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Prognostic Factors Predicting Poor Outcome in Cancer Patients with Febrile Neutropenia in the Emergency Department: Usefulness of qSOFA

Prognostic Factors Predicting Poor Outcome in Cancer Patients with Febrile Neutropenia in the... Hindawi Journal of Oncology Volume 2018, Article ID 2183179, 7 pages https://doi.org/10.1155/2018/2183179 Research Article Prognostic Factors Predicting Poor Outcome in Cancer Patients with Febrile Neutropenia in the Emergency Department: Usefulness of qSOFA Seung Jae Lee, Ji Hye Kim, Seung Baik Han, Jin Hui Paik, and Areum Durey Department of Emergency Medicine, Inha University School of Medicine, Incheon, Republic of Korea Correspondence should be addressed to Areum Durey; areum.durey@gmail.com Received 14 July 2018; Accepted 3 October 2018; Published 11 October 2018 Academic Editor: om Th as R. Chauncey Copyright © 2018 Seung Jae Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background/Aims. Febrile neutropenia is considered as one of the most important and potentially life-threatening oncologic emergencies, which requires prompt medical assessment and treatment with antibiotics. is Th was a single-center retrospective study that investigated the prognostic factors predicting poor outcome in patients with cancer who presented with febrile neutropenia at the emergency department (ED). Methods. eTh medical records of patients diagnosed with febrile neutropenia in the ED from January 2014 to December 2017 were reviewed. Patients aged>18 years who were diagnosed with a malignancy were included in 3 ∘ the analysis. Febrile neutropenia was defined as an absolute neutrophil count < 1,000/mm with a temperature greater than 38 C. Patients were divided into two groups: those who were admitted at the intensive care unit (ICU) or those who died in the hospital (case group) and those who were admitted at general wards and were discharged (control group). eTh two groups were compared to determine the factors associated with poor prognosis. Results. We identified 104 patients (25 and 79 from the case and control groups, respectively) with cancer who presented with febrile neutropenia at the ED during the study period. Lower blood pressure, platelet count, and HCO level, higher CRP and creatinine level, and the presence of bacteremia were more commonly observed in the case group than in the control group. In the multiple logistic regression analysis, the following independent predictors significantly correlated with ICU admission and in-hospital mortality: quick sequential (sepsis-related) organ failure assessment (qSOFA) score (odds ratio [OR]: 4.62; 95% confidence interval [CI]: 1.17–18.22; p= 0.285), hemoglobin level (OR: 0.51; 95% CI: 0.33–0.78; p=0.002), total bilirubin level (OR: 7.69; 95% CI: 1.29–45.8; p=0.025), and respiratory tract infection (OR: 29.65; 95% CI: 3.81–230.7; p=0.0012). Conclusions. eTh qSOFA can be a useful bedside tool for patients with cancer who present with febrile neutropenia at the ED. Moreover, it can help emergency physicians in identifying patients at risk of poor prognosis and in initiating prompt empirical antimicrobial therapy. Further studies must be conducted to validate the efficacy of the qSOFA in these patients in the ED. 1. Introduction mortality, with a limited number of patients developing serious medical complications [5], and the identification Neutrophils constitute the main mechanism of host defense of patients at risk is challenging for physicians. Notably, a against infection and serve as an essential component of prospective study in France has revealed that the severity innate immunity. The degree and duration of neutropenia was under-evaluated, and the management of patients with were identified as key factors related to the risk and outcome cancer who present with febrile neutropenia at the ED is of infection in 1979 [1] and it is as true today as when it insufficient [6]. was written [2, 3]. Therefore, febrile neutropenia is con- This study aimed to identify the prognostic factors pre- sidered as one of the most important and potentially life- dicting poor outcome in patients with cancer who presented threatening oncologic emergencies, which requires prompt with febrile neutropenia at the ED. Moreover, the charac- medical assessment and treatment with antibiotics [4]. teristics and outcomes in these patients were retrospectively However, patients with febrile neutropenia may be a analyzed, and the independent variables that can be easily heterogeneous group in terms of medical complications and assessed and used at the ED to predict patients who are 2 Journal of Oncology at risk of developing potentially serious complications were 3. Profound neutropenia is defined as an ANC lower than identified. 100/mm upon ED arrival. When focal infection could not be identified, the source was categorized as undetermined. The time from ED visit 2. Material and Methods to the administration of antibiotics is defined as the time in minutes from presentation to triage to the first dose 2.1. Study Design. This was a single-center retrospective of parental antibiotics and is considered as a continuous study that investigated the prognostic factors predicting poor variable. The initial empirical antimicrobial therapy was outcome in patients with cancer who presented with febrile considered appropriate if the initial antibiotics included neutropenia at the ED from January 2014 to December 2017. at least one antibiotic that was active in vitro and if the This study was conducted in a university hospital in Korea, dosage was in accordance with current medical standards. which is a tertiary hospital with 60,000 patients according Otherwise, initial antimicrobial therapy was considered inap- to an annual census of ED visits, and was approved by the propriate. institutional review board of the hospital (IRB no. 2018-05- 004). The need for informed consent was waived. 2.5. Statistical Analyses. Data with a normal distribution were expressed as mean± standard deviation and were analyzed 2.2. Study Protocol and Population. The medical records of using the independent samples t-test. Data with a skewed patients diagnosed with febrile neutropenia at the ED during distribution were expressed as medians and interquartile the 5-year study period were reviewed from the computer ratios and were analyzed using the Mann–Whitney U test. database. Patients with malignancies and those who were Categorical variables were compared using𝜒 test or Fisher older than 18 years were included. Febrile neutropenia was exact test depending on the sample size. A simple logistic den fi ed as an absolute neutrophil count (ANC) < 1,000/mm ∘ regression analysis followed by a stepwise multiple logistic with a temperature greater than 38 C. Only the rst fi episode regression analysis was performed to identify discriminative of febrile neutropenia in a patient during the study period was variables between the groups at the ED. A p value< 0.05 considered. was considered statistically significant. All statistical analyses Patients were divided into two groups: those who were were performed using MedCalc for Windows version 17.6 admitted at the intensive care unit (ICU) or those who died (MedCalc Statistical Sowa ft re, Ostend, Belgium). during hospitalization (case group) and those who were admitted at general wards and were discharged (control group). The two groups were compared to determine the 3. Results factors associated with poor prognosis. 