as age and severity, the risk of death continued to be significantly higher in the group with hospital-acquired sepsis, suggesting that intrinsic variables of the patients seem to have an effect on the risk of death associated with sepsis.
In the last 15 years, several studies conducted in emergency departments have shown that the early management of sepsis using resuscitation bundles is associated with a reduction in mortality.(77 Westphal GA, Koenig A, Caldeira Filho M, Feijó J, de Oliveira LT, Nunes F, et al. Reduced mortality after the implementation of a protocol for the early detection of severe sepsis. J Crit Care. 2011;26(1):76-81.,99 Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2): 580-637.
10 Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-77.
11 Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM; ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-11.
12 ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683-93.-1313 ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371(16):1496-506.) One may infer that aggressive strategies for compliance with the resuscitation bundle also contribute to reducing mortality in patients with hospital-acquired sepsis. Our results contradict this inference considering that there were no significant differences in adherence to the complete resuscitation bundle or in the time to diagnosis, and adherence to early antibiotic therapy and compliance with hemodynamic resuscitation were similar in the two groups (Table 3). In this respect, some authors suggest that there is not sufficient evidence to indicate that the components of the resuscitation bundle can alter the outcome.(2121 Marik PE, Raghunathan K, Bloomstone J. Rebuttal From Dr Marik et al. Chest. 2013;144(2):379-80.
22 Ferrer R, Artigas A, Levy MM, Blanco J, González-Díaz G, Garnacho-Montero J, Ibáñez J, Palencia E, Quintana M, de la Torre-Prados MV; Edusepsis Study Group. Edusepsis Study Group. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. 2008;299(19):2294-303.
23 Westphal GA, Koenig A, Caldeira Filho M, Feijó J, de Oliveira LT, Nunes F, et al. Reduced mortality after the implementation of a protocol for the early detection of severe sepsis. J Crit Care. 2011;26(1):76-81.-2424 Shiramizo SC, Marra AR, Durão MS, Paes ÂT, Edmond MB, Pavão dos Santos OF. Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting. Plos One 2011;6(11):e26790.) The Edusepsis study demonstrated a reduction of mortality in septic patients, although adherence to the resuscitation bundle had only increased from 5.3% to 10%.(2222 Ferrer R, Artigas A, Levy MM, Blanco J, González-Díaz G, Garnacho-Montero J, Ibáñez J, Palencia E, Quintana M, de la Torre-Prados MV; Edusepsis Study Group. Edusepsis Study Group. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. 2008;299(19):2294-303.) In 2011, our group published a before-and-after study involving emergency and ward patients who demonstrated an association between the speed of diagnosis of sepsis (34 ± 48 hours versus 11 ± 17 hours; p < 0.001) and mortality reduction (61.7% versus 38.2%; p < 0.001), while adherence to the 6-hour bundle remained constant (32.3% versus 28.7%; p = 0.55).(2323 Westphal GA, Koenig A, Caldeira Filho M, Feijó J, de Oliveira LT, Nunes F, et al. Reduced mortality after the implementation of a protocol for the early detection of severe sepsis. J Crit Care. 2011;26(1):76-81.) Similar results have been reported by Shiramizo et al.(2424 Shiramizo SC, Marra AR, Durão MS, Paes ÂT, Edmond MB, Pavão dos Santos OF. Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting. Plos One 2011;6(11):e26790.) In this context, some studies suggest that probably only the early use of antimicrobials is important when the general care of patients is suitable. A prospective, observational multicenter cohort study in 44 German ICUs showed that the delay in source control beyond 6 hours may have a major impact on patient mortality, and there was only indirect evidence regarding the impact of timing of antimicrobial therapy on sepsis mortality, despite poor compliance with sepsis guideline recommendations.(2525 Bloos F, Thomas-Ru¨ddel D, Ru¨ddel H, Engel C, Schwarzkopf D, Marshall JC, Harbarth S, Simon P, Riessen R, Keh D, Dey K, Weiß M, Toussaint S, Schädler D, Weyland A, Ragaller M, Schwarzkopf K, Eiche J, Kuhnle G, Hoyer H, Hartog C, Kaisers U, Reinhart K; MEDUSA Study Group. Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study. Crit Care. 2014;18(2):R42.) A retrospective study involving 185 hospitals in the New York State Department of Health database showed that longer times to complete the three-hour treatment package for patients with sepsis and to administer broad-spectrum antibiotics were associated with higher risk-adjusted hospital mortality.(2626 Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376(23):2235-44.)
