Hospital. 50%1. of the body surface, that is, such patients in. area of full-thickness skin-loss are percentages of the

Transcription

1 J. clin. Pth. (1957), 1, 1. From the THE CLINICAL CONTROL OF RED CELL LOSS IN BURNS BY Medicl ELIZABETH TOPLEY AN D D. MAcG. JACKSON Reserch Council industril Injuries nd Burns Reserch Unit, Birminghm Accident Hospitl (RECEIVED FOR PUBLICATION APRIL 14, 1956) The purpose of this pper is to define the red cell loss in burned ptients when the hemoglobin nd blood volume re kept bove 75% of norml. Our im hs been to present the results in mnner which will be useful to surgeons mnging the blood trnsfusion of these ptients. With this in view the predictbility of red cell loss hs been reviewed in reltion to the res of prtly nd completely burned skin, to hemtocrits, hemoglobin vlues, nd red cell counts on the peripherl blood, to red cell volume estimtions, nd to clinicl signs such s hemoglobinuri. The development of nemi in bdly burned ptients hs been recognized by surgeons for mny yers, nd hs been ttributed to obvious externl loss such s bleeding grnultions or blood loss t opertion. An impired rte of red cell formtion hs been suggested s one cuse of the more chronic nemi (Cope, 1947). Only recently hs n unexplined internl disppernce of red cells been considered to ply mjor role. The work of Shen nd Hm (1943), Brown (1946), nd more recently Dvies nd Topley (1956) shows tht the immedite effect of het is responsible for red cell loss mounting on verge to only bout 5 to 1% of the red cell volume. The pioneer work of Moore, Pecock, Blkely, nd Cope (1946) hs been followed by lter evidence (Dvies nd Topley, 1956) which grees tht there is further unexplined internl disppernce of ptients' nd trnsfused cells tht my show s erly s eight hours fter injury nd continue for mny weeks. For exmple, one of Moore's cses (Moore et l., 1946) showed loss of bout 3 ml. of pcked red cells dy for the first three dys, nd required frequent blood trnsfusions for 1 weeks. This mssive unexplined disppernce of red cells fter extensive burns presents surgeons with such clinicl questions s, "When does this destruction occur?" "How gret is it?", nd " How urgent is its replcement?" B METHODS Ptients The dt hve been obtined from 15 cses treted in the Birminghm Accident Hospitl Burns Unit between 1952 nd They were selected so s to include prepondernce of burns involving 15-5%1. of the body surfce, tht is, such ptients in whom previous experience hd shown tht nemi ws likely to develop (Brithwite nd Moore, 1948). Occsionl smller burns hve been included in the study, nd during the lst yer some of the more extensive burns with poor prognosis hve been studied in detil. Mesurement of the Burn The figures given for the totl re burned nd the re of full-thickness skin-loss re percentges of the totl surfce re of the body. " Full-thickness skinloss " implies complete destruction of ll epithelil elements in the skin, so tht epitheliliztion cn only occur from the edge of the wound or by grfting. The re of totl skin-loss excludes res burned to the degree of erythem only, nd the method of estimtion is bsed on tht of Berkow (1924, 1931). Ares of full-thickness skin-loss re checked two to three weeks fter injury when grnultions pper. Peripherl Blood Findings Becuse it ws rre to find gross chnges in the interreltionship between hemoglobin, hemtocrit, nd red cell count, these vlues cn be used interchngebly in our clcultions of blood loss ccording to convenience. We used hemtocrits during the shock stge becuse they were being crried out bout hourly for clinicl resons. We used red cell counts in our clcultions of blood loss becuse the dt were being used lso for clculting the differentil disppernce of ptients' nd trnsfused cells reported elsewhere (Dvies nd Topley, 1956). The norml hemoglobin nd red cell count for ge nd sex hs been tken from Wintrobe (1951). Hemoglobin.-Hemoglobin ws estimted s oxyhemoglobin using the Spekker photo-electric colori- J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

2 2 ELIZABETH TOPLEY nd D. McG. JACKSON meter, nd checking the clibrtion by monthly supply of blood of known hemoglobin content. Red Cell Counts.-Red cell counts were mde by visully counting t lest 1,2 cells. Hemtocrit.-In the bsence of venous hemtocrit the cpillry hemtocrit ws used s guide to the venous hemtocrit. During shock tretment, most hemtocrits were estimted on er cpillry blood. Smples were tken into specilly designed smll hemtocrit tube nd spun t high speed on n ngle centrifuge for bout 1 minutes. At the time of blood volume estimtions venous blood ws tken nd the hemtocrit estimted in Wintrobe tubes t speed of 3, r.p.m. in centrifuge of hed rdius 15 cm. for 55 minutes. Comprison of the two methods showed tht the ngle centrifuge gve reding bout.5% higher thn the Wintrobe method nd greter vrition (±3%). In order to llow for "trpped" plsm in the hemtocrit fter centrifuging, the following further figures were subtrcted from the reding to get the true venous hemtocrit (Chplin nd Mollison, 195): Hemtocrit Reding (%) Subtrct for Trpped Plsm (%) venous hemtocrit, ssuming norml body/venous hemtocrit rtio (Reeve, 1948). Blood volume ws clculted from red cell volume nd venous hemtocrit, ssuming norml body / venous hemtocrit rtio (Reeve, 1948). The norml vlues hve been tken from figure (Dvies nd Topley, 1956) summrizing published dt. Fig. 1 is more recent version which includes " norml " follow-up results on ptients in the Birminghm Accident Hospitl. The height is often more precise guide thn ge or weight. Individul ptients, especilly the dolescent, the very musculr, the very thin, or the very ft, my hve red cell volumes more thn 2% outside the norml vlue for height. Estimtes of Red Cell Loss The words " red cell loss " used here cover ll forms of red cell loss, whtever the cuse; thus, it my include hemorrhge, internl red cell destruction, nd impired rte of red cell formtion. Shock Stge.-During the shock stge, becuse the totl blood volume frequently vries, the peripherl blood findings re not relible guide to red cell loss. To estimte red cell loss we hve therefore relied entirely on red cell volume studies. The red cell loss is the difference between the expected "norml" red cell volume (Fig. 1) plus the volume of red cells trnsfused nd the ctul red cell The norml venous hemtocrit nd the HEIGHT, WEK;HT HAEMATCCRIT RB.C P.V. TOTAL B.V. vrition round the norml hs not been ccurtely defined in children or dults. (cm.) kq.) yr.) VENOUS eody (litres) (litres) (litres) The dt in Fig. 1 re bsed on vriety 4 33 *I -2 of sources (Seckel, 193; Gibson nd Evns, 1937; Brines, Gibson, nd Kunkel, I 1941; Russell, 1949; Wintrobe, 1951) ~3 * Blood Volumes Red cell volumes were crried out by injecting lbelled red cells intrvenously I.4 nd mesuring their dilution in the 6 blood strem by tking blood smple 2 F 12 IB from nother vein fter mixing hd 132 I I_ occurred. The ccurcy of this method in burned ptients is still under criticl 36 I review (Dvies nd Topley, 1956). The I 1 4 3" 1 -I possibility of flse low or flse high results 4 36 I4 I 2 should be continully borne in mind, prti- 16 5I culrly during the first four dys fter 4 injury The red cell volume is the dilution of lbelled cells multiplied by venous hemt ocrit. Rdioctive phosphte (Reeve nd Vell, 1949), rdioctive chromte (Mol lison nd Vell, 1955), nd group N cells trnsfused to group M ptients (Reeve, ) hve been used s lbelling gents. FIG. 1.-Averge norml vlues for plsm volume, red cell volume, nd blood The red cell volume hs lso been derived volume for different ges, weights, nd heights. *The figures for venous hemtocrithveboencorrectedfortrppedplsm (see text). The smples from the Evns blue plsm volume nd were centrifuged for 55 minutes t 3, r.p.m. J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

