cone Ciriani Arterial lactate levels in an emergency department are associated with mortality: a prospective > Adana mata s Dublshed onine on. To iow piece wth jour ole thtpdedoo 10.1136) ‘nee 2013703541) Emerge Medicine Resesch Grup Einurgh EMERGE Deparment of Erergerey Medn, Roja iran of Fein OHS Lain, le France Gescet, Edneurh ue “cial Care Deparment, Sth’ Hospital (NS {atin ington, Uk Belem Tr Cini seach Fadi, ese Sever Hosp, Unies of dng. Enough UK Correspondence to Dr Deepa Data Emergency Medic Resear GtoupEaburgh EMERGE, Depart of Emergency ecko, Roy may of Ednusgh (HS Lotion, ie Fence Cresent Erbugh, Seatnd 6 454 Uk eepatcadatanhs ret een 28 December 2013, Reseed 27 Novber 2014 acpi 28 Nebr 2014 Pablhed nine Fast, 18 anuay 2015, CB) Linked > opal 0.1136 ‘reed 2014204305, hop og/0.1136) termed 2015201764 ® CrossMark a ct: bata 0, Wake G Geo Aleta og Med 201532673-67, observational cohort study Deepankar Datta, Craig Walker,'"? Alasdair James Gray,’ Catriona Graham? ABSTRACT Objectives Lactate measurements ae routinely cared ‘ut in emergency departments and ae associated wth increased meaty in septic patients. However, no definitive esearch as been cared out ito iether lactate measurements canbe used asa prognostic marker in a ciniclly unwell population in the emergency department. Methods We cared oxt a prospective observational cohort study in consecutive patients whose atl lactate concentration was measured in the emergency department ofa tertiary refeal hospital assessing 110 000 patients per year between 11th May and 1th August 2011. ‘Te main outcome measure was 30-day moray Results There were 120 deaths (16.1%) a 30 das postattendance in our cohort of 747 patents. Multivariate logistic regression revealed loner latte levels were associated with 30-day surival: ORs for 30-day death ‘compared with lactate 24 were 0.125 (95% CI 0.068 to (0.228) for lactate <2 ane 0,273 (95% C10.140 100.533) {or lactate 2—<4, Kaplan-Meier analysis showed a sunival ference when dividing lactate concenttations int srata (0.0001), This survival dfeence was maintained when septic diagnoses were taken into acount. Conclusions A single arterial lactate measurement on presentation tothe emergency department predicts 30-day ‘mortality independent of other measures of ines severity. BACKGROUND Elevated serum lactate is recognised as a marker of tissue hypoperfusion and organ dysfunction." ? Lactate is produced and cleared as part of normal homeostasis.” A serum arterial lactate of less than 2 mmolL is considered normal.* However, in states where there is a mismatch of oxygen supply and demand, cellular lactate is produced through anaer- ‘bic pachways, It has been shown that in critically ill patients, lactate is produced by organs chat do not normally produce lactate as well as in areas of tissue inflammation.” Additionally, elevated lactate levels may be present before clinical signs of shock are present (‘occult shock’)? Serum lactate is used as a biomarker ro identity patients with tisue hypoperfusion” and is measured routinely in critically ill pariens presenting to the emergency department (ED). Following the work of Rivers et al and the Surviving Sepsis Campaign, the ‘measurement of lactate is integral to the early asses- ‘ment and resuscitation of septic patients * Moreover, arerial lactate levels >4 mmol/L. have been shown to have a higher 28-day mortality inde~ pendent of hypotension.” Hyperacraraemia is also associated with increased mortality in patients with ‘What is already known on this subject? Lactate measurements are routinely cared out in emergency departments and are associated with increased mortality in septic patients. However, no definitive research has been carried out into whether lactate measurements can be used as a prognostic marker in a clnically unwell population in the emergency department What this study adds? ‘single arterial lactate in clinically unwel patients ‘on presentation tothe emergency department i 2 predictor of 30-day mortality independent of other measures of ness severity. SST elevation myocardial infarction," pulmonary emboli! stroke! and orthopaedic trauma." Additionally, there is increasing evidence that lactate clearance is an important resuscitation end point in sepsic and trauma patients and associated with ‘improved clinical ontcomes.'