Patients in the hospital-acquired sepsis group received more resuscitation fluids, but it was not possible to evaluate their relationship with the outcome because there were other confounding factors interfering with the results. Some authors suggest that early liberal fluids are harmful to sepsis patients because there is no optimal MAP target, which causes a wide variability in fluid input among large sepsis studies. In addition, there might be a high prevalence of non-fluid-responsive patients for whom the excess fluid may be harmful.(2727 Genga K, Russell JA. Early liberal fluids for sepsis patients are harmful. Crit Care Med. 2016;44(12):2258-62.) However, the adverse effect of positive balance is more commonly seen after the initial rescue phase of resuscitation.(2828 Acheampong A, Vincent JL. A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care. 2015;19:251.) In this study, we did not evaluate fluid infusion after the resuscitation phase or parameters of fluid responsiveness of the patients.
Overall mortality (24.4%) and mortality among patients with community-acquired (15.6%) and nosocomial sepsis (30.7%) were lower than the Brazilian mortality reported by the SPREAD study (55.7%) and PROGRESS study (57.4%).(55 Machado FR, Cavalcanti AB, Bozza FA, Ferreira EM, Angotti Carrara FS, Sousa JL, Caixeta N, Salomao R, Angus DC, Pontes Azevedo LC; SPREAD Investigators; Latin American Sepsis Institute Network. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study. Lancet Infect Dis. 2017;17(11):1180-9.,66 Beale R, Reinhart K, Brunkhorst FM, Dobb G, Levy M, Martin G, Martin C, Ramsey G, Silva E, Vallet B, Vincent JL, Janes JM, Sarwat S, Williams MD; PROGRESS Advisory Board. Promoting Global Research Excellence in Severe Sepsis (PROGRESS): lessons from an international sepsis registry. Infection. 2009;37(3):222-32.) This difference might be explained in part by the private nature of the hospital where the study was conducted since better infrastructure conditions and human resources could have influenced the results. In the SPREAD study, a high mortality was observed in centers with less availability of resources, without the necessary infrastructure for the treatment of sepsis and a lack of ICU beds, resulting in inadequate treatment and a delay in the first dose of antibiotics.(55 Machado FR, Cavalcanti AB, Bozza FA, Ferreira EM, Angotti Carrara FS, Sousa JL, Caixeta N, Salomao R, Angus DC, Pontes Azevedo LC; SPREAD Investigators; Latin American Sepsis Institute Network. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study. Lancet Infect Dis. 2017;17(11):1180-9.) On the other hand, the early rates (prior to early detection strategies) of sepsis-related mortality in our hospital reported in previous studies(2323 Westphal GA, Koenig A, Caldeira Filho M, Feijó J, de Oliveira LT, Nunes F, et al. Reduced mortality after the implementation of a protocol for the early detection of severe sepsis. J Crit Care. 2011;26(1):76-81.,2929 Westphal GA, Feijó J, Andrade PS, Trindade L, Suchard C, Monteiro MA, et al. Early detection strategy and mortality reduction in severe sepsis. Rev Bras Ter Intensiva. 2009;21(2):113-23.) were similar to the national rates. These findings suggest that early detection may influence the reduction in mortality related to both community-acquired and hospital-acquired sepsis.
Our study had some limitations. It was an observational study, and potentially unrecognized confounding variables may have influenced outcomes. Since it was conducted at a private hospital in southern Brazil, the results may not be generalized to the public health system or to other centers in the region and in Brazil. The selection, diagnosis and treatment of patients were performed following the SSC guidelines, and the new definitions published in 2016 were not taken into consideration.(11 Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-10.,99 Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2): 580-637.,3030 Antonelli M, DeBacker D, Dorman T, Kleinpell R, Levy M, Rhodes A. Surviving Sepsis Campaign Responds to Sepsis-3. 2016. Available from: http://www.survivingsepsis.org/SiteCollectionDocuments/SSC-Statements-Sepsis-Definitions-3-2016.pdf (accessed April 2017).
http://www.survivingsepsis.org/SiteColle...
,3131 Surviving Sepsis Campaign: updated bundles in response to new evidence. 2014. Available from: http://www.survivingsepsis.org/sitecollectiondocuments/ssc_bundle.pdf (accessed April 2017).
http://www.survivingsepsis.org/sitecolle...