3 CLINICAL CONTROL OF RED CELL LOSS IN BURNS volume found using one of the methods described bove. The loss cn be expressed s percentge of the expected norml vlue, nmely, Expected RBCV from height or ge + volume RBC trnsfused - RBCV found x 1 Expected RBCV from height or ge The volume of red blood cells trnsfused is tken s one-third of the citrted blood trnsfused, becuse on n verge trnsfused blood hs hemtocrit of 33%. Admission to Opertion.-From dmission to opertion blood loss hs been clculted from peripherl blood findings. The chnges in the peripherl blood cn be used s guide to red cell loss if one ssumes tht the ptient hd norml red cell count for his ge t the time of the ccident, nd tht the blood volume hd returned to norml by the time of the first opertion two or three weeks lter. Twenty red cell volumes fter the first week nd before opertion by the P32, Cr51, or Evns blue methods showed on verge norml blood volume. There ws, however, firly wide sctter of results: 15 out of 2 ptients hd blood volume within 25% of norml. The red cell loss is the difference between the expected norml nd the pre-opertive red cell count expressed s percentge of the expected norml red cell count. Allownce hs to be mde for blood trnsfusion given t ny time before opertion. The expected effect on the ptient's red cell count by blood trnsfusion is the number of red cells trnsfused divided by the norml blood volume for the ge or height. The number of cells trnsfused hs been estimted on bottles trnsfused in this hospitl by testing specific grvity, weight, nd red cell count of the bottled blood before nd fter trnsfusion. A one-pint bottle in which bout 5 ml. of citrted blood hs been trnsfused is equivlent to bout 2 x 1' red cells. The expected red cell count from trnsfused cells therefore becomes: 2 x IO'J x volume of citrted blood trnsfused in ml. 5xBV in c.mm. x 16 millions /c.mm. At Opertion.-Red cell loss t opertion hs been clculted in number of different wys: (1) By Swb Weighing.-Guze swbs of predetermined weight were used nd reweighed fter use. The difference in weight ws lrgely due to whole blood loss of specific grvity 1.4. Moistened swbs were not used nd rubber sheet ws lid under the ptient. Generous use of lrge swbs reduced uncollected blood loss to minimum (Bronofsky, Trelor, nd Wngensteen, 1946). (2) By Red Cell Volume Studies.-A red cell volume estimtion ws occsionlly performed both before nd fter grfting opertion. (3) Peripherl Blood Findings.-If the blood volume ws norml on the dy of the tests the difference between the lst pre- nd first post-opertive red cell count is guide to red cell loss, fter llowing for the effect of blood trnsfused. The clcultion is exctly similr to tht described bove for blood loss from dmission to opertion, except tht the preopertive red cell count is tken insted of the expected norml for the ge. In most cses there ws not gret difference between the red cell count one dy fter opertion nd few dys lter, the results described below being essentilly similr if the red cell count the dy fter opertion or the lowest figure during the ensuing dys ws tken s the postopertive result. Between nd After Opertions.-Blood loss between nd blood loss fter opertions hve been clculted from peripherl blood findings. For blood loss between opertions the first postopertive red cell count hs been compred with the count before the next opertion. For the loss fter opertion the first post-opertive count hs been compred with count on dischrge from hospitl. RESULTS The verge red cell loss t different periods fter dmission is shown in Fig. 2. The gretest mount of blood is lost during opertion; in these studies, when more thn one skin-grfting opertion hs been necessry, the sum of the blood loss in ll op.rtions hs been dded together: the verge loss nd lso the mount trnsfused during this prt of tretment hs mounted to 135% of the ptient's red cells (Fig. 2). The next most importnt period in this respect is the two to three weeks from injury to opertion: red cell loss during this time hs verged 45% of the red cells. Prt of this loss occurs during the shock stge, rbitrrily fixed t the first 48 hours, nd this is of specil importnce, not so much due to the nemi produced, but becuse filure to pprecite the degree of red cell destruction my hide severe oligemi which my prove ftl. By the time of dischrge from hospitl the ptient's E; gj 33 OPERATIONS BETWEEN AFTER OPERATIOS OPERATONS FIG. 2.-Averge red cell loss, bsed on peripherl blood findings, t different stges fter injury. Figures bove ech column refer to numbers of ptients studied. 3 J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

4 HAEMOGLOBIN VALUES BURN TO OPERATION "'EARLY CASES I8 4 35% w.si.l 12 F ~ t % w.s.i. x -- 18% w.sil. / < ~~~~~~~~~~17 % W. S.. 12t---~~~~~~~~~~~~~~'-- - -r^ 14% w.s.i W. S.I r n6o W. s _5 17 no w.s.l glate' CASES 6 5% W.S.i. 8 36% w.s. t 18ii 34% w.s.. (7-279% w.s.l. 9 'ii ~ 23% W.S.l. 15 2%7' w.s.l. z LU ---x '5 2% w.s.l l navc AFTFQ RliPNIIN, DAYS AFTER BURNING LUAYb Ar V1s14 WSL.= AREA OF WHOLE SKIN LOSS. t = BLOOD TRANSFUSIONS. --- = NORMAL Hb. FOR AGE. 15 2% w.s.l. 9i) 2% w.s z I99 I54 19 ~~~~~~12%o w.s.l. -15% w.s.i. 15% w.s % w.s.&i. r 12~ ~~~~~~% ~ w.s % 615 w.s-i. w.s.l. W1-8-_ 21j -t _.3f w.si. 21- FI. 3.-Hemoglobin chrts of ptien's given blood "erly" nd "lte." w.s.l.=re of whole skin-1lhss; I =blood trnsfusion; - -= norml hemoglobin for ge. J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

5 CLINICAL totl red cell loss verged 185 % of the ptient's red cells. The extent of red cell loss is described below in the order in which it occurs. Red Cell Loss from Burn to Opertion Guide to Red Cell Loss During Whole Period from Burn to Opertion.-Evidence is presented on how the dily hemoglobin chnges nd the re of the burn hve been used s guides in ssessing more precisely the red cell loss in individul ptients. Dily Hemoglobin.-Dily hemoglobin estimtions show chrcteristic pttern. The chnges in the peripherl blood re shown in Fig. 3. Ech chrt represents one ptient, nd the ptients re rnked in order of decresing re of full-thickness skin-loss. The level remined stedy or even rose during the first dy or two, fell shrply, nd then often continued to fll until opertion two to three weeks fter dmission. If blood trnsfusion hd been given on dmission (Fig. 3 " erly ") the hemoglobin level ws t first high nd fell towrds nd often below norml. If blood trnsfusion ws withheld until nemi developed (Fig. 3 " lte") the hemoglobin level, t first slightly bove or ner norml, fell to levels -4- Un J -3- U-2 C o- +1~ S CONTROL OF RED CELL LOSS IN BURNS below norml, often reching 2% below norml between the sixth nd tenth dy fter dmission. Comprison of these hemoglobin curves (Fig. 3 "lte ") with our red cell volume dt (Fig. 4) shows tht, during the first two dys when the hemoglobin concentrtion in the peripherl blood ws ner norml, red cell loss hd lredy occurred. The hemoglobin therefore often underestimted the red cell loss. As shown under " methods " bove, from the seventh dy onwrd the hemoglobin ws modertely good guide to the red cell loss, nd low figure due to excessive hemodilution ws rre. Since the rte of red cell loss is so very vrible from ptient to ptient, we emphsize the need for seril hemoglobin estimtions in order to know in individul ptients when the hemoglobin, nd therefore probbly the red cell volume, hs fllen to levels tht my indicte the need for further blood trnsfusion. It is importnt to emphsize the limited vlue of these results during the first few dys fter injury. Are of Full-thickness Skin-loss.-Fig. 5 is sctter digrm showing the reltionship between the estimted re of full-thickness skin-loss nd the red cell loss between burn nd opertion clculted from the chnges in the peripherl blood i ' r.,29 v v.25h--i --i I 6 56, 29 -i =H-i- I -. I 9 7 dr-w is. ib 26 * AREA OF FULL SKIN LOSS 6 (. B. k d 4 5 TOTAL AREA OF BURN t OF BODY SURFACE FIG. 4.-Rei cell loss, bsed on red cell volume studies, hours fter injury relted to () re of full-thickness skin-loss (36 cses), (b) totl re of burn (38 cses). M=P32. O=GG1 *=Evns blue. S 5 J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

