Americn Journl of Emergency Medicine (2013) 31, 206 214 www.elsevier.com/locte/jem Originl Contribution A community-bsed comprison of trum ptient outcomes between D- nd L-lctte fluids, Kzuki Kuwbr PhD,, Akihito Hgiwr PhD, Shiny Mtsud PhD b, Kiyohide Fushimi PhD c, Koichi B. Ishikw PhD d, Hiroms Horiguchi PhD e, Kenji Fujimori PhD f Deprtment of Helth Cre Administrtion nd Mngement, Grdute School of Medicl Sciences, Kyushu University, Fukuok 812-8582, Jpn b Deprtment of Preventive Medicine nd Community Helth, University of Occuptionl nd Environmentl Helth, Kitkyushu 807-8555, Jpn c Deprtment of Helth Policy nd Informtics, Tokyo Medicl nd Dentl University, Tokyo 113-8510, Jpn d Economics Section, Surveillnce Division, Center for Cncer Control nd Informtion Services, Ntionl Cncer Center, Tokyo 104-0045, Jpn e Deprtment of Helth Mngement nd Policy, Tokyo University Grdute School of Medicine, Tokyo 113-0033, Jpn f Center for Regionl Helthcre nd Certified Eductor Support, Hokkido University, Spporo 060-8638, Jpn Received 22 April 2012; revised 21 June 2012; ccepted 15 July 2012 Abstrct Purpose: Ringer's lctte is used for ptient resuscittion. Lctte nturlly occurs in 2 stereoisometric forms, D- nd L-lctte, tht re dded to fluid in equl mounts. Animl studies hve demonstrted potentilly deleterious effects of D-lctte on vitl orgns. Using n dministrtive dtbse, we exmined whether D- or L-lctte volume ws ssocited with mortlity in ptients with trum. Bsic procedures: The Trum nd Injury Severity Score could be clculted in 24 616 of 528 219 ptients dmitted in 2006 to 2009. Demogrphic chrcteristics, the use of blood products, mechnicl ventiltion, nd mortlity were compred mong the following 3 groups of ptients dministered Ringer's lctte: group 1, fluids other thn Ringer's lctte; group 2, fluids including Ringer's DLlctte; nd group 3, no D-lctte. The men volume (in millimoles per dy) of D- nd L-lctte dministered ws clculted. Multivrite nlyses were used to mesure the impct of lctte volume on mortlity, nd mechnicl ventiltion strted more thn 48 hours fter dmission. Min findings: Groups 2 nd 3 consisted of 2 827 (11.5%) ptients (88 hospitls) nd 12 036 (48.9%) ptients (145 hospitls), respectively. The use of mechnicl ventiltion best explined the vrition in mortlity. Greter D-lctte volume, but not fluid mngement ctegory or L-lctte volume, ws ssocited with mortlity. L-Lctte decresed nd D-lctte incresed the use of mechnicl ventiltion more thn 48 hours fter dmission. Sources of support: This study ws funded, in prt, by Grnts-in-Aid for Reserch on Policy Plnning nd Evlution (Jpnese Ministry of Helth, Lbour nd Welfre, H22 Seisku-Sitei 001). The uthors declre tht they hve no conflicts of interest. Nme of orgniztion nd dte of ssembly: This rticle hs not been presented nywhere. Corresponding uthor. Tel.: +81 92 642 6955; fx: +81 92 642 6961. E-mil ddresses: kzu228@bsil.ocn.ne.jp (K. Kuwbr), hgihr@hsmp.med.kyushu-u.c.jp (A. Hgiwr), smtsud@med.uoeh-u.c.jp (S. Mtsud), kfushimi.hci@tmd.c.jp (K. Fushimi), kishikw@ncc.go.jp (K.B. Ishikw), hiroms-tky@umin.c.jp (H. Horiguchi), fujimori@med.hokudi.c.jp (K. Fujimori). 0735-6757/$ see front mtter 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jem.2012.07.013
Outcomes of L-lctte fluids 207 Conclusions: Becuse erly dministrtion of D-lctte ws ssocited with mortlity nd ventiltion, physicins nd policy mkers should recognize the dvntges of L-lctte nd encourge reserch on the qulity of D- nd L-lctte in cse mixes beyond trum. 2013 Elsevier Inc. All rights reserved. 