) The evaluation of organ dysfunction was also performed using the SSC definitions instead of the Sepsis-related Organ Failure Assessment (SOFA). Another limitation was that the study did not discriminate patients with healthcare-associated sepsis, whose prevalence and severity differed from community-acquired and hospital-acquired sepsis.(1414 Page DB, Donnelly JP, Wang HE. Community-, healthcare-, and hospital-acquired severe sepsis hospitalizations in the University Health System Consortium. Crit Care Med. 2015;43(9):1945-51.) The inclusion criteria did not consider patients who were readmitted during the period. Since the data were collected based on the electronic vital sign chart, some clinical signs of infection and organ dysfunction were not used for screening the patients, and it was not possible to classify patients with septic shock based on serum lactate levels. Another limitation was that we did not evaluate the cause of hospitalization for patients with hospital-acquired sepsis. Despite these limitations, the scarcity of literature and data on this topic highlights the importance of this study, which describes the profile of these two groups of patients and their hospital outcomes, reinforcing the need to adopt and maintain strategies for early detection.
CONCLUSION
Hospital-acquired sepsis is associated with poorer outcomes, including higher mortality and longer intensive care unit and hospital stays, compared to community-acquired sepsis. Mortality was higher in patients with hospital-acquired sepsis despite the same time to antibiotic administration and even more aggressive fluid resuscitation. Overall mortality in our sample was lower than the previously reported sepsis mortality rate in Brazil. Despite some limitations, the knowledge of the profile of these two groups of patients and their respective outcomes helps define strategies for the detection and treatment of patients with community-acquired and hospital-acquired sepsis.
REFERÊNCIAS
-
1Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-10.
-
2Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303-10.
-
3Sogayar AM, Machado FR, Rea-Neto A, Dornas A, Grion CM, Lobo SM, Tura BR, Silva CL, Cal RG, Beer I, Michels V, Safi J, Kayath M, Silva E; Costs StudyGroup - Latin American Sepsis Institute. A multicentre, prospective study to evaluate costs of septic patients in Brazilian intensive care units. Pharmacoeconomics. 2008;26(5):425-34.
-
4Liu V, Escobar GJ, Greene JD, Soule J, Whippy A, Angus DC, et al. Hospital deaths in patients with sepsis from 2 independent cohorts. JAMA. 2014;312(1):90-2.
-
5Machado FR, Cavalcanti AB, Bozza FA, Ferreira EM, Angotti Carrara FS, Sousa JL, Caixeta N, Salomao R, Angus DC, Pontes Azevedo LC; SPREAD Investigators; Latin American Sepsis Institute Network. The epidemiology of sepsis in Brazilian intensive care units (the Sepsis PREvalence Assessment Database, SPREAD): an observational study. Lancet Infect Dis. 2017;17(11):1180-9.
-
6Beale R, Reinhart K, Brunkhorst FM, Dobb G, Levy M, Martin G, Martin C, Ramsey G, Silva E, Vallet B, Vincent JL, Janes JM, Sarwat S, Williams MD; PROGRESS Advisory Board. Promoting Global Research Excellence in Severe Sepsis (PROGRESS): lessons from an international sepsis registry. Infection. 2009;37(3):222-32.
-
7Westphal GA, Koenig A, Caldeira Filho M, Feijó J, de Oliveira LT, Nunes F, et al. Reduced mortality after the implementation of a protocol for the early detection of severe sepsis. J Crit Care. 2011;26(1):76-81.
-
8Sales Júnior JA, David CM, Hatum R, Souza PC, Japiassú A, Pinheiro CT, Friedman G, Silva OB, Dias MD, Koterba E, Dias FS, Piras C, Luiz RR; Grupo de Estudo de Sepse do Fundo AMIB. An epidemiological study of sepsis in intensive care units: Sepsis Brazil study. Rev Bras Ter Intensiva, 2006;18(1):9-17. Portuguese.
-
9Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2): 580-637.
-
10Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368-77.
-
11Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, Jahan R, Harvey SE, Bell D, Bion JF, Coats TJ, Singer M, Young JD, Rowan KM; ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301-11.
-
12ProCESS Investigators, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, Pike F, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370(18):1683-93.
-
13ARISE Investigators, ANZICS Clinical Trials Group, Peake SL, Delaney A, Bailey M, Bellomo R, Cameron PA, Cooper DJ, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371(16):1496-506.
-
14Page DB, Donnelly JP, Wang HE. Community-, healthcare-, and hospital-acquired severe sepsis hospitalizations in the University Health System Consortium. Crit Care Med. 2015;43(9):1945-51.
