original article interventions to improve emergency

Introduction

Community-acquired pneumonia (CAP) is theleading cause of death from infectious disease inour setting (8-14% of cases) and the leadingcause of severe sepsis (SS) and septic shock in theemergency department (ED)1-3. In Spain the inci-dence is around 2-5 cases per 1000 inhabitants /year (15-35 cases per 1000 inhabitants / year intimes of viral epidemics, patients > 65 years andin patients with chronic or toxic habits)3-5. Of all

radiologically confirmed CAP, 75% are attended inEDs at some point, which highlights the role ofthe emergency physician (EP) in the initial man-agement of these processes, with impact on evo-lution, morbidity and mortality1,3,6. There is greatvariability between centers and even colleagues inthe diagnostic and therapeutic approach andmanagement of CAP patients7,8, but the applica-tion or implementation of clinical practice guide-lines (CPG) is known to improve care, treatmentand prognosis of these patients5,9,10. EPs must rap-

Emergencias 2013; 25: 379-392 379

ORIGINAL ARTICLE

Objectives: To determine the impact of emergency-department interventions based onclinical practice guidelines for treating community-acquired pneumonia by analyzingand comparing management decisions (discharge vs admission; adequacy and timing ofantibiotic treatment; additional tests ordered), results over time (until patient’s conditionstabilized, duration of hospital stay, emergency department revisits), and mortality(before and after interventions and up to 5 years).Methods: Prospective, pre and postintervention study of cases between January 1,2008, and July 31, 2012, in 4 phases (2 periods before introduction of interventions and2 periods afterwards).Results: In the patient groups just after introduction of the guidelines-basedinterventions and at the end of the study, time until the patient was stabilized decreased(by 0.54 days, P<.001), and hospital stay was shorter (by 2.25 days, P<.001). Mortalityalso fell: in-hospital mortality decreased from 20% to 4.3% (P<.001), and 30-daymortality decreased from 15% to 5.5%, P=.003). Early, adequate use of antibioticsincreased, and the total time on antibiotics decreased (by 2.25 days); time onintravenous antibiotics also decreased (by 1.96 days) (all comparisons, P<.001). Thepneumonia severity index (PSI) and biomarkers were helpful for making decisions toadmit or discharge patients (P<.001).Conclusion: After implementation of clinical practice guidelines and use of the PSI, theemergency care of patients with community-acquired pneumonia improved.[Emergencias 2013;25:379-392]

Keywords: Community-acquired pneumonia. Emergency health services. Clinicalpractice guidelines. Biomarkers. Procalcitonin. Pneumonia Severity Index. Antibiotic.Mortality.

CORRESPONDENCE:Agustín Julián JiménezServicio de UrgenciasHospital Virgen de la SaludAvda. Barber, 3045004 Toledo, SpainE-mail: [email protected]

RECEIVED:17-3-2013

ACCEPTED:29-4-2013

CONFLICT OF INTEREST:The authors declare no conflictof interest in relation with thepresent article.

ACNOWLEDGEMENTS:The authors wish to thank thedepartments of admission,documentation andMicrobiology, ComplejoHospitalario de Toledo, for helpin data collection and draftingthe manuscript; and all thephysicians whose adherence tothe guidelines made this studyposible as well as improving theattention of patients withpneumonia.

Interventions to improve emergency-departmentmanagement of community-acquired pneumonia

AGUSTÍN JULIÁN-JIMÉNEZ1, RAQUEL PAREJO MIGUEZ2, RAFAEL CUENA BOY3,MARÍA JOSÉ PALOMO DE LOS REYES1, NATIVIDAD LAÍN TERÉS1, AGUSTÍN LOZANO ANCÍN1

1Servicio de Urgencias, Hospital Virgen de la Salud, Toledo, Spain. 2Centro de Salud Pedro Fuente de Bargas,Toledo, Spain. 3Farmacología Clínica, Complejo Hospitalario de Toledo, Toledo, Spain.

idly decide when and where to admit CAP pa-tients and what care these patients require. Theadequacy or otherwise of these decisions affectsthe prognosis of the patient as do the lab testsand microbiological studies requested, the choiceof antimicrobial regimen and the use of health re-sources5,11. Along with the decision on where toplace the patient, the early administration of anappropriate antimicrobial regimen and the hemo-dynamic measures and respiratory support neces-sary are the most important factors in the evolu-tion and mortality of these patients12,13. In ourexperience5,14, and that of other authors9,10,15,16, theimplementation of a CPG is the main tool to de-crease clinical variability and improve manage-ment of the infectious process. But how long doesthe beneficial effect of implementing a CPG last?Is it equally beneficial for all patients regardless ofseverity level or admission? After a preliminarystudy in 2008 in our ED, we found that there wasgreat variability in practice with very poor adhe-sion to the recommended CPG17. That year wepublished "Management of CAP in the ED"18 pre-pared by a working group composed of membersof SEMES (Spanish Society of Emergency Medi-cine) and SEPAR (Spanish Society of Pneumologyand Thoracic Surgery) in order to serve as a CPGfor EPs and thus reduce clinical variability and im-prove the comprehensive management of CAP inthe ED1. Three years later (2011)19, that documentwas updated by the SEMES infections group (IN-FURG-SEMES) according to new international12

and national recommendations4 adapted for Span-ish ED use. The aim of this study was to evaluatethe impact of interventions, with implementationof CPGs referred to above (SEMES-SEPAR 2008and INFURG-SEMES 2011), on the care process ofCAP, comparing indicators (appropriate dischargeor admission, early antibiotics, complementarytests) and outcomes (length of hospital stay andclinical stabilization, mortality, revisits to the ED,etc.) before and after each intervention and sincethe beginning in 2008 to the end of the study in2012.

Method

We performed an observational, single-blindstudy with prospective pre- and post-interventionfollow up of patients in four phases or groups(G1, G2, G3 and G4): before and after two inter-ventions over five years, involving the implanta-tion and / or refresher courses on the CPG "Man-agement of CAP in the ED" (SEMES-SEPAR 200818

and INFURG-SEMES 201119) along with sessionsfor all EPs and residents of the center, as de-scribed below. The study followed the samemethodology as the previous one performed withonly G1 and G2.It was performed at the Hospital of Toledo, a

786-bed tertiary level center serving 437,000 peo-ple. The ED had an area for internal medicinearea serviced by our own staff EPs and residentsof various medical specialties. During the years2008-2012 it served an average 416-446 visits /day and the incidence of CAP in patients > 15was 0.62%-0.98% of all patients seen in the ED(3.21 – 4.12 cases per 1000 inhabitants / year, re-spectively ). CAP patients could be dischargedfrom the ED (including those who remained un-der observation for 24 hours), be admitted to theintensive care unit (ICU) or the short stay unit(SSU) for <72 hours, or the departments of pul-monology, internal medicine or geriatrics and, toa lesser extent, other services with specialists oncall 24 hours (e.g. nephrology and oncology orhematology). EPs made the admission decisionand the initial area of care, except for ICU admis-sions. Discharge from the ED was determined bythe ED physician, referring some to the patient’sprimary care physician or to a specialist accordingto the characteristics of each patient.The study period and population was organ-

ized by two independent collaborators, experi-enced EPs who participated in the drafting of theCPG, without other doctors knowing this.Throughout the study they assessed the initial eli-gibility of ED cases from January 1, 2008 to July31, 2012, to include 200 consecutive patients ateach stage or group (G): G1 or pre-interventionfrom 1/1/2008 to 30/09/2008; G2 or post-inter-vention from 04/10/2008 to 1/8/2009 (from02/08/2009 until 1-1-2011 patients were not in-cluded – washout period – after the first interven-tion which also coincided with the influenza AH1N1 pandemic), G3 or prior to the 2nd interven-tion from 2/1/2009 to 15/9/2011, and G4 from29/11/2011 to 31/7/2012. To be included, pa-tients had to meet the following criteria: be agedless than 15 years and diagnosed with CAP (de-fined as the existence of a compatible acutesymptoms including cough, dyspnea, fever, pleu-ritic chest pain, altered level of consciousness etc.,and its radiological demonstration of new lung in-filtrates) in the ED by the physician responsible.Immunocompromised patients were excluded (in-fection by human immunodeficiency virus, solidviscera transhospital ward, splenectomy, treatedwith 10 mg or more of prednisone daily or equiv-

