Point-of-care Ultrasonography for the Diagnosis of Acute Cardiogenic Pulmonary Edema in Patients Presenting With Acute Dyspnea: A Systematic Review and Meta-analysis

Acute dyspnea is a common presenting complaint to the emergency department (ED), and point-of-care (POC) lung ultrasound (US) has shown promise as a diagnostic tool in this setting. The primary objective of this systematic review was to determine the sensitivity and specificity of US using B-lines in diagnosing acute cardiogenic pulmonary edema (ACPE) in patients presenting to the ED with acute dyspnea. A systematic review protocol adhering to Cochrane Handbook guidelines was created to guide the search and analysis, and we searched the following databases: PubMed, EMBASE, Ovid MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, and the Cochrane Database of Systematic Reviews. References of reviewed articles were hand-searched, and electronic searches of conference abstracts from major emergency medicine, cardiology, and critical care conferences were conducted. The authors included prospective cohort and prospective case-control studies that recruited patients presenting to hospital with symptomatic, acute dyspnea, or where there was a clinical suspicion of congestive heart failure, and reported the sensitivity and specificity of B-lines in diagnosing ACPE. Studies of asymptomatic individuals or in patients where there was no suspicion of ACPE were excluded. The outcome of interest was a diagnosis of ACPE using US B-lines. A final diagnosis from clinical follow-up was accepted as the reference standard. Two reviewers independently reviewed all citations to assess for inclusion, abstracted data, and assessed included studies for methodologic quality using the QUADAS-2 tool. Contingency tables were used to calculate sensitivity and specificity. Three subgroup analyses were planned a priori to examine the effects of the type of study, patient population, and lung US protocol employed. Seven articles (n = 1,075) were identified that met inclusion criteria (two studies completed in the ED, two in the intensive care unit [ICU], two on inpatient wards, and one in the prehospital setting). The seven studies were rated as average to excellent methodologic quality. The sensitivity of US using B-lines to diagnosis ACPE is 94.1% (95% confidence interval [CI] = 81.3% to 98.3%) and the specificity is 92.4% (95% CI = 84.2% to 96.4%). Preplanned subgroup analyses did not reveal statistically significant changes in the overall summary estimates, nor did exclusion of three potential outlier studies. This study suggests that in patients with a moderate to high pretest probability for ACPE, an US study showing B-lines can be used to strengthen an emergency physician's working diagnosis of ACPE. In patients with a low pretest probability for ACPE, a negative US study can almost exclude the possibility of ACPE. Further studies including large numbers of ED patients presenting with undifferentiated dyspnea are required to gain more valid and reliable estimates of test accuracy in ED patients. La disnea aguda es un motivo de consulta frecuente en el servicio de urgencias (SU) y la ecografía (Eco) pulmonar en el lugar de atención se ha mostrado prometedora como herramienta diagnóstica en este escenario. El objetivo principal de esta revisión sistemática fue determinar la sensibilidad y la especificidad de la Eco usando las líneas B en el diagnóstico del edema agudo de pulmón cardiogénico (EAPC) en pacientes que acuden con disnea aguda al SU. Se creó un protocolo de revisión sistemática adherido a las guías clínicas del Manual Cochrane para guiar la búsqueda y el análisis, y se buscó en las siguientes bases de datos: PubMed, EMBASE, Ovid MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, y la Cochrane Database of Systematic Reviews. Se buscaron manualmente las referencias de los artículos revisados y de forma electrónica los resúmenes de las principales conferencias de medicina de urgencias y emergencias, cardiología y cuidados intensivos. Se incluyeron estudios de cohortes prospectivos y estudios de casos y controles prospectivos que reclutaron pacientes que acudieron al hospital con disnea aguda sintomática, o donde había una sospecha clínica de insuficiencia cardiaca congestiva, y se documentó la sensibilidad y especificidad de las líneas B en el diagnóstico del EAPC. Se excluyeron los estudios de sujetos asintomáticos o de pacientes donde no había sospecha de EAPC. El resultado de interés fue un diagnóstico de EAPC usando las líneas B mediante la Eco. Se aceptó como estándar de referencia el diagnóstico definitivo mediante el seguimiento clínico. Dos revisores comprobaron de manera independiente todas las citas para evaluar la inclusión, los datos extraídos y evaluaron la calidad metodológica de los estudios incluidos mediante la herramienta QUADAS-2. Se usaron tablas de contingencia para calcular la sensibilidad y especificidad. Se planificaron a priori tres análisis de subgrupos para examinar los efectos del tipo de estudio, la población de pacientes y el protocolo de Eco pulmonar empleado. Se identificaron siete artículos (N = 1.075) que cumplieron los criterios de inclusión (dos estudios llevados a cabo en los SU, dos en unidades de cuidados intensivos, dos en las plantas de hospitalización y uno en el escenario extrahospitalario. La calidad metodológica de los siete estudios fue valorada de media a excelente. La sensibilidad de la Eco usando