-
15Westphal GA, Lino AS. Systematic screening is essential for early diagnosis of severe sepsis and septic shock. Rev Bras Ter Intensiva. 2015;27(2):96-101.
-
16Oltean S, Tatulescu D, Bondor C, Slavcovici A, Cismaru C, Lupse M, et al. Charlson's weighted index of comorbidities is useful in assessing the risk of death in septic patients. J Crit Care. 2012;27(4):370-5.
-
17Adrie C, Alberti C, Chaix-Couturier C, Azoulay E, De Lassence A, Cohen Y, et al. Epidemiology and economic evaluation of severe sepsis in France: age, severity, infection site, and place of acquisition (community, hospital, or intensive care unit) as determinants of workload and cost. J Crit Care. 2005;20(1):46-58.
-
18Tsertsvadze A, Royle P, McCarthy N. Community-onset sepsis and its public health burden: protocol of a systematic review. Syst Rev. 2015;4:119.
-
19Hoenigl M, Wagner J, Raggam RB, Prueller F, Prattes J, Eigl S, et al. Characteristics of hospital-acquired and community-onset blood stream infections, South-East Austria. PLoS One 2014;9(8):e104702.
-
20Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A, et al. Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med. 2002;28(2):108-21.
-
21Marik PE, Raghunathan K, Bloomstone J. Rebuttal From Dr Marik et al. Chest. 2013;144(2):379-80.
-
22Ferrer R, Artigas A, Levy MM, Blanco J, González-Díaz G, Garnacho-Montero J, Ibáñez J, Palencia E, Quintana M, de la Torre-Prados MV; Edusepsis Study Group. Edusepsis Study Group. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. 2008;299(19):2294-303.
-
23Westphal GA, Koenig A, Caldeira Filho M, Feijó J, de Oliveira LT, Nunes F, et al. Reduced mortality after the implementation of a protocol for the early detection of severe sepsis. J Crit Care. 2011;26(1):76-81.
-
24Shiramizo SC, Marra AR, Durão MS, Paes ÂT, Edmond MB, Pavão dos Santos OF. Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting. Plos One 2011;6(11):e26790.
-
25Bloos F, Thomas-Ru¨ddel D, Ru¨ddel H, Engel C, Schwarzkopf D, Marshall JC, Harbarth S, Simon P, Riessen R, Keh D, Dey K, Weiß M, Toussaint S, Schädler D, Weyland A, Ragaller M, Schwarzkopf K, Eiche J, Kuhnle G, Hoyer H, Hartog C, Kaisers U, Reinhart K; MEDUSA Study Group. Impact of compliance with infection management guidelines on outcome in patients with severe sepsis: a prospective observational multi-center study. Crit Care. 2014;18(2):R42.
-
26Seymour CW, Gesten F, Prescott HC, Friedrich ME, Iwashyna TJ, Phillips GS, et al. Time to treatment and mortality during mandated emergency care for sepsis. N Engl J Med. 2017;376(23):2235-44.
-
27Genga K, Russell JA. Early liberal fluids for sepsis patients are harmful. Crit Care Med. 2016;44(12):2258-62.
-
28Acheampong A, Vincent JL. A positive fluid balance is an independent prognostic factor in patients with sepsis. Crit Care. 2015;19:251.
-
29Westphal GA, Feijó J, Andrade PS, Trindade L, Suchard C, Monteiro MA, et al. Early detection strategy and mortality reduction in severe sepsis. Rev Bras Ter Intensiva. 2009;21(2):113-23.
-
30Antonelli M, DeBacker D, Dorman T, Kleinpell R, Levy M, Rhodes A. Surviving Sepsis Campaign Responds to Sepsis-3. 2016. Available from: http://www.survivingsepsis.org/SiteCollectionDocuments/SSC-Statements-Sepsis-Definitions-3-2016.pdf (accessed April 2017).
» http://www.survivingsepsis.org/SiteCollectionDocuments/SSC-Statements-Sepsis-Definitions-3-2016.pdf -
31Surviving Sepsis Campaign: updated bundles in response to new evidence. 2014. Available from: http://www.survivingsepsis.org/sitecollectiondocuments/ssc_bundle.pdf (accessed April 2017).
» http://www.survivingsepsis.org/sitecollectiondocuments/ssc_bundle.pdf
Edited by
Data availability
Publication Dates
-
Publication in this collection
Jan-Mar 2019
History
-
Received
09 Jan 2018 -
Accepted
04 Dec 2018