A. Julián-Jiménez et al.

380 Emergencias 2013; 25: 379-392

alent for more than 30 days, or treated with otherimmunosuppressive agents) and patients hospital-ized in the previous 14 days. The two collabora-tors also assessed final eligibility, removing pa-tients who at 30 days did not meet the criteria fora final diagnosis of CAP (codes 481, 482, 483,485, 486 and 507 of the International Classifica-tion of Diseases 9th revision clinical Modification:ICD-9CM), and who received a final diagnosis oftuberculosis, cases of viral etiology, flu, fungal in-fection or lung abscess (corresponding to codes480, 487, 484 and 513 of the ICD-9CM). Also ex-cluded were patients diagnosed with a secondepisode of CAP during the entire period. Thestudy met the ethical standards of our hospitaland was approved by the Clinical Research EthicsCommittee. The monitoring of all patients wasperformed through computerized ED and PCmedical records, with telephone consultation withthe patient or family (subject to consent) or PCdoctor on occasions.Study interventions consisted of CPG imple-

mentation and evaluation of adherence. Between1-3 October 2008 (1st intervention) and 15-25November 2011 (2nd intervention) the CPG weredistributed, both complete1,3 and in pamphlet for-mat18,19, and training sessions were held for all EPsand residents. Both times the physicians were re-quested to consistently apply all the CPG recom-mendations. Furthermore, in the second interven-tion we showed them the results of the first andhow the management of CAP had improved inour ED. Also, and specifically, we included trainingon the usefulness of both the systematic applica-tion of the Pneumonia Severity Index (PSI)16 andother criteria11 which included biomarkers20,21.The two independent collaborators, unknown tothe rest of the doctors, were responsible for ap-plying the criteria for evaluation of patients. Toevaluate and analyze the performance of doctorsin each case "proper management" was definedas agreement with each of the measures andtreatments as recommended in the CPG, and"mismanagement " if not. This assessment wasperformed independently for the request for com-plementary studies from the ED (laboratory andmicrobiological tests, and biomarkers), for theprognostic assessment and decision on destina-tion according to the modified PSI11 (additionalcriteria) and to the choice and administration oftreatment in the ED.We excluded cases in which there was a dis-

crepancy between the two raters. CAP was de-fined as severe and needing ICU assessment whenpatients fulfilled one major or three minor criteria

established by ATS / IDSA (American Thoracic So-ciety – Infectious Diseases Society of America)200712. To assess the severity and prognosis of pa-tients with CAP and the decision on admission weused the PSI, whose risk groups were created ac-cording to those proposed by the original au-thors22 to which various additional criteria were in-cluded (Table 1 ) (also explained and transmittedin all training sessions) according to the recom-mendations by SEMES-SEPAR 2008 and INFURG-SEMES 2011. Thus, all patients belonging to riskgroups PSI IV- V and those belonging to PSI riskgroups I- III with any of the risk factors or criteriain Table 1 were considered as those requiring hos-pital admission.We collected all the socio-demographic, clini-

cal, exploratory, analytical and radiological vari-ables included in PSI22, in the 2007 ATS/IDSA12 cri-teria for ICU admission and in the criteria for thedefinition of sepsis, SS and Septic shock accordingto the expert conference 200123. We calculatedthe PSI value and grade, the original Charlson24

index weighted for age and the presence of sep-sis, SS, Septic shock and severe CAP. The follow-ing variables were added: previous antimicrobialtreatment (within 72 hours before ED visit), physi-cian profile (resident, emergency physician, otherspecialists), presence of diabetes or chronic ob-structive pulmonary disease (COPD ), the numberof comorbidities (including those contained in thePSI plus diabetes and COPD), the lab tests indicat-ed by the CPG (including in each case bloodcount, coagulation, biochemistry and blood gas-es), appropriate microbiological tests (blood, urineantigen assays, sputum), pulse oximetry (O2 satu-ration), C reactive protein (CRP) and procalcitonin(PCT), the administration and time (within 4hours) of an antibiotic, the choice of antibioticand appropriate dosage, change in antibiotic regi-men in patients admitted within 48 hours or inthe home dosage for patients discharged homewithin 72 hours after discharge, the overall treat-ment duration and any adverse effects and com-plications. Finally, as outcome measures, we in-cluded: ED revisits and readmission within 30days, clinical stabilization times (according to thecriteria of Halm and Teirstein25) and hospital stay,microbiological diagnosis when available, the pa-tient's initial destination (discharge, observation,SSU, hospital ward or ICU). Re-assessment within24-72 hours of discharged patients, clinical andradiological status at 3-6 weeks and mortality indischarged patients, hospitalized patients or thoseadmitted to the ICU, and overall mortality at 30days.

INTERVENTIONS TO IMPROVE EMERGENCY-DEPARTMENT MANAGEMENT OF COMMUNITY-ACQUIRED PNEUMONIA

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In the statistical analysis we used means andstandard deviations (SD), ranges, medians andpercentages, as appropriate, to describe the de-mographic, clinical, evolution and treatment ofpatients in the four phases. In addition, to esti-mate population values, 95% confidence intervals(CI) of averages and percentages were calculated.Comparisons between groups (G1-G4) were per-formed using ANOVA with Tukey post hoc analy-sis and, where appropriate, equality of means(Welch test), Student's t test, Mann Whitney Utest, chi-square and Fisher 's exact test, depend-ing on both the number of groups to be com-pared (two or more) and the type of measure-ment of the variable (scale, ordinal or nominal). Inorder to control for possible confounders, weused an unconditional logistic regression model.As dependent variables we used in-hospital mor-tality and mortality at 30 days, and as independ-ent variables we used the phase or group (G1-G4), age, number of comorbidities, the Charlsonindex, the PSI group and coexistence of sepsis, SSand Septic shock (variables that could influencemortality and heterogeneously distributed be-tween phases). Thus, we calculated the odds ratio(OR) for mortality and phase with their 95% CI.With the same purpose of controlling for con-founders, we also used a multiple linear regressionmodel to determine whether the possible associa-tion between overall duration of antibiotic and in-travenous therapy and group (G1-G4) remainedafter controlling for patient destination (discharge,observation, SSU, hospital ward or ICU) and PSIrisk group. The estimation and comparison be-tween groups (G1-G4) to the end of admission

(hospital stay) and the time until clinical stabiliza-tion were done using Kaplan – Meier method andlog-rank test. Also, using a Cox proportional haz-ards model (with Schoenfeld study of residuals tocompare their applicability), we estimated hazardratios (HR) of these results (end of admission andmedical stabilization) for the groups G2-G4 versusG1, adjusted for PSI group and destination of thepatient. Statistical analysis was performed withIBM – SPSS Statistics 19 for Windows and differ-ences with a p value of < 0.05 were consideredstatistically significant.

Results

200 patients were included in each of the 4groups (G1-G4) after excluding, respectively, 52,37, 42 and 29 cases with no diagnosis of CAPduring follow up according to the defined codes.Similarly, we excluded 5, 3, 3 and 6 patients inwhom there was disagreement between the eval-uators on performance in the ED. There were nosignificant differences in the profile of the physi-cian in the ED (emergency physician / resident /other specialists) between the 4 groups with ratiosof 41-52-6% vs 42-54-3% vs 46-50-4% vs 43-53-4%, respectively, p = 0.238.Table 2 shows the socio-demographic, clinical

and severity characteristics, comorbidities, Charl-son index (original and weighted), and distribu-tion of all study patients as classified by the PSI.There were no differences between groups formost variables except for the variable taking an-tibiotics within 72 hours, a greater proportion ofnursing home patients with COPD, increasedCharlson index and PSI and more patients withSS criteria in group G4. There were no signifi-cant differences between groups in relation toradiological presentation (multilobar and / or bi-lateral CAP and pleural effusion) or laboratory orblood gas parameters (Table 3), except for agreater proportion of patients with PaO2 lessthan 60 mmHg in the G4 and G3 versus G2 andG1 (p = 0.010) and a greater proportion of renalfailure and hyponatremia in G4. Final microbio-logical confirmation of the diagnosis did showsignificant differences between G1 and G2 versusG3 and G4 (12%, 15%, 40.5% and 38.5%, re-spectively, p < 0.0001), but not in the distribu-tion of pathogens (p = 0.12) (Table 4). As re-f lected in Table 3, there were s ignif icantdifferences between G1-G4 in ED request forCRP and / or PCT (19.3%, 90%, 40% and93.5%, respectively, p < 0.001). However, and


382 Emergencias 2013; 25: 379-392

Table 1. Additional criteria and risk factors that condition thedecision to admit or discharge patients according torecommendations of the clinical practice guidelines used– Respiratory failure with PaO2 < 60 mmHg or O2 saturation by pulseoximetry < 90%.