1. Introduction Sydney Ringer first described tht specific nd precise concentrtion of slt is necessry for frog myocrdil contrction. Since the introduction of Ringer's solution in 1882, Ringer's lctte solution hs been used worldwide for the resuscittion of criticl ptients, prticulrly fter trum. This is becuse metbolic cidosis is hrmful nd often ccompnies the criticl condition of hemorrhgic shock but is normlly buffered by sodium crbonte slowly converted from lctte in the liver [1-5]. Lctte exists nturlly in rcemic mixture of D- nd L- lctte [1]. Since its introduction into clinicl use, Ringer's DL-lctte hs been prepred with equl mounts of D- nd L- lctte. However, severl studies using nimls or humn tissue ex vivo hve demonstrted greter toxicity of D- lctte in terms of cell injury nd poptosis in pulmonry tissue, which seem to mimic reperfusion injury nd cute respirtory distress syndrome [1,3,6-8]. Neurotoxicity cused by ccumulted D-lctte ws lso reported in humn cse series [9]. Since the studies confirming the beneficil effects in niml models, some lterntives to Ringer's lctte, such s Ringer's cette nd Ringer's L- lctte, hve been developed nd re incresingly being used to void these potentil hrmful effects [8]. However, becuse lctte is component of hypotonic or isotonic fluids, other thn Ringer's solution, tht re used for resuscittion, mny criticlly ill ptients my still be exposed to the potentilly deleterious effects of lctte present in these other fluids. However, the effects of D- or L-lctte on clinicl outcomes remin specultive becuse the studies to dte hve only focused on Ringer's lctte. Therefore, comprtive studies should lso consider the presence of D-/ L-lctte in fluids other thn Ringer's lctte s well s in Ringer's lctte itself. Using Jpnese dministrtive dtbse, we exmined whether the dministrtion of D- or L-lctte is ssocited with mortlity of ptients with trum by compring severl fluid mngement ctegories defined ccording to the presence of Ringer's lctte nd the presence of D-lctte in Ringer's lctte. 2. Methods This ws retrospective clinicl evlution study using study dtbse tht hs been used by the Ministry of Helth, Lbour nd Welfre (MHLW) nd by our reserch tem since 2001 to determine the per-diem pyment system, to refine the Jpnese cse mix, nd to profile hospitl performnce. All 82 cdemic hospitls in Jpn hve prticipted in this project since its inception, nd the number of prticipting community hospitls hs incresed nnully, rising from 92 community hospitls in 2003 to 1 564 in 2010 [10]. The dtbse contins clinicl dt s well s dt regrding the dte, cost, nd quntity of medicl cre items tht re used during hospitliztion. Dt from ptients dischrged between July 1 nd December 31 were gthered nd compiled into stndrdized electronic formt by the MHLW. For ptients dignosed s hving trum t dmission between 2006 nd 2009, systolic blood pressure (SBP), respirtory rte (RR), Glsgow Com Scle (GCS), nd Abbrevited Injury Scle (AIS) were used to estimte the trum cre system of the hospitl nd the hospitl's bility to deliver criticl cre. The originl dtbse contined totl of 9 320 681 ptients who were treted cross 1 045 hospitls for 4 yers. Of 528 219 ptients with trum, 24 616 ptients treted cross 188 hospitls hd the necessry dt to mesure the probbility of survivl (PS) by the Trum nd Injury Severity Score method nd hd received fluid mngement during hospitliztion. These 188 hospitls recorded dt for 4 consecutive yers (Fig. 1). This project ws pproved by the ethics committee of the University of Occuptionl nd Environmentl Helth, Kitkyushu, Fukuok, Jpn. 2.1. Definition of vribles The fluids evluted in this study included crystlloids of Ringer's lctte or cette, other hypotonic or isotonic fluids tht contined totl prenterl nutrition, ft emulsion, nd sline or crystlloids with n electrolyte composition tht differed from Ringer's fluid. Blood products (lbumin, red blood cells, nd fresh-frozen plsm) were exmined seprtely becuse they ddressed the severity of unstble conditions including dehydrtion, nemi, nd cogulopthy. Ptient chrcteristics