6 6 ELIZABETH TOPLEY nd D. McG. JACKSON The rtionle of our present trnsfusion policy is bsed on these results. (1) Full-thickness skin-loss up to 1% of the body surfce: it cn be seen from Fig. 5 tht no cses (/16) showed red cell loss of more thn 4% of their red cells from burn to opertion. In only hlf the ptients did the loss exceed 25% of the red cells. In bout hlf the cses therefore no blood trnsfusion ws required t ny time before opertion. On the bsis of this dt we do not give blood trnsfusion on dmission to ptients with less thn 1% full-thickness skin-loss. A blood trnsfusion is given when the hemoglobin hs fllen below 75 to 8% of the expected norml for the ge. I.- U) U) -.3 JI O% I.- UA -j -J hi hli so 4 3 I(.--I IV T c ~ S.. *: ;' o. 7 DAYS AER DM I I p r,. 7b AREA OF FULL SKIN LOSS ( b OF BODY SURFACE),~. ~ ~ ~ ~ ~ ~ C) X _ * 2+_ * MMgCfLTAJgM ( 2r4-3rd week ter burn) 4 *. *9 * 1. s. %. r t S *: s5 6 AREA OF FULL SKIN LOSS ('/o OF OM SUFAE) FIG. 5.-Red cell loss, bsed on peripherl blood findings, between burn nd first opertion relted to re of full-thickness skinloss (74 cses). 9 J J CM J Q I K)O O-. 7; so o- - I S;t eel İ TOrAL AREA OF BURN(/O OF Y SURFACE) RMOMMM (2 dwmk fter burn) ~~~~~~ *.. *: S : 9 *g e * * *.* *. ' ' * TOTAL AEA of mmrn (% of BODY SUcE) FIG. 6.-Red cell loss, bsed on peripherl blood findings, between burn nd first opertion relted to totl re of burn (74 cses). (2) Full-thickness skin-loss 15% or more of body surfce: it cn be seen from Fig. 5 tht only 1 out of 54 ptients hd red cell loss of less thn 25% from burn to opertion. Thirty-two out of 54 ptients showed red cell losses of 2 to 6%. Fourteen out of 54 ptients hd greter losses (6-115%) of red cells tht necessitted repeted blood trnsfusions before opertion. These 14 ptients could not be differentited cliniclly from the other cses tht lost less red cells, but were detected by repeted hemoglobin tests. On the bsis of this dt blood trnsfusion equivlent to 2 to 4% of the ptient's norml red cell volume is given during shock tretment to burns with more thn 15% of full-thickness skin-loss, nd the need for further trnsfusion is checked by hemoglobin tests. J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

7 CLINICAL CONTROL OF RED CELL LOSS IN BURNS Totl Are of Burn.-Fig. 6 is sctter digrm showing the reltionship between the estimted totl re of the burn nd the red cell loss between burn nd opertion. It cn be seen tht burns of totl re less thn 2% often showed red cell loss of less thn 25% of the red cells nd my therefore not require blood trnsfusion before opertion. Lrger burns often lost enough red cells to necessitte blood trnsfusion equivlent to 4% of the norml red cell volume before opertion. Timing of Blood Trnsfusion Equivlent to 4% of Norml Red Cell Volume.-We hve ccepted the desirbility of reducing s fr s possible the number of blood trnsfusions, prtly becuse of shortge of veins when limbs re burned nd prtly to prevent wste of blood. In mny children trnsfusion of less thn 4% of the blood volume involves using only frction of 5 ml. bottle of blood. Aginst this bckground we hve concluded s described bove tht blood trnsfusion of 4% of the norml red cell volume will be required in most ptients with burns involving more thn 15% of full-thickness skin-loss. Such lrge erly trnsfusion theoreticlly hs possible disdvntges s well s dvntges. A controlled tril ws therefore crried out in which hlf the ptients hd trnsfusion " erly," tht is immeditely creful nd complete typing nd cross-mtching hd been crried out, of 3 to 4 % of the norml blood volume for the ge (21 cses). The other hlf did not receive such blood trnsfusion until the hemoglobin hd fllen to 2% below norml ("lte," 18 cses). Ptients who on dmission were considered to hve less thn 1% or more thn 4% of fullthickness skin-loss were excluded from the tril, s the former often never require blood nd, s described below, the ltter were considered to need it during the shock stge. Whether the blood ws to be given erly or lte ws decided from prerrnged list in which the deciding fctor ws the hospitl number llotted in the receiving sttion before dmission to the Burns Unit. Tble I summrizes some of the findings nd Fig. 3 shows the res of full-thickness skin-loss, blood trnsfusions, nd hemoglobin chrts of the first 3 cses in the tril. The two series of ptients proved comprble s regrds ge nd res burned. This very smll controlled tril showed no overriding clinicl dvntge of replcing the red cell loss erly. The expected nd ctul mortlity ws similr in the two series. There were two cses of septicemi mong the ptients TABLE I RESULTS OF CONTROLLED TRIAL OF "EARLY" AND " LATE" BLOOD TRANSFUSION Blood trnsfusion.... " Erly" "Lte" Number of ptients Mortlity: Expected from ge nd re Died 3 2 Blood trnsfusions before opertion: Totl trnsfusions required Men volume per ptient, expressed s 7 norml blood volume % 4/ Peripherl blood trend.. Initil polycyth- Initil normlity, emi, devel- developing oping lter erly nemi nemi Pre-opertion hemoglobin, s % of expected norml for ge: Number of ptients observed 2 18 Rnge % % Men 1% 98% Highest reticulocyte counts up to opertion (count per 1 red cells): Number of ptients observed Rnge Men receiving blood lte (totl re 3% nd 55% of the body surfce) nd none mong those receiving blood erly, but the numbers of cses re too smll to sy tht this could not hve occurred by chnce lone. The pulse, temperture, nd respirtion were similr in the two series if one excludes the two cses of septicemi. The biochemicl bnormlities of the nemi s reflected in the serum iron, the iron-binding cpcity, nd the erythrocyte protoporphyrin content were on the verge not significntly different in the two series, nor ws the men cell hemoglobin or the men cell dimeter. Individul children, however, given blood lte did show greter drop in men cell hemoglobin nd in serum iron thn observed in ny cse given blood erly. The possible prcticl dvntges of giving blood lte ws tht polycythemi ws voided nd some sving obtined in the number of blood trnsfusions required. It cn be seen from Fig. 4 tht two " lte" ptients (3% nd 12% fullthickness skin-loss) never required blood trnsfusion, nd from Tble I tht 28 trnsfusions were given to 21 ptients given blood erly nd only 18 trnsfusions to 18 ptients given blood lte. The totl volume of blood trnsfused nd the preopertive hemoglobin levels obtined were not very different in the two series. Although it is theoreticlly likely tht the rte of red cell formtion ws greter in ptients given blood lte, the 7 J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

8 8 ELIZABETH TOPLEY nd D. Mc-G. JACKSON difference in reticulocyte count in these cses ws not significntly higher sttisticlly thn in the erly cses. On blnce therefore we found in this smll series of cses no importnt dvntge or disdvntge of giving blood erly to ptients with less thn 4% burns. Our guess is tht those who did not lose more thn 2% of their red cells during the shock stge might well hve blood lte; those who did lose more thn 2% of their red cells would be better for hving it erly. We hve lernt tht ptients with less thn 2% burns re unlikely to suffer this loss; the difficulty is to define beforehnd which of the ptients with burns involving totl re of more thn 2% (or 15% of full-thickness skin-loss) will suffer this loss of blood. Guide to Red Cell Loss During Shock Stge.- The gretest single fctor in the production of burns shock is the loss of "plsm," nd the rte of loss becomes criticl when the burn is more thn bout 1 % of the body surfce in child, or 15 in n dult, excluding erythem. The im of tretment is to keep the blood volume norml by replcing the plsm loss s it occurs. If the red cell volume remins constnt, the hemtocrit will reflect the blnce between the plsm lost nd trnsfused, nd it cn in fct be used to mesure the degree nd rte of the loss from hour to hour. If, however, red cell loss is occurring the blood volume my fll while the hemtocrit does not. Replcement of the vrible red cell loss must clerly be bsed on mesurement, nd the dt presented here were collected in n ttempt to define how the degree of red cell loss could be ssessed during the shock stge nd the blood volume ccurtely controlled. Degree nd Time of Red Cell Loss.-It hs been shown (Dvies nd Topley, 1956) tht during the first 12 hours on verge only 12% of circulting red cells re lost fter burn involving 5 to 8% of the body surfce. It is rre for more thn 25% of red cells to dispper in this time (1 in 14 cses using the most ccurte methods). For this reson we my ssume in mnging n individul ptient tht somewhere between nd 25% of red cells hs been lost, nd tht therefore in most cses the blood volume will not fll more thn 2% below norml if the hemtocrit is kept t the expected norml for the ge. More dt re required to check the vlidity of this ssumption, prticulrly in very extensive (more thn 4%) burns. Between 12 nd 48 hours fter injury cliniclly importnt nd even mssive red cell loss cn occur. Fig. 4 is sctter digrm relting re of burn to extent of red cell loss estimted by vriety of red cell volume techniques. It cn be seen tht in 11 instnces (eight ptients) 4 to 7% of the red cell volume hd disppered. Red Cell Volume Studies. These re themselves open to criticism in the shock stge, prtly becuse of the dely in mixing time of ny redcell suspension or fluid injected intrvenously, prtly becuse of the possibility of very lrge volumes of " trpped " unmesured blood, nd prtly becuse the ptient's norml red cell volume is not precisely known. Our knowledge of the estimted norml red cell volume (Fig. 1) is bsed lrgely on other people's reported results (see bove). The relibility of red cell volume estimtes needs further checking by duplicte nd repeted mesurements on the sme ptient, nd by comprison of results with other clinicl nd lbortory evidence. In spite of these limittions the probble vlue of repeted red cell volume estimtions s the only mens of mesuring cliniclly importnt red cell loss when it occurs is shown in cses such s 2, 3, nd 4 below. Are of Burni. Both the totl re nd the re of full-thickness skin-loss ws not useful guide for excluding the risk of cliniclly importnt red cell loss in ptients with burns involving 2% or more of the body surfce. It cn be seen from the sctter digrms (Fig. 4, nd b) tht number of ptients with burns even s smll s 2%/ of the totl body surfce showed disppernce of red cells equl to 4' or more of the red cell volume during the first 48 hours fter injury. Red cell volume studies hve not been done on mnx! smller burns t present, but the lter hemoglobin levels suggest tht much less red cell loss occurs. Losses of more thn 5% of the red cell volume in the first 48 hours hve been found so fr minly in burns involving more thn 7" of totl re. Hemoglobin, Hemintocrit, nd Other Clhnges in Peripherl Blood.-Peripherl blood findings were of limited vlue s guide to cliniclly importnt red cell loss during the shock stge. It is uncommon (Cse 4) to find fll in red cell volume to be ssocited with fll in hemtocrit of greter degree thn tht expected from the rtes of plsm therpy nd expected plsm loss t the time. Further repeted red cell volume studies re required to define this position more clerly. Free Hemoglobin in Urine nd Plsm.-Free hemoglobin, hemturi, or both, hs been seen in some burns involving more thn 2% of the body surfce, sometimes on dmission nd often J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