líneas B para el diagnóstico del EAPC es un 94,1% (intervalo de confianza [IC] 95% = 81,3% a 98,3%) y la especificidad es 92,4% (IC 95% = 84,2% a 96,4%). Los análisis por subgrupos previamente planificados no revelaron cambios estadísticamente significativos en las estimaciones globales, ni tampoco la exclusión de tres estudios potencialmente atípicos. Este estudio indica que en los pacientes con una probabilidad pretest moderada o alta de EAPC, un estudio de Eco mostrando líneas B puede ser usado para reforzar el diagnóstico de EAPC por los urgenciólogos. En pacientes con probabilidad pretest baja para EAPC, un estudio por Eco negativo casi puede excluir la posibilidad de EAPC. Se requieren estudios posteriores con gran número de pacientes del SU que acudan por disnea de causa no filiada para obtener estimaciones más válidas y fiables de la certeza de la prueba. CME Editor: Corey Heitz, MD Authors: Mohammad Al Deeb, MD, FRCP, Skye Barbic, PhD, Robin Featherstone, MLIS, Jerrald Dankoff, MD, and David Barbic, MD, MSc, FRCP Article Title: Point-of-care Ultrasonography for the Diagnosis of Acute Cardiogenic Pulmonary Edema in Patients Presenting With Acute Dyspnea: A Systematic Review and Meta-analysis If you wish to receive free CME credit for this activity, please refer to the website: http://www.wileyhealthlearning.com/aem. Accreditation and Designation Statement: Blackwell Futura Media Services designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM. Physicians should only claim credit commensurate with the extent of their participation in the activity. Blackwell Futura Media Services is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Educational Objectives After reading the article, participants will be better able to describe the effectiveness of using bedside pulmonary ultrasonography to determine the presence or absence of pulmonary edema. Activity Disclosures No commercial support has been accepted related to the development or publication of this activity. Faculty Disclosures: CME Editor: Corey Heitz, MD has no relevant financial relationships to disclose. Authors: Mohammad Al Deeb, Jerrald Dankoff, David Barbic, Robin Featherstone, and Skye Barbic have no relevant financial relationships to disclose. This manuscript underwent peer review in line with the standards of editorial integrity and publication ethics maintained by Academic Emergency Medicine. The peer reviewers have no relevant financial relationships. The peer review process for Academic Emergency Medicine is double-blinded. As such, the identities of the reviewers are not disclosed in line with the standard accepted practices of medical journal peer review. Conflicts of interest have been identified and resolved in accordance with Blackwell Futura Media Services's Policy on Activity Disclosure and Conflict of Interest. Instructions on Receiving Free CME Credit For information on applicability and acceptance of CME credit for this activity, please consult your professional licensing board. This activity is designed to be completed within an hour; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity during the valid credit period, which is up to two years from initial publication. Follow these steps to earn credit: This activity will be available for CME credit for twelve months following its publication date. At that time, it will be reviewed and potentially updated and extended for an additional twelve months. Dyspnea due to acute cardiogenic pulmonary edema (ACPE) is a common presenting complaint to the emergency department (ED).1, 2 The rapid diagnosis of ACPE is critical for prompt and appropriate treatment. However, this is often challenging in elderly3 or obese patients4 or those with underlying chronic obstructive pulmonary disease (COPD). In addition, establishing the wrong diagnosis can have detrimental effects for the patient.5 Point-of-care (POC) lung ultrasound (US) has been shown to be quick and efficacious for multiple indications in emergency medicine. Recent studies suggest that the use of POC lung US may aid in the diagnosis of ACPE in patients presenting with acute dyspnea.6, 7 The primary objective of this systematic review was to determine the diagnostic accuracy of POC lung US using B-lines in patients presenting to the ED with acute dyspnea, compared to a final diagnosis from clinical follow-up. Our a priori secondary objectives were to investigate how test accuracy varies with the type of study (cohort and case-control), patient population, and type of POC lung US protocol used (the Volpicelli method8 vs. other), as well as to investigate if a threshold effect exists. A systematic review protocol, as guided by the PRISMA guidelines and the Cochrane Handbook for Diagnostic Test Accuracy (DTA) Reviews,9 was created to guide the search and analysis. It was reviewed and agreed upon by all coinvestigators a priori (Data Supplement S1, available as supporting information in the online version of this paper). The Cochrane Handbook for DTA Reviews9 and guidelines set forth by Leeflang et al.10 were followed for the purpose of reporting this systematic review of DTA. With the assistance of an experienced National Library of Medicine–trained health sciences librarian, we conducted a systematic search of the following databases for all dates prior to January 11, 2012: PubMed, EMBASE, Ovid MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, and all of the evidence-based medicine reviews included in the