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TH E FAT EM BO L ISM SYNDROM EALAN R . GURD and R . I. W IL soN , BELFA ST , NORTHERN IRELAND

From the Ro ya l V ic to r ia H osp ita l, B e lfas t

T he fa t em bo lism syndrom e , o ften a com p licatio n o f m a jo r traum a, frequ en tly passe sund iag nosed . T he c las sica l p ictu re o f cereb ral con fusio n , re sp irato ry d istre ss and p etech iaeof sk in and m uco sa is no t a lw ay s seen .

A d istinc tion m u st be m ade b etw een th e c lin ica l en tity an d fa t em bo lism dem onstra tedpa th o log ica lly . Pos t-m ortem , fa t em bo lism is o f ten fou nd afte r dea ths from cau ses o ther thantraum a (S ev itt 1957 , 1962 , Bergen tz 1968). It is a lso fo und in d ea th s fo llow in g frac tu re w ithou tc lin ical ev iden ce o f th e synd rom e (W arren 1946 , S cu lly 1956). Th e fin d ing o f p u lm ona ry fa tem bo li is o f do ub tfu l s ig n ificance in case s w h ere the clin ica l fea tu res o f the sy ndrom e are ab sen t.

TABLE ID IAGNOS IS OF TH E FAT EM BOL ISM SYNDROME

In juryLatent periodM ajor fea tures- I ) R esp ira tory in su ffic ien cy; 2 ) C erebra l

inv o lvem en t; 3 ) P ete ch ial ra shM inor fea tu res - 1 ) P yrex ia ; 2 ) T achycard ia ; 3 ) R e tina l

chang es; 4 ) Jaun d ice ; 5) Rena l changesL abo ra to ry fea tu res -I) A naem ia ; 2 ) T hrom bocy topen ia ;

3) H igh e ry th ro cy te sed im en tatio n ra te ;4 ) F at m ac ro glo bu la em ia

In th is se rie s 10 0 cases o f th e sy ndrom e seen o ve r a p e riod of fo u r y ea rs are an aly sed .C erta in clin ica l fea tu re s w ere loo ked fo r in su spec ted cases (T ab le I) and in add itio n b loo dsam ples w ere checked fo r pa tho log ica l fa t g lobu les . A po sitive d iagno sis w as m ad e on fin d inga t lea st on e m ajo r fea tu re , fo u r m inor fea tu re s , and fa t m acrog lo bu laem ia (G u rd 1970). T heasse ssm en t o f p ath o log ica l fat g lob u laem ia h as b een c riticised by N o lte, O lo fs son , S che rstenand Lew is (1 974 ), w ho rep ort f ind ing la rge fat g lobu les a s o ften in n orm a l p atien ts an d inpa tien ts w ith frac tu res as in p ro ven cases o f fa t em bo lism syndrom e . In the o rig in a l desc rip tio nof the te st it w as po in ted ou t th at pa th o log ica l fat w as seen , o f ten in co nsid erab le quan titie s ,a fte r frac tu re s . I t w as fo und neces sary to asse ss b loo d va lues da ily becau se th e im po rtan tfea tu re w as no t m ere ly the d em on stra tion o f fa t g lobu les bu t the fin d ing of e ithe r a recen ton se t o f fa t m ac rog lo bu laem ia , o r an inc rea se in the num ber o f g lob u le s , o r a ch an ge in the irappea ran ce asso cia ted w ith the onse t o f the clin ica l cond ition .

