Hrev_master [page 24] [Emergency Care Journal 2017; 13:6600] Laboratory testing in the emer- gency department: an Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) and Academy of Emergency Medicine and Care (AcEMC) consensus report Giuseppe Lippi,1 Mauro Panteghini,2 Sergio Bernardini,3 Laura Bonfanti,4 Paolo Carraro,5 Ivo Casagranda,6 Mario Cavazza,7 Ferruccio Ceriotti,8 Marcello Ciaccio,9 Daniele Coen,10 Davide Giavarina,11 Fabrizio Giostra,12 Ciro Paolillo,13 Mario Plebani,14 Giorgio Ricci,15 Gianfranco Cervellin4 1Section of Clinical Biochemistry, University of Verona; 2Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan Medical School, Milan; 3Department of Experimental Medicine and Surgery, Division of Clinical Biochemistry, University of Rome Tor Vergata, Rome; 4Emergency Department, Academic Hospital of Parma, Parma; 5Department of Laboratory Medicine, ULSS3 Serenissima, Mestre-Venice; 6Emergency Department, Santi Antonio e Biagio e Cesare Arrigo General Hospital, Alessandria; 7Emergency Department, University Hospital S. Orsola-Malpighi, Bologna; 8Servizio di Medicina di Laboratorio, Ospedale San Raffaele, Milan; 9Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnology, University of Palermo - U.O.C. Laboratory Medicine, Policlinico University Hospital, Palermo; 10Emergency Departement, Niguarda Metropolitan Hospital, Milan; 11Clinical Laboratory, St. Bortolo Hospital, Vicenza; 12Emergency Department, ASUR Marche Area Vasta 4 Fermo; 13Emergency Department, Academic Hospital of Udine; 14Department of Laboratory Medicine, University of Padua; 15Emergency Department, University Hospital of Verona, Italy Abstract The mainstay of patient-oriented labo- ratory testing in emergency settings entails selecting number and type of tests accord- ing to valid criteria of appropriateness. Since the pattern of urgent tests requesting is variable across different institutions, we designed a joined survey between the Academy of Emergency Medicine and Care (AcEMC) and the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) for reaching tentative consensus about the most informative diag- nostic tests in emergency settings. A survey, containing the most commonly performed urgent laboratory tests and the relative clin- ical indications, was disseminated to eight relevant members of AcEMC and eight rel- evant members of SIBioC. All contributors were asked to provide numerical scores for the different laboratory parameters, where 1 indicated strongly recommended, 2 recom- mended in specific circumstances, and 3 strongly discouraged. The mean results of the survey were presented as the mean of responders’ values, and the parameters were finally classified as strongly recommended (mean value, 1.0-1.5), somehow recom- mended (mean value, 1.5-2.0), discouraged (mean value, 2.0-2.5) and strongly discour- aged (mean value, 2.5-3.0). The results of the survey allowed defining a hierarchy of priority, wherein 24 tests were strongly rec- ommended. The use of 5 common tests was instead strongly discouraged. For 16 addi- tional parameters in the list, the consensus ranged between somehow recommended and discouraged. We hope that results pre- sented in this joint AcEMC-SIBioC consen- sus document may help harmonizing panel of tests and requesting patters in emergency setting, at least at a national level. Introduction Despite it is now undeniable that labo- ratory tests are central to the clinical deci- sion making in patients with both acute and chronic conditions, the appropriateness of test ordering remains crucial. Indeed, the large number of tests that become available in modern clinical laboratories thanks to automation may erode human and econom- ic resources, especially when their prescrip- tion does not fulfill evidence-based criteria1 or else inappropriate analyses may trigger additional, unjustified and even invasive investigations when eventually generating the so-called laboratory incidentalomas (i.e., abnormalities detected by coincidence, without clinical symptoms or suspicion).2 Notably, it was also shown that the median length of stay (LOS) in the emergency department (ED), even in a very developed setting, may increase by up to 10 minutes for every five additional tests