Cochrane Database of Systematic Reviews. The search strategy was independently reviewed by two librarians and validated against a sample result set of 21 studies identified by the primary investigator. The search strategy is detailed in Data Supplement S2 (available as supporting information in the online version of this paper). The search strategy was developed for use in MEDLINE and it was adapted as minimally as possible before executing in the Ovid EMBASE and the Cochrane Library. Duplicate citations were removed and final references were formatted to be compatible with EndNote citation software. No language restrictions were applied. Our grey literature search included hand-searching the reference lists of potentially eligible articles and electronic searches of the previous 2 years’ conference abstracts of major emergency medicine, cardiology, and critical care conferences (Society for Academic Emergency Medicine, American College of Emergency Physicians, Canadian Association of Emergency Physicians, American Heart Association, European Society of Cardiology, Society of Critical Care Medicine, Canadian Cardiovascular Congress, Canadian Critical Care Forum, and the International Symposium on Intensive Care and Emergency Medicine). We contacted abstract authors for additional information, and we also searched the abstracts subsection of the EMBASE database. We included prospective cohort and prospective case-control studies that reported on sensitivity and specificity of B-lines in diagnosing ACPE. Case reports, retrospective studies, and other types of case-control studies were excluded. Studies including patients in the primary care setting or inpatients with complaints of dyspnea and clinical suspicion of ACPE were included. Only patients with undifferentiated acute dyspnea were included, since we felt that these patients represented a similar patient population to those presenting to the ED. Studies of asymptomatic individuals or in patients where there was no suspicion of ACPE were excluded. No restriction was made on the protocol of lung US used to diagnose ACPE, as long as the authors specified that they used B-lines to make the diagnosis. No restriction on the type of machine or probe was applied. No restriction was placed on the type of physician performing the US as long as it was done by a nonradiologist physician at the patient's bedside. For the diagnosis of ACPE, or more specifically diffuse interstitial syndrome, the Volpicelli method8 (which divides the chest into eight zones) requires at least two zones to be positive on each side of the chest. A zone is positive if at least three B-lines are in an et used a of eight B-lines in the chest to be and et used a of more to a cardiogenic of acute dyspnea. there is not a threshold for the diagnosis of ACPE, there is a the of B-lines and the of lung congestive heart can be to from ACPE and POC lung US should be used in to the patient's clinical The primary outcome of interest was the clinical diagnosis of ACPE using POC lung US with B-lines. A final diagnosis from clinical follow-up was accepted as the reference standard. Two reviewers independently the and abstracts of the references identified in the electronic and searches to determine articles were relevant to the study The two reviewers compared their inclusion and exclusion The two reviewers reviewed the in the of references using inclusion and exclusion criteria to determine which studies to in the final analysis. A was developed for the of this study and was for accuracy and Data were independently by the two authors were contacted for or were resolved by with a of this review Two reviewers independently reviewed the included studies for quality using the QUADAS-2 The was = 95% confidence interval [CI] = to were resolved by with a The QUADAS-2 is that are assessed in of of and the applicability to the The patient reference and and The of was high if the study was a case-control the study did not a or a sample of or the study did not To assess if patients were not assessed in the ED or were assessed the of chest or the of applicability was If the US were with of the of the reference the of was to be For the applicability of the if the of the test was not the applicability was to be The of was high if the reference standard was to the or the reference standard was with of the of the The of was high if there was an interval the test and the reference not all patients the reference not all patients the reference or not all patients were included in the analysis. study for sensitivity and specificity were on a to assess for The a priori was to if appropriate using the summary as by and The is a statistically for the of DTA The that there is an underlying within each study and is similar to effects in that is within and of the potential of the is the to for the of a reference which is a common of DTA version was used for all We a three of related to disease and of US We planned subgroup We that case-control studies a sensitivity and specificity prospective cohort studies. We that studies that included patients lung US done in intensive care unit patients or a of sensitivity and specificity. We used the or other The Volpicelli the chest into eight zones (two and two on each side of the A for diffuse interstitial is positive at least two zones are positive in Other not the chest only which provide estimates of sensitivity and Diagnostic test threshold effect was using For this study, we