*"!* Lactate measurement has given physicians in the ED a quantitative marker of abnormal physiology to support risk stratification and as a treatment end point in sepsis and trauma. However, inital lactate levels in patients presenting to EDs while fre~ quently performed have not been rigorously inves- tigated for use as a prognostic factor outside of the above population groups, The aim of this study is v0 investigate whether a single arterial lactate measurement can be used as prognostic marker in a clinically unwell population presenting tothe ED. ‘METHODS Study design and setting ‘We performed a prospective observational cohort study of consecutive patients presenting to the ED ‘who had an arterial lactate sample obtained during initial clinical assessment in a single UK NHS ED (110 000 adult atendances annually) for a planned 3:month period between Ith May and 11th August 2011, No intervention or change to clinical ‘management was institated. Participants and recruitment Patients were included if during ED clinical assess- ment they had a serum arterial lactate performed as part of their routine care as judged by clinician dis- cretion. Patients were excluded if they had BMJ Data, eral ei Med 2018 3267S-A77 510.1 36lenered RSH evTable 1 Categorical anges for selected physiological data ‘erable Below normal Normal Above normal rt ate Ui) <0 50-99 29 Spt 3 ro Ho) a0 100-199 719 8 Une) s #20 320 Bicarbonate mat) a nae > Create malt) < fon0 210 previously been included in the study. All samples were taken ‘within 4 h of presentation to the ED. Data sources, variables and missing data Al samples ‘were analysed in the ED ABG analyses, an Instrumentation Laboratory Gem Premier 3000 analyser.” The ABG analyser was set upto require unique patent identifier for cach sample enabling optimal patient capture. Unidentifable, venous and serial samples were excluded. Wisables obtained from the analyser incinded lactate, PO,, PCOs, H+, bicarbonate and standard base excess. Patients with valid arterial samples were recorded and followed-up through the ED and hospital parent administration system (TakCare, InterSystems Corporation, Cambridge, Massachusetts, USA). Data variables collected included: patient demographics, past medical hor, vial signs on ED presentation, Inboratory blood samples during ED asessment, presumed diag nosis on ED discharge, hospital discharge diagnosis, source of Table 2 Patent characteristics by 30-day survival patient and patient disposition from the ED. Data were also cok lected on 30-day mortality and 30-day critical care admision Critical care was defined as admission to level 2(high-dependency unit) or level 3 (icensive care) facilites All missing data were recorded as an empry value, All data thar were measured above ot below an extreme of reference range were recorded at chat extreme range, Statistical analysis, Comparisons were made between subjects alive at 30 days and those dead at 30 days. The variables ro be analysed were limited by the authors to parameters that were noted to be the most clinically significant and easily available to prevent type I erzors bby multiple comparisons. Physiological variables were cate gorised into low, normal and high categories; due to. small group sizes heart rate, systolic BP and RR have only been con- sidered with earegories (table 1). Categorical variables where more than two categoties were present were analysed using a 3 testy p values from Fishers ‘exact test were presented where appropriate due %0 small ‘counts. For variables with two categories, results are presented 8 ORs with 95%6 Cls [A mutivariate logistic regression model was created to detet= ‘mine if arterial Lactate concentration is associated with 30-day ‘mortality when adjusted for any other factors. Variables with a univariate p value of <0.1 were used in the development of the regression model, which was then further refined by exchiding variables which did not significantly improve the model. The final analysis used age category, shock (defined as reported ‘lve ot 30 dys Dead at 30 days nce) a0) Totel__ORof death (95%) pValue Al pats 27 39) 0 (161) 7 Sender Mule 319183) 1167) 3B 110075016) on Ae group attendance 4 mmol/L); p<0.0001. ‘There was no statistically significant