in the study included ge, sex, use of n mbulnce, comorbidities, mechnism of injury (blunt or penetrting), nd number nd ntomicl loction of injuries, s designted by the AIS, Revised Trum Score (RTS), Injury Severity Score (ISS), hospitl function (cdemic or community), nd fiscl yer. Study cre processes nd outcomes included surgicl procedures, dministrtion of fluids contining D- nd/or L-lctte, fluid volume, lctte volume, number of dys in which study fluids nd blood products were dministered, number of dys on mechnicl ventiltion, complictions, nd mortlity t dischrge. In Jpn, the totl chrge for hospitl cre is the totl cost of ll medicl items provided, which is uniformly determined under the stndrdized fee-for-service pyment system nd is listed
208 K. Kuwbr et l. Fig. 1 Ptient flow. Becuse the number of dys tht blood products re dministered prtly determines the use of mechnicl ventiltion lter thn 48 hours fter dmission, only men volume per dy ws considered. Of 24 616 ptients cross 188 hospitls eligible for this nlysis, 9 753 ptients received fluids other thn Ringer's lctte (group 1), 2 827 received fluids including Ringer's DL-lctte (group 2), nd 12 036 received Ringer's lctte fluids other thn D-lctte (group 3). on the ntionlly uniformed fee tble [11]. Becuse medicl items lso specify the volume or mount (eg, in milligrms, milliliters, millimoles, unit, nd clorie) per service unit, volume-relted vribles (ie, milliliters per dy nd millimoles per dys) cn be clculted. Ptients were strtified into 2 ge groups: younger thn 55 yers or 55 yers or older. We used trnsfer by mbulnce s proxy for emergency sttus. The dtbse included 6 ctegories of severity within the AIS. One corresponds to superficil injury; 2 corresponds to moderte injury; 3 corresponds to severe but not lifethretening injury; 4 corresponds to severe, life-thretening injury; 5 corresponds to criticl injury, survivl uncertin; nd 6 corresponds to unslvgeble injury in which trum hs occurred to 1 or more of 6 ntomicl regions (hed nd neck, fce, thorcic, bdomen, pelvic orgns, extremities, pelvic girdle, nd skin ) [12]. Injury Severity Score ws clculted s the sum of the squres of AIS severity (1-5) of the single worst injury in ech of the 3 most ffected body regions. It must be between 1 nd 75 (mximum). Ptients with n AIS severity of 6 in ny of the 6 body regions were excluded [12]. The number of injured sites rnged from 1 to 6. Revised Trum Score ws clculted using the following eqution: RTS = 0.9368 GCS (0 if GCS = 3, 1 if GCS = 4-5, 2 if GCS = 6-8, 3 if GCS = 9-12, or 4 if GCS = 13-15) + 0.7326 SBP (0 if SBP = 0, 1 if SBP = 1-49, 2 if SBP = 50-75, 3 if SBP = 76-89, or 4 if SBP 90) + 0.2908 RR (0 if RR = 0, 1 if RR = 1-5, 2 if RR = 6-9, 3 if RR is N29, or 4 if RR = 10-29). Probbility of survivl ws clculted using the following eqution: PS = 1/1+e x,wherex = 1.2470 + 0.9544 RTS 0.0768 ISS 1.9052 ge (0 if ge b55 yers or 1 if ge 55 yers) for blunt injury, or x = 0.6029 + 1.1430 RTS 0.1516 ISS 2.6676 ge (0 if ge b55 yers or 1 if ge 55 yers) for penetrting injury [13,14]. For peditric ptients younger thn 15 yers, the blunt model ws used. Both RTS nd PS re widely used s indictors for qulity improvement inititives to prevent unexpected deth mong ptients with trum [15,16]. The dtbse records mximum of 4 comorbidities or complictions per ptient tht re individully recorded using the Interntionl Clssifiction of Diseses, 10th Edition. To ssess the severity of preexisting conditions, we used the weighted Chrlson comorbidity index [17]. Complictions were designted s procedure-relted complictions corresponding to the Interntionl Clssifiction of Diseses, 10th Edition codes of T81 to T87 (hemtom or lcertion, or disruption of the treted orgns by instrumenttion or mnipultion) [18]. We lso divided ptients ccording to the use of mechnicl ventiltion within 48 hours of dmission or lter thn 48 hours fter dmission. The former represents the severity of injury becuse ptients with trum re likely to be intubted on dmission becuse of concurrent hed, fce, nd chest injury, wheres the ltter represents sequentil pulmonry complictions. 2.2. Sttisticl nlysis To exmine fluid mngement strtegies, we ctegorized ptients into 3 groups ccording to the dministrtion of fluids contining Ringer's lctte nd the presence of D-