9 CLINICAL CONTROL OF RED CELL LOSS IN BURNS gin or for the first time during the ensuing 48 hours (Shen nd Hm, 1943). The lrge mjority of our cses showing hemoglobinuri hve shown red cell loss rnging from 1 to 25% during the first 12 hours, nd of more thn 25% between 12 nd 48 hours fter injury. The results demonstrte tht cliniclly serious flls in red cell volume often occur in the first 48 hours in the presence of hemoglobinuri. More investigtions re required to know how often red cell loss greter thn 25 % of norml cn occur in the first 48 hours in the bsence of hemoglobinuri. So fr we hve seen such loss in only smll minority of cses. Very Smll Red Cells nd Frgments Seen in Blood Films.-The morphologicl chnges in red cells hve been described in detil by Brown (1946) nd Shen nd Hm (1943). We hve rbitrrily defined microcyte s ny pink-stining cell in Romnowski-stined film less thn.3,u in mximum dimeter (Fig. 7). These microcytes hve constituted from to 2% of the cells in the hed of blood film tken within the first few hours fter injury. Only smll minority re true spherocytes: most re probbly het-frgmented red cells. Experience on smll number of cses suggested tht ptients with more thn 2% of microcytes in the blood film on dmission frequently developed lter hemoglobinuri even if this ws bsent on dmission, nd frequently both ptient's nd trnsfused cells disppered to lrge extent during the next few dys. For this reson our red cell volume studies so fr hve concentrted on ptients showing more thn 2% of FIG. 7.-Blood filnm microcytes on dmission. When more thn 2k', of microcytes were seen on dmission, cliniclly importnt (more thn 25%) red cell loss occurred lter in nine out of 13 cses. Red cell losses of more thn 25 % of the norml volume hve not been found in ny of the six ptients whose blood film showed less thn 1 % of microcytes. But it is too erly to be confident tht the bsence of microcytes entirely precludes the risk of cliniclly serious red cell loss. Skin Temperture nd Vsculr Response to Skin Pressure.-Circultion often ppered norml in ptients with red cell nd totl blood volume more thn 2% below norml. Only in rre cses, such s Cse 4 described below, did mrked increse in skin coldness nd pllor develop with the cute red cell loss due to melen. In some ptients cold skin with poor circultion ws present when the blood volume ws only some 1% below norml. To summrize, in burns involving more thn 15% of full-thickness skin-loss, or 2% totl re, red cell volume studies pper to be the only wy of checking tht the red cell volume does not fll more thn 2%' below norml during the 48 hours fter burning. At the present time the presence of hemoglobinuri, or more thn 2% of microcytes in the hed of blood film, or burn involving more thn 5% of the body surfce, re regrded s specil indiction for such red cell volume studies. Cse records to illustrte the significnce nd prcticl ppliction of these guides to red cell loss re given below: they show how hemtocrit nd blood volume estimtions cn be combined in controlling the ptient's blood ff volume. The cses re pre- / r X sented in order of incresing / severity nd show incresing -rbc /rbc of ptient on dmission showing " microcytes." m = microcytes; rbc = norml red blood cell; p=pltelets. clinicl evidence of serious red cell loss. Illustrtive Cses Cse 1.-An 11-yer-old girl received 16 o burn of both legs nd buttocks when her clothes were set light : 14,% of the body surfce ws full-thickness skin-loss. (Her height ws 13 cm. nd verge norml vlues for this height were: blood volume (B.V.) 1.85 litres; red blood cell volume (R.B.C.V.).67 litres; body hemtocrit 9 J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

10 1 : 2- s- 3 R.QC.V. B.H B.V 8- ml i4- ELIZABETH TOPLEY nd D. McG. JACKSON ---_---- INITIAL EXPECTED HCRIT I~~~~~ 75 L. 612) 42, 78 L. (967/ ^] III...E Kn r t1tlti=...selsl]l 75 L(1121) 43% 1.73 L(93%) [rffl Ih Of1 'iihi]iiiinnirn i"iiiiiiii Fiiin HOURS 6 73 L 69%) 43% 1.68 L(91%) FIG. 8.-Cse 1, 11 yers; 16% burn. No microcytes on dmission blood film. (B.H.) 36y, ; venous hemtocrit (V.H.) 4 O.) Fig. 8 illustrtes the findings. On ccount of the size of this burn serious red cell loss in the shock stge ws unlikely, lthough wtch ws kept for signs of it. The first venous hemtocrit estimtion two hours fter injury ws 49% : this corresponds with body hemtocrit of 44%o. Using the verge red cell volume figure for her height (67 ml.) nd ssuming no red cell loss, her blood volume t this time ws 1.52 litres. which is equivlent to plsm loss of 33 ml. This rte of loss ws therefore 165 ml. n hour. Three times this hourly loss of plsm (5 ml.) should hve been given in the third hour to restore the hemtocrit to norml. Actully 7 ml. ws given with consequent lowering of the hemtocrit below norml. For the first 1 hours n ttempt ws mde to keep the blood volume nd the hemtocrit round norml; fter this the venous hemtocrit ws llowed to rise to 45%, which theoreticlly should hve reduced the blood volume to 9% of norml, n oligemi for which the body cn esily compenste. However, red cell volume estimtion t 24 hours showed the red cell volume little higher thn the expected verge (112%h) nd the blood volume virtully norml (96%). The plsm trnsfusion ws stopped t 34 hours. fter 1.89 litres hd been given. During this time the verge urinry output since injury ws 4 ml.,' hour. This cse illustrtes the routine methods of blood volume control. In the smller shock cse with less thn 15 o1 full-thickness skin-loss seril hemtocrit estimtions re good clinicl guide to the blood volume, the error being probbly less thn 2',,. They should be used in conjunction with the urine output, nd, in ptients over the ge of 1 yers. with the rough formul tht 1 1- litres of plsm will be required for ech 1o body surfce re burned. Cse 2.-A 4-yer-old girl received 46% burn of the trunk nd legs when her nightdress cught fire: 4' of the body surfce ws full-thickness skin-loss. (Her height ws 15 cm.; verge norml vlues for this height were: blood volume 1.25 litres; red blood cell volume.44 litres; body hemtocrit 35o, nd venous hemtocrit 39 ".) Fig. 9 illustrtes these dt. Two hours fter burning plsm trnsfusion ws strted, nd the hemtocrit, which ws 47., ws brought down to norml over six hours. During this time blood film showed moderte number of microcytes nd she produced 35 ml. of bloodstined vomit. She ws then given 5 ml. of blood (bout 4o of the blood volume) in the next two hours. Assuming tht none of the red cells were destroyed this trnsfusion would hve incresed the red cell volume to.6 litres, nd when the blood volume ws norml the body hemtocrit would be 48' nd venous hemtocrit 53. I,) 55-? 35 FRBLCV BL R v. 4- ml 8 ~2 -j -J. uj lo z - & FINITIAL EXPECTED H'CRIT 4 4~4~!~ li. 5 L(113%.48 L(CO9%) 34% 41% 49 L (119%) 116 L (93) HOJRS 57 L(13%) 33% 71 L (132%) FIG. 9.-Cse 2, 4 yers; 46% burn. Microcytes on dmission blood film. J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