– Evidence of existing comorbidity of the decompensated ED patient.– Existence of pleural effusion (encapsulated or > 2 cm on chest x-rayin lateral decubitus position).

– Radiological multilobular involvement (� 2 lobes ipsilateral or bila-teral involvement).

– CAP with criteria of severe sepsis or septic shock.– Great probability or suspicion of bacteremia due to clinical situationand/or biomarkers (CRP � 90 mg/ml and/or Procalcitonin > 1ng/ml).

– Existence of situations or factors that impede correct treatment.Such as oral intolerance, social problems (dependent patient wi-thout available caregiver, psychiatric disorders, alcohol abuse, etc.).

– Failure to respond to previous antibiotic treatment (72h after initia-ting adequate antibiotic therapy before clinical or radiological dete-rioration).

PaO2: partial arterial pressure of oxygen; ED: Emergency Department;CAP: community acquired pneumonia; CRP: C-reactive protein.Adapted from reference 5.

perhaps because of their greater use in G2 andG4, the levels of CRP and PCT were lower inthese groups with respect to G1 with p < 0.0001in both cases. Table 3 also shows greater magni-tude of both markers in PSI groups III. On com-paring CRP means, significant differences werefound between subgroups of patients accordingto clinical severity criteria (p < 0.001). Similarly,on comparing PCT means, significant differenceswere found (p < 0.001) between patients withand without sepsis, SS, Septic shock and severeCAP. Significant differences in CRP and CPT lev-els were also found between patients who diedwithin 30 days and those who survived (Table5). Moreover, in all study patients we confirmed

the existence of a significant relationship (p< 0.001) between request for biomarker testsand early administration (< 4 hours) of antibi-otics in the ED (81.6% vs 67.8%), with thechoice of an appropriate antibiotic regimen(87.8% vs 65.6% ), with the right choice of pa-tient destination (87.5% vs 71.2%), with the re-quest for appropriate lab tests (92% vs 66.6%)and the request for the appropriate microbiolog-ical studies (86.8% vs 61.4%), reflecting compli-ance and adherence to all CPG.In relation to antimicrobial administration and

the guidelines (Table 6), there was a clear differ-ence between groups (G1-G4) in all cases(p < 0.001) and large proportional differences in


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Table 2. Socio-demographic and clinical characteristics of patients treated in the Emergency Department (ED) for community-acquired pneumonia (CAP)

Characteristics of patients Group 1 Group 2 Group 3 Group 4 P-value P-value(n = 800) n = 200 n = 200 n = 200 n = 200 Intergroup1 Groups 1 and 42

n (%) n (%) n (%) n (%)

Demographic dataAge (years) [mean (SD)] 56 (22) 58 (22) 55 (21) 59 (21) 0.204 0.639Median (range) 58 (18-99) 60 (18-99) 56 (15-98) 60 (19-98)

Male sex 118 (59%) 122 (61%) 125 (62.5%) 130 (65%) 0.653 0.129Origin of residence 19 (9.5%) 20 (10%) 25 (12.5%) 34 (17%) 0.087 0.027AB taken within 72 hours 47 (23.5%) 65 (32.5%) 75 (37.5%) 84 (42%) 0.001 < 0.0001ComorbiditiesBlood cancer 13 (6.5%) 12 (6%) 17 (8.5%) 14 (7%) 0.783 0.500Liver disease 6 (3%) 11 (5.5%) 6 (3%) 12 (5.5%) 0.299 0.114Congestive heart disease 26 (13%) 29 (14.5%) 31 (15.5%) 33 (16.5%) 0.788 0.119Cerebrovascular disease 17 (8.5%) 14 (7%) 17 (8.5%) 15 (7.5%) 0.926 0.427Chronic kidney disease 14 (7%) 14 (7%) 15 (7.5%) 17 (8.5%) 0.933 0.354Diabetes 27 (13.5%) 33 (16.5%) 34 (17%) 39 (19.5%) 0.453 0.069COPD 30 (15%) 38 (19%) 39 (19.5%) 47 (23.5%) 0.198 0.021Number Comorbidities [mean (SD)]* 0.68 (0.80) 0.77 (0.83) 0.81 (0.85) 0.91 (0.91) 0.058 0.036Median (range) 1 (0-4) 1 (0-4) 1 (0-4) 1 (0-5)

Charlson index [mean (SD)] 1.29 (1.41) 1.31 (1.31) 1.59 (1.49) 1.63 (1.44) 0.021 0.086Median (range) 1 (0-6) 1 (0-6) 1 (0-7) 1 (0-7)

Charlson index weighted [mean (SD)]* 2.90 (2.73) 3.05 (2.66) 3.21 (2.81) 3.42 (2.77) 0.277 0.240Median (range) 2 (0-10) 3 (0-10) 3 (0-10) 3 (0-11)

Clinical and severity dataConfusion-alteration of consciousness 22 (11.2%) 28 (14.07%) 26 (13.1%) 30 (15%) 0.712 0.163Hypothermia (temperature < 35 ºC) 14 (7.10%) 14 (7%) 18 (9.1%) 18 (9.1%) 0.790 0.306Criteria for sepsis 129 (64.5%) 138 (69%) 134 (67%) 146 (73%) 0.311 0.067Criteria for severe sepsis 29 (14.5%) 43 (21.5%) 39 (19.5%) 46 (23%) 0.156 0.029Criteria for septic shock 8 (4.12%) 11 (5.52%) 10 (5%) 12 (6%) 0.825 0.359Utilización ventilación mecánica invasivao no invasiva 14 (7.21%) 22 (11%) 19 (9.5%) 24 (12%) 0.364 0.088

SCAP* 43 (21.5%) 48 (24%) 52 (26%) 57 (28%) 0.403 0.100PSIPSI (years) value [mean (SD)] 93 (46) 101 (51) 97 (45) 108 (48) 0.020 0.015Median (range) 85 (17-230) 92.5 (10-268) 90 (17-231) (13-268)

Distribution by PSI group 0.019 0.033PSI I 36 (18%) 38 (19%) 25 (12.5%) 22 (11%) 0.662 0.348PSI II 40 (20%) 26 (13%) 48 (24%) 27 (13.5%) 0.184 0.069PSI III 33 (16.5%) 34 (17%) 30 (15%) 41 (20.5%) 0.346 0.116PSI IV 52 (26%) 43 (21.5%) 50 (25%) 52 (26%) 0.459 0.256PSI V 39 (19.5%) 59 (29.5%) 47 (23.5%) 58 (29%) 0.102 0.079

The percentages exclude the lost data if any. SD: standard deviation; AB: antibiotic; COPD: chronic obstructive pulmonary disease; PSI: PneumoniaSeverity Index; NS: not significant or without sufficient sample. Group 1: Pre-protocol; Group 2: post-protocol group; Group 3: Pre-protocol of the 2ndintervention; Group 4: Post-protocol of the 2nd intervention. * Includes: neoplasia, liver disease, congestive heart disease, cerebrovascular disease,kidney disease, diabetes and COPD. *Charlson Index weighted by age (add a point to the Charlson index value for each decade starting at age 50).*SCAP: severe community-acquired pneumonia (defined in the text). 1Qualitative variables comparison by Chi square and ANOVA with post-hoc Tukeycorrection or non-parametric tests as appropriate for the comparison of means. 2 2 X 2 comparison of groups 1 and 4 by chi squared or Fisher exacttest as appropriate.