A s w ith the post-m o rtem find ing of p u lm ona ry fa t em bo li, so , too , fa t m acrog lobu laem iain the asym p tom a tic p atien t is p ro bab ly irrelev an t. B ergen tz (19 68) a sse rts tha t th e o n lyfind in g w hich is spec ific in fat em bo lism is o ne o f in travascu la r fat d ro p le ts . T he d iag nosiso f the con d ition und er d iscussio n he re is m ade w hen fa t m ac rog lo bu laem ia is fo und inassoc ia tion w ith accep ted c lin ica l fea tu re s . T he cond ition is th en refe rred to as th e fa tem bo lism synd rom e ra the r than the m islead ing te rm fat em bo lism , w h ich d en o te s theem bo lism of fa t d ro p le ts w ith o r w ithou t c lin ical ev idence o f th eir p re sence .40 8 TH E JOURNAL OF BONE AND JO INT SURGER Y

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THE FAT EM BOL ISM SYNDROM E 40 9PRESENT STUDY

O f th e 10 0 pa tien ts seven ty -seven w ere m ale and tw en ty -th ree fem ale . The ages o f th em ales ranged from fourteen to n ine ty -one y ears (average th irty -th ree ) and of the fem ales fromsix teen to six ty -six yea rs (ave rag e th irty -n ine ). T he m ean ave rage age w as th ir ty -fou r and aha lf yea rs .

F o rty -n in e case s fo llow ed m u ltip le fractu re w ith tw o or m ore lon g bones invo lved(T ab le II) . T h ir ty fo llow ed fem o ra l sha ft fractu re , ten tib ia l frac tu re and fou r pe lv ic frac tu re s .In seven cases the synd rom e fo llow ed in ju ry w ith e ithe r m ino r b one in ju ry o r no dem onstrab le

TABLE 11NA TUR E OF THE INJUR Y IN 10 0 CA SES OF

FA T EMBOLISM SYNDROM E

In jury Numbe rM ultip le frac tu res . 49Fem o ral sha ft fra ctu re . 30T ib ial fra ctu re . . 10P elv ic fractu re . . 4T raum a: m in or f rac tu re 4T raum a: no fractu re . 3

f ractu re. T hu s tw o pa tien ts fell from step ladders , bo th su sta in ing soft-tissue in ju ry and afrac tu red ca lcan eu s. A g ir l w as invo lved in a ca r acc iden t and lay u na ttended fo r six hou rs ;sh e dev elo ped a seve re fa t em bo lism synd rom e six hou rs a fte r b ein g adm itted w ith h ypo the rm ia,b ru isin g and a fractu red m and ib le . A you th w as seve re ly assau lted an d h ad b ilate ral frac tu redpa te llae . A n e ld erly m an fe ll dow n s tairs and w as bad ly b ru ised ; tw o days a fte r in ju ry h edeve lop ed a c la ssical synd rom e and d ied th irty -six ho urs la te r; no frac tu re had b een foundc lin ica lly o r rad io log ica lly and none w as foun d a t necropsy . Two pa tien ts sus ta in ed severec rush in ju ries o f the up per abdom en , ch es t and arm s w itho u t ev iden t frac tu re .

PRESENTAT IONIn a ll ca se s th ere w as a laten t pe riod be tw een in ju ry an d the on se t o f sym p tom s. Th is

varied from fo ur hou rs to f if teen days , w ith an av erage tim e of fo rty -s ix hours. T he recordedla ten t period of fifteen days in on e case m ay b e m islead ing : th e p atien t d eve loped sym ptom sof em bo lism tw o day s afte r rem an ipu la tion of a fem oral frac tu re , fif te en d ays a fte r the o rig ina lin ju ry . N o s ign if ican t co rre la tion w as fou nd be tw een th e tim e of onset an d the seve rity o f thesubseq uen t co urse .

Th ere w as m ark ed v aria tion in the c lin ica l p re sen ta tion . In th irty -fou r cases the earlie streco rded sym ptom s w ere ce reb ra l, u sua lly d row siness o r con fu sion . In tw en ty -n in e , o the rw iseun exp la in ed tach ycard ia and pyrex ia h era lded m ore specif ic signs . R esp ira to ry dysfun ctio nw as obse rved f irst in tw enty pa tie n ts w ith d ysp noea , tachypnoea or h aem op tys is . A pe tech ia lrash w as th e p resen ting sig n in o n ly sev en teen cases.