11 CLINICAL CONTROL OF RED CELL LOSS IN BURNS The red cell volume estimte t the end of trnsfusion ws.5 litres, showing there hd been loss of 25% of red cells by 1 hours. Accordingly n ttempt ws mde to keep the hemtocrit round 44%, the figure corresponding to red cell volume of.5 litres nd norml blood volume. A second red cell volume estimte t 24 hours showed only slight further fll in red cell volume, showing tht the seril hemtocrits hd proved useful guide to plsm therpy. It seemed tht n unusully lrge mount of plsm ws required in this cse, nd ttempts were mde during tretment to reduce the rte of dministrtion. This resulted in trnsient rise of hemtocrit nd oliguri, nd it ws therefore ssumed tht this cse required more plsm thn norml. A third red cell volume estimtion t 48 hours ctully showed rised figure (.57 litres), which could be due to mobiliztion of bout 2% more red cells. The trnsfusion ws finlly stopped t 53 hours, fter giving 8 litres of plsm nd 5 ml. of citrted blood. The seril hemtocrit findings nd the blood volume estimtion t 48 hours (132% of norml) both suggested over-trnsfusion in the lst eight hours of plsm therpy. Further progress ws uneventful: fter two grfting opertions the burn ws finlly heled in 8 dys. This ptient lost 25% of her red cells during the first 12 hours fter burning nd lost little lter; this is in contrst to some other ptients who lost considerble mount lter (Cse 4). The first blood volume mesurement ws guide to the correct level t which to keep the hemtocrit (44%), nd the lter seril hemtocrits proved useful in giving sufficient colloid to mintin norml blood volume. It my be tht more plsm is required thn is used in common prctice to-dy if norml blood volume is to be preserved throughout the shock stge, but whether it is cliniclly desirble to mintin norml blood volume by giving more plsm is s yet unproved. An unexplined rise in red cell volume nd of blood volume during the second or third dy occurred in this nd other ptients. Although not evident in this ptient, the possibility exists tht the hypervolemi my cuse serious crdic embrrssment. Cse 3.-A 1-yer-old girl received 65% burn of her trunk, rms, nd legs when her frock cught light from n ungurded fire: 6% of the body surfce ws full-thickness skin-loss (Fig. 1). (Her height ws 129 cm.; verge norml vlues for this height were: blood volume 1.8 litres; red blood cell volume.65 litres; body hemtocrit 36% ; venous hemtocrit 4%.) Forty minutes fter burning the hemtocrit ws 46%' nd it ws brought below norml within n hour by 8 ml. of plsm. During the following hour. while the hemtocrit ws kept stedy, ctheteriztion reveled hemoglobinuri, blood film showed moderte number of microcytes, nd the extremities remined cold: ll evidence therefore - I > 4 -. NEW EXPECTED H'CRIT IF NO RED CELL LOSS 42% (11%) 1 8 L (1%) 48 6 HOURS FIG. 1.-Cse 3, 1 yers; 65% burn. Microcytes on dmission blood film. pointed to some red cell destruction. One litre of blood ws given (equivlent to bout 5% of the red cell volume), together with more plsm to mintin the plsm volume. This would be expected to rise the red cell volume to.98 litres if there ws no red cell destruction, nd when the blood volume ws norml the body hemtocrit would be 55%, nd the venous hemtocrit 6%. A blood volume estimtion t the end of the blood trnsfusion six hours fter injury showed the red cell volume to be.85 litres (131% of norml); the body hemtocrit ws 43% nd the blood volume 1.98 litres (11%/o of norml). There hd been loss of 2%' of the ptient's own red cells. Hemoglobinuri continued till 17 hours nd then clered, but it returned second time from 29 to 47 hours before finlly cesing. Following the blood trnsfusion nd red cell volume estimtion n ttempt ws mde to keep the hemtocrit round 47%, which ws the expected figure to fit in with the mesured 2% loss of red cells nd norml blood volume. But t 3 hours second blood volume estimtion ws indicted when hemoglobinuri reppered. This second estimte showed red cell volume of.75 litres (115% of norml), nd, since the body IL I1I J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

12 I 12 I I. ELIZABETH TOPLEY nd D. McG. JACKSON hemtocrit ws 42%, the blood volume ws bout of blood ws given (equl to bout hlf his blood 1.8 litres (norml). In other words, by 3 hours volume), together with more plsm. If no red cells the red cell loss hd incresed to 36%. hd been destroyed this trnsfusion would hve rised It is usully possible to terminte the plsm trnsfusion t 36 to 48 hours without oligemi resulting. volume ws norml the body hemtocrit would hve the red cell volume to.63 litres, nd when the blood but in this cse it ws continued, s further red been 52/,h nd the venous hemtocrit 57 O. cell loss ws considered possible. A third red cell In prctice red cell volume estimtion t the end volume estimtion ws mde t 76 hours nd showed of trnsfusion, eight hours fter burning, ws.66 there hd been no further red cell loss since the litres (157% of norml): the body hemtocrit ws second estimte t 3 hours, but the blood volume 34 nd the blood volume ws therefore 1.92 litres hd been rised 2% bove norml by unnecessrily (152X of norml). These results supported the prolonging plsm therpy. hemtocrit in showing tht too much plsm hd By the tenth dy red cell volume estimte showed been given in the first four hours, nd tht we hd tht there hd been 7% loss of circulting red cells. been wrong in supposing tht ny cell destruction hd On the twelfth dy the child ws grfted with utogrfts nd homogrfts, but her condition grdully As tretment continued the rte of plsm trnsfu- tken plce by this time. deteriorted nd she died on the sixteenth dy. sion ws cut down stedily nd the hemtocrit An importnt feture of the shock stge of this stedied t round 45% the child's extremities were child ws the serious red cell destruction within six wrm nd the urine output high. A second red cell hours of injury, with further loss in the next 24 hours. volume estimtion ws mde t 14 hours nd this The first red cell volume mesurement enbled the ws now.5 litres (119%o of norml): since the body hemtocrit to be set t the correct level to obtin hemtocrit t the time ws 39o, the blood volume norml blood volume. The second confirmed tht regultion of the plsm NEFv EXPECTED H'CRIT IF NO RED CELL LOSS therpy by the hemtocrit did, in fct, mintin ner norml blood volume. 5- The third blood volume estimtion con- F firmed the hemtocrit evidence tht too 4 IDITIAL INTA\/XEPCTED EXPECTED HR --H much plsm hd been given, nd in s CRIT retrospect it ppers tht the trnsfusion 'n might well hve been stopped t hours. An unusul feture of the shock stge ws tht the blood volume ws 2 mintined t or bove norml insted R2C 66L 32 L (77%) of being llowed to fll somewht below 34% H. 39% 29% norml, s it commonly does in exten- B. 92Lt sive burns. A peculir nd possibly (152%) 3 L (17%) 11 L (92%) ssocited feture of the post-mortem 5 exmintion ws the bsence of diffuse ml. distl tubulr necrosis, which is lmost invribly seen fter such lrge burn (Sevitt, 1956). Cse 4. A boy, ged 4, received z 7 ' burn of the whole trunk nd both rms nd legs when his nightdress cught light; lmost ll the burn ws full-thickness skin-loss. (His height ws 14 cm.; verge norml vlues for this height were: blood volume 1.2 litres. red blood cell volume.42 litres, body hemtocrit 35%, venous hemtocrit 39%.) Within four hours of dmission the venous hemtocrit ws brought down from 39% to 3' : the im ws to bring z the hemtocrit little below norml, becuse blood film which hd been exmined during the time showed gross red cell destruction. During the second four-hour period trnsfusion of 62 ml. HOURS FIG. 11.-Cse 4, 4 yers; 7% burn. Microcytes on-dmission blood film. J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