Outcomes of L-lctte fluids lctte in these fluids. Group 1 consisted of ptients dministered fluids other thn Ringer's lctte. Group 2 consisted of ptients dministered with Ringer's lctte contining DL-lctte. Group 3 consisted of ptients dministered Ringer's lctte without D-lctte. The frequencies nd proportions of ech ctegoricl vrible in the study were determined nd compred mong the 3 groups using Fisher exct test. Continuous vribles re expressed s mens (SD) nd were compred by nlysis of vrince. In terms of fluid volume relted vribles, we determined the men volume of fluid used for resuscittion (in milliliters per dy) nd the volume of L- nd D-lctte (in millimoles per dy) dministered during hospitliztion nd before receiving mechnicl ventiltion. We used multiple logistic regression nlyses to estimte the impct of D- nd L-lctte volume on mortlity nd the use of mechnicl ventiltion strting lter thn 48 hours fter dmission. Becuse the number of dys in which fluid nd blood products re dministered prtly predicts the dy on which mechnicl ventiltion is strted fter dmission, only men volume dministered per dy ws included in the model. Sttisticl nlysis ws performed using SPSS 19.0 (SPSS-IBM, Chicgo, IL). All P vlues re 2 tiled, nd the level of significnce ws set t P b.05. 3. Results 209 Overll, there were 9753 ptients cross 146 community nd 26 cdemic hospitls in group 1, 2827 ptients cross 69 community nd 19 cdemic hospitls in group 2, nd 12 036 ptients cross 126 community nd 19 cdemic Tble 1 Ptient chrcteristics ccording to fluid mngement Group 1 Group 2 Group 3 P Totl no. of ptients 9753 2827 12036 No. of hospitls Community 146 69 126 Acdemic 27 19 19 Age Men ± SD (y) 56.1 ± 28.4 59.5 ± 24.3 60.4 ± 24.8 b.001 b 55 y 5963 (61.1) 1820 (64.4) 7967 (66.2) b.001 Sex, mle 4887 (50.1) 1467 (51.9) 5950 (49.4).060 Use of n mbulnce 4668 (47.9) 1664 (58.9) 6056 (50.3) b.001 Chrlson comorbidity index 1 1331 (13.6) 430 (15.2) 1727 (14.3) b.001 2 592 (6.1) 134 (4.7) 583 (4.8) 3 218 (2.2) 37 (1.3) 173 (1.4) 4 118 (1.2) 16 (0.6) 63 (0.5) Mechnism of injury, blunt 9175 (94.1) 2613 (92.4) 11445 (95.1) b.001 No. of ffected sites 2 1022 (10.5) 367 (13) 1330 (11.1) b.001 3 501 (5.1) 216 (7.6) 651 (5.4) Loction of injury Hed nd neck injury 2125 (21.8) 588 (20.8) 2685 (22.3).199 Fcil injury 764 (7.8) 223 (7.9) 731 (6.1) b.001 Thorcic injury 926 (9.5) 321 (11.4) 1049 (8.7) b.001 Abdominl injury 642 (6.6) 218 (7.7) 728 (6.0).004 Extremity injury 6303 (64.6) 1955 (69.2) 8332 (69.2) b.001 Externl skin injury 1337 (13.7) 446 (15.8) 1473 (12.2) b.001 RTS, men ± SD 7.693 ± 0.544 7.551 ± 0.874 7.435 ± 1.047 b.001 b ISS, men ± SD 6.9 ± 5.5 8.6 ± 6.9 7.4 ± 5.8 b.001 b Hospitl type, cdemic 834 (8.6) 291 (10.3) 424 (3.5) b.001 Fiscl yer 2006 2222 (41.5) 547 (10.2) 2589 (48.3) b.001 2007 1686 (37.4) 644 (14.3) 2176 (48.3) 2008 1372 (30.8) 592 (13.3) 2486 (55.9) 2009 4473 (43.4) 1044 (10.1) 4785 (46.4) Vlues re n (%) unless otherwise indicted. Group 1: ptients dministered fluids other thn Ringer's lctte; group 2: ptients dministered Ringer's DLlctte; group 3: ptients dministered Ringer's lctte fluids without D-lctte. A totl of 1505 (53.2%) ptients mong 61 hospitls received both Ringer's DL- nd L-lctte. b P vlues were determined by nlysis of vrince. Other vlues were determined by χ2 tests.