CL IN ICA L FEATURESR esp ira to ry in vo lv em en t w as p redom inan t in sev en ty -five p atien ts , m ost o f w hom had

dy spn oea and tachypnoea w ith m oist ra les ov er the w ho le o f th e lu ng fie ld s. C yano sis w asuncomm on ev en w hen a rter ia l h ypox ia w as m arked , p re sum ab ly becau se o f con com itan tan aem ia. Th e a rte r ia l oxy gen tension w as m on ito red in o n ly fifty case s. In tw en ty -fou rVOL . 56B . NO . 3, AUGUST 1974

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F IG . IAn antero -po ster io r ra d io graph of the lung fie lds show in g typ ical ap pea ran ces .

41 0 A . R . GURD AND R . I. W ILSON

THE JOURNA L OF BONE AND JO INT SURGER Y

cases the m in im um p02 leve l w as le ss than 50 m illim etre s of m e rcu ry ; in sev en teen cases itrang ed from 51 to 80 , and in n in e pa tien ts it w as g reate r than 8 1 .

F ifty -tw o pa tien ts had rad iog raph ic exam ina tion of th e chest. In fo rty - th ree th e film ssh ow ed typ ica l b ilate ral d iffu se pa tchy a reas o f con so lida tion (F ig . 1 ). O f seven pa tien ts w ithnorm al rad io graphs , tw o had a p02 lev el o f un de r 8 0 m illim e tre s o f m ercu ry . Tw o pa tien tsw ith clin ica lly n orm a l lu ngs had m oderate rad io log ica l changes. H aem optysis occu rred intw en ty -tw o pa tien ts .

T he re w as som e cereb ral inv o lvem en t in eig h ty pa tien ts , o f w hom eleven had assoc ia tedhead in ju r ie s . S ix ty -n in e w ere aw ake and fu lly o rien ta ted on adm ission , and of th ese n inebecam e con fu sed , th irty -fiv e d row sy , an d tw en ty -f ive deep ly com ato se during the peak ofthe ir sym ptom s.

A pe tech ial ra sh w as o bse rved in fif ty -seven pa tien ts; typ ica lly it w as firs t seen o ve r thean ter io r ax illa ry fo ld and th e ro o t o f the neck (F ig . 2 ) . I t w as also fo und in the bu cca l m u cosaand the co n jun c tiv a . Th e d istr ibu tio n and in tens ity o f th e rash va ried : at tim es it cou ld bed etec ted on ly w ith the a id o f a m agn ify in g g la ss .

P y rex ia o f 3 9 4 d eg rees C e ls iu s o r abov e and tachyca rd ia o f 1 20 p er m in u te o r m orew ere n o ted in e ig h ty -th ree cases . O ph th a lm o scopy w as recorded in six ty -th ree pa tien ts andw as norm a l in f ifty -fou r . R e tina l exud a te s an d haem orrh ag es w ere n o ted in sev en , an d fatd ro p le ts in the re tina l v es sels in tw o . F ive pa tien ts b ecam e jau nd iced b u t th e p igm en ta tio na lw ays sub sided w ith in ten day s. S om e ren al in vo lv em en t w as m an ife st in tw en ty -tw o p atien ts ;seven teen becam e o ligu ric, th ree w ere anur ic and requ ired d ia lys is, one had h aem a tu ria andone b ecam e incon tin en t.

LABO RATO RY INVE ST IG ATIO NSD aily haem og lob in estim a tion s w ere reco rd ed in six ty -e igh t pa tien ts . A d ro p of m ore

th an 20 p er cen t w as foun d in fo rty pa tien ts , th e m ax im um fa ll b e in g from l6 3 to 8 g ram sin six teen h ou rs. D a ily p la tele t coun ts w ere m on ito red in on ly th irty -e igh t ca se s: a d rop o f

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..