used a at of (two the of were required for to be significant We used this to for 1 was for each study included in to examine the effect of studies with large high on the overall Studies were identified electronic search and other including hand-searching After the abstracts of articles and the of we seven articles (n = for the final 11, The QUADAS-2 quality that all included studies were of average to high quality In all studies, all were to the of the reference standard. Only one study was a case-control Two studies were done in the ED, two in the two in a hospital and one in the prehospital setting. studies used a similar US protocol, where they the chest to for with a positive the presence of at least three B-lines in each in at least two zones on each Two studies used a for the diagnosis of ACPE The US were completed by physicians from the hospital and prehospital study used physicians and medical to complete of the US has the of the of performing US Three of the included studies reported Data of quality to of studies was not available from the studies included in this review. 2 the of the study sensitivity and specificity The summary sensitivity of POC lung US using B-lines to diagnosis ACPE is 94.1% (95% CI = 81.3% to and the summary specificity is 92.4% (95% CI = 84.2% to 96.4%). the of the primary The positive is (95% CI = to and the negative is (95% CI = to The diagnostic is (95% CI = to In subgroup study patient population, and type of lung US protocol did not the estimates for sensitivity and specificity. the for a diagnostic threshold effect no significant = = of the three studies that the overall summary estimates for sensitivity and specificity. The study by et = and the two studies by et = and were from the primary to examine the effects on the overall summary The sensitivity was (95% CI = to and the specificity was (95% CI = to please refer to for a of the including all seven studies and the with these three studies The objective of this study was to assess the test accuracy of POC lung US using B-lines for the diagnosis of ACPE in patients presenting to the ED with acute dyspnea. The two studies including patients from the ED = of sensitivity and studies the Volpicelli POC lung US methodologic the studies may these the study by et medical conducted the of the US the study by et used only physicians. the study by et have included patients with more diagnostic it included only patients in the physician a the test of POC In addition, in the study by et the POC US was done in the of the ED and a significant of these patients have been with and This have the of ACPE and interstitial lung in these and the sensitivity of the This may have to test accuracy the studies. ED studies of this in patients are The of other as chest and in the diagnosis of ACPE, are for the sensitivity and specificity of chest in ACPE from to and to Two of in patients presenting to the ED with acute dyspnea have shown to the use of to or diagnose there are often or of with chest and in the diagnosis of ACPE in the ED setting. test is available to in the prehospital and is often to in not in and in Canadian and European by January January POC US is a and reliable test that has been to clinical in the hospital and prehospital The of suggest that the DTA of POC lung US using B-lines the available to at the bedside. the of this tool may not in the diagnosis of ACPE, in to ACPE and other of acute dyspnea acute in the prehospital and the hospital This may for more appropriate and of patients in acute The of this systematic review are the search strategy to relevant articles and to standards for the and reporting of systematic of this review the use of and validated and to and of this is the of studies included in the final to for publication In addition, the included studies are from patient using patient lung US US and of of We have to for this with subgroup and sensitivity A is the potential for in the reference standards used in each study due to the and of and diagnostic criteria for ACPE. The of B-lines using the Volpicelli is a protocol of the of the may on patient and how long the patient has been in that of the seven included studies US with patients in the or 11, one study used of and one study did not on patient It is this may have in the of this and is to determine the patient for the DTA of US with B-lines for ACPE. We also that the for quality for the studies was low = this the quality tool by the Cochrane studies using this tool have reported similar from to quality were not included in the study quality was The of this suggest that point-of-care ultrasound using B-lines may aid in the diagnosis of acute cardiogenic pulmonary edema. In patients with a moderate to high pretest a point-of-care ultrasound study showing B-lines can be used to strengthen an emergency physician's working diagnosis of acute cardiogenic pulmonary edema. In patients with a low pretest a negative point-of-care ultrasound study can almost exclude the possibility of acute cardiogenic pulmonary edema. Further studies including large numbers of ED patients presenting with undifferentiated dyspnea are required to gain more valid and reliable estimates of test accuracy in ED patients. The authors all of the authors of the included primary studies for to their In addition, the authors for and and for their and The is not for the or of supporting information by the should be to the for the

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