210 K. Kuwbr et l. Tble 2 Cre process nd outcomes ccording to fluid mngement Group 1 Group 2 Group 3 P Surgicl procedures 6803 (69.8) 2399 (84.9) 9327 (77.5) b.001 Presence of D- ord-lctte in the fluid dministered No lctte 3269 (33.5) 212 (7.5) 0 (0.0) b.001 L-lctte only 4076 (41.8) 884 (31.3) 8862 (73.6) DL-lctte only 1626 (16.7) 355 (12.6) 0 (0.0) Both L- nd DL-lcttes 782 (8.0) 1376 (48.7) 3174 (26.4) Blood products received during hospitliztion Albumin 209 (2.1) 207 (7.3) 376 (3.1) b.001 Fresh-frozen plsm 833 (8.5) 599 (21.2) 1506 (12.5) b.001 Red blood cells 113 (1.2) 171 (6.0) 215 (1.8) b.001 Use of ventiltion 240 (2.5) 223 (7.9) 351 (2.9) b.001 Within 48 h of dmission 172 (1.8) 167 (5.9) 226 (1.9) b.001 Lter thn 48 h fter dmission 68 (0.7) 56 (2.0) 125 (1.0) Time from dmission to strting 5.0 ± 11.9 3.4 ± 6.4 5.5 ± 10.3.044 ventiltion (d), men ± SD Durtion of ventiltion (d), men ± SD 7.9 ± 15.7 11.9 ± 18.6 8.4 ± 14.0.013 Blood products dministered before strting ventiltion Albumin 51 (21.3) 73 (32.7) 77 (21.9).005 Fresh-frozen plsm 91 (37.9) 121 (54.3) 123 (35) b.001 Red blood cells 50 (20.8) 94 (42.2) 72 (20.5) b.001 Men volume nd durtion of blood products dministered during hospitliztion, volume (ml) ± SD, durtion (d) ± SD Albumin 259.2 ± 252.6, 3.3 ± 3.9 382.7 ± 370.2, 4.5 ± 7.1 309.7 ± 526.5, 3.2 ± 3.7.013,.006 Fresh-frozen plsm 594.6 ± 462.5, 2.1 ± 2.5 737.6 ± 480.9, 2.8 ± 5.2 617.3 ± 474.7, 1.8 ± 1.5.016,.013 Red blood cells 577.9 ± 370.1, 1.6 ± 1.2 790.2 ± 673.8, 2 ± 1.8 604.4 ± 476.3, 1.7 ± 1.3 b.001, b.001 Blood products received fter strting ventiltion Albumin 48 (20.0) 77 (34.5) 71 (20.2) b.001 Fresh-frozen plsm 70 (29.2) 92 (41.3) 100 (28.5).003 Red blood cells 38 (15.8) 50 (22.4) 40 (11.4).002 Men volume nd durtion of blood products received before strting ventiltion, volume (ml) ± SD, durtion (d) ± SD Albumin 457.2 ± 359.5, 1.5 ± 1 616.7 ± 523.4, 1.3 ± 0.9 583.7 ± 572.6, 1.6 ± 1.209,.167 Fresh-frozen plsm 870.8 ± 702.4, 1.4 ± 1.3 981.2 ± 652, 1.3 ± 0.7 838.5 ± 632.4, 1.2 ± 0.6.347,.573 Red blood cells 1232 ± 1000.9, 1.3 ± 0.8 1696.3 ± 1511.6, 1.5 ± 1.1 1413 ± 1283.8, 1.3 ± 0.6.033,.336 Outcome, deth 148 (1.5) 75 (2.7) 233 (1.9) b.001 Procedure-relted complictions 164 (1.7) 80 (2.8) 272 (2.3) b.001 Group 1: ptients dministered fluids other thn Ringer's lctte; group 2: ptients dministered Ringer's DL-lctte; group 3: ptients dministered