C

V OL . 56B , NO . 3, AUGUST 1974

THE FAT EM BOL ISM SYNDROM E 41 150 pe r cen t o r m ore w as fo und in tw en ty -th ree, w ith m in im um valu es o f u nde r 90 ,000 , cub icm illim e tre in tw e lve pa tien ts . In e igh ty -seven cases th e e ry th rocy te sed im en ta tion rate w asra ised , w ith v alu es o f 30 to 5 0 m illim e tre s in six teen cases, 51 to 7 0 m illim etres in sev en teencases, an d o ve r 7 1 m illim e tre s in f ifty -fo u r cases . F a t g lobu le s la rge r than 8 m ic rons w erefou nd circu la ting in a ll ca se s. The am oun t o f c ircu latin g fa t d id no t ap pear to co rrela te w ithth e clin ica l seve rity o f the co nd itio n .

F IG . 2A photograp h show ing th e d is tribu tion of pe tech iae .

COURSE AND TREATM ENTThir ty -six pa tien ts recovered w ith ou t an y trea tm en t. In th e rem a in in g cases treatm en t

w as d irec ted tow ards: 1 ) th e resto ra tion of c ircu latin g v o lum e w ith fresh b lo od o r a ph ysio -log ica l substitu te; 2 ) the co rrec tion of ac ido sis ; and 3 ) im m obilisa tio n o f the a ffec ted pa rt.A dditio na l trea tm en t w as pr im arily co ncerned w ith resp irato ry supp ort. In tw en ty casesro u tine w ard care w ith ch est phy sio the rapy an d oxygen by m ask w as su ffic ien t. T h ir ty -fo u rrequ ired fu l l resp ira to ry care w ith assis ted ven tila tion an d 40 p er cen t ox ygen , eig h t w ithendo trachea l in tub a tion ; tw en ty -six had tracheostom ies. T en com a tose pa tien ts w ho d id no trequ ire ven tila tion rece ived a ll th e ro u tine ca re o f the un co nsc iou s pa tien t.

A n tib io tic s w ere g iv en to the fifty -fou r p a tien ts w ith m ode rate o r seve re lun g inv o lvem en t.D ig ox in w as requ ired in tw e lve cases, s ix w ith unco n tro llab le tachyca rd ia, fo u r w ith atr ia lfib rilla tion an d tw o w ith r igh t h ea rt fa ilu re . E igh t p atien ts w ere g iven in traveno us ca lc iumfo r hy po ca lcaem ia . A pro tea se in h ib ito r (T ra sy lo l) w as g iven to th irty pa tien ts in a dose o f500 ,0 00 un its in traveno usly fo llow ed by a fu rth e r 2 00 ,00 0 un its six hourly b y con tin uou sin fusion fo r th ree to s ix d ay s .

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41 2 A . R . GURD AND R . I. W ILSONSeven ty -seven pa tien ts reco ve red fu lly , s ev en reco ve red w ith som e res id ua l d efic it (one

w ith ep ilepsy , o ne w ith sco tom a ta an d five w ith pe rson ality ch an ges) an d six teen d ied . E igh to f the dea ths w ere from seve re p u lm ona ry in su ffic iency o f the fa t em bo lism synd rom e andeig h t from oth er traum a tic causes.

DISCUSS IONIn th is se ries o f 10 0 cases o f th e fa t em bo lism synd rom e , the d iagn osis w as m ade from

a com bina tion ofw ell kn ow n bu t va riab le clin ica l fin d ing s p lu s the dem onstratio n of c ircu la tingg lob u le s o f p ath o log ical fa t. F a t m acrog lo bu laem ia h as been show n to o ccu r a fte r m ino ro pe ra tion s, m in or traum a and in a v a rie ty o f m ed ica l illne sses (B ryans and E isem an 1955 :Tedesch i, C aste lli, K rop p and T edesch i 1968). A ltho ugh the re la tionsh ip o f these large fatg lob u le s to the pa tho genesis o f th e c lin ical p ictu re rem a in s o bscu re , w e h av e fo und thedem onstra tion of the ir p re sence he lp fu l in d iagn osis .