ordered, and by up to 17 minutes for each 30-minute increase in turnaround time.3 Reliable evidence attests that urgent testing represents a large part of laboratory activity, with median percentage of stat analyses approximating 33% of all tests per- formed in clinical laboratories.4 Additional evidence suggests that the panels of tests made available to the emergency physicians are extremely heterogeneous and variegated worldwide, so highlighting a rather poorly standardized scenario.5,6 A multicenter Spanish study involving 36 hospitals showed that the rate of request of stat tests ranged from 44 to 412 per 1000 ED patient admissions.7 The same study showed that the Spanish hospitals would have saved up to 1,000,000 unnecessary tests if every sin- gle laboratory would have achieved the appropriate indicator.7 The mainstay of patient-oriented labo- ratory testing in the ED encompasses the selection of number and type of tests Emergency Care Journal 2017; volume 13:6600 Correspondence: Giuseppe Lippi, Section of Clinical Biochemistry, University Hospital of Verona, P.le La Scuro 10, 37134 Verona, Italy. E-mail: giuseppe.lippi@univr.it Key words: Laboratory testing; Urgent test- ing; Emergency medicine; Consensus docu- ment. Conflict of interest: the funding organization(s) played no role in the study design; in the collection, analysis, and inter- pretation of data; in the writing of the report; or in the decision to submit the report for pub- lication. Contributions: all the authors have accepted responsibility for the entire content of this submitted manuscript and approved submis- sion. As a result of an agreement among the editors, this article will be contextually sub- mitted for publication in Clinical Chemistry and Laboratory Medicine, in Biochimica Clinica, the official journals of the Italian Society of Clinical Biochemistry and Laboratory Medicine (SIBioC-Medicina di Laboratorio), and in Emergency Care Journal, the official journal of the Academy of Emergency Medicine and Care (AcEMC). Tertiary publication: this article has been also published in Clin Chem Lab Med (doi: 10.1515/cclm-2017-0077) and in Biochimica Clinica (doi: 10.19186/BC_2017.014). Received for publication: 27 January 2017. Accepted for publication: 3 April 2017. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright G. Lippi et al., 2017 Licensee PAGEPress, Italy Emergency Care Journal 2017; 13:6600 doi:10.4081/ecj.2017.6600 Non co mmerc ial us e o nly [Emergency Care Journal 2017; 13:6600] [page 25] according to solid criteria of appropriate- ness. Despite some reliable guidance about appropriate laboratory testing in the ED has been provided by the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC-Laboratory Medicine; SIBiOC),8 both SIBioC and the Academy of Emergency Medicine and Care (AcEMC) have recognized the need to reach a tentative consensus about the panel of tests that could be considered more informative and hence appropriate in spe- cific emergency conditions. Materials and Methods The Board of the two Societies prelimi- nary identified eight members each to whom a questionnaire containing a compre- hensive list of the most commonly per- formed urgent laboratory tests and the rela- tive clinical indications was administered. Briefly, the survey was disseminated by sending personal emails to eight relevant members of AcEMC and eight relevant members of SIBioC, providing a short deadline for collecting responses. All con- tributors were asked to indicate a numerical value for each of the different laboratory parameters included in the questionnaire, in which 1 indicated strongly recommended, 2 indicated recommended in exceptional cir- cumstances and 3 indicated strongly dis- couraged. The results of the survey were then pooled and analyzed by calculation of the mean and standard deviation (SD) of all replies. Differences between AcEMC and SIBiOC replies were analyzed with Student’s T test (Analyse-it, Analyse-it Software Ltd, Leeds, UK). The scored parameters were finally classified as fol- lows: mean value between 1.0-1.5: strongly recommended; mean value between 1.5- 2.0: somehow recommended; mean value between 2.0-2.5, discouraged; mean value between 2.5-3.0, strongly discouraged. Results