Ringer's lctte fluids without D-lctte. P vlues were determined by nlysis of vrince. Other vlues were determined by χ 2 tests. hospitls in group 3. For ptients in group 2, 61 hospitls dministered both Ringer's DL-lctte nd Ringer's L-lctte to 1505 ptients. There were sttisticlly significnt differences in ptient chrcteristics mong the 3 fluid mngement ctegories, except in terms of sex nd the presence of hed nd neck injury (Tble 1; Fig. 1). D-Lctte ws dministered to 3174 (26.4%) ptients in group 1. Surgicl procedures, mechnicl ventiltion, nd dministrtion of blood products were more frequently provided in group 2. Mechnicl ventiltion ws strted erlier in group 2 thn in groups 1 nd 3 (Tble 2). Probbility of survivl ws lower in group 3. The men volume nd number of dys on which study fluid nd blood products were dministered during hospitliztion were significntly greter in group 2 (Fig. 2A). There were sttisticlly significnt differences in the men volumes of L- nd D-lctte dministered during hospitliztion nd before strting mechnicl ventiltion mong the fluid mngement ctegories (Fig. 2B). The volume nd number of dys on which blood products were dministered were not significntly different, except for the volume of red blood cells dministered (P =.033; Tble 2). After djustment for PS nd other covrites, the fluid mngement ctegory ws not ssocited with mortlity. Ech 1-mmol/d increse in D-lctte, but not L-lctte, influenced mortlity (D-lctte: odds rtio [OR], 1.011; 95% confidence intervl [CI], 1.000-1.022). Mechnicl ventiltion strting within (OR, 16.925; 95% CI, 12.095-23.684) nd or lter thn (OR, 54.938; 95% CI, 38.373-78.654) 48 hours fter dmission showed greter ssocitions with mortlity thn did the other vribles. Ech 1-mmol/d increse in L-lctte (OR, 0.919;
Outcomes of L-lctte fluids 211 Fig. 2 A, Probbility of survivl, men fluid volume, nd durtion of fluid dministrtion during hospitliztion, ccording to fluid mngement. B, Volume of L- nd D-lctte dministered during hospitliztion nd before strting mechnicl ventiltion, ccording to fluid mngement. The evlution of n extensive rnge of fluid types nd volumes in this study is justified becuse they my ffect mortlity. All dt re presented s mens with SDs. Group 1: ptients dministered fluids other thn Ringer's lctte; group 2: ptients dministered Ringer's DL-lctte; group 3: ptients dministered Ringer's lctte without D-lctte.