difference in survival (p=0.1078) when stratified by the presence of sepsis (figure 2), Individually in the septic and non-septic popula- tions, it can be seen thar difference in survival (p<0,0001) when stratified by lactate (see online supplementary figures S1 and $2) is still maintained. DISCUSSION ‘These results demonstrate that a single arterial lactate on presen tation to the ED predicts 30-day mortality independent of other measures of illness severity Table 4 Final logistic regression model against death at 30 days iota 0, at al Ee Med | 2015 3R6TS-B77 010, ]9oemered 2013-203541 = 95% wad confidence lis Point estimate for Sentenes Imi 30-day death Lower Upper See ama 170 6.110 Age gop 9 om nse 3487 (sage) sess 375 amo 1179 oe 41m tah 12487 m9 678 238819383 >a 10982 3003-30897 Locate 2 os 006 0229 (ace 24) pao amo 0533 “resco fal ober varie ae ae =Product-Limit Survival Estimates |Win Number of Suoecs at Risk and 95% Confidence Limi Survival Probability + Censored on Logrank p «0001 <2 is o a ” we a bee a i 2 oy oo a ©. = = = = 0 1s 2 Ea % ‘SURVIVAL fact 0 ——— ae ae Figure 1 In sepsis, the presence of hyperlactataemia has been used to promote, early prognostication’ and early treatment of patients." There is limited evidence on the clinical utility of lactate measurements in non-septic patients in the ED. Kruse ct al" noted in a systemic review that while the literatare sug- Jess the use of blood lactate monitoring for prognostication, there is uncertainty regarding optimal lactare cut-offs and the relevance of guiding therapy by lactate measurement. Apart Kaplan-Meier 30-day survival curve, stratified by lactate group (with 95% CIs). fom the, recommendations fom the Surviving Sepsis Campaign,’ there are no guidelines for which patient popula: tion would benefit from lactate sampling. These data suggest a single arterial lactate is associated with 30-day morality in aclincally unwell ED population requiring AABG sampling. It may, therefore, be useful asa screening too] ‘specially if formal study identified agreement between arte and venous or capillary lactate measurements, removing the Product-Limit Survival Estimates z 3 é Bo. a 5 0 om (wan Number of Subjects at Risk and 95% Confidence Lins + Concorea Logeank ps0 1078, 16 SURVIVAL Figure 2 Kaplan-Meier 30-day sunival cv, stratified by septic status (with 95% Cs). ae ‘Data Det al Ererg Med J 201532673 677, 6010.1 3Gtemered 2015 205881Pirie REFERENCES ssccessty for arterial sampling to be performed in addition t0 ‘enous sampling (anless required for other reasons eg, respi sory distress). It has been shown that 2 standardised early warning score can predict inhospital mortality and acts as a marker of illness severity highlighting the need for early inter- vention.'"" Jo et al” reporced additional predictive value for mortality by including lactate measurement to theit local early warning score. Further work is required to elucidate whether the addition of lactate to early warming or triage scores in the ED will improve ouscome and target early assessment and intervention. ‘When measuring lactate in the general population, it is important to consider the optimal cutoff to define “high- risk’ hyperlactataemia, Different cut-off concentrations have been suggested,’ '* with the Surviving Sepsis Campaign suggesting. a lactate concentration of 4mmol/L.®® A recent ICU study conducted suggests that lactate concentrations of >1.4 mmol/L are associated with increased mortality.™* ‘Most research on lactate has focused on patients in or being admitted to a critical care facility." "* Fucure research into lactate treatment thresholds and lactate clearance in the ED and its effect on patient disposition and outcomes would be valuable. ‘There were limitations to our study, which may have intro- duced selection bias. First, as arterial samples were recorded as part of the patients’ routine treatment, we could only record a relatively clinically unwell population presenting t0 the ED: patients requiring arterial lactare sampling may have been more likely 10 be sicker, and may have had a higher level of respiratory problems. Second, although the blood gas analyser required entry of patient-dentfiable data, in some ‘eases this was done incorrectly and therefore data could not be linked to