The results of the survey are shown in Table 1, including the mean values (±SD) and the statistical significance between SIBioC and AcEMC responders. Twenty- four parameters received such a high prior- ity score, so that they could be defined as highly recommended. For two of these [i.e., total creatine kinase (CK) in trauma patients and D-dimer for diagnosing venous throm- boembolism], the difference of values assigned by the member of the two societies reached statistical significance, but only for total CK the priority was finally different between SIBioC and AcEMC (highly rec- ommended for SIBioC and recommended for AcEMC, respectively). The consensus could be listed as satisfactory (i.e., P value comprised between 0.05-0.50) or optimal (i.e., P>0.50) for the remaining 22 highly recommended tests (Table 1). For the other parameters mentioned in the survey, the final consensus ranged between somehow recommended and discouraged, whereas high consensus was found for strongly dis- couraging the use of CK isoenzyme MB and myoglobin for diagnosing acute myocardial infarction, cystatin C for diag- nosing renal disease, presepsin in patients with suspected infections and hemoglobin A1c for evaluating glycemic status. The range of recommendations for the other parameters was comprised between some- how recommended (10 tests) and discour- aged (6 tests) (Table 1). Among those, a dis- agreement between AcEMC and SIBioC was found for fibrinogen (P<0.001; strong- ly recommended for SIBioC and discour- aged for AcEMC), CK-MB (P=0.02; strongly discouraged for SIBioC and dis- couraged for AcEMC), natriuretic peptides (P<0.01; somehow recommended for SIBioC and discouraged for AcEMC), urea (P=0.02; recommended for SIBioC and highly recommended for AcEMC), myoglo- bin in trauma (P=0.02; highly recommend- ed for SIBioC and discouraged for AcEMC) and total calcium (P=0.01; highly recom- mended for SIBioC and recommended for AcEMC). Discussion Previous evidence emphasized that the pattern of urgent tests requesting in emer- gency setting is highly variable,7 thus underpinning the need to reach a more widespread consensus for harmonizing requesting attitudes. The main drivers for prescribing urgent laboratory tests in emer- gency settings entails obtaining data that may actually imply a substantial change in the diagnostic reasoning and/or managed care, combined with a low turnaround time (TAT), so that a timely intervention can be effectively established.9 Rather understand- ably, inappropriateness of test ordering may have a dramatic impact on both laboratory organization and patients care. In the former case, excessive diagnostic testing may pro- duce a negative impact on laboratory effi- ciency, by increasing the TAT, but also unnecessarily enhancing laboratory expen- ditures. More importantly, patient outcome may also be affected, since performing a large volume of inappropriate tests may encumber the possibility to rapidly analyze the samples of patients really needing urgent data or else may potentially produce some laboratory incidentalomas, i.e., values outside the conventional reference interval but with little clinical significance, which may then trigger unjustified, expensive and even invasive investigations.10 The term appropriateness in laboratory medicine conventionally implies the opti- mization of human and economic resources, contextually offering the most useful data for improving outcomes and maintaining a high level of safety.11 Implicitly comprised within this concept is the fact that inappro- priateness may also be referred to underuti- lization of diagnostic tests, which may potentially lead to underdiagnosis or delayed diagnosis when essential laboratory analyses are overlooked.12 A promising approach for enhancing appropriateness of urgent testing encom- passes obtaining widespread consensus between emergency physicians and labora- tory professionals about a list of informa- tive tests according to specific emergency conditions. This consideration has prompt- ed the AcEMC and SIBioC to merge their efforts and try identifying a potential list of urgent tests that can be recommended in ED patients with the most frequently diagnosed pathologies. Our survey, disseminated to eight relevant members of either society, has ultimately allowed to identify a group of 24 high priority tests, which were defined as strongly recommended, as well as assign- ing low priority to other five commons tests, instead defined as strongly discour- aged (Table 1). 