212 K. Kuwbr et l. Tble 3 Vribles ssocited with mortlity nd strting ventiltion lter thn 48 hours fter dmission Mortlity Ventiltion OR 95% CI OR 95% CI Sex, mle (vs femle) 0.906 0.726-1.131 0.864 0.595-1.256 Use of n mbulnce 1.296 1-1.679 0.417 0.250-0.694 Chrlson comorbidity index (vs zero) 1 1.785 1.340-2.378 1.047 0.661-1.657 2 4.783 3.438-6.654 1.220 0.618-2.407 3 4.997 2.935-8.507 1.007 0.313-3.245 4 9.829 5.346-18.072 42.547 1.772-1021.394 Procedure-relted complictions 0.986 0.483-2.012 Surgicl procedures 0.263 0.206-0.337 Teching sttus, cdemic (vs community hospitl) 0.618 0.409-0.932 0.615 0.379-0.996 Fiscl yer (for ech dditionl yer) 0.977 0.891-1.071 0.970 0.835-1.126 PS (for ech point increse in probbility) 0.073 0.047-0.113 5.882 2.847-12.154 Men fluid volume during hospitliztion (per 1-L increse per dy) 1.070 1.016-1.127 0.831 0.765-0.903 Durtion of fluid dministrtion (for ech dditionl dy) 1.004 0.997-1.012 Fluid mngement (vs group 1) Group 2 0.864 0.599-1.248 1.476 0.893-2.441 Group 3 1.281 0.974-1.684 2.643 1.680-4.159 Men quntity of L-lctte (per 1-mmol increse per dy) 0.998 0.990-1.005 0.919 0.899-0.939 Men quntity of D-lctte (per 1-mmol increse per dy) 1.011 1.000-1.022 1.025 1.003-1.048 Blood products Men volume of lbumin dministered (for ech dditionl milliliter per dy) 1.001 0.999-1.001 1.000 b 0.999-1.001 Durtion of lbumin dministrtion (for ech dditionl dy) 1.096 1.047-1.147 Men volume of fresh-frozen plsm dministered (for ech dditionl 1.834 1.123-2.994 0.844 b 0.488-1.461 milliliter per dy) Durtion of fresh-frozen plsm dministrtion (for ech dditionl dy) 0.916 0.824-1.019 Men volume of red blood cells dministered (for ech dditionl 1.000 0.999-1.000 1.000 b 0.999-1.000 milliliter per dy) Durtion of red blood cell dministrtion (for ech dditionl dy) 0.970 0.872-1.079 Use of ventiltion Within 48 h of dmission 16.925 12.095-23.684 Lter thn 48 h fter dmission 54.938 38.373-78.654 Hosmer-Lemeshow goodness of model fit. 0.054 0.441 Group 1: ptients dministered fluids other thn Ringer's lctte; group 2: ptients dministered Ringer's DL-lctte; group 3: ptients dministered Ringer's lctte fluids without D-lctte. Age ws not included in the model becuse the PS ws lredy evluted using ge ctegories. Not included in the model. b Men fluid volume before strting ventiltion. 95% CI, 0.899-0.939) nd D-lctte (OR, 1.025; 95% CI, 1.003-1.048) dministered before strting mechnicl ventiltion ws significntly ssocited with erly mechnicl ventiltion (Tble 3). 4. Discussion To the best of our knowledge, this is the first communitybsed pprisl of the effects of D- nd L-lctte on mortlity of ptients with trum in n dministrtive dtbse. The use of mechnicl ventiltion explined most of the vrition in mortlity, wheres D-lctte volume, but not Ringer's DLor Ringer's L-lctte, explined some of the vrition in mortlity. In ddition, greter L-lctte nd lower D-lctte volume reduced the likelihood of mechnicl ventiltion strting lter thn 48 hours fter dmission. Ringer's solution, which mimics the electrolyte composition of the extrcellulr fluid, hs become stndrd of cre, prticulrly in hemorrhgic shock, to correct extrcellulr fluid deficits [3]. Lctic cidosis my occur, nd the resulting nerobic conditions could result in multiple-orgn filure nd deth [4,5]. Lctte my become villin becuse D-lctte ws reported to hve higher toxicity compred with L-lctte, which is metbolized quicker thn D-lctte [1]. Therefore, Ringer's L-lctte is incresingly being used in rel clinicl settings, s indicted in this study. Nevertheless, this study lso showed wide vritions in the types nd men volume of fluids dministered per dy, beyond Ringer's solution, nd some of these fluids were ssocited with mortlity. The evlution of n extensive rnge of fluid types nd volumes in this study is justified becuse blood products, proxy of cogulopthy, were lso ssocited with mortlity (Tble 3) s were other fluids tht contined DL-lctte (Fig. 2). Although