3.1. Clinical Characteristics. We identified 104 patients with cancer who presented with febrile neutropenia at the ED 2.3. Variables. The following information on the case and during the study period. The case group consisted of 25 control groups was obtained by reviewing the medical charts: patients who were admitted at the ICU or those who died age, sex, comorbidities, clinical manifestations (ED visit on during hospitalization, whereas the control group included weekends, change in mental status, duration of fever [> 24 h], the remaining 79 patients who were admitted at general presence of central venous catheter, and hospital-acquired wards and were discharged. Demographic and clinical data infection), type and origin of malignancy, and history of comparing the groups are presented in Table 1. chemotherapy. Vital signs at triage and laboratory results, The mean age of the participants was 61 years, and including microbiologic test results, were recorded, and the diabetes mellitus was the most frequent comorbidity (18%). quick sequential (sepsis-related) organ failure assessment Approximately 35% of the patients visited the ED during (qSOFA) score was calculated. The presumed source of weekends, and 32% had fever for more than 24 h prior to their infection, empirical antimicrobial therapy, time from ED visit. Moreover, 16% of the patients had central venous line visit to the administration of antibiotics, appropriateness in place, and 9% presented with hospital-acquired infection. of the empirical therapy, and use of granulocyte colony- No statistical difference was observed between the groups in stimulating factor were identified. Clinical outcome variables, terms of comorbidities, ED visit during weekends, duration of such as vasopressor use, need for mechanical ventilation, ICU fever, presence of a central venous line, and hospital-acquired admission, do not resuscitate (DNR) order, and duration of infection. hospitalization, were also documented. Of the 104 patients, 69 had a solid tumor, and 35 presented with hematological malignancies. Among the solid tumors, 2.4. Den fi itions. The time from fever onset to ED admission the most frequent origin was the breast, followed by the was defined as the time from the onset of subjective symp- gastrointestinal tract and the lungs. Around 49% (34 out toms (based on patient history) to ED visit. Central venous of 69) of the patients presented with stage IV solid tumor. catheter included medication ports and peripherally inserted Leukemia occurred in 11% of the patients. central catheters. The qSOFA score included a systolic blood Approximately 89 patients (18 and 71 from the case and pressure (BP) ≤ 100 mmHg, RR ≥ 22/minute, and altered control groups, respectively) received chemotherapy within mental status [7]. Each of the above-mentioned conditions 2 months, and the median delay between chemotherapy and corresponded to one point, and the score ranged from 0 to ED visit was 12.5 days, ranging from 10 to 15 days. Journal of Oncology 3 Table 1: Comparison of clinical characteristics of 104 cancer patients presented with febrile neutropenia to the emergency department including 25 case patients who admitted to the intensive care unit or died in the hospital and 79 control patients who admitted to general wards and discharged. Characteristics Total (n = 104) Case (n = 25) Control (n = 79) P value Age 60.8± 13.6 63.6± 12.9 61 (51-69) 0.255 Male, no. (%) 41 (39) 14 (56) 27 (34) 0.052 Comorbid conditions, no. (%) Diabetes mellitus 14 (13) 5 (20) 9 (11) 0.316 Cardiovascular disease 6 (6) 1 (4) 5 (6) 1.0 Respiratory disease 5 (8) 1 (4) 4 (5) 1.0 Chronic renal failure 8 (8) 3 (12) 5 (6) 0.394 Liver cirrhosis 3 (3) 1 (4) 2 (3) 0.565 Rheumatologic disease 1 (1) 1 (4) 0 0.240 Neurodegenerative disease 6 (6) 2 (8) 4 (5) 0.628 Clinical manifestation ED visits on weekends 36 (35) 9 (36) 27 (34) 0.868 Mental change 6 (6) 3 (12) 3 (4) 0.148 Fever> 24 hr 33 (32) 4 (16) 27 (34) 0.343 Presence of central venous catheter 17 (16) 4 (16) 13 (16) 1.0 Hospital-acquired type 9 (9) 2 (8) 7 (9) 1.0 Solid tumor, no. (%) 69 (66) 14 (56) 55 (70) 0.211 Breast 34 (33) 5 (20) 29 (37) 0.146 Gastrointestinal tract 14 (13) 4 (16) 10 (13) 0.738 Lung 7 (7) 0 7 (9) 0.191 Hepatobiliary tract 6 (6) 2 (8) 4 (5) 0.628 Ovary 3 (3) 0 3 (4) 1.0 Others 5 (5) 3 (12) 2 (3) 0.088 Stage IV 34 10 24 0.712 Hematological malignancy, no. (%) 35 (34) 11 (44) 24 (30) Leukemia 11 (11) 5 (20) 6 (8) 0.211 History of Chemotherapy none 3 1 2 oral chemotherapy 5 3 2 Intravenous chemotherapy 96 21 75 Latency> 2months 7 3 4 < 2months, days 12.5 (10-15) 11 (7.7-13.0) 12.5 (10-15) 0.043 ∗ ∗∗ ∗∗∗ <0.05, p<0.01 p<0.001: significant change from baseline values. ED: emergency department. 3.2. Vital Signs and Laboratory Findings. Table 2 shows the 3.3. Source of Infection and Microbiology. The presumed vital signs and laboratory n fi dings of the patients upon ED source of infection and the results of the microbiologic study visit. Patients who died or those who were admitted at the are summarized in Table 3. With regard to the source of ICU had lower systolic and diastolic BP and higher pulse infection, pneumonia was more common in patients who rates than those in the control group. Notably, the mean died or those who were admitted at the ICU (52% vs. 16%, value of the qSOFA was signicfi antly higher in the case respectively; p=0.0004), whereas undetermined origin was group than in the control group (0.88 vs. 0.36, p=0.0003). more frequently observed in the control group than in the With regard to complete blood cell counts, no difference case group (66% vs. 24%, respectively; p=0.0003) was observed between the groups in terms of ANC or Bacteremia was more frequently observed in the case profound neutropenia. However, the case group had a lower group than in the control group (24% vs. 8%, respectively; hemoglobin level, platelet count, and HCO level and a p=0.035). Among the case patients, 6 had bacteremia; 2 higher total bilirubin, creatinine, and C-reactive protein presented with Escherichia coli,2with Pseudomonas aerugi- (CRP) level than the control group. nosa,1 with Klebsiella pneumoniae,and 1 with Staphylococcus 4 Journal of Oncology Table 2: Comparison of vital signs and laboratory findings of 25 case patients and of 79 control patients with neutropenic fever in the emergency department. Characteristics Total (n = 104) Case (n = 25) Control (n = 79) P value Vital signs on presentation ∗∗ SBP, mm Hg 119.1± 21.6 106.7± 24.6 122 (110-135) 0.001 ∗∗∗ DBP, mm Hg 70.8± 14.3 62.0± 14.1 73.6± 13.3 0.0003 PR, beats/min 110 (92-128) 119.7± 18.9 106.0 (88.5-124.7) 0.013 RR, breaths/min 18 (18-20) 20 (18-24) 18 (18-20) 0.252 Body temperature, C 38.4 (38-38.9) 38.5 (38.0-38.1) 38.3 (38.0-38.7) 0.649 ∗∗ Saturation, % 97 (96-98) 96.0 (93.1-97.0) 97 (96-98) 0.001 ∗∗∗ qSOFA 0.49± 0.63 0.88± 0.78 0.36± 0.53 0.0003 Complete blood cell counts Leukocyte count, x10 cells/mL 1120(615-1570) 710 (462-1473) 1170 (702-1625) 0.056 ANC 205 (84-567) 174 (67-335) 222 (101-666) 0.087 Profound neutropenia, no. (%) 29 (28) 10 (25) 19 (24) 0.123 ∗∗∗ Hemoglobin, g/dL 9.6± 2.1 8.1± 2.2 10.3 (9.1-11) < 0.0001 3 ∗∗ Platelet, x10 /𝜇 l 95 (52-178) 52 (27-114) 123 (68-188) 0.002 Other laboratory findings ∗∗∗ CRP, mg/dL 5.5 (3-12.6) 10.2 (6.5-17.7) 4.0 (2.2-9.5) < 0.0001 Lactic acid, mmol/L 1.9 (1.4-2.5) 2.15 (1.4-5.0) 1.75 (1.4-2.35) 0.126 Glucose, mg/dL 131 (112-161) 159± 55.4 129 (112-147) 0.106 Total bilirubin, mg/dL 0.7 (0.5-1.1) 0.9 (0.5-1.2) 0.6 (0.4-0.9) 0.029 ∗∗ Creatinine, mg/dl 0.77 (0.62-0.96) 0.97 (0.74-2.01) 0.72 (0.62-0.89) 0.001 ∗∗∗ Albumin, g/dL 3.5 (3.2-3.8) 3.1± 0.4 3.7 (3.3-3.8) 0.0004 Arterial blood gas pH 7.47 (7.44-7.49) 7.46(7.43-7.49) 7.47± 0.03 0.124 PCO ,mm Hg 31.5± 5.7 30.6± 8.1 31.9± 4.6 0.334 PO , mm Hg 81.2 (73.7-94.8) 78.7 (69.6-95.9) 81.6 (78.8 -91.4) 0.402 − ∗∗∗ HCO , mmol/L 22.7 (20.8-24.9) 20.2± 4.8 23.4± 2.8 0.0002 SpO , mm Hg 96.7 (95.3-97.7) 96.2 (94-97.5) 96.8 (95.5-97.7) 0.150 ∗ ∗∗ ∗∗∗ <0.05, p<0.01 p<0.001: significant change from baseline values. qSOFA: quick sepsis-related organ failure assessment; ANC: absolute neutrophil count; CRP: C-reactive protein. aureus. No resistant bacteria, such as extended-spectrum𝛽 - rate was 12% (12 out of 104 patients), and 5 patients with DNR lactamase (ESBL)-producing Enterobacteriaceae, multidrug- order were not admitted at the ICU and then died within 24 resistant P. aeruginosa, or methicillin-resistant S. aureus, were hours of ED visit. observed in the case group. Among the control patients, 6 had bacteremia; 3 presented with E. coli,1 with K. pneumoniae, 3.5. Predictive Factors for ICU Admission or Mortality. Table 4 1with Enterobacter,and 1 with Streptococcus agalactiae,of shows the variables associated with poor prognosis in patients which 2 tested positive for ESBL. with cancer who presented with febrile neutropenia at the ED based on a simple logistic regression analysis. In the 3.4. Treatment and Outcome. Table 3 shows the treatment at multiple logistic regression analysis, the independent pre- the ED and clinical outcomes. With regard to antimicrobial dictors signicfi antly correlated with ICU admission, and treatment, 20% of the patients were treated with combination mortality was significantly associated with the qSOFA (odds therapy. Anti-pseudomonal 𝛽 -lactam antibiotics (cefepime ratio [OR]: 4.62; 95% confidence interval [CI]: 1.17–18.22; and piperacillin tazobactam) were used empirically in 65% p=0.285), hemoglobin level (OR: 0.51; 95% CI: 0.33–0.78; and 87% of the case and control patients, respectively. The p=0.002), total bilirubin level (OR: 7.69; 95% CI: 1.29–45.8; median time from ED presentation to the start of antibiotic p=0.025), and respiratory tract infection (OR: 29.65; 95% CI: therapy was 107 minutes, and no difference was observed 3.81–230.7; p=0.0012) between the groups in terms of the latency of the rfi st dose of antibiotics. With regard to clinical outcomes, vasopressor was used 4. Discussion in 15% of the patients and in 6% of the patients who were intubated at the ED. Moreover, 20 out of the 104 (20%) Two models were used to predict the outcome of febrile patients were admitted at the ICU. The in-hospital mortality neutropenic episode. Talcott et al. [8] have established a Journal of Oncology 5 Table 3: Comparison of source of infection and treatment outcome of 25 case patients and of 79 control patients with neutropenic fever in the emergency department. Characteristics Total (n = 104) Case (n = 25) Control (n = 79) P value ∗∗∗ Source of infection, no. (%) 26 (25) 13 (52) 13 (16) 0.0004 Respiratory tract 9 (9) 3 (12) 6 (8) 0.446 Urinary tract 6 (6) 1 (4) 5 (6) 1.0 Gastrointestinal tract 2 (2) 1 (4) 1 (1) 0.424 Hepatobiliary tract 3 (3) 1 (4) 2 (3) 0.565 ∗∗∗ Skin and soft tissue 58 (26) 6 (24) 52 (66) 0.0003 Unknown Bacteremia, no (%) 12 (12) 6 (24) 6 (8) 0.035 Combination therapy, no (%) 21 (20) 8 (32) 13 (16) 0.093 Time from ED visit to antibiotics, min 107 (83-135) 101 (85-119) 110.5 (83-139) 0.324 Inappropriateness of antibiotics, no (%) 1 out of 7 1 out of 11 1.0 Use of G-CSF, no. (%) 58 (56) 14 (56) 44 (56) 0.978 ∗∗∗ Use of vasopressor, no. (%) 16 (15) 14 (56) 2 (3) < 0.0001 Intubation, no. (%) 6 (6) 6 (24) 0 ICU care, no. (%) 20 (19) 20 (80) 0 DNR order, no. (%) 7 (28) 0 Hospital days 7 (5-12) 11 (6.7-22) 7 (4-10.7) 0.010 In-hospital death, no (%) 12 (12) 12 (48) 0 ∗ ∗∗ ∗∗∗ <0.05, p<0.01 p<0.001: significant change from baseline values. ED: emergency department; G-CSF: granulocyte-colony stimulating factor; ICU: intensive care unit; DNR: do not resuscitate. Table 4: Logistic regression analysis of prognostic factors in cancer patients with febrile neutropenia in the emergency department. Simple logistic analysis Multiple logistic analysis Characteristics OR (95% CI) P value OR (95% CI) P value Vital signs on presentation ∗∗∗ SBP, mm Hg 0.95 (0.93-0.98) 0.0005 ∗∗∗ DBP, mm Hg 0.94 (0.90-0.97) 0.0003 PR, beats/min 1.02 (1.00-1.05) 0.011 ∗∗ Saturation, % 0.84 (0.71-1.00) 0.002 qSOFA 4.62 (1.17-18.22) 0.285 Laboratory findings on presentation ∗∗ Hemoglobin, g/dL 0.51 (0.33-0.78) 0.002 3 ∗∗ Platelet, x10 /𝜇 l 0.99 (0.98-0.99) 0.002 ∗∗∗ CRP, mg/dL 1.09 (1.03-1.15) 0.0006 Total bilirubin, mg/dL 7.69 (1.29-45.8) 0.025 ∗∗∗ Creatinine, mg/dl 3.52 (1.48-8.37) 0.0004 ∗∗∗ Albumin, g/dL 0.17 (0.06-0.50) 0.0004 Bacteremia, no (%) 3.84 (1.11-13.2) 0.036 Arterial blood gas − ∗∗∗ HCO , mmol/L 0.77 (0.66-0.90) 0.0002 Infection focus, no. (%) ∗∗ Respiratory tract 29.65 (3.81-230.7) 0.0012 ∗ ∗∗ ∗∗∗ <0.05, p<0.01 p<0.001: significant change from baseline values. CI:confidence interval;OR: odds ratio. clinical prediction rule based on clinical features; however, seven independent prognostic factors [5]. The MASCC risk- the model requires information that included tumor response index score has been internationally validated under various to chemotherapy, which is not easily determined at the ED. clinical conditions [9, 10]. However, it includes variables, Then, the Multinational Association of Supportive Care in such as burden of illness, severity of symptoms, and history Cancer (MASCC) developed a scoring system based on of fungal infection, which could be obtained only through 6 Journal of Oncology a detailed review of the patient’s medical history or might variables associated with unfavorable outcomes in our study be aec ff ted by the subjective judgement of the physician. were also the components of the full SOFA, which include Therefore, the use of the models is limited in the ED. hypotension, platelet count, and bilirubin and creatinine level. To the best of our knowledge, only a few studies [11–13] This study has several limitations. First, this is single- that aimed to identify independent factors associated with the center retrospective study. Moreover, it is possible that the serious complications of febrile neutropenia in patients with significant prognostic factors related to ICU admission or cancer have been conducted in ED settings. In 2009, Moon et in-hospital mortality were not identified due to the small al. have reported that laboratory parameters, such as a platelet sample size of the study. For instance, other studies have count< 50,000/mm , serum CRP level> 10 mg/dL, and pul- identified chronic obstructive pulmonary disease (COPD) monary infiltration on chest radiography, were independent [16], leukemia [17], polymicrobial bacteremia [18], and inap- factors that can predict the development of complications propriateness of antimicrobial therapy [19] as independent [12].In 2013, Lynn et al.have also shown the association of risk factors. However, only 8%, 11%, and 12% of the enrolled pneumonia, a platelet count≤ 50,000/mm and the latency patients in our study had COPD, leukemia, and bacteremia, of the rfi st dose of antibiotics in the ED with serious compli- respectively. The appropriateness of using empirical antibi- cations [13]. Our study also aimed to identify the risk factors otics was only evaluated in 17% of the study population. that can predict ICU admission and mortality in patients Emergency physicians must identify patients who are at with cancer who presented with febrile neutropenia at the risk because the prognosis of patients with severe infection ED. Nevertheless, there are two important differences from depends on their initial management. The qSOFA and the the others. Unlike other studies that only enrolled patients presence of pneumonia can be a useful