16 additional tests were either ranked as somehow recommended or discouraged, so leaving some wiggle room for their implementation or elimination from the list of tests made available to the ED. This particularly refers to the 10 parameters scored as somehow recommend- ed by the surveyed AcEMC-SIBioC repre- sentatives. Along with the tests for which a general consensus was reached by the responders of the survey, other tests have necessarily to be added to the offered panel, since they allow the diagnosis and/or monitoring of certain emergency conditions. This refers, for instance, to the cerebrospinal fluid (CSF) analysis for diagnosing infections and other acute disorders of the central nervous sys- tem (i.e., subarachnoid haemorrhage, acute neuroimmunological disorders, intracranial hypertension), serum β-HCG in the case of suspected pregnancy, specific drug testing (e.g., anticonvulsants, direct oral coagula- tion inhibitors, etc.), drug of abuse screen- ing (including ethanol) and carboxyhemo- globin measurement for suspect poisoning or intoxication. Supplementary tests to the Opinion Report Non co mmerc ial us e o nly [page 26] [Emergency Care Journal 2017; 13:6600] Opinion Report Table 1. Summary of scores for laboratory testing proposed for use in the emergency department. Overall, Italian Society of Clinical Biochemistry and Laboratory Medicine and Academy of Emergency Medicine and Care mean values are reported. Parameters Overall SIBioC AcEMC P Recommendation Anemia Hemoglobin 1.00 (0.00) 1.00 (0.00) 1.00 (0.00) 1.00 Strongly recommended Hematocrit 1.19 (0.53) 1.00 (0.00) 1.38 (0.70) 0.09 Strongly recommended RBC count 1.06 (0.24) 1.13 (0.33) 1.00 (0.00) 0.17 Strongly recommended MCV 1.13 (0.33) 1.25 (0.43) 1.00 (0.00) 0.07 Strongly recommended RDW 2.00 (0.87) 2.25 (0.83) 1.75 (0.83) 0.14 Discouraged Bleeding PT 1.06 (0.24) 1.00 (0.00) 1.13 (0.33) 0.17 Strongly recommended APTT 1.06 (0.24) 1.00 (0.00) 1.13 (0.33) 0.17 Strongly recommended Fibrinogen 1.56 (0.50) 1.13 (0.33) 2.00 (0.00) <0.001 Somehow recommended Platelet count 1.00 (0.00) 1.00 (0.00) 1.00 (0.00) 1.00 Strongly recommended Venous thromboembolism D-dimer 1.25 (0.01) 1.00 (0.00) 1.50 (0.50) 0.01 Strongly recommended Acute pancreatitis mylase (total) 2.50 (0.87) 2.75 (0.66) 2.25 (0.97) 0.14 Discouraged Amylase (pancreatic) 2.00 (0.71) 1.88 (0.78) 2.13 (0.60) 0.26 Discouraged Lipase 1.25 (0.43) 1.25 (0.43) 1.25 (0.43) 0.50 Strongly recommended Liver disease ALT 1.00 (0.00) 1.00 (0.00) 1.00 (0.00) 1.00 Strongly recommended AST 1.81 (0.81) 2.13 (0.78) 1.50 (0.71) 0.07 Somehow recommended GGT 2.06 (0.56) 2.25 (0.66) 1.88 (0.33) 0.10 Discouraged Bilirubin (total) 1.25 (0.56) 1.13 (0.33) 1.38 (0.70) 0.20 Strongly recommended Bilirubin (conjugated) 1.94 (0.56) 1.88 (0.33) 2.00 (0.71) 0.34 Somehow recommended Acute myocardial infarction cTnI or cTnT 1.00 (0.00) 1.00 (0.00) 1.00 (0.00) 1.00 Strongly recommended CK-MB 2.69 (0.58) 3.00 (0.00) 2.38 (0.70) 0.02 Strongly discouraged Myoglobin 2.94 (0.24) 2.88 (0.33) 3.00 (0.00) 0.17 Strongly discouraged Natriuretic peptides 2.25 (0.56) 1.88 (0.33) 2.63 (0.48) <0.01 Discouraged Renal disease Creatinine 1.00 (0.00) 1.00 (0.00) 1.00 (0.00) 1.00 Strongly recommended eGFR 1.63 (0.78) 1.50 (0.71) 1.75 (0.33) 0.28 Somehow recommended Urea 1.50 (0.50) 1.75 (0.43) 1.25 (0.43) 0.02 Somehow recommended Cystatin C 2.69 (0.46) 2.63 (0.48) 2.75 (0.43) 0.31 Strongly discouraged Neutrophil gelatinase-associated lipocalin 2.25 (0.66) 2.13 (0.78) 2.38 (0.48) 0.24 Discouraged Muscle trauma CK, total 1.38 (0.60) 1.00 (0.00) 1.75 (0.66) <0.01 Strongly recommended Myoglobin 1.81 (0.81) 1.38 (0.70) 2.25 (0.66) 0.02 Somehow recommended Creatinine 1.00 (0.00) 1.00 (0.00) 1.00 (0.00) 1.00 Strongly recommended LDH 2.50 (0.61) 2.38 (0.70) 2.63 (0.48) 0.22 Strongly discouraged Infection WBC 1.00 (0.00) 1.00 (0.00) 1.00 (0.00) 1.00 Strongly recommended C-reactive protein 1.13 (0.33) 1.00 (0.00) 1.25 (0.43) 0.07 Strongly recommended