the variables that can change and influence thedevelopment, evolution and prognosis of patientswith CAP. Antibiotic administration in the ED, ear-ly administration, the appropriate choice anddosage, and early antibiotic administration with

fluid therapy in cases of SS and Septic shock inthe ED were greater in G2 and G4. Conversely,patients whose antibiotic regimen was initiallychanged was significantly lower in groups G2 andG4. The duration of total antibiotic treatment in


384 Emergencias 2013; 25: 379-392

Table 3. Radiological and gasometric characteristics and laboratory findings in patients with community-acquired pneumonia (CAP)treated in the Emergency Department (ED)

Patient characteristics (n = 800) Group 1 Group 2 Group 3 Group 4 P-value P-valuen = 200 n = 200 n = 200 n = 200 Intergroup1 Groups 1 and 42n (%) n (%) n (%) n (%)

Radiological and gasometric dataInfiltrate 0.627 0.732Unilobar 141 (70.5%) 145 (72.5%) 129 (64.5%) 134 (67%)Multilobar 44 (22%) 42 (21%) 56 (28%) 48 (24%)Bilateral 15 (7.5%) 13 (6.5%) 15 (7.5%) 18 (9%)

Pleural effusion 35 (17.5%) 37 (18.5%) 36 (18%) 49 (24%) 0.253 0.055Arterial pH < 7.35 23 (11.5%) 25 (12.5%) 28 (14%) 33 (16.5%) 0.330 0.094PO2/FiO2 < 250 25 (13.80%) 34 (17.5%) 32 (17%) 39 (19.9%) 0.478 0.075PO2 < 60 mmHg 75 (37.5%) 82 (41%) 88 (44%) 91 (45.5%) 0.010 0.001Laboratory findingsUrea > 64 mg/dl or Cr >1.5 mg/dl 45 (23.43%) 55 (27.63%) 60 (30.6%) 68 (34.2%) 0.117 0.019Sodium < 130 mEq/L 15 (7.81%) 22 (11.2%) 22 (11.2%) 31 (15.6%) 0.117 0.017Blood glucose > 250 mg/dl 22 (11.45%) 26 (13.06%) 28 (14.3%) 29 (14.6%) 0.798 0.223Hematocrit < 30% 20 (10.41%) 16 (8.04%) 25 (12.7%) 22 (11.1%) 0.502 0.470Leukocytosis > 12.000/mm3 114 (59.37%) 132 (66.33%) 116 (58.9%) 133 (66.3%) 0.223 0.094Leucopenia < 4.000/mm3 28 (14.58%) 21 (10.55%) 34 (17.3%) 27 (13.6%) 0.287 0.459Thrombocytopenia < 100.000/mm3 27 (14.06%) 28 (14.07%) 33 (16.8%) 29 (14.6%) 0.848 0.484BiomarkersRequested in the ED 38 (19.3%) 180 (90%) 80 (40%) 187 (93.5%) < 0.0001 < 0.001CRP (mg/L) levels [mean (SD)](all patients) 74.82 (18.72) 58.90 (22.01) 71.63 (25.96) 65.48 (26.99) 0.001 0.242CRP (mg/L) ± SD en PSI I – 45.82 (24.58) 56.78 (22.05) 45.12 (19.26) 0.575 0.262CRP (mg/L) ± SD en PSI II 54.55 (31.34) 51.02 (18.51) 62.28 (26.14) 51.44 (22.99) 0.332 0.812CRP (mg/L) ± SD en PSI III 69.92 (19.69) 49.25 (16.06) 68.18 (36.10) 53.56 (19.94) 0.079 0.179CRP (mg/L) ± SD en PSI IV 78.69 (14.64) 66.46 (18.28) 76.49 (27.08) 73.40 (22.16) 0.139 0.993CRP (mg/L) ± SD en PSI V 78.34 (15.06) 70.04 (20.11) 79.77 (27.44) 76.69 (25.13) 0.261 0.995

PCT (ng/ml) levels [mean (SD)] 4.89 (11.31) 2.51 (12.88) 2.81 (9.56) 2.87 (10.28) 0.229 0.402PCT (ng/ml) ± SD en PSI I – 0.60 (0.32) 1.34 (1.15) 0.76 (0.83) 0.106 0.898PCT (ng/ml) ± SD en PSI II 3.31 (4.47) 1.22 (1.47) 1.55 (1.71) 0.83 (0.56) 0.305 0.039PCT (ng/ml) ± SD en PSI III 3.63 (2.82) 1.31 (1.47) 1.09 (0.87) 1.05 (1.32) 0.136 < 0.001PCT (ng/ml) ± SD en PSI IV 3.79 (4.00) 1.56 (1.31) 2.75 (2.03) 1.48 (1.78) 0.164 0.245PCT (ng/ml) ± SD en PSI V 4.56 (3.65) 5.16 (4.92) 4.78 (6.32) 5.45 (12.92) 0.778 0.913

Group 1: Pre-protocol; Group 2: post-protocol group; Group 3: Pre-protocol of the 2nd intervention; Group 4: Post-protocol of the 2nd intervention.1Qualitative variables compared by Chi squared or Fisher exact test and ANOVA with post-hoc Tukey correction or non-parametric tests as appropriatefor the comparison of means. 22 X 2 comparison of groups 1 and 4 by chi squared or Fisher exact test as appropriate.

Table 4. Confirmed microbiological diagnoses

Total Group 1 Group 2 Group 3 Group 4N = 800 n = 200 n = 200 n = 200 n = 200n (%) n (%) n (%) n (%) n (%)

Not identified 588 (73.5%) 176 (88%) 119 (59.5%) 170 (85%) 123 (61.5%)Streptococcus pneumoniae 123 (15.3%) 11 (5.5%) 48 (24%) 18 (9%) 46 (21%)Legionella pneumophila 20 (2.5%) 3 (1.5%) 7 (3.5%) 4 (2%) 6 (3%)Mycoplasma pneumoniae 21 (2.62%) 3 (1.5%) 7 (3.5%) 3 (1.5%) 8 (4%)Chamydophila pneumoniae 13 (1.62%) 2 (1%) 5 (2.5%) 2 (1%) 4 (2%)Haemophilus influenzae 8 (1.0%) 2 (1%) 3 (1.5%) 1 (0.5%) 2 (1%)Moraxella catarrhalis 2 (0.25%) 0 (0%) 1 (0.5%) 0 (0%) 1 (0.5%)Pseudomonas aeruginosa 11 (1.37%) 2 (1%) 4 (2%) 1 (0.5%) 4 (2%)Staphylococcus aureus 3 (0.37%) 0 (0%) 2 (1%) 0 (0%) 1 (0.5%)Klebsiella pneumoniae 2 (0.25%) 0 (0%) 1 (0.5%) 0 (0%) 1 (0.5%)Gram-negative bacilli 9 (1.12%) 1 (0.5%) 3 (1.5%) 1 (0.5%) 4 (2%)The diagnosis was made by isolation of the pathogen in blood cultures, sputum culture, antigenuria or by serology when the first test was requested inthe ED and seroconversion during follow-up (a comprehensive diagnostic protocol was not defined in all patients for serology extraction, which wascarried out on the basis of clinical and/or epidemiologic suspicion in each case). Group 1: Pre-protocol; Group 2: post-protocol group; Group 3: Pre-protocol of the 2nd intervention; Group 4: Post-protocol of the 2nd intervention.

hospitalized patients was higher in G1 and G3,both globally [G1: 11.8 (3.8), G2: 10.4 (3.3) G3:11.8 (3.7), G4: 9.6 (3.1) days, p < 0.001] as ineach of the groups based on PSI (Table 6). Thesame occurred with the duration of intravenousantibiotic therapy in all patients [G1: 6.8 (4.5),G2: 5.8 (3.0), G3: 7.1 (4.6), G4: 4.8 (2.5) days,p < 0.001] and the PSI subgroups (Table 6). Afteradjusting for group (G1-G4), patient destination(discharge, observation, SSU, hospital ward orICU) and group according to PSI, mean differ-ences remained significant, so that the coefficientfor G2 versus G1 for total time of antibiotic use[–1.56 days on average (95% CI –2.63 to –0.50),p = 0.004] and time of intravenous antibiotic use[–1.37 days (95% CI –2.15 to –0.55), p = 0.001remained different. And also for G4 compared toG1 for the total time of antibiotic use [–2.66 days(95% CI: –3.70 to –1.63), p < 0.001] and intra-venous antibiotic time [–2.25 days (95% CI: –3.03to –1.47), p < 0.001].As for decisions regarding specific care action