bedside tool for with an ANC< 500/mm , the present study included patients patients with cancer who present with febrile neutropenia in 3 3 with an ANC between 500/mm and 1,000/mm .The risk the ED. The results of the present study may help emergency of developing clinically important infection increases with physicians identify high-risk patients, thus preventing the the decrease in neutrophil count below 500/mm .Moreover, development of complications by ordering prompt blood cul- individuals with prolonged neutropenia (> 7 days) are at ture and subsequently administering broad-spectrum antibi- higher risk [14]. However, this is not significant for emergency otics. physicians because neither the duration of nor the course of neutropenia is predictable in patients with cancer who visit the ED, and this can only be determined retrospectively. Data Availability Therefore, we included patients with neutropenia (ANC < The data used to support the findings of this study are 1,000/mm ) [15] to prevent overlooking patients who are at available from the corresponding author upon request. risk. Surprisingly, 4 of the 12 patients who died in our study had an ANC> 500/mm . The second difference is that our study did not only focus Additional Points on chemotherapy-induced neutropenia. In fact, it included all Key Messages. (1) TheqSOFA can beauseful bedside tool for causes of neutropenia in patients with cancer. Neutropenia patients with cancer who present with febrile neutropenia at can develop in patients with cancer because of the dis- the ED. ease itself that involves the bone marrow. However, severe infection can also cause neutropenia. Because the present study aimed to identify the prognostic factors of febrile Conflicts of Interest neutropenia, which were generally applicable to patients with cancer who visit the ED, we included all causes of neutropenic The authors of this study have no conflicts of interest to episodes. In fact, 15 out of 104 patients in our study presented report. with neutropenia despite the absence of recent chemotherapy within 2 months, of which 8 patients were either admitted References at the ICU or died. Consequently, the possibility of febrile neutropenia and the subsequent development of complica- [1] P.A. Pizzo, K. J.Robichaud,F.A. Gill et al.,“Durationof empiric tions should still be considered in patients with cancer even antibiotic therapy in granulocytopenic patients with cancer,” without the history of recent chemotherapy. American Journal of Medicine,vol.67,no. 2,pp.194–200, 1979. Based on our study, the independent predictors sig- [2] National Institute for Clinical Excellence and the National nificantly correlated with ICU admission, and in-hospital Collaborating Centre for Cancer, “Neutropenic sepsis: mortality was associated with the qSOFA score, hemoglobin prevention and management of neutropenic sepsis in cancer level, total bilirubin, and respiratory tract infection. The patients,” Cardiff: NCC-C, 2012, (Accessed 15 September 2018), qSOFA is a new screening tool for sepsis that has a prognostic http://www.nice.org.uk/nicemedia/live/13905/60864/60864 performance equal to the full SOFA for patients with sus- .pdf. pected infection outside the ICU [7]. According to our study, [3] T. Wilson, T. Cooksley, S. Churchill, J. Radford, and P. Dark, patients with cancer who presented with febrile neutropenia “Retrospective analysis of cancer patients admitted to a ter- and who are likely to have a poor prognosis can be rapidly tiary centre with suspected neutropenic sepsis: Are C-reactive identified at the bedside with the qSOFA. Interestingly, other protein and neutrophil count useful prognostic biomarkers?” Journal of Oncology 7 JournaloftheIntensiveCareSociety,vol. 19, no.2,pp. 132–137, [17] C. Viscoli, P. Bruzzi, and E. Castagnola, “Factors associated 2018. with bacteremia in febrile, granulocytopenic cancer patients,” European Journal of Cancer,vol.30,pp.430–437,1994. [4] A. G. Freifeld, E. J. Bow, K. A. Sepkowitz et al., “Clinical practice guideline for the use of antimicrobial agents in neutropenic [18] M.Ortega, F.Marco,A.Soriano et al., “Epidemiology and patients with cancer: 2010 update by the infectious diseases outcome of bacteraemia in neutropenic patients in a single society of america,” Clinical Infectious Diseases,vol.52, no. 4, institution from 1991-2012,” Epidemiology and Infection,vol. 143, pp. e56–e93, 2011. no. 4, pp. 734–740, 2015. [5] J. Klastersky, M. Paesmans, E. B. Rubenstein et al., “The multi- [19] M. Fletcher, H. Hodgkiss, S. Zhang et al., “Prompt adminis- national association for supportive care in cancer risk index: tration of antibiotics is associated with improved outcomes in a multinational scoring system for identifying low-risk febrile febrile neutropenia in children with cancer,” Pediatric Blood & neutropenic cancer patients,” Journal of Clinical Oncology,vol. Cancer,vol.60,no. 8, pp.1299–1306,2013. 18, no. 16, pp. 3038–3051, 2000. [6] S. Andre, P. Taboulet, C. Elie et al., “Febrile neutropenia in French emergency departments: results of a prospective multicentre survey,” Critical Care,vol.14,no.2, 2010. [7] M.Singer,C.S.Deutschman, C.W.Seymour et al., “eTh third international consensus definitions for sepsis and septic shock (sepsis-3),”JournaloftheAmericanMedicalAssociation,vol.315, pp. 801–810, 2016. [8] J.A. Talcott,R.D. Siegel, R.Finberg,and L.Goldman, “Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule,” Journal of Clinical Oncology,vol.10,no. 2,pp.316–322, 1992. [9] A.Uys,B.L.Rapoport,H.Fickl, P. W.A.Meyer, and R. Ander- son, “Prediction of outcome in cancer patients with febrile neutropenia: comparison of the multinational association of supportive care in cancer risk-index score with procalcitonin, C-reactive protein, serum amyloid A, and interleukins-1𝛽 ,-6, -8 and -10,” European Journal of Cancer Care,vol.16,no. 6,pp. 475–483, 2007. [10] E. P. Hui, L. K. S. Leung, T. C. W. Poon et al., “Prediction of outcome in cancer patients with febrile neutropenia: a prospective validation of the Multinational Association for Supportive Care in Cancer risk index in a Chinese population and comparison with the Talcott model and artificial neural network,” Supportive Care in Cancer,vol. 19, no.10,pp.1625– 1635, 2011. [11] J.H. Lim, H.Kim, W. G.Choi,K.H.Kim,D.W. Shin,and M. H. Lee, “Outcomes in 102 patients that present to the emergency department with chemotherapy-induced febrile neutropenia,” Turkish Journal of Hematology,vol.28, no. 3,pp.193–197, 2011. [12] J.M.Moon and B.J.Chun, “Predictingthe complicated neutropenic fever in the emergency department,” Emergency Medicine Journal,vol.26,no. 11, pp.802–806,2009. [13] J. Lynn, K. Chen, Y. Weng, and T. Chiu, “Risk factors associated with complications in patients with chemotherapy-induced febrile neutropenia in emergency department,” Hematological Oncology, vol. 31, no. 4, pp. 189–196, 2013. [14] S. Ahn, Y.-S. Lee, Y.-H. Chun et al., “Predictive factors of poor prognosis in cancer patients with chemotherapy-induced febrile neutropenia,” Supportive Care in Cancer, vol.19,no.8, pp. 1151–1158, 2011. [15] US Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Common terminology criteria for adverse events (CTCAE), https://ctep .cancer.gov/protocoldevelopment/electronic applications/docs/ CTCAE v5 Quick Reference 5x7.pdf (Accessed on March 22, 2018). [16] J. Klastersky, M. Paesmans, and A. Georgala, “Outpatient oral antibiotics for febrile neutropenic cancer patients using a score predictive for complications,” Journal of Clinical Oncology,vol. 24, no. 25, pp. 4129–4134, 2006. 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Prognostic Factors Predicting Poor Outcome in Cancer Patients with Febrile Neutropenia in the Emergency Department: Usefulness of qSOFA