13 CLINICAL CONTROL OF RED CELL LOSS IN BURNS ws bout 1.3 litres (17% of norml). By this time there hd therefore been bout 3% loss of the ptient's own cells, nd, in view of the blood volume still being slightly rised, there ws n indiction to reduce the rte of plsm therpy even further. Throughout the first three dys orl nd intrvenous non-colloid fluids were given t n verge rte of bout 6 ml. hourly (1,5 ml. dy). Between 24 nd 27 hours the child's hemtocrit begn to fll steeply, lthough only smll mount of plsm ws being given hourly: t 32 hours hemoglobinuri ppered. These findings were interpreted s internl hemorrhge or hemolytic rection, nd plsm trnsfusion ws continued stedily to correct the oligemi till further blood could be crossmtched: this ws done with considerble difficulty. At 37 hours mssive red cell loss ws confirmed by third red cell volume estimtion, which mesured.32 litres (77% of norml); the loss hd therefore incresed from 3% of the ptient's red cells t 14 hours to 74% t 37 hours. Since the body hemtocrit ws 29%, the blood volume ws bout 1.1 litres (92% of norml). At 44 hours jundice becme evident nd hemoglobinuri ws still present; t 48 hours the child hd melen. Between 5 nd 62 hours, 2.35 litres of blood ws given very slowly, n mount more thn the norml blood volume: this succeeded in restoring the hemtocrit to norml levels, the jundice fded, nd the hemoglobinuri cesed, but the urine ws very scnty nd poorly concentrted. During the fourth dy jundice returned. The child died on the fifth dy, nd post-mortem exmintion reveled bsl cerebrl hemorrhgend jundice. There ws diffuse distl tubulr necrosis (lower nephron nephrosis) (Sevitt, 1956), possibly due to the period of oligemi. An importnt feture of this cse is the time of red cell destruction: in contrst to Cse 2 the mjor loss ws fter 24 hours, nd lmost none before eight hours. This illustrtes the vrition from cse to cse. During the erly hours of tretment the hemtocrit suggested over-trnsfusion, but this informtion ws not cted upon until it ws confirmed by blood volume figure: this reluctnce to follow the hemtocrit findings in the cse of very extensive, deep burn, in which gross red cell destruction ws expected, proved mistken. Finlly, this cse illustrtes how mssive the red cell loss cn be when internl brekdown of red cells is combined with hemorrhge. Red Cell Loss During Opertion Those who re used to treting very extensive burns will gree tht stedy deteriortion of the ptient's generl condition is still the rule during the first three weeks fter injury, whtever the tretment nd in spite of ll supportive mesures. Our im in treting these cses hs been to strt nd continue the necessry skin grfting opertions with s little dely s possible so tht the burn wound is closed t the erliest moment. This hs usully involved stripping off the grnultions nd dherent slough by rpid blunt dissection during the third week, rther thn witing for the grnulting surfce to become clen by nturl processes week or two lter. Hemostsis is secured by elevtion, pressure, hot pcks, nd ligtures. The pre-opertive preprtion of the ptient hs included ensuring hemoglobin of over 8% of norml, nd hving sufficient homologous blood cross-mtched to stisfy ll resonble likelihood of opertion loss. The trnsfusion must, of course, be running stisfctorily before the opertion is strted when such lrge loss is expected. We hve shown tht the pre-opertive blood volume is on verge norml during the third week. Dily Post-opertive Hemoglobin.-Blood loss t opertion unreplced by blood trnsfused is reflected in flling hemoglobin during the ensuing three dys. We hve found the hemoglobin fll one nd three dys fter opertion useful clinicl guide, lthough in rre instnces the hemoglobin my continue to fll steeply for more thn three dys. The Are Grfted.-The mount of blood lost t opertion hs been mesured by the chnges in the peripherl blood in 75 ptients, nd it hs been compred with the proportion of the body surfce prepred nd grfted (Fig. 12). Two striking 34 fetures pper from this comprison. The first is tht the volume of blood lost t opertion is often surprisingly gret, nd its mesurement nd replcement re therefore very importnt. The second is the wide vrition in the mount of blood loss in ptients undergoing similr grfting pro *... 4X 22 P m 2- < t,6. - < 4 2 o * o * *o OFK - I * oo S. % RED CELLS LOST FIG. 12.-Blood loss during opertion, blood findings, relted to re * Children. Adults. ISO bsed on lter peripherl grfted (75 opertions).. J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

14 14 ELIZABETH TOPLEY nd D. McG. JACKSON cedures, nd this mkes the re to be grfted poor guide to the mount of blood which will be lost t the opertion. It cn be seen in Fig. 12 tht n opertion to grft 1% of the body surfce involved blood loss rnging from less thn 1% to 12% of the norml blood volume. Age of the Ptient.-Fig. 12 lso shows how much more blood is lost by children thn by dults in grfting the sme proportion of the body surfce. The blood loss for dults never exceeded 6% of their blood volume, but the loss in children not infrequently reched 1%, nd even 2% in one cse. There seems little doubt tht this is due primrily to the greter vsculrity of the skin in children, which leds to much greter loss when grfts re cut nd the grnultions re removed: in contrst, the elderly hve very vsculr skin nd my lose no more thn n ounce or two when grfts re cut from the whole of both legs. Site to be Grfted.-On number of occsions lrger blood loss thn usul hs been noted when 125- % OF NORMAL 75. BLOOD VOLUME) VOLUME TPANSF 1- SO- 25- /~~~~~ / i+ ^ +/ o // */ + A / + +* / -1" I 25 so */ / vsculr res such s the fce nd hnds hve been grfted in dults. An exmple is provided by young mn with 12% full-thickness burn of the fce nd hnds. Two dys before opertion he hd norml red cell count. During opertion the loss ws clerly lrge nd he received five bottles of blood (bout 3% of his norml red cell volume). During the following four dys the hemoglobin nd red cell count gin grdully fell severely, nd further six bottles of blood (35% of the red cell volume) were required to return the red cell count to its norml level. Assessment during Opertion.-The usul clinicl criteri for the mount of blood required re nevertheless surprisingly relible, even with very lrge trnsfusions. Our im t opertion hs been to keep up with the blood loss s it occurred. Both surgeon nd nesthetist estimted the visible blood loss, nd this mount ws given together with bout nother 25 ml. of citrted blood: more thn this ws only given if the nesthetist / + em / * I /X VOLUME TrsF EOUALLED O = It OPERATION 7S 125 so RED CELLS LOST ± =THER OPERATIONS FIG. 13.-Volume of blood trnsfused during opertion relted to blood loss bsed on lter peripherl blood findings (69 opertions). 11 7*1. LOST J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

15 CLINICAL CONTROL OF RED CELL LOSS IN BURNS thought tht the clinicl condition wrrnted it. A review of 69 opertions mnged in this wy showed tht in 8% of the cses the trnsfusion given proved to be within 2% of the blood loss (Fig. 13). In eight ptients there ws gin of more thn 2% nd in five deficit of more thn 2%. It ws not uncommon for dequtely trnsfused ptients to shiver nd become cynosed fter the nesthetic ws stopped nd they begn to regin consciousness. This ppernce is deceptive nd is not sign of oligemi. This my be the body's rection to the low temperture which is usully present t the end of one or two hours of complete exposure during opertion with much of the body surfce wet; the rectl temperture hs been s low s 9' F. t the end of such n opertion. Greter ccurcy of blood replcement cn be obtined by swb weighing. In three ptients in whom blood loss ws mesured in this wy, s well s by chnges in the peripherl blood, swb weighing underestimted the blood loss by 2% or less. In our opinion clinicl experience mkes swb weighing unnecessry for routine opertions on ptients in the third week fter burning, who probbly strt opertion with norml blood volume. More recently, however, investigtion of the vlue of lrge primry excisions within six to eight hours of burning hs shown tht not only is swb weighing vluble but blood volume estimtions re necessry before nd fter opertion to ensure norml pre-opertive blood volume nd to prevent post-opertive oligemi if there hs been internl red cell loss during or fter opertion. It my be tht in time swb weighing will prove sufficient in these cses, but t present the clinicl vilbility of red cell volume estimtions t short notice is essentil for sfety in this procedure. In the few cses when extensive excision nd grfting ws postponed till bout the fourth dy, severl children tolerted the procedure poorly. Recent blood volume estimtions now suggest tht the pre-opertive blood volume in these cses my hve been low with the tretment current t the time. It is probble, therefore, tht pre-opertive blood volume mesurement nd swb weighing would be beneficil t this period lso. Red Cell Loss between nd fter Opertions At these times the blood loss is very much less thn either before the first opertion or t the opertions themselves (Fig. 2). Scrutiny of the results suggests tht in the mjority of ptients it ws bsent or miniml nd only in minority of cses does it become cliniclly importnt. In detecting these unusul cses with cliniclly importnt blood loss, the re of remining fullthickness skin-loss nd the hemoglobin chnges re both importnt s guides to red cell loss. Are of Remining Full-thickness Skin-loss.- Once skin cover hd been obtined for the whole re of the burn, the peripherl blood picture lmost lwys showed stedy return to normlity from the slightly high or low vlues found fter the opertion. On verge (Fig. 2) there ws virtully no red cell loss fter opertion s clculted from the peripherl blood findings. When complete skin cover hd not been ttined there ws on n verge (Fig. 2) loss of 15% of circulting cells between ll opertions. Among ptients with less thn 2% of full-thickness skin-loss (Tble II) only two out of 34 ptients showed flls in red cell count to more thn 5 % TABLE II LOW RED CELL COUNT BETWEEN OPERATIONS RELATED TO AREA STILL TO BE GRAFTED Are Still to be Grfted O-ly% -1%j2-1', 2-1% More thn 1%. Red cell count 8-95% 2 12,1,,,,, more thn 95% Totl ptients % ptients with red cell count 8-95% 6% 33% 5% x2 distribution of cses with 2%' or more to be grfted --12 (P<-1). below norml. Among ptients with more thn 2% of full-thickness skin-loss, however, one-third showed flls in red cell counts to more thn 5% below norml. In only minority of these cses did the hemoglobin level fll below 8% of norml, necessitting blood trnsfusion. Given tht there ws more thn 2% remining full-thickness skin-loss, the exct re ws not useful guide to which ptients would show this unusul excessive red cell loss. Hemoglobin Levels-In the rre cses showing excessive red cell loss nemi my lst mny weeks, nd by the policy of never letting the hemoglobin fll below 75 to 8% of norml the ptient my require repeted blood trnsfusions. Such cses re usully recognized before or fter the first opertion, nd the experience of pst hemoglobin results becomes useful guide to the frequency with which future tests should be crried out. The losses of red cells developed firly slowly, nd could therefore be dequtely checked cliniclly by twice weekly hemoglobin levels. It ws unusul, for exmple, for the 1 5 J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