patients; such cases were therefore excluded from the study: In conclusion, a single arterial lactate on presentation to the ED predicts 30-day mortality independent of other measures of illness severity. There is potential for lactate to be used as a screening tool for clinically unwell patients presenting to the ED. Acknowledgements Moya Nason ad iy Co, Reseach Nuss Emergency ‘die Reseach Group Eanburgh EMeRGE), Deparment of Emaaeny Nee, Royalty of ESrourgh Edinburgh Satan, UKE sinbuighenerencyredcie.con): Med 1 Crrtable Ts, Deparment of Energency Medien, Roya inna of Erba, Ecrauigh, Scoland, UR? ‘mr adbugremepeeymedicnecorymedc- bow), Collaborators Mora Mason 1 Cove. Contributors OD an CW pl te sud, a ako pesorras data clon and da ery AUG sapere the suy and ata cole, ar assed wih dktaig restoch greene approval. CG anahed the a. ll authors ‘ont othe Sia wtp ana Fev ofthe manus DD 3s cnespoding tutor wl be reconsle fr he oval cocet a gaara. A autos Kae roe the maruscipt and age wit is subrisson to re Eereancy Medkne ‘eral, Al ahs sted have cored sicily othe project to be inde aubes. Competing interests Nove Ethics approval South Es Scotland Research thes Serie Provenance and peer review Nat canmisions: exer pee ewe Data sharing statement The ram anes ata ae held onthe corpater ses of HS Lathan. as ro been made aalabl fr sharing ousie of the rosa etn, a 2 a Cohen 8, Snpstn sca metablem, Anes 975H661-72.m ‘edo r/10.1057000005¢2- 1975200020013 (kre ON, Delnge Laat: omar an pots haapetc xe (ht awe Cin 201.27.298-328, hap Addon 10 1016}.x.201012013 aL La aon: fom ou rk saps. J ere Ca Med 27005 20255-71. hypxicds oO 1 7HOeRSEGED5zTeEas foes gwen Hava a. Eon acd tea he went of Severe Sep a sep shock Eg Med 2001305: 1365-7, ped To Tosenentna0307 Clg, Cet, Ma Siig spss compl udelins for management of sere spss and ec shock. Cot Cre Med 20832 858-73. Fax clerg T0870. ccu. 090017317 tena E¢ Sapo Ni Hone MO, Tor Dea Seu cae a pedro mnay in crepe) desarert pats wih econ am Ener ed [0545528 pide 10.1016) amemergmed 200412006 owe tD, Dora M Cl et at cals popes ad marty fans th upc icine Cae Med 200733 1852-9. Rep igi0oo7s00t3420726803 Mien, Mice AN, Gals OF, a Seam is uted wth bly sree Sep nependet fen alr and sho. Cit Cre Met 200937: 1670-7 ip. dl 0 10SEC. C338 hes ‘Waker Cc Gran 0, yA a. ay cae dtc inept “rh lies oct leat om he rear) dartmet wo herse artnet Ne? 7 Co Cae 2013 26832—7 \ermeden RF, Hokie Me Clic condts ofa aca les paters wih ST-segment myocar fron asin desc tty. Cit Cae 2010, ERT, pa de on. 118253 ar, Vi 6, Bln eo Pogue of plasma late lee among ters wih ception entire ono-enlan ae aueone ‘ay Arn Eng Med 2073613308, po o/10 106) amend 22 10022 10S, eng Te, a. ital praca nthe EDs aac wih poe ‘cane pte th ric la Jeg Med 201230 888-5, por 1016p 2011.12 019| on AC, Your, oer DU, eal Oxeut hypersonic with inated may in pers uoegag ea rut Face fat, Tana 200 68:260-7, po. 108700005375 700002000-20011 un 8, es EP, Kobe? ot. Ey ace cence sce wth imaed oucone sere saps and spc Sk Crt ae Mad 200432163742. ptr 108707, CCROON0T 2903571347 Seo, Amana V, Gut 6, ea Two cat excep neat tara n pets th ears alco rt Cv es Pat Sor02010- 6 pdf 20108 7052 ‘arson D, clea TM, Hic et Lace cst and sna fing jy) Tama 1983355848 588-8 ps6 co.og/01087/ cnc 1993 1000-0014 Irsruretaton Lautan. GE Pie 300 pets mana. 3 eh \esrurenion Laboany, 202. hip Jw stone con! sec otaris Podut 25ers ral 20Cae 200g Insets 20Perier03000%204rh' 200 spaced I 2012, Yous 0, Guet , Bafed Cod lata a predca frintostal mn tr gaers antes aol to honta 2tenate rven Sand Tau Pesce Eno Med 29111974 Meng 10 181757 281-19°78 Noto or Cll Excelence. Ace pens nossa. Ladee ston ist fr sy an Cita xen 2007. Fol Coleg cl Ppa. Natl Early arg Save NEWS staderding the asset of ace les Severty oe NAS Rea of «woking pay Lond RCP, 2012, Buch VC, Ta G Monon C Mefied et wang sr pts he ee or hospital adison ard osama, eyed J 208256748, hp, .09/10.136en 2007057661, 10, Lae, Jn YH eta Modi ey wang twit i aa ein “lca ae! pons: the VEWL see Een Med 201330 123-9. Ipecac /0 emer 2011 200760, align RL MM, Cate I, a. Suing sepsis carpi reamatioral ees or ranagerent of sere span sep Sho; 208. Cot Care et 2008.35 296-377.healdl 00S Cew.coe238158 210141, ‘rat, Malada TF Boy, ea. 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