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Copyright © 2018 Seung Jae Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Journal of Oncology Volume 2018, Article ID 2183179, 7 pages https://doi.org/10.1155/2018/2183179 Research Article Prognostic Factors Predicting Poor Outcome in Cancer Patients with Febrile Neutropenia in the Emergency Department: Usefulness of qSOFA Seung Jae Lee, Ji Hye Kim, Seung Baik Han, Jin Hui Paik, and Areum Durey Department of Emergency Medicine, Inha University School of Medicine, Incheon, Republic of Korea Correspondence should be addressed to Areum Durey; areum.durey@gmail.com Received 14 July 2018; Accepted 3 October 2018; Published 11 October 2018 Academic Editor: om Th as R. Chauncey Copyright © 2018 Seung Jae Lee et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background/Aims. Febrile neutropenia is considered as one of the most important and potentially life-threatening oncologic emergencies, which requires prompt medical assessment and treatment with antibiotics. is Th was a single-center retrospective study that investigated the prognostic factors predicting poor outcome in patients with cancer who presented with febrile neutropenia at the emergency department (ED). Methods. eTh medical records of patients diagnosed with febrile neutropenia in the ED from January 2014 to December 2017 were reviewed. Patients aged>18 years who were diagnosed with a malignancy were included in 3 ∘ the analysis. Febrile neutropenia was defined as an absolute neutrophil count < 1,000/mm with a temperature greater than 38 C. Patients were divided into two groups: those who were admitted at the intensive care unit (ICU) or those who died in the hospital (case group) and those who were admitted at general wards and were discharged (control group). eTh two groups were compared to determine the factors associated with poor prognosis. Results. We identified 104 patients (25 and 79 from the case and control groups, respectively) with cancer who presented with febrile neutropenia at the ED during the study period. Lower blood pressure, platelet count, and HCO level, higher CRP and creatinine level, and the presence of bacteremia were more commonly observed in the case group than in the control group. In the multiple logistic regression analysis, the following independent predictors significantly correlated with ICU admission and in-hospital mortality: quick sequential (sepsis-related) organ failure assessment (qSOFA) score (odds ratio [OR]: 4.62; 95% confidence interval [CI]: 1.17–18.22; p= 0.285), hemoglobin level (OR: 0.51; 95% CI: 0.33–0.78; p=0.002), total bilirubin level (OR: 7.69; 95% CI: 1.29–45.8; p=0.025), and respiratory tract infection (OR: 29.65; 95% CI: 3.81–230.7; p=0.0012). Conclusions. eTh qSOFA can be a useful bedside tool for patients with cancer who present with febrile neutropenia at the ED. Moreover, it can help emergency physicians in identifying patients at risk of poor prognosis and in initiating prompt empirical antimicrobial therapy. Further studies must be conducted to validate the efficacy of the qSOFA in these patients in the ED. 1. Introduction mortality, with a limited number of patients developing serious medical complications [5], and the identification Neutrophils constitute the main mechanism of host defense of patients at risk is challenging for physicians. Notably, a against infection and serve as an essential component of prospective study in France has revealed that the severity innate immunity. The degree and duration of neutropenia was under-evaluated, and the management of patients with were identified as key factors related to the risk and outcome cancer who present with febrile neutropenia at the ED is of infection in 1979 [1] and it is as true today as when it insufficient [6]. was written [2, 3]. Therefore, febrile neutropenia is con- This study aimed to identify the prognostic factors pre- sidered as one of the most important and potentially life- dicting poor outcome in patients with cancer who presented threatening oncologic emergencies, which requires prompt with febrile neutropenia at the ED. Moreover, the charac- medical assessment and treatment with antibiotics [4]. teristics and outcomes in these patients were retrospectively However, patients with febrile neutropenia may be a analyzed, and the independent variables that can be easily heterogeneous group in terms of medical complications and assessed and used at the ED to predict patients who are 2 Journal of Oncology at risk of developing potentially serious complications were 3. Profound neutropenia is defined as an ANC lower than identified. 100/mm upon ED arrival. When focal infection could not be identified, the source was categorized as undetermined. The time from ED visit 2. Material and Methods to the administration of antibiotics is defined as the time in minutes from presentation to triage to the first dose 2.1. Study Design. This was a single-center retrospective of parental antibiotics and is considered as a continuous study that investigated the prognostic factors predicting poor variable. The initial empirical antimicrobial therapy was outcome in patients with cancer who presented with febrile considered appropriate if the initial antibiotics included neutropenia at the ED from January 2014 to December 2017. at least one antibiotic that was active in vitro and if the This study was conducted in a university hospital in Korea, dosage was in accordance with current medical standards. which is a tertiary hospital with 60,000 patients according Otherwise, initial antimicrobial therapy was considered inap- to an annual census of ED visits, and was approved by the propriate. institutional review board of the hospital (IRB no. 2018-05- 004). The need for informed consent was waived. 2.5. Statistical Analyses. Data with a normal distribution were expressed as mean± standard deviation and were analyzed 2.2. Study Protocol and Population. The medical records of using the independent samples t-test. Data with a skewed patients diagnosed with febrile neutropenia at the ED during distribution were expressed as medians and interquartile the 5-year study period were reviewed from the computer ratios and were analyzed using the Mann–Whitney U test. database. Patients with malignancies and those who were Categorical variables were compared using𝜒 test or Fisher older than 18 years were included. Febrile neutropenia was exact test depending on the sample size. A simple logistic den fi ed as an absolute neutrophil count (ANC) < 1,000/mm ∘ regression analysis followed by a stepwise multiple logistic with a temperature greater than 38 C. Only the rst fi episode regression analysis was performed to identify discriminative of febrile neutropenia in a patient during the study period was variables between the groups at the ED. A p value< 0.05 considered. was considered statistically significant. All statistical analyses Patients were divided into two groups: those who were were performed using MedCalc for Windows version 17.6 admitted at the intensive care unit (ICU) or those who died (MedCalc Statistical Sowa ft re, Ostend, Belgium). during hospitalization (case group) and those who were admitted at general wards and were discharged (control group). The two groups were compared to determine the 3. Results factors associated with poor prognosis. 