16 16 ELIZABETH TOPLEY nd D. McG. JACKSON hemoglobin to fll more rpidly thn 1 g. % per dy. Becuse of findings such s these it is the policy in this Unit to continue repeted hemoglobin estimtions fter the first opertion until there is less thn 2% of the full-thickness skinloss ungrfted. DISCUSSION If the red cell loss following severe burns is unreplced it cuses n nemi when hemodilution restores the blood volume to norml. When hemodilution does not occur the loss cuses low blood volume. Both nemi nd oligemi my contribute to the illness nd mortlity from burns. During the first few dys oligemi is probbly the more common nd importnt clinicl fctor. The controlled tril of " erly " versus " lte " blood trnsfusion described bove suggests tht in burns of less thn 4% of the body surfce nemi is cliniclly not importnt s cuse of illness t this erly stge. After the first few dys nemi is more common, but oligemi my still contribute to the postshock syndrome. Both oligemi nd nemi cn be corrected by blood trnsfusion soon fter they develop provided the blood volume nd hemoglobin level re known. The clinicl desirbility of giving blood to void blood volumes or hemoglobin levels less thn 6% of norml rests on niml experiments nd the experience of clinicl prctice tht is, when possible, voided to-dy. Mny workers, including Grnt nd Reeve (1951), hve demonstrted tht blood volume cutely developing nd mintined less thn 75% of norml is very often ftl. Our own erly experience in burns demonstrted t lest three ptients where red cell volumes were found to be 5% below norml, ll of whom died. These clinicl observtions, combined with niml experiments (e.g., Wiggers, 195), hve shown tht when the blood volume is mintined below criticl level deth occurs from "irreversible shock" or lter from renl filure. The cse for not llowing the hemoglobin level to fll to less thn 6% of norml is less drmtic but now firly well estblished s clinicl prctice. It seems likely tht trin of clinicl hzrds, including delyed heling, incresed sepsis, pneumoni, nd septicemi, re more common in ptients who re llowed to become grossly nemic (Brithwite nd Moore, 1948). The optimum level t which to keep blood volume nd hemoglobin is much more debtble. We hve felt it to be cliniclly unjustifible to llow either to fll below 75% of norml, nd our own evidence is therefore bsed on the tretment of ptients whom we hve ttempted to mintin bove this level. Dngers of Oligemi Our blood volume dt suggest tht blood volumes 7-9% of norml re common during the first few dys fter severe burn with present resuscittion methods, nd tht oligemi my therefore still be contributing to the illness nd mortlity from burns. Very few ptients hve so fr been treted by us with volumes of plsm or blood tht keep the blood volume norml, nd it ppers tht clinicl experience of the results of such tretment is very limited. Cution in ttempting to return the blood volume to norml is wrrnted until its dvntges nd disdvntges re understood. In hospitls where the mortlity from burns is higher thn ours (Bull nd Fisher, 1954) there is chnce of incresing survivl by more creful control of blood volume during the shock stge. The Bull nd Fisher figures, however, show little chnge in the expecttion of life of bdly burned ptient since 1942 in spite of improvement in control of oligemi, red cell volume, nd mny other mesures to prevent infection nd hel the burn quickly. But it is only in the lst yer tht blood volume studies hve been crried out frequently enough (every 12 or 24 hours) to mke it likely tht oligemi ws relly prevented. More dt re therefore required to know whether or not mortlity cn be reduced by more thorough control of blood volume. Renl dmge is nother dnger of oligemi. Histologicl nlysis of the kidneys of ptients who died fter burning hs shown tht tubulr necrosis is frequent nd generlly cn be divided into diffuse nd focl types. The diffuse kind is ssocited with uremi-either with or without oliguri-whilst the focl type is generlly subclinicl nd unrelted to renl filure (Sevitt, 1956b). Three ptients with extensive burns, who died one to three weeks fter injury nd in whom it hd so fr been possible to mintin ner norml blood volume with certinty during the shock stge, merely hd focl tubulr necrosis nd not the diffuse kind which might hve been expected from the extent of burning nd severity of hemoglobinuri. More dt must be collected. but menwhile it seems possible tht significnt tubulr necrosis nd renl filure my be preventble by voiding oligemi with more generous plsm nd blood trnsfusion during the first few dys fter injury. When erly opertion to excise nd grft lrge burn is contemplted it is specilly importnt to J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

17 CLINICAL CONTROL OF RED CELL LOSS IN BURNS hve the oligemi fully corrected pre-opertively, otherwise the ptient will strt the opertion in stte of ltent or thretened shock. Filure to correct this deficiency my result in the ptient collpsing on the tble or t best n nxious or hurried opertion. Anlogy with other forms of trum such s limb injuries suggests the mnner in which the mintennce of norml blood volume my modify the clinicl picture. Clrke nd his collegues (Fler nd Clrke, 1955; Br nd Topley, 1956; Topley nd Fisher, 1956) hve demonstrted the probble contribution of oligemi following limb injuries to slt nd wter retention, to bnorml nitrogen metbolism, to bnorml hemoglobin metbolism, to temperture, pulse, nd the generl illness of trum. The chnce tht correct blood volume control is fctor of rel clinicl importnce in extensive burns is likely enough to wrrnt detiled studies of the complicted chnges tht follow these injuries. Dngers of Anemi The " erly " versus " lte " blood trnsfusion tril described bove showed tht, in burns involving less thn 4% of the body surfce, ptients llowed to become nemic to the 8% level before blood ws given were cliniclly not demonstrbly different from those tht were trnsfused erly nd in whom therefore this degree of nemi ws delyed. Dngers of Blood nd Plsm Trnsfusion Our own results support the evidence of mny others, tht the risks of trnsfusion of smll volumes of blood re not gret but must lwys be borne in mind (Mollison, 1951). Thrombophlebitis ws the gretest single risk of plsm nd blood trnsfusion where the drip hd to be run for mny hours or dys. Crdic overloding immeditely fter blood trnsfusion ws very rre indeed, either during the " erly " trnsfusion of blood or lter when nemi developed: it hs been seen by us once only, when blood hd been given rpidly in the presence of n lredy high blood volume 1 dys fter injury. The risks nd disdvntges of trnsfusing the very lrge volumes of plsm nd blood sometimes necessry to mintin norml blood volume nd composition hve to be considered seriously, for the risks of this procedure hve yet to be defined. If more red cells re trnsfused thn hve disppered the hemtocrit nd viscosity of the blood both rise. Becuse of the conc tinul lek of plsm, enormous volumes of plsm my hve to be given to mintin norml blood volume. Some ptients, especilly those with burns involving 15-5% of the body surfce, show n unexplined rise in mesured red cell volume hours fter injury. If the blood volume hs been mintined t norml up to this time there my be hypervolemi subsequently. We hve seen possible signs of crdic overloding during the third to fifth dy fter injury s evidenced by dilted hert, crdio-respirtory filure, nd deth. It is not possible to sy whether such cses were cused by policy of mintining norml blood volume by generous plsm nd blood trnsfusions. Also, the lrger the plsm trnsfusion the greter the chnce of heptitis. These risks must be weighed ginst the dvntges of mintining the ner norml blood volumes discussed bove. During opertion, when more thn one blood volume of citrted blood hs hd to be trnsfused rpidly, e.g., over two hours, crdic rrest hs occurred. We hve felt tht this compliction my possibly hve been ssocited with the mount of citrte in the blood, nd our prctice now is to void unduly rpid rtes of trnsfusion nd to give 5-1 ml. of clcium gluconte intrvenously if citrted blood mounting to whole blood volume or more is given within n hour (Mollison, 1951). Economy of Blood Blood cn be sved by delying trnsfusion. until severe nemi develops. Delibertely letting the hemoglobin fll below 8% does conserve blood, nd frequently the hemoglobin will cese to fll t level somewhere between 65% nd 8% of norml. In hospitl where blood is vilble, however, we feel, s described bove, tht such tretment is unjustifible. If we re seeking the optimum tretment for the individul we do not think tht blood is wsted by using it to keep the hemoglobin bove 8% of norml. Economy in the use of veins is frequently of mjor importnce to the ptient, nd it is therefore sometimes beneficil to trnsfuse 4% of the blood volume when the hemoglobin is 8% below norml, so s to rise it to 12% of norml nd thereby dely the time of the next trnsfusion. Blood my be sved by voiding complictions such s cute infection which cuse further loss of red cells, nd lso by erly opertion. Severl dys' dely in grfting lrge burn results in further red cell loss ssocited with the ungrfted re. 17 J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