T h e o rig in o f the pa tho lo g ica l fat h as rem a in ed co n trove rsial fo r m ore th an a cen tu ry .B as ica lly tw o concep ts have ev o lved , th e m ech an ical and th e m e tabo lic . In th e m ech an ica ltheo ry it is a lleg ed tha t fa t is lib era ted from the m arrow of in ju red b ones, d riven o u t byan in crease o f in tram edu lla ry p re ssu re and tran sm itted v ia the d ra in in g ve ins to the p u lm ona rycap illa rie s , w he re it lodg es . Th e m e tab o lic theo ry su ggests th at em bo li ar ise in the p la sm afrom cong lom era tion and fusion ofa p re-ex isting physio log ica l su spensio n o ftiny ch y lom ic ron s(u sua lly le ss than on e m ic ron ), pos sib ly du e to som e b iochem ical ch an ge in itia ted b y in ju ry .

O the r ch an ges occur w hich augm en t the em bo lic e ffec t o f the la rge fa t g lobu les , su ch asagg lu tina tion of the fo rm ed e lem en ts o f b lood -pa rticu la rly p la te lets and red ce lls-and aninc rease in the v iscosity o f p la sm a and w ho le b loo d (B erg en tz, G e lin , R udens tam and Zede r-fe ld t 19 61). A ggrega tion o f p late le ts , chy lom ic ro ns an d red ce lls can b e p ro duced by in jectio nof th rom bop la stic su bstances, w h ich a lso cause the fo rm a tion of fat d rop le ts (B e rg en tz 1 961 ,A dk in s, F oste r an d O S aile 19 62). T he pa tho log ica l sequence of even ts is no t y et p ro ven , b u t thetrig ge rin g m echan ism app ea rs to be an o ve r-com pen sa tion in re spon se to in ju ry , haem orrhag e,decreased v en ou s re tu rn an d inc reased ca rd iac ou tp u t (F ig . 3 ). R eac tive v aso co nstr ic tionfo llow s , caus in g lo ca l tis su e hypox ia ; ca rbohydra te m etabo lism is alte red an d th ere is aninc rea sed lactic ac id p ro duc tion . In add itio n , po st-traum a tic ac tiva tio n o f th e co ag u la tionfacto rs re su lts in the fo rm a tion of m ic ro th rom b i (d issem ina ted in travascu la r co ag u la tion )w h ich fu rthe r in creases the local oxy gen de fic iency an d th e m e tabo lic ac idos is . A low ered pHac tiva te s tissue p ro tea se s w hich in tu rn libe rate vasoac tive po ly pep tid es, am ong them th ek in ins, w h ich are ve ry p o ten t in th e p ro duc tion o f p ost- traum a tic sho ck . Indeed the fa tem bo lism syndrom e is p rob ab ly on ly o ne particu lar face t o f the pos t-traum atic sh ock sy ndrom e.A n assoc ia tion be tw een pu lm ona ry fa t em bo lism and in trav ascu lar coagu la tion has frequen tlybeen repo rted (B rad fo rd , F oste r an d N osse l 19 70 ; S a ldeen 1970 ; So low ay and R ob inso n 1972).It h a s b een said tha t fa t em bo lism po ten tiate s sho ck (Porter 191 7), b u t in rea lity th e reve rseapp lie s (P e ltier 19 65 , V o lz 19 66).

I t is ou r im p ressio n th at the clin ica l synd rom e is n o t uncomm on: it occu rred in 1 9 p ercen t o f the p atien ts adm itted to th e R oya l V ic to ria H osp ita l, B e lfast, w ith m a jo r traum a .Over a th ird o f the cases w ere so m ild tha t no trea tm en t w as requ ired , and these m igh t haverem a ined und iag nosed h ad they no t b een sc reened bo th c lin ica lly and fo r fa t m ac rog lobu les .Pulm onary in vo lvem en t w as th e m o st comm on fea tu re , usua lly w ith tach ypno ea , d ysp noeaan d ev idence of b ila te ra l d iffu se p u lm ona ry oedem a . A rte ria l oxy gen tensio n estim atio np roved va luab le bo th in d iagno sis and fo r m onito ring treatm en t. A lm ost h alf o f th osein vestiga ted had m in im um valu es o f un de r 50 m illim etre s o f m ercu ry . R oss (1 970 ) be lievesa