Procalcitonin 1.81 (0.53) 1.63 (0.70) 2.00 (0.00) 0.09 Somehow recommended Presepsin 2.88 (0.33) 2.88 (0.33) 2.88 (0.33) 0.50 Strongly discouraged Lactate 1.19 (0.39) 1.13 (0.33) 1.25 (0.43) 0.28 Strongly recommended Ion imbalance Calcium (total) 1.50 (0.61) 1.13 (0.33) 1.88 (0.60) 0.01 Somehow recommended Calcium (ionized) 1.25 (0.43) 1.13 (0.33) 1.38 (0.48) 0.14 Strongly recommended Magnesium 1.94 (0.66) 2.13 (0.78) 1.75 (0.43) 0.14 Somehow recommended Sodium 1.00 (0.00) 1.00 (0.00) 1.00 (0.00) 1.00 Strongly recommended Chloride 1.06 (0.24) 1.00 (0.00) 1.13 (0.33) 0.17 Strongly recommended Potassium 1.00 (0.00) 1.00 (0.00) 1.00 (0.00) 1.00 Strongly recommended Blood gas analysis 1.00 (0.00) 1.00 (0.00) 1.00 (0.00) 1.00 Strongly recommended Diabetes Glucose 1.00 (0.00) 1.00 (0.00) 1.00 (0.00) 1.00 Strongly recommended Hemoglobin A1c 2.69 (0.46) 2.88 (0.33) 2.50 (0.50) 0.06 Strongly discouraged Osmolality 1.50 (0.61) 1.50 (0.71) 1.50 (0.50) 0.50 Somehow recommended SIBioC, Italian Society of Clinical Biochemistry and Laboratory Medicine; AcEMC, Academy of Emergency Medicine and Care; RBC, red blood cell; MCV, mean corpuscular volume; RDW, RBC distribution width; PT, pro- thrombin time; APTT, activated partial thromboplastin time; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transferase; cTnI or cTnT, cardiac troponin I or T; CK-MB, reatine kinase MB; e-GFR, estimated glomerular filtration rate; CK, creatine kinase; LDH, lactate dehydrogenase; WBC, white blood cell count. Difference between SIBioC and AcEMC. Values within brackets express the stan- dard deviation. Non co mmerc ial us e o nly [Emergency Care Journal 2017; 13:6600] [page 27] basic list that were indicated by one or more responders included ammonia, coagulation protein C, antithrombin, thyroid-stimulating hormone (TSH), surface antigen of the hep- atitis B virus (HBsAg) hepatitis B core anti- body (HBcAb), malaria testing, reticulocyte count, blood culture, indirect Coombs test, estimate of cardiac troponin slope, serum albumin and white blood cell (WBC) differ- ential. Conclusions Despite a few emergencies can hardly affect efficiency of laboratory services, multiple emergencies, accompanied by many tests to be performed, may disrupt the ability to timely provide test results, so influencing patient management and extending the LOS in short stay units. We hope that this joint AcEMC-SIBioC consen- sus report will help harmonizing the panel of tests and the requesting patters in emer- gency settings, at least at the national level. References 1. Lippi G, Plebani M. Laboratory eco- nomics. Risk or opportunity? Clin Chem Lab Med 2016;54:1701-3. 2. Lippi G, Plebani M. Laboratory "inci- dentalomas": facts or fiction? Eur J Intern Med 2010;21:572. 3. Li L, Georgiou A, Vecellio E, et al. The effect of laboratory testing on emer- gency department length of stay: a mul- tihospital longitudinal study applying a cross-classified random-effect model- ing approach. Acad Emerg Med 2015;22:38-46. 4. Lippi G, Mattiuzzi C, Plebani M. Stat testing utilization in clinical laborato- ries. National survey of Italian Society of Clinical Biochemistry and Molecular Biology (SIBioC). Clin Chem Lab Med 2014;52:e79-84. 5. Hardin E. Emergency medicine and the laboratory. J Natl Med Assoc 1996;88:279-82. 6. Lippi G, Cervellin G, Plebani M. The ten commandments of laboratory test- ing for emergency physicians. Clin Chem Lab Med 2014;52:183-7. 7. Salinas M, Lòpez-Garrigòs M, Uris J. Differences in laboratory requesting patterns in emergency departments in Spain. Ann Clin Biochem 2013;50:353- 9. 8. Carraro P. Recommendations for appro- priate laboratory tests in emergency department typical conditions. Biochim Clin 2011;35:207-28. 9. Smellie WS. Appropriateness of test use in pathology: a new era or reinventing the wheel? Ann Clin Biochem 2003;40: 585-92. 10. Plebani M, Lippi G. Closing the brain- to-brain loop in laboratory testing. Clin Chem Lab Med 2011;49:1131-3. 11. Lippi F, Favaloro EJ. Exploring the ice- berg of inappropriateness in hemostasis testing. Diagnosis, in press. 12. Ferraro S, Panteghini M. The role of laboratory in ensuring appropriate test requests. Clin Biochem 2017;50:555- 61. Opinion Report Non co mmerc ial us e o nly