18 18 ELIZABETH TOPLEY nd D. McG. JACKSON Much of the opertion loss is due to removing the grnultions by rpid blunt dissection nd mking the recipient re idel for grfting. Grfting could probbly be done s well by delying it for further two weeks or so, nd prepring the surfce of the grnultions with frequent dressings during this time: it is our impression, however, tht this dely crries morbidity nd mortlity greter thn the risk of giving more blood t n erlier opertion, but there might be indictions for this lterntive course if citrted blood ws in short supply. Clinicl Mngement from Injury to First Opertion When the rtionle for keeping the blood volume norml is exmined it must be dmitted tht we re not sure tht some degree of oligemi is hrmful; conversely, we re not sure tht keeping the blood volume norml t the price of using more plsm nd producing more oedem is beneficil. However, prevention of more thn 2% reduction in blood volume seems resonble im. If this is so, it is not sufficient to pprecite tht lrge red cell loss my hve occurred nd to give n mount of blood bsed on the extent of deep burning. The wide vrition in degree nd time of the loss hs been described nd illustrted bove, nd control of the blood volume in extensive burns must depend on seril red cell volume nd hemtocrit mesurements if temporry oligemi is to be prevented. This is n idel nd stndrd which cn only be reched t -present in burns unit where blood volume estimtions cn be mde t short notice nd s prt of 24-hour service. It is quite wrong, however, to conclude tht we my be stisfied without this guide. It is in cses with extensive burns which hve chnce of survivl tht mssive red cell loss occurs most often, nd it is the prevention of oligemi in these cses which is most likely to improve present results. In other words, t the present time we re filing most to pprecite the degree nd time of red cell loss where this filure is most serious in its results. But to offer no clinicl guide to the likely need for blood when the red cell volume cnnot be mesured would be unrelistic. The following is suggested s prcticl clinicl guide bsed on the common types of burns which hve been followed with red cell volume mesurement. Some overlpping of the groups is inevitble if totl re nd full-thickness skin-loss re both considered; for this reson the totl re of the burn is used s the principl guide. 1. Less thn 1% totl re (especilly with less thn 2% full-thickness skin-loss); blood trnsfusion nd seril hemoglobin estimtions re not clled for s routine. 2. Ten to twenty per cent. totl re (usully with 2-1% full-thickness skin-loss); erly blood trnsfusion is probbly unnecessry, but seril hemoglobin estimtions re indicted every two or three dys until less thn 2% full-thickness skinloss remins unheled. 3. Twenty to forty per cent. totl re (usully 1-3% full-thickness skin-loss); blood trnsfusion equl to 2% of the ptient's blood volume should be given in the first 12 hours nd the hemtocrit kept between 1% nd 2% bove norml for the ptient's weight nd height, ssuming -1% red cell loss. A further 2% should be given in the next 36 hours if indicted cliniclly by oliguri, cold extremities, cynosis, hemoglobinuri, or more thn 2% microcytes in the hed of stined blood film on dmission. Subsequently, repeted hemoglobin tests re required. 4. Over 4% totl re (usully over 3% fullthickness skin-loss); 2% of the ptient's blood volume should be given in the first 12 hours nd the hemtocrit kept t norml for the ptient's height nd weight, ssuming 2% red cell loss. One should then be prepred to give further blood trnsfusion equl to 2 to 6% of the ptient's blood volume in the next 36 hours if indicted cliniclly. These re the ptients in whom seril blood volume estimtions re most vluble, provided their prcticl errors re pprecited. Subsequently, repeted hemoglobin tests re required. SUMMARY Repeted observtions hve been mde on the peripherl blood of 15 ptients with burns involving -8% full-thickness skin-loss of the body surfce. Eighty-six ptients hve hd red cell volume studies. The findings re used to discuss the wys in which it is possible to ssess red cell loss:- () During the first 48 hours; emphsis is plced on the cute unexplined nd lrgely unpredictble red cell loss tht cn occur hours fter injury in burns involving more thn 2% full-thickness skin-loss. (b) Between burn nd opertion; emphsis is lid on the re of full-thickness skin-loss s crude guide, nd the need for repeted hemoglobin tests. J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.

19 CLINICAL CONTROL OF RED CELL LOSS IN BURNS (c) During opertion; emphsis is lid on clinicl judgment, swb weighing, nd the need for post-opertive hemoglobin checks. (d) After opertion; emphsis is lid on the continuing fll in hemoglobin tht cn occur in burns with more thn 2% of full-thickness skin-loss ungrfted. The desirbility of giving very lrge volumes of plsm nd blood to mintin norml blood volume is criticlly discussed. No cliniclly importnt difference ws found in controlled tril of " erly " versus " lte " blood trnsfusion in 39 "shock cses" of moderte extent. The red cell volume studies were crried out with the collbortion of Mr. John Dvies, B.Sc., Mrs. Ann Foster, Miss Jnet Frost, B.Sc., nd the clinicl stff of the Burns Unit, especilly Mr. J. Cson nd Dr. Mry Fisher. The hemtology hs been possible with the ssistnce of Mr. H. Lilly, A.I.M.L.T., Mrs. M. Evns, A.I.M.L.T., nd their technicl ssistnts. The chrts were lrgely prepred by Mrs. M. Evns, A.I.M.L.T. We re indebted to the close coopertion of ll these collegues, nd especilly to Dr. S. Sevitt nd Dr. W. Weiner, of the hospitl nd regionl blood trnsfusion services. REFERENCES Br, S., nd Topley, E. (1956). Act med. scnd., 153, 319. Bronofsky, I. D., Trelor, A. E., nd Wngensteen,. H. (1946). Surgery, 2, 761. Berkow, S. G. (1924). Arch. Surg. (Chicgo), 8, (1931). Amer. J. Surg., 11, 315. Brithwite, F., nd Moore, F. T. (1948). Brit. J. plst. Surg., 1, 81. Brines, J. K., Gibson, J. G., nd Kunkel, P. (1941). J. Pedit., 18, 447. Brown, A. (1946). J. Pth. Bct., 58, 367. Bull, J. P., nd Fisher, A. J. (1954). Ann. Surg., 139, 269. Chplin, H., nd Mollison, P. L. (1952). Blood, 7, 227. Clrke, R., Topley, E., nd Fler, C. T. G. (1955). Lncet, 1, 629. Cope,. (1947). Surg. Gynec. Obstet., 84, 999. Dvies, J. W. L., nd Topley, E. (1956). Clin. Sci., 15, 135. Fler, C. T. G., nd Clrke, Ruscoe (1955). Ibid., 14, 575. Gibson, J. G., nd Evns, W. A. (1937). J. clin. Invest., 16, 317. Grnt, R. T., nd Reeve, E. B. (1951). Spec. Rep. Ser. med. Res. Coun. (Lond.), No Mollison, P. L. (1951). Blood Trnsfusion in Clinicl Medicine. Blckwell, Oxford. - nd Vell, N. (1955). Brit. J. Hemt., 1, 62. Moore, F. D., Pecock, W. C., Blkely, E., nd Cope,. (1946). Ann. Surg., 124, 811. Reeve, E. B. (1948). Nutr. Abstr. Rev., 17, 811. nd Vell, N. (1949). J. Physiol. (Lond.), 18, 12. Russell, S. J. M. (1949). Arch. Dis. Childh., 24, 88. Seckel, H. (193). Jb. Kinderheilk., 127, 149. Sevitt, S. (1956). Personl communiction nd Journl of Clinicl Pthology, 1956, 9, 279. (1956b). Journl of Clinicl Pthology, 9, 12. Shen, S. C., nd Hn, T. H. (1943). New EngI. J. Med., 229, 7t.. Topley, E., nd Fisher, M. (1956). Brit. J. clin. Prct., 1, 77. Wiggers, C. J. (195). Physiology of Shock. Commonwelth Fund' New York. Wintrobe, M. M. (1951). Clinicl Hemtology, 3rd ed. Le nd Febiger, Phildelphi. 19 J Clin Pthol: first published s /jcp on 1 Februry Downloded from on 2 August 218 by guest. Protected by copyright.