Outcomes of L-lctte fluids we ctegorized ptients ccording to the presence of D-lctte in Ringer's solution, D-lctte ws still present in some isotonic or hypotonic fluids tht were dministered during hospitliztion. Therefore, physicins should py ttention to the presence of D-lctte in resuscittion fluids. The reltionships between DL-or L-lctte nd subsequent dverse events in humns hve not been sufficiently exmined, except in one cse series [9]. In ddition, mortlity rtes were influenced by other fctors such s PS, s evluted by the Trum nd Injury Severity Score method. Similrly, the use of blood products nd mechnicl ventiltion s proxies of hemtologic bnormlities nd respirtory filure, respectively should lso be included in models tht re used to evlute mortlity. Fluid mngement strtegies nd DL-lctte volume were not ssocited with mortlity. Insted, strting mechnicl ventiltion lter thn 48 hours fter dmission best predicted mortlity. In n ttempt to estblish cuslity mong these prdigmtic reltionships, we exmined volume-relted vribles ccording to the dy on which mechnicl ventiltion ws strted. In these nlyses, the likelihood of strting mechnicl ventiltion lter thn 48 hours postdmission incresed nd decresed bsed on the dministrtion of greter volumes of D- nd L-lctte dministered per dy, respectively, before strting mechnicl ventiltion. Accordingly, D- nd L-lcttes re indirectly ssocited with mortlity. These findings might endorse the reports tht prolonged exposure to high lctte concentrtions nd higher lctte concentrtions is correlted with multiple-orgn filure. Furthermore, D-lctte is considered deleterious becuse it impirs leukocytes nd ccelertes cell poptosis [1,4]. In ddition, the findings lso support the recommendtion tht Ringer's DL-lctte should not be used s n excipient for hemoglobin-bsed oxygen crriers [6,7]. It hs long remined to be tested whether the use of Ringer's lctte contining different lctte isomers ctully ffects the outcomes of ptients with trum. Thus, the present study should encourge physicins nd helth service reserchers to shift the fluid mngement strtegy from Ringer's DL-lctte to Ringer's L-lctte, to be wre of the presence of D-lctte in other fluids, nd to conduct similr studies in clinicl settings other thn trum. Such studies should lso simultneously evlute the impct of colloid or hydroxyethyl strch on ptient outcomes [3]. Helth policy mkers should lso encourge hospitls nd mnufcturers to bndon Ringer's DL-lctte s soon s possible nd to stop dding D-lctte to fluid formul. Some limittions regrding the design of our study nd the interprettion of our findings should be mentioned. First, informtion ws gthered from dischrged ptients for only 6 months during ech study yer. However, since 2010, the dtbse hs strted to include ptients dmitted throughout the yer nd hs strted to collect informtion such s the height nd weight of ptients. Becuse the use of Ringer's DL-lctte hs not been chnged over the 4 yers, s shown in Tble 1, more precise estimtes of the effects of lctte my be possible by normlizing fluid volume by the number of dys on which the fluid ws dministered nd body weight. Second, this study lcked informtion regrding lbortory findings of ph or fluid blnce, s well s cute physiology nd chronic helth evlutions. Insted, processbsed severity ws considered bsed on the finding tht the use of mechnicl ventiltion explined most of the vrition in mortlity. Third, vritions in hospitl prctices regrding the use of mechnicl ventiltion were not considered in this nlysis. The choice of Ringer's DL-lctte or L-lctte ws minly t the discretion of ech hospitl, except in 61 hospitls tht dministered both Ringer's DL- nd L-lcttes to the sme ptients. The MHLW determined the verge cost of Ringer's DL-lctte nd L-lctte to be US $20 (7 sources) nd US $20 (19 sources), respectively, for 250-mL bottles; US $19 (36 sources) nd US $26 (29 sources), respectively, for 500-mL bottles; nd US $29 (6 sources) nd US $55 (9 sources), respectively, for 1000-mL bottles. Although Ringer's L-lctte is more expensive thn Ringer's DL-lctte, economic incentives, under the current cost continment pyment in Jpn, would be overcome by the prctice of using Ringer's L-lctte in hospitls, except in the 61 hospitls tht use both fluids. Fluid mngement strtegies might ccount for some vritions in hospitl prctices becuse ptients receiving fluids other thn Ringer's D- lctte were more likely to receive mechnicl ventiltion lter thn 48 hours fter dmission (Tble 3). In conclusion, we used n dministrtive dtbse to exmine the impct of D- or L-lctte dministrtion on the outcomes of ptients with trum. D-Lctte, but not L- lctte, ws significntly ssocited with incresed mortlity. 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