3.1. Clinical Characteristics. We identified 104 patients with cancer who presented with febrile neutropenia at the ED 2.3. Variables. The following information on the case and during the study period. The case group consisted of 25 control groups was obtained by reviewing the medical charts: patients who were admitted at the ICU or those who died age, sex, comorbidities, clinical manifestations (ED visit on during hospitalization, whereas the control group included weekends, change in mental status, duration of fever [> 24 h], the remaining 79 patients who were admitted at general presence of central venous catheter, and hospital-acquired wards and were discharged. Demographic and clinical data infection), type and origin of malignancy, and history of comparing the groups are presented in Table 1. chemotherapy. Vital signs at triage and laboratory results, The mean age of the participants was 61 years, and including microbiologic test results, were recorded, and the diabetes mellitus was the most frequent comorbidity (18%). quick sequential (sepsis-related) organ failure assessment Approximately 35% of the patients visited the ED during (qSOFA) score was calculated. The presumed source of weekends, and 32% had fever for more than 24 h prior to their infection, empirical antimicrobial therapy, time from ED visit. Moreover, 16% of the patients had central venous line visit to the administration of antibiotics, appropriateness in place, and 9% presented with hospital-acquired infection. of the empirical therapy, and use of granulocyte colony- No statistical difference was observed between the groups in stimulating factor were identified. Clinical outcome variables, terms of comorbidities, ED visit during weekends, duration of such as vasopressor use, need for mechanical ventilation, ICU fever, presence of a central venous line, and hospital-acquired admission, do not resuscitate (DNR) order, and duration of infection. hospitalization, were also documented. Of the 104 patients, 69 had a solid tumor, and 35 presented with hematological malignancies. Among the solid tumors, 2.4. Den fi itions. The time from fever onset to ED admission the most frequent origin was the breast, followed by the was defined as the time from the onset of subjective symp- gastrointestinal tract and the lungs. Around 49% (34 out toms (based on patient history) to ED visit. Central venous of 69) of the patients presented with stage IV solid tumor. catheter included medication ports and peripherally inserted Leukemia occurred in 11% of the patients. central catheters. The qSOFA score included a systolic blood Approximately 89 patients (18 and 71 from the case and pressure (BP) ≤ 100 mmHg, RR ≥ 22/minute, and altered control groups, respectively) received chemotherapy within mental status [7]. Each of the above-mentioned conditions 2 months, and the median delay between chemotherapy and corresponded to one point, and the score ranged from 0 to ED visit was 12.5 days, ranging from 10 to 15 days. Journal of Oncology 3 Table 1: Comparison of clinical characteristics of 104 cancer patients presented with febrile neutropenia to the emergency department including 25 case patients who admitted to the intensive care unit or died in the hospital and 79 control patients who admitted to general wards and discharged. Characteristics Total (n = 104) Case (n = 25) Control (n = 79) P value Age 60.8± 13.6 63.6± 12.9 61 (51-69) 0.255 Male, no. (%) 41 (39) 14 (56) 27 (34) 0.052 Comorbid conditions, no. (%) Diabetes mellitus 14 (13) 5 (20) 9 (11) 0.316 Cardiovascular disease 6 (6) 1 (4) 5 (6) 1.0 Respiratory disease 5 (8) 1 (4) 4 (5) 1.0 Chronic renal failure 8 (8) 3 (12) 5 (6) 0.394 Liver cirrhosis 3 (3) 1 (4) 2 (3) 0.565 Rheumatologic disease 1 (1) 1 (4) 0 0.240 Neurodegenerative disease 6 (6) 2 (8) 4 (5) 0.628 Clinical manifestation ED visits on weekends 36 (35) 9 (36) 27 (34) 0.868 Mental change 6 (6) 3 (12) 3 (4) 0.148 Fever> 24 hr 33 (32) 4 (16) 27 (34) 0.343 Presence of central venous catheter 17 (16) 4 (16) 13 (16) 1.0 Hospital-acquired type 9 (9) 2 (8) 7 (9) 1.0 Solid tumor, no. (%) 69 (66) 14 (56) 55 (70) 0.211 Breast 34 (33) 5 (20) 29 (37) 0.146 Gastrointestinal tract 14 (13) 4 (16) 10 (13) 0.738 Lung 7 (7) 0 7 (9) 0.191 Hepatobiliary tract 6 (6) 2 (8) 4 (5) 0.628 Ovary 3 (3) 0 3 (4) 1.0 Others 5 (5) 3 (12) 2 (3) 0.088 Stage IV 34 10 24 0.712 Hematological malignancy, no. (%) 35 (34) 11 (44) 24 (30) Leukemia 11 (11) 5 (20) 6 (8) 0.211 History of Chemotherapy none 3 1 2 oral chemotherapy 5 3 2 Intravenous chemotherapy 96 21 75 Latency> 2months 7 3 4 < 2months, days 12.5 (10-15) 11 (7.7-13.0) 12.5 (10-15) 0.043 ∗ ∗∗ ∗∗∗ <0.05, p<0.01 p<0.001: significant change from baseline values. ED: emergency department. 3.2. Vital Signs and Laboratory Findings. Table 2 shows the 3.3. Source of Infection and Microbiology. The presumed vital signs and laboratory n fi dings of the patients upon ED source of infection and the results of the microbiologic study visit. Patients who died or those who were admitted at the are summarized in Table 3. With regard to the source of ICU had lower systolic and diastolic BP and higher pulse infection, pneumonia was more common in patients who rates than those in the control group. Notably, the mean died or those who were admitted at the ICU (52% vs. 16%, value of the qSOFA was signicfi antly higher in the case respectively; p=0.0004), whereas undetermined origin was group than in the control group (0.88 vs. 0.36, p=0.0003). more frequently observed in the control group than in the With regard to complete blood cell counts, no difference case group (66% vs. 24%, respectively; p=0.0003) was observed between the groups in terms of ANC or Bacteremia was more frequently observed in the case profound neutropenia. However, the case group had a lower group than in the control group (24% vs. 8%, respectively; hemoglobin level, platelet count, and HCO level and a p=0.035). Among the case patients, 6 had bacteremia; 2 higher total bilirubin, creatinine, and C-reactive protein presented with Escherichia coli,2with Pseudomonas aerugi- (CRP) level than the control group. nosa,1 with Klebsiella pneumoniae,and 1 with Staphylococcus 4 Journal of Oncology Table 2: Comparison of vital signs and laboratory findings of 25 case patients and of 79 control patients with neutropenic fever in the emergency department. Characteristics Total (n = 104) Case (n = 25) Control (n = 79) P value Vital signs on presentation ∗∗ SBP, mm Hg 119.1± 21.6 106.7± 24.6 122 (110-135) 0.001 ∗∗∗ DBP, mm Hg 70.8± 14.3 62.0± 14.1 73.6± 13.3 0.0003 PR, beats/min 110 (92-128) 119.7± 18.9 106.0 (88.5-124.7) 0.013 RR, breaths/min 18 (18-20) 20 (18-24) 18 (18-20) 0.252 Body temperature, C 38.4 (38-38.9) 38.5 (38.0-38.1) 38.3 (38.0-38.7) 0.649 ∗∗ Saturation, % 97 (96-98) 96.0 (93.1-97.0) 97 (96-98) 0.001 ∗∗∗ qSOFA 0.49± 0.63 0.88± 0.78 0.36± 0.53 0.0003 Complete blood cell counts Leukocyte count, x10 cells/mL 1120(615-1570) 710 (462-1473) 1170 (702-1625) 0.056 ANC 205 (84-567) 174 (67-335) 222 (101-666) 0.087 Profound neutropenia, no. (%) 29 (28) 10 (25) 19 (24) 0.123 ∗∗∗ Hemoglobin, g/dL 9.6± 2.1 8.1± 2.2 10.3 (9.1-11) < 0.0001 3 ∗∗ Platelet, x10 /𝜇 l 95 (52-178) 52 (27-114) 123 (68-188) 0.002 Other laboratory findings ∗∗∗ CRP, mg/dL 5.5 (3-12.6) 10.2 (6.5-17.7) 4.0 (2.2-9.5) < 0.0001 Lactic acid, mmol/L 1.9 (1.4-2.5) 2.15 (1.4-5.0) 1.75 (1.4-2.35) 0.126 Glucose, mg/dL 131 (112-161) 159± 55.4 129 (112-147) 0.106 Total bilirubin, mg/dL 0.7 (0.5-1.1) 0.9 (0.5-1.2) 0.6 (0.4-0.9) 0.029 ∗∗ Creatinine, mg/dl 0.77 (0.62-0.96) 0.97 (0.74-2.01) 0.72 (0.62-0.89) 0.001 ∗∗∗ Albumin, g/dL 3.5 (3.2-3.8) 3.1± 0.4 3.7 (3.3-3.8) 0.0004 Arterial blood gas pH 7.47 (7.44-7.49) 7.46(7.43-7.49) 7.47± 0.03 0.124 PCO ,mm Hg 31.5± 5.7 30.6± 8.1 31.9± 4.6 0.334 PO , mm Hg 81.2 (73.7-94.8) 78.7 (69.6-95.9) 81.6 (78.8 -91.4) 0.402 − ∗∗∗ HCO , mmol/L 22.7 (20.8-24.9) 20.2± 4.8 23.4± 2.8 0.0002 SpO , mm Hg 96.7 (95.3-97.7) 96.2 (94-97.5) 96.8 (95.5-97.7) 0.150 ∗ ∗∗ ∗∗∗ <0.05, p<0.01 p<0.001: significant change from baseline values. qSOFA: quick sepsis-related organ failure assessment; ANC: absolute neutrophil count; CRP: C-reactive protein. aureus. No resistant bacteria, such as extended-spectrum𝛽 - rate was 12% (12 out of 104 patients), and 5 patients with DNR lactamase (ESBL)-producing Enterobacteriaceae, multidrug- order were not admitted at the ICU and then died within 24 resistant P. aeruginosa, or methicillin-resistant S. aureus, were hours of ED visit. observed in the case group. Among the control patients, 6 had bacteremia; 3 presented with E. coli,1 with K. pneumoniae, 3.5. Predictive Factors for ICU Admission or Mortality. Table 4 1with Enterobacter,and 1 with Streptococcus agalactiae,of shows the variables associated with poor prognosis in patients which 2 tested positive for ESBL. with cancer who presented with febrile neutropenia at the ED based on a simple logistic regression analysis. In the 3.4. Treatment and Outcome. Table 3 shows the treatment at multiple logistic regression analysis, the independent pre- the ED and clinical outcomes. With regard to antimicrobial dictors signicfi antly correlated with ICU admission, and treatment, 20% of the patients were treated with combination mortality was significantly associated with the qSOFA (odds therapy. Anti-pseudomonal 𝛽 -lactam antibiotics (cefepime ratio [OR]: 4.62; 95% confidence interval [CI]: 1.17–18.22; and piperacillin tazobactam) were used empirically in 65% p=0.285), hemoglobin level (OR: 0.51; 95% CI: 0.33–0.78; and 87% of the case and control patients, respectively. The p=0.002), total bilirubin level (OR: 7.69; 95% CI: 1.29–45.8; median time from ED presentation to the start of antibiotic p=0.025), and respiratory tract infection (OR: 29.65; 95% CI: therapy was 107 minutes, and no difference was observed 3.81–230.7; p=0.0012) between the groups in terms of the latency of the rfi st dose of antibiotics. With regard to clinical outcomes, vasopressor was used 4. Discussion in 15% of the patients and in 6% of the patients who were intubated at the ED. Moreover, 20 out of the 104 (20%) Two models were used to predict the outcome of febrile patients were admitted at the ICU. The in-hospital mortality neutropenic episode. Talcott et al. [8] have established a Journal of Oncology 5 Table 3: Comparison of source of infection and treatment outcome of 25 case patients and of 79 control patients with neutropenic fever in the emergency department. Characteristics Total (n = 104) Case (n = 25) Control (n = 79) P value ∗∗∗ Source of infection, no. (%) 26 (25) 13 (52) 13 (16) 0.0004 Respiratory tract 9 (9) 3 (12) 6 (8) 0.446 Urinary tract 6 (6) 1 (4) 5 (6) 1.0 Gastrointestinal tract 2 (2) 1 (4) 1 (1) 0.424 Hepatobiliary tract 3 (3) 1 (4) 2 (3) 0.565 ∗∗∗ Skin and soft tissue 58 (26) 6 (24) 52 (66) 0.0003 Unknown Bacteremia, no (%) 12 (12) 6 (24) 6 (8) 0.035 Combination therapy, no (%) 21 (20) 8 (32) 13 (16) 0.093 Time from ED visit to antibiotics, min 107 (83-135) 101 (85-119) 110.5 (83-139) 0.324 Inappropriateness of antibiotics, no (%) 1 out of 7 1 out of 11 1.0 Use of G-CSF, no. (%) 58 (56) 14 (56) 44 (56) 0.978 ∗∗∗ Use of vasopressor, no. (%) 16 (15) 14 (56) 2 (3) < 0.0001 Intubation, no. (%) 6 (6) 6 (24) 0 ICU care, no. (%) 20 (19) 20 (80) 0 DNR order, no. (%) 7 (28) 0 Hospital days 7 (5-12) 11 (6.7-22) 7 (4-10.7) 0.010 In-hospital death, no (%) 12 (12) 12 (48) 0 ∗ ∗∗ ∗∗∗ <0.05, p<0.01 p<0.001: significant change from baseline values. ED: emergency department; G-CSF: granulocyte-colony stimulating factor; ICU: intensive care unit; DNR: do not resuscitate. Table 4: Logistic regression analysis of prognostic factors in cancer patients with febrile neutropenia in the emergency department. Simple logistic analysis Multiple logistic analysis Characteristics OR (95% CI) P value OR (95% CI) P value Vital signs on presentation ∗∗∗ SBP, mm Hg 0.95 (0.93-0.98) 0.0005 ∗∗∗ DBP, mm Hg 0.94 (0.90-0.97) 0.0003 PR, beats/min 1.02 (1.00-1.05) 0.011 ∗∗ Saturation, % 0.84 (0.71-1.00) 0.002 qSOFA 4.62 (1.17-18.22) 0.285 Laboratory findings on presentation ∗∗ Hemoglobin, g/dL 0.51 (0.33-0.78) 0.002 3 ∗∗ Platelet, x10 /𝜇 l 0.99 (0.98-0.99) 0.002 ∗∗∗ CRP, mg/dL 1.09 (1.03-1.15) 0.0006 Total bilirubin, mg/dL 7.69 (1.29-45.8) 0.025 ∗∗∗ Creatinine, mg/dl 3.52 (1.48-8.37) 0.0004 ∗∗∗ Albumin, g/dL 0.17 (0.06-0.50) 0.0004 Bacteremia, no (%) 3.84 (1.11-13.2) 0.036 Arterial blood gas − ∗∗∗ HCO , mmol/L 0.77 (0.66-0.90) 0.0002 Infection focus, no. (%) ∗∗ Respiratory tract 29.65 (3.81-230.7) 0.0012 ∗ ∗∗ ∗∗∗ <0.05, p<0.01 p<0.001: significant change from baseline values. CI:confidence interval;OR: odds ratio. clinical prediction rule based on clinical features; however, seven independent prognostic factors [5]. The MASCC risk- the model requires information that included tumor response index score has been internationally validated under various to chemotherapy, which is not easily determined at the ED. clinical conditions [9, 10]. However, it includes variables, Then, the Multinational Association of Supportive Care in such as burden of illness, severity of symptoms, and history Cancer (MASCC) developed a scoring system based on of fungal infection, which could be obtained only through 6 Journal of Oncology a detailed review of the patient’s medical history or might variables associated with unfavorable outcomes in our study be aec ff ted by the subjective judgement of the physician. were also the components of the full SOFA, which include Therefore, the use of the models is limited in the ED. hypotension, platelet count, and bilirubin and creatinine level. To the best of our knowledge, only a few studies [11–13] This study has several limitations. First, this is single- that aimed to identify independent factors associated with the center retrospective study. Moreover, it is possible that the serious complications of febrile neutropenia in patients with significant prognostic factors related to ICU admission or cancer have been conducted in ED settings. In 2009, Moon et in-hospital mortality were not identified due to the small al. have reported that laboratory parameters, such as a platelet sample size of the study. For instance, other studies have count< 50,000/mm , serum CRP level> 10 mg/dL, and pul- identified chronic obstructive pulmonary disease (COPD) monary infiltration on chest radiography, were independent [16], leukemia [17], polymicrobial bacteremia [18], and inap- factors that can predict the development of complications propriateness of antimicrobial therapy [19] as independent [12].In 2013, Lynn et al.have also shown the association of risk factors. However, only 8%, 11%, and 12% of the enrolled pneumonia, a platelet count≤ 50,000/mm and the latency patients in our study had COPD, leukemia, and bacteremia, of the rfi st dose of antibiotics in the ED with serious compli- respectively. The appropriateness of using empirical antibi- cations [13]. Our study also aimed to identify the risk factors otics was only evaluated in 17% of the study population. that can predict ICU admission and mortality in patients Emergency physicians must identify patients who are at with cancer who presented with febrile neutropenia at the risk because the prognosis of patients with severe infection ED. Nevertheless, there are two important differences from depends on their initial management. The qSOFA and the the others. Unlike other studies that only enrolled patients presence of pneumonia can be a useful bedside tool for with an ANC< 500/mm , the present study included patients patients with cancer who present with febrile neutropenia in 3 3 with an ANC between 500/mm and 1,000/mm .The risk the ED. The results of the present study may help emergency of developing clinically important infection increases with physicians identify high-risk patients, thus preventing the the decrease in neutrophil count below 500/mm .Moreover, development of complications by ordering prompt blood cul- individuals with prolonged neutropenia (> 7 days) are at ture and subsequently administering broad-spectrum antibi- higher risk [14]. However, this is not significant for emergency otics. physicians because neither the duration of nor the course of neutropenia is predictable in patients with cancer who visit the ED, and this can only be determined retrospectively. Data Availability Therefore, we included patients with neutropenia (ANC < The data used to support the findings of this study are 1,000/mm ) [15] to prevent overlooking patients who are at available from the corresponding author upon request. risk. Surprisingly, 4 of the 12 patients who died in our study had an ANC> 500/mm . The second difference is that our study did not only focus Additional Points on chemotherapy-induced neutropenia. In fact, it included all Key Messages. (1) TheqSOFA can beauseful bedside tool for causes of neutropenia in patients with cancer. Neutropenia patients with cancer who present with febrile neutropenia at can develop in patients with cancer because of the dis- the ED. ease itself that involves the bone marrow. However, severe infection can also cause neutropenia. Because the present study aimed to identify the prognostic factors of febrile Conflicts of Interest neutropenia, which were generally applicable to patients with cancer who visit the ED, we included all causes of neutropenic The authors of this study have no conflicts of interest to episodes. In fact, 15 out of 104 patients in our study presented report. with neutropenia despite the absence of recent chemotherapy within 2 months, of which 8 patients were either admitted References at the ICU or died. Consequently, the possibility of febrile neutropenia and the subsequent development of complica- [1] P.A. Pizzo, K. J.Robichaud,F.A. Gill et al.,“Durationof empiric tions should still be considered in patients with cancer even antibiotic therapy in granulocytopenic patients with cancer,” without the history of recent chemotherapy. American Journal of Medicine,vol.67,no. 2,pp.194–200, 1979. Based on our study, the independent predictors sig- [2] National Institute for Clinical Excellence and the National nificantly correlated with ICU admission, and in-hospital Collaborating Centre for Cancer, “Neutropenic sepsis: mortality was associated with the qSOFA score, hemoglobin prevention and management of neutropenic sepsis in cancer level, total bilirubin, and respiratory tract infection. The patients,” Cardiff: NCC-C, 2012, (Accessed 15 September 2018), qSOFA is a new screening tool for sepsis that has a prognostic http://www.nice.org.uk/nicemedia/live/13905/60864/60864 performance equal to the full SOFA for patients with sus- .pdf. pected infection outside the ICU [7]. According to our study, [3] T. Wilson, T. Cooksley, S. Churchill, J. Radford, and P. Dark, patients with cancer who presented with febrile neutropenia “Retrospective analysis of cancer patients admitted to a ter- and who are likely to have a poor prognosis can be rapidly tiary centre with suspected neutropenic sepsis: Are C-reactive identified at the bedside with the qSOFA. Interestingly, other protein and neutrophil count useful prognostic biomarkers?” Journal of Oncology 7 JournaloftheIntensiveCareSociety,vol. 19, no.2,pp. 132–137, [17] C. Viscoli, P. Bruzzi, and E. Castagnola, “Factors associated 2018. with bacteremia in febrile, granulocytopenic cancer patients,” European Journal of Cancer,vol.30,pp.430–437,1994. [4] A. G. Freifeld, E. J. Bow, K. A. Sepkowitz et al., “Clinical practice guideline for the use of antimicrobial agents in neutropenic [18] M.Ortega, F.Marco,A.Soriano et al., “Epidemiology and patients with cancer: 2010 update by the infectious diseases outcome of bacteraemia in neutropenic patients in a single society of america,” Clinical Infectious Diseases,vol.52, no. 4, institution from 1991-2012,” Epidemiology and Infection,vol. 143, pp. e56–e93, 2011. no. 4, pp. 734–740, 2015. [5] J. Klastersky, M. Paesmans, E. B. Rubenstein et al., “The multi- [19] M. Fletcher, H. Hodgkiss, S. Zhang et al., “Prompt adminis- national association for supportive care in cancer risk index: tration of antibiotics is associated with improved outcomes in a multinational scoring system for identifying low-risk febrile febrile neutropenia in children with cancer,” Pediatric Blood & neutropenic cancer patients,” Journal of Clinical Oncology,vol. Cancer,vol.60,no. 8, pp.1299–1306,2013. 18, no. 16, pp. 3038–3051, 2000. [6] S. Andre, P. Taboulet, C. Elie et al., “Febrile neutropenia in French emergency departments: results of a prospective multicentre survey,” Critical Care,vol.14,no.2, 2010. [7] M.Singer,C.S.Deutschman, C.W.Seymour et al., “eTh third international consensus definitions for sepsis and septic shock (sepsis-3),”JournaloftheAmericanMedicalAssociation,vol.315, pp. 801–810, 2016. [8] J.A. Talcott,R.D. Siegel, R.Finberg,and L.Goldman, “Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule,” Journal of Clinical Oncology,vol.10,no. 2,pp.316–322, 1992. [9] A.Uys,B.L.Rapoport,H.Fickl, P. W.A.Meyer, and R. Ander- son, “Prediction of outcome in cancer patients with febrile neutropenia: comparison of the multinational association of supportive care in cancer risk-index score with procalcitonin, C-reactive protein, serum amyloid A, and interleukins-1𝛽 ,-6, -8 and -10,” European Journal of Cancer Care,vol.16,no. 6,pp. 475–483, 2007. [10] E. P. Hui, L. K. S. Leung, T. C. W. Poon et al., “Prediction of outcome in cancer patients with febrile neutropenia: a prospective validation of the Multinational Association for Supportive Care in Cancer risk index in a Chinese population and comparison with the Talcott model and artificial neural network,” Supportive Care in Cancer,vol. 19, no.10,pp.1625– 1635, 2011. [11] J.H. Lim, H.Kim, W. G.Choi,K.H.Kim,D.W. Shin,and M. H. Lee, “Outcomes in 102 patients that present to the emergency department with chemotherapy-induced febrile neutropenia,” Turkish Journal of Hematology,vol.28, no. 3,pp.193–197, 2011. [12] J.M.Moon and B.J.Chun, “Predictingthe complicated neutropenic fever in the emergency department,” Emergency Medicine Journal,vol.26,no. 11, pp.802–806,2009. [13] J. Lynn, K. Chen, Y. Weng, and T. Chiu, “Risk factors associated with complications in patients with chemotherapy-induced febrile neutropenia in emergency department,” Hematological Oncology, vol. 31, no. 4, pp. 189–196, 2013. [14] S. Ahn, Y.-S. Lee, Y.-H. Chun et al., “Predictive factors of poor prognosis in cancer patients with chemotherapy-induced febrile neutropenia,” Supportive Care in Cancer, vol.19,no.8, pp. 1151–1158, 2011. [15] US Department of Health and Human Services, National Institutes of Health, National Cancer Institute, Common terminology criteria for adverse events (CTCAE), https://ctep .cancer.gov/protocoldevelopment/electronic applications/docs/ CTCAE v5 Quick Reference 5x7.pdf (Accessed on March 22, 2018). [16] J. Klastersky, M. Paesmans, and A. Georgala, “Outpatient oral antibiotics for febrile neutropenic cancer patients using a score predictive for complications,” Journal of Clinical Oncology,vol. 24, no. 25, pp. 4129–4134, 2006. 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