(Table 7), there were significant differences in fa-vor of G2 and G4 as to analytical and microbio-logical studies (blood, urinary antigen, sputumculture). There was also a greater number ofchanges in decisions (antimicrobials or destinationof the patient) after interpreting biomarkers in G2and G4 (G1: 10.8%, G2: 26.1%, G3: 10.7%, G4:29.6%, P = 0.007). Finally, it is striking that O2

saturation was not reflected in 12.5% of G1 and11.5% of G3 patients compared to 2% in G2 and1% in G4 (p < 0.001); and these differences weremore pronounced in the PSI I subgroup.Direct discharge from the ED was higher in G1

and G3, while for G2 and G4 in most cases it wasdecided to leave the patient under observationand there was a higher percentage of ICU admis-sions from the ED (Table 8). 35.5% of patients inG1 and 34.5% of G3 had an inappropriate initialdestination (incorrect discharge or admission) ver-sus 3.5% of G2 and 2% of G4 (p < 0.001) ac-cording to PSI recommendations and the addi-tional criteria listed in Table 1. In particular,"incorrect discharge" decreased in the PSI groupIV-V from 25.5% (G1) and 28.9% (G3) to 2%(G2) and 1% (G4) (p < 0.001) and inadequateadmission or discharge in PSI groups I-III de-creased from 44% (G1) and 39.8% (G3) to 5.1%(G3) and 3.4% (G4) (p < 0.001). On the otherhand, both patient follow up 24-72 hours afterdischarge and clinical and radiological at 3-6weeks was significantly higher in G2 and G4(p < 0.001), while the number of ED revisits inthe first 72 hours and 30 days and the rate ofreadmissions among these was lower in G2 andG4, with significant differences (Table 8).Regarding hospital stay times and achieving

clinical stabilization (Halm and Teirstein criteria25)results are listed in Table 8. Median time to clini-cal stabilization in patients admitted to the obser-vation area, SSU and hospital ward was signifi-cantly higher in G1 and G3 than in G2 and G4.After adjusting for PSI group and location this re-sult was sustained for G2 with a HR of 1.548(95% CI: 1.216-1.969, p < 0.001) and for G4with a HR of 1.973 (95% CI: 1.556 to 2.504,p < 0.001), the reference group being G1. Therewere also differences between groups (G1-G4) inthe length of hospital stay (G1: 8.7 ± 5.5, G2:7.6 ± 4.0, G3: 9.4 ± 6.0 and G4: 6.5 ± 4.0 days,p = 0.001). After adjusting for PSI group and des-tination of the patient (discharge, observation,SSU, hospital ward or ICU) using G1 as the refer-ence group, differences remained (p < 0.001) forboth G2 [HR 1.733 (95% CI: 1.278 to 2.351)]and G4 [HR of 2.609 (95% CI: 1.924-3.537)]. Fig-ure 1 shows comparative hospital stay times.Table 9 shows the results related to mortality.

No significant differences were found betweengroups (G1-G4) in patients discharged or admit-ted to the ICU. But there were differences in hos-pital mortality (G1 20%, G2 6.6%, G3 15.6% andG4 4.3%, p = 0.001) and overall mortality at 30days (G1 15%, G2 8.5%, G3 11.5% and G4


Emergencias 2013; 25: 379-392 385

Table 5. Relationship between levels of biomarkers and clinicalseverity and mortality

CRP (mg/L) PCT (ng/ml)Mean (SD) P-value Mean (SD) P-value

Criteria for severe CAP p < 0.001 p < 0.001Yes 78.68 (23.5) 7.99 (10.1)No 58.10 (22.9) 1.42 (1.9)Criteria for sepsis p < 0.001 p = 0.001Yes 68.77 (24.2) 5.16 (11.4)No 53.49 (23.8) 1.62 (2.9)Severe sepsis p < 0.001 p < 0.001Yes 79.04 (25.6) 11.19 (17.3)No 59.71 (22.8) 1.73 (2.5)Septic shock p < 0.001 p < 0.001Yes 82.37 (34.9) 22.83 (22.5)No 63.27 (23.4) 2.77 (6.9)Mortality in the ICU p < 0.001 p < 0.001Yes 60.62 (27.6) 34.80 (25.0)No 89.01 (25.1) 12.00 (18.7)In-hospitalmortality p = 0.040 p < 0.001Yes 76.91 (15.5) 8.83 (7.7)No 68.46 (21.4) 2.34 (2.6)Global mortalityat 30 days p = 0.022 p < 0.001Yes 72.40 (20.1) 15.15 (18.1)No 63.86 (25.4) 2.97 (7.7)CRP: C-reactive protein: PCT: Procalcitonin; SD: standard deviation;CAP: community-acquired pneumonia; ICU: intensive care unit.

5.5%, p = 0.012). These differences were greateron comparing G1 to G4. The results based on PSIgroup are also reflected in Table 9.In addition, incorrect versus correct choice of

antibiotic in the ED was associated with hospitalmortality and overall mortality at 30 days (bothp < 0.001). Moreover, early administration of an-tibiotics in the ED was associated with lower hos-pital mortality (p < 0.001) and overall mortality at30 days (p = 0.003) (data and percentages areshown in Table 10). Finally, a comparison be-tween groups (G1-G4) controlling for related co-variates (age, number of comorbidities, Charlsonindex, PSI group and existence of sepsis, SS orSeptic shock) the differences remained significantfor G2, with p = 0.001 and OR: 0.184 (95% CI:0.067-0.511) and G4, with p < 0.0001 and OR:0.078 (95% CI: 0.022 to 0.269). And similarly foroverall mortality at 30 days adjusted for the samecovariates, differences were also found for G2,with p = 0.001 and OR: 0.284 (95% CI: 0.133-0.603) and G4, with p < 0.001 and OR: 0.141(95% CI: 0.060 to 0.331).

Discussion

The implementation of a CPG for CAP in anED, including biomarkers of inflammation and in-fection20,21, the PSI16 as a prognostic scale and dif-ferent additional criteria for assessing severity11

and admission/discharge decision has proved tobe an effective tool for reducing the variability ofimportant decisions taken by emergency physi-cians (ordering analytical and microbiologicalstudies, early administration of appropriate thera-py and appropriate destination)5. It has also im-proved overall mortality, decreased the rate of in-appropriate discharge and admission, reducedthe time required to achieve stabilization andhospital stay time5,9,10. But, how long is this bene-ficial effect maintained after implementation ofthe CPG? Is it equally useful for all patients re-gardless of severity and treatment site? In anycase, after the implementation of a CPG, oneshould evaluate both the overall impact of eachvariable and indicator, to identify areas for im-provement and to confirm achievement of theobjectives.


386 Emergencias 2013; 25: 379-392

Table 6. Related factors and indicators of antibiotic management of patients with community-acquired pneumonia (CAP)

Group 1 Group 2 Group 3 Group 4 P-value P-valuen = 200 n = 200 n = 200 n = 200 Intergroup1 Groups 1 and 42n (%) n (%) n (%) n (%)

Confirmed administration of ABa 151 (76.3%) 196 (99.0%) 162 (81.4%) 200 (100%) < 0.001 < 0.001Early ABb (within 4 hours) 85 (44.7%) 171 (89.1%) 93 (47%) 184 (92.5%) < 0.001 < 0.001Adequate choice of ABb 119 (60.4%) 190 (95.5%) 123 (61.8%) 195 (97.5%) < 0.001 < 0.001Correct doses and routesa 112 (57.1%) 190 (95.5%) 117 (59.1%) 194 (97.5%) < 0.001 < 0.001Change of AB treatment in patients admitted* 59 (49.6%) 14 (10.5%) 68 (51.1%) 10 (6.9%) < 0.001 < 0.001Change of AB treatment in patientsdischarged home** 25 (34.7%) 3 (4.5%) 26 (38.2%) 0 (0%) < 0.001 < 0.001

Early AB, fluid therapy and request for lactatein patients with severe sepsis or septic shock 10 (31.2%) 48 (92.3%) 24 (49%) 60 (98.4%) < 0.001 < 0.001

Side effects attributed to the AB*** 18 (6.1%) 6 (3.0%) 17 (8.6%) 6 (3.03) 0.006 0.011ED revisit attributed or due to AB side effects 11 (14.9%) 3 (5%) 9 (12.9%) 3 (4.8%) 0.103 0.087AB treatment (days) [mean (SD)] 11.84 (3.8) 10.43 (3.3) 11.82 (3.7) 9.59 (3.1) < 0.001 < 0.001PSI I 10.26 (2.1) 7.45 (1.5) 10.04 (1.8) 6.86 (1.6) < 0.001 < 0.001PSI II 10.89 (2.0) 8.77 (2.3) 10.36 (2.4) 7.11 (1.6) < 0.001 < 0.001PSI III 12.42 (2.2) 9.85 (2.2) 11.53 (2.7) 8.49 (2.0) < 0.001 < 0.001PSI IV 13.23 (4.3) 11.98 (2.6) 12.94 (4.2) 10.87 (2.7) 0.004 0.005PSI V 13.84 (5.6) 12.39 (3.8) 13.23 (4.8) 11.40 (3.2) 0.170 0.690

Days of intravenous AB in admitted[mean (SD)] 6.76 (4.5) 5.76 (3.0) 7.12 (4.6) 4.80 (2.5) < 0.001 < 0.001PSI III 4.16 (1.9) 3.62 (1.9) 4.20 (2.8) 2.84 (1.7) 0.118 0.183PSI IV 7.57 (3.9) 5.40 (2.5) 7.22 (3.8) 4.71 (2.2) < 0.001 < 0.001PSI V 9.08 (5.0) 7.30 (2.9) 9.66 (4.9) 6.29 (2.1) < 0.001 0.003

The percentages exclude missing data; AB: antibiotic; ED: Emergency Department; iv: intravenous; Group 1: Pre-protocol; Group 2: post-protocol group;Group 3: Pre-protocol of the 2nd intervention; Group 4: Post-protocol of the 2nd intervention. *Includes any change of type of antimicrobial and/or yourdosage within 48 hours of admission to the short stay unit, hospital ward or intensive care unit. This difference is more relevant (p < 0.05) in PSI groupsIV and V between groups 1 vs 2, 1 vs 4 and 3 vs 4. **Includes any change of type of antimicrobial and dosage within 72 hours by the primary carephysician, ED or outpatient clinic in directly or ED observation discharged patients. This difference is relevant (p < 0.05) in the PSI I groups betweengroups 1 and 2, 1 and 4, and 3 and 4. ***Includes those in the 30 days after ED diagnosis attributed to the AB (vomiting. diarrhea. intolerance.hepatotoxicity or nephrotoxicity or allergic reactions). b there were also differences (p < 0.05) between subgroups according to degrees of PSI betweenthe groups 1 versus 2-4 and 3 versus 4. b There were also differences (p < 0.05) between subgroups according to degrees of PSI and clinical severitygrades (patients with sepsis. severe sepsis and septic shock) between groups 1 and 2-4 and 3 versus 4. 1Qualitative variables comparison by Chi squareand ANOVA and post-hoc Tukey correction or non-parametric tests as appropriate for the comparison of means. 22 x 2 comparison of groups 1 and 4 bychi squared or exact Fisher test as appropriate.

We can say that every intervention was effectivefor the patient and efficient for the system: all the in-dicators showed significant positive change betweenG1 and G2 and between G3 and G4, or between

G1 and G4, or at least with a certain magnitude ofeffects, reinforcing previously published findings5,14.Our results are very similar to those of

Capelastegui et al.9 who, after implementing a


Emergencias 2013; 25: 379-392 387

Table 7. Factors relating to the appropriateness of emergency department (ED) care of patients with community-acquiredpneumonia (CAP)

ED care variables (n = 800) Group 1 Group 2 Group 3 Group 4 P-value P-valuen = 200 n = 200 n = 200 n = 200 Intergroup1 Groups 1 and 42n (%) n (%) n (%) n (%)

Non-performance of pulse oximetry in ED 25 (12.5%) 4 (2%) 23 (11.5%) 1 (0.5%) < 0.0001 < 0.0001Change of decision in ED after interpretingbiomarker values when requesteda 4 (10.8 %) 41 (26.1%) 6 (10.7%) 48 (29.6%) 0.007 0.022

Correct request for lab tests 130 (65.6%) 184 (92%) 148 (74%) 191 (95.5%) <0.0001 < 0.0001Correct request for microbiological tests 117 (58.5%) 183 (91.5%) 125 (62.5%) 190 (95%) < 0.0001 < 0.0001Request for blood cultures 98 (49.5%) 157 (78.5%) 117 (58.5%) 173 (86.5%) < 0.0001 < 0.0001Request for antigenuria* 94 (47.5%) 155 (77.5%) 113 (56.5%) 175 (87.5%) < 0.0001 < 0.0001Request for sputum culture 20 (10.1%) 36 (18%) 20 (10%) 40 (20%) 0.004 0.007Microbiological diagnosis obtained** 24 (12%) 81 (40.5%) 30 (15%) 77 (38.5%) < 0.0001 < 0.0001The percentages exclude missing data; ED: Emergency Department; Group 1: Pre-protocol; Group 2: post-protocol group; Group 3: Pre-protocol of the2nd intervention; Group 4: Post-protocol of the 2nd intervention. *Request for pneumococcal antigen and if negative and/or epidemiologic suspicion,then Legionella. **Sputum culture, blood culture, antigenuria after final serological diagnosis if requested in the ED first sample. aConsidered when thisfact was reflected in the clinical history. 1Qualitative variables comparison by Chi square and ANOVA and post-hoc Tukey correction or non-parametrictests as appropriate for the comparison of means. 22 X 2 comparison of groups 1 and 4 by chi squared or exact Fisher test as appropriate.

Table 8. Factors and indicators of the evolution and destination of patients diagnosed with community-acquired pneumonia (CAP)

Group 1 Group 2 Group 3 Group 4 P-value P-valuen = 200 n = 200 n = 200 n = 200 Intergroup1 Groups 1 and 42n (%) n (%) n (%) n (%)

Destination of the patient fromED Discharge 73 (36.5%) 39 (19.5%) 54 (27%) 36 (18%) < 0.0001 < 0.0001Observation and discharge 18 (9%) 32 (16%) 18 (9%) 27 (13.5%) 0.032 0.044SSU 24 (12%) 27 (13.5%) 28 (14%) 28 (14%) 0.546 0.656Hospital ward 73 (36.5%) 75 (37.5%) 86 (43%) 77 (38.5%) 0.456 0.757ICU 12 (6%) 24 (12%) 14 (7%) 26 (13%) 0.020 0.012Deaths in the ED 0 (0%) 3 (1.5%) 0 (0%) 2 (1%) 0.193 0.198

Correct destination according to PSIand additional criteria* 129 (64.5%) 190 (96.5%) 131 (65.5%) 195 (98%) < 0.0001 < 0.0001

Correct decision in PSI IV-V 68 (74.4%) 97 (98%) 69 (71.1%) 108 (99%) < 0.0001 < 0.0001Correct decision in PSI I-III 61 (56%) 93 (94.9%) 62 (60.2%) 87 (96.6%) < 0.0001 < 0.0001ED revisit within 24-72 hours 39 (69.6%) 63 (95.5%) 41 (63.1) 57 (95%) < 0.0001 < 0.0001ED revisit within 3-6 weeks 87 (62.6%) 164 (91.6%) 115 (69.7%) 173 (92.5%) < 0.0001 < 0.0001ED revisit within 72 hours after the initialdischarge 13 (14.28%) 2 (2.81%) 10 (13.88%) 1 (1.58%) 0.003 < 0.0001

ED revisit within 30 days after discharge,motivated by CAP 22 (28.57%) 3 (4.5%) 20 (22%) 2 (3.2%) 0.001 < 0.0001

Admission after ED revisit by the patient 13 (63.6%) 2 (66.7%) 12 (60%) 0 (0%) 0.025 0.009Hospital stay in days [mean (SD)] 8.73 (5.5) 7.59 (4.0) 9.39 (6.0) 6.48 (4.0) < 0.0001 0.001PSI I 1.60 (0.9) 1.50 (0.7) 5.67 (2.9) 3.67 (3.8) 0.329 0.635PSI II 3.10 (2.3) 4.60 (3.3) 5.05 (3.3) 2.50 (1.6) 0.097 0.966PSI III 6.15 (2.9) 4.62 (2.3) 6.55 (5.9) 3.41 (2.0) 0.011 0.047PSI IV 10.06 (4.8) 7.57 (3.6) 9.80 (5.1) 6.37 (3.1) < 0.0001 < 0.0001PSI V 10.97 (6.1) 9.46 (3.8) 12.33 (6.4) 8.83 (4.1) 0.003 0.046

Stabilization in days [mean (SD)]** 3.45 (1.4) 3.08 (1.4) 3.72 (1.7) 2.91 (1.3) < 0.0001 0.008PSI I 2.40 (1.0) 1.94 (0.62 2.90 (0.8) 1.82 (0.7) < 0.0001 0.094PSI II 2.64 (1.0) 2.28 (0.9) 2.98 (1.1) 2.11 (0.6) 0.001 0.174PSI III 3.24 (0.9) 2.50 (0.8) 3.17 (0.9) 2.12 (0.6) < 0.0001 < 0.0001PSI IV 4.31 (1.3) 3.48 (1.1) 4.08 (1.1) 3.22 (1.0) < 0.0001 < 0.0001PSI V 4.92 (1.0) 4.61 (1.4) 5.45 (2.5) 4.21 (1.4) 0.017 0.531

The percentages exclude missing data; CAP: community-acquired pneumonia; AB: antibiotic; ED: Emergency Department; OR: odds ratio; CI:confidence interval; NS: not significant. *In addition to PSI group and additional criteria (Table 1), the clinical assessment or argument made by thedoctor. **According to the criteria of Halm et al (reference 25): heart rate < 100 bpm, respiratory frequency < 24 bpm, temperature < 37.2 °C, systolicblood pressure > 90 mmHg. O2 saturation > 90%, good level of consciousness and oral tolerance. Group 1: Pre-protocol; Group 2: post-protocolgroup; Group 3: Pre-protocol of the 2nd intervention; Group 4: Post-protocol of the 2nd intervention. 1Qualitative variables compared by Chi squareand ANOVA and post-hoc Tukey correction or non-parametric tests as appropriate for the comparison of means. 22 X 2 comparison of groups 1 and 4by chi squared or exact Fisher test as appropriate.

CPG in their hospital, achieved a reduction of an-tibiotic treatment times (global 1.5 days and intra-venous 1.3 days), hospital stay (1.8 days) and in-adequate antibiotic regimen (from 28.6% to11.8%). These authors also reported a reduction inhospital mortality (OR 2.46, 95% CI: 1.37 to 4.41)and overall mortality at 30 days (OR 2.14, 95% CI:1.23-3.72). However, two fundamental differencesexist between the Capelastegui study and ours.They had an external control group from othercenters and only included hospitalized patients.Blasi et al.10 also focused on hospitalized patients,and their results are similar to ours. Physician ad-herence to their CPG on the management of CAPwas very low (33%), as in our case before the first(25%) and second (40%) intervention in our ED,but the effectiveness was evident with reducedmortality (OR 0.77, 95% CI: 0.51 to 0.98) and in-creased appropriate choice of antibiotic, identifiedas one of the most important factors related tomortality reduction (9.1% to 5.7%), as in ourstudy (shown in Table 9) where the choice of anincorrect antibiotic in the ED was associated withboth in-hospital and overall 30-day mortality.Early administration of antibiotics in the ED

was also associated with lower in-hospital and 30-

day mortality. In a study of 780 hospitalized pa-tients with CAP, Dambrada et al.26 confirmed dif-ferences in mortality according to CPG-recom-


388 Emergencias 2013; 25: 379-392

Table 9. Mortality of patients with community-acquired pneumonia (CAP) after being treated in the emergency department (ED)

Mortality (n = 800) Group 1 Group 2 Group 3 Group 4 P-value P-valuen = 200 n = 200 n = 200 n = 200 Intergroup1 Groups 12n (%) n (%) n (%) n (%) and 4

Mortality in patients dischargedafter initial visit to the ED 1 of 87 (1.1%) 0 of 71 (0%) 0 of 69 (0%) 0 of 62 (0%) 0.507 1

In-hospital mortality 20 of 100 (20%) 7 of 106 (6.60%) 19 of 122 (15.6%) 5 of 117 (4.3%) 0.001 < 0.0001in hospital ward or SSUaccording to PSI group:PSI I 0 (0%) 0 (0%) 0 (0%) 0 (0%) NS NSPSI II 1 (10%) 0 (0%) 2 (10.5%) 1 (12.5%) NS NSPSI III 0 (0%) 0 (0%) 0 (0%) 0 (0%) NS NSPSI IV 5 (12.8%) 1 (2.6%) 4 (10.8%) 1 (2.2%) NS NSPSI V 14 (45.2%) 6 (14.6%) 13 (31.7%) 3 (7.5%) 0.001 0.001

In-hospital mortality in those admittedto the ICU 5 of 13 (38.5%) 6 of 24 (25%) 2 of 15 (13.3%) 5 of 29 (17.2%) 0.363 0.238According to PSI group:PSI I 0 (0%) 0 (0%) 0 (0%) 0 (0%) NS NSPSI II 0 (0%) 0 (0%) 0 (0%) 0 (0%) NS NSPSI III 0 (0%) 0 (0%) 0 (0%) 0 (0%) NS NSPSI IV 2 (28.6%) 0 (0%) 1 (14.3%) 0 (0%) NS NSPSI V 3 (60%) 6 (33.3%) 1 (12.5%) 5 (22.7%) NS NS

Mortality at 30 days consideringall patients 30 of 200 (15%) 17 of 200 (8.5%) 23 of 200 (11.5%) 5 of 200 (5.5%) 0.012 0.003According to PSI group:PSI I 0 (0%) 0 (0%) 0 (0%) 0 (0%) NS NSPSI II 1 (2.5%) 0 (0%) 2 (4.2%) 1 (3.7%) NS NSPSI III 0 (0%) 0 (0%) 0 (0%) 0 (0%) NS NSPSI IV 9 (17.3%) 1 (2.3%) 6 (12%) 1 (1.9%) 0.013 0.013PSI V 20 (51.3%) 16 (27.1%) 16 (34%) 10 (17.2%) 0.004 0.004

PSI: Pneumonia Severity Index; NS: not significant or excessively low sample size; Group 1: Pre-protocol; Group 2: post-protocol group; Group 3: Pre-protocol of the 2nd intervention; Group 4: Post-protocol of the 2nd intervention. 1Qualitative variables compared by Chi square and ANOVA and post-hoc Tukey correction or non-parametric tests as appropriate for the comparison of means. 22 X 2 comparison of groups 1 and 4 by chi squared or exactFisher test as appropriate.

Figure 1. Distribution of discharges and beds occupied. Ka-plan-Meier survival curves showing the proportion of beds oc-cupied (stay) by patients in each study group.

Days from admission

Beds occupied (cumulative proportion)

Group 1Group 2Group 3Group 4

P < 0,001

0 5 10 15 20 25 30

1.0

0.8

0.6

0.4

0.2

0.0

mended antibiotic adherence or not (3% vs10.6%). These differences are comparable tothose that we observed (5.5% vs. 15%).We believe these results reflect the importance

of early and appropriate antibiotics for the prog-nosis of CAP as outlined in the CPGs1,4,18,19. Evenwhen only some physicians adhere to CPG recom-mendations, as Dean et al.15 showed with their10% rate of adherence, one can achieve a de-crease in mortality (OR 0.92, 95% CI: 0.87 to0.98, p = 0.007). Hence the importance of peri-odic interventions and training since the benefitsof CPG application decrease with the passage oftime.Along with the systematic use of PSI and addi-

tional criteria, the inclusion of biomarkers (PCRand PCT) as complementary to the prognosticseverity scales (PSI and / or CURB- 65)11 or as pre-dictors of bacteriemia27 and mortality28 is increas-ingly common in the ED. Therefore, as previouslydescribed, in our study, PCT value > 1 ng / mlwas included as an additional criterion for admis-sion to hospital (or at least observation), as wellas blood cultures and early antibiotic therapy dueto the likelihood of bacteremia and / or progres-sion to SS or septic shock, as recommended byvarious authors11,20,27.The present study confirmed that high concen-

trations of biomarkers (especially PCT) were asso-ciated with bacteremia, and mortality. Therefore,and in accordance other authors11,20,27 we wouldrecommend that CAP patients with PCT > 0.5-1ng / ml require blood cultures and early antibiotictherapy, and use this as an additional criterion inprognostic evaluation with PSI. The decision toadmit or discharge the patient determines theprognosis and evolution. Routine use in the ED ofCPG that incorporate a PSI results in a decrease ofincorrect hospitalization, better placement (ambu-latory or hospital) and adequacy of early antibiotic

therapy16,29. The variability in rate of hospitalizationbetween different medical centers is great whenCPG are not followed. Aujesky et al.30 in a studyconducted in 12 EDs with high physician adher-ence to CPG with PSI found that 37.4% of pa-tients with PSI I- III were admitted and 3.2% withPSI IV-V were discharged home. In another recentstudy, Hinojosa et al.31 assessed the appropriate-ness of hospital admissions for CAP and found alower proportion of inappropriate admissions(6.1%) in the low-risk group (PSI I-III), but a largeproportion of inappropriate discharges (accordingto the PSI and additional criteria) which reached32.9%. In our study, inappropriate admissions sig-nificantly decreased in G2 and G4 (from 35.5% to3.5% and from 34.5 to 2%, p < 0.001), but, as inthe work by Hinojosa31, incorrect discharge wasobserved in low-risk patients (PSI I-III) rather thaninappropriate admission. We believe that the im-provement in admission/discharge decision in ourstudy was due to several factors: direct dischargefrom the ED was higher in G1 and G2 versus G3and G4 (36.5% and 19.5% vs. 27% and 18%,p < 0.001 ); G2 and G4 patients were referred toED observation more often than G1 and G3 (16%and 13.5% vs 9% and 9%, p = 0.032), and aPCT > 1 ng / ml was the criterion that changedthe decision from discharge to admission in 28%of PSI I-III patients (assuming a high inflammatoryresponse and / or probability of bacteremia).In addition to greater effectiveness for the pa-

tient, the introduction of the CPG also resulted ingreater efficiency for the system, since there werefewer unnecessary admissions, hospital stay wasreduced, as was antibiotic treatment time (from2.25 days from G1 to G4). Another aspect wasthe reduction of clinical stabilization time (0.54days), which as we have seen was related to earlyadministration of antibiotic therapy in the ED andfaster release of hospital beds.Although this work reflects the change in CAP

management and improved overall care in ourED, after each intervention and from the begin-ning (2008) to the end of the study (2012), cer-tain limitations should be addressed. It was a sin-gle-center study, without an external comparisongroup, and for certain comparisons the samplesize was small, e.g. comparisons between sub-groups according to PSI or clinical severity (sepsis,SS and septic shock). The physicians responsiblefor the four groups were not the same (there wasan estimated 80% turnover of emergency physi-cians and residents between the four periods) so abias may exist according to experience and CPGadherence. Although quantified, the causes of in-


Emergencias 2013; 25: 379-392 389

Table 10. Relationship between mortality and administrationof antibiotic therapy

In-hospital 30-dayMortality Mortality

Yes No p Yes No p

AB administration in the ED 0.507 0.705No 10.8% 89.2% 8.1% 91.9%Yes 11.6% 88.4% 10.4% 89.6%

Early* AB administration < 0.0001 0.003No 21.3% 78.7% 15% 85%Yes 7.5% 92.5% 7.9% 92.1%

Appropriate dosage of AB < 0.0001 < 0.0001No 34.5% 65% 22.6% 77.4%Yes 5.9% 94.1% 6.9% 93.1%

AB: antibiotic; ED: emergency room. *Early: during the first four hoursof ED stay.

appropriate admission were not analyzed, andsome may have been justified on the basis of oth-er factors and clinical judgment of experiencedemergency physicians. Another aspect is that therecruitment period was not a calendar year fordifferent groups (which would remove possibleetiological variation according to seasonality).However, there were no differences in the propor-tion of diagnoses, only in absolute numbers whichwere greater in G2 and G4. We must also consid-er that the assessment by two independent exter-nal reviewers (although cases with discrepancieswere excluded) could include a subjective compo-nent. The study did not include the duration ofclinical CAP, which could affect certain values andthe interpretation of biomarkers. Finally, we didnot differentiate or exclude possible cases of noso-comial pneumonia since this was not covered inthe PSI or in previous studies with which we com-pared our work.Despite these limitations, we believe that this

study can serve as a reference and example ofhow to improve care for all patients attending theED with CAP, and that the use of biomarkers mayrepresent a decisive decision criterion in some cas-es. In this regard we need future research to vali-date the role of biomarkers in the management ofCAP.In conclusion, training interventions with CPG

implementation and refresher courses that includethe use of PSI and biomarkers significantly im-prove the management of CAP patients, reducein-hospital and 30-day mortality, and improve de-cision-making on admission/discharge. They alsoincrease the early administration of appropriateantibiotic therapy, and reduce clinical stabilizationtime and hospital stay. Finally this study alsoshowed that the beneficial effects of such inter-vention diminish over time, so they must be re-peated periodically to maintain or enhance theseeffects.

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392 Emergencias 2013; 25: 379-392

Intervenciones para mejorar el manejo de la neumonía adquirida en la comunidaddesde el servicio de urgencias

Julián-Jiménez A, Parejo Miguez R, Cuena Boy R, Palomo de los Reyes MJ, Laín Terés N, Lozano Ancín A

Objetivos: Determinar el impacto de distintas intervenciones consistentes en la implantación de una guía de prácticaclínica (GPC) en el proceso asistencial de la neumonía adquirida en la comunidad (NAC) en un servicio de urgencias(SU), analizar y comparar las decisiones de manejo (alta o ingreso, adecuación y precocidad de la antibioterapia, solici-tud de estudios complementarios), los resultados de evolución (tiempo de estabilización clínica, tiempo de estanciahospitalaria, reconsultas en el SU) y la mortalidad, antes y después de las intervenciones y a lo largo de 5 años.Métodos: Estudio prospectivo pre y postintervención realizado desdel 1 enero de 2008 al 31 julio de 2012 en cuatrofases (se evaluaron dos periodos pre-implantación y dos periodos post-implantación de las GPC).Resultados: En los grupos tras la implantación de las GPC y al final del estudio se logró reducir el tiempo hasta la esta-bilización clínica (0,54 días, p < 0,001), la estancia hospitalaria (2,25 días, p < 0,001) y la mortalidad intrahospitalaria(de 20% a 4,3%, p < 0,001) y la global a los 30 días (de 15% a 5,5%, p = 0,003), con un aumento de la administra-ción adecuada y precoz del antibiótico (p < 0,001) y una disminución del tiempo de tratamiento antibiótico total(2,25 días, p < 0,001) e intravenoso (1,96 días, p < 0,001). El uso del Pneumonia Severity Index (PSI) y los biomarcado-res ayudaron a mejorar la adecuación de la decisión alta o ingreso (p < 0,001).Conclusiones: Tras cada implementación de una GPC con el uso del PSI y los biomarcadores se mejoró de forma sig-nificativa todo el proceso asistencial en urgencias de la NAC. [Emergencias 2013;25:379-392]

Palabras clave: Neumonía adquirida en la comunidad. Servicio de Urgencias. Guía práctica clínica. Biomarcadores.Procalcitonina. Pneumonia Severity Index. Antibiótico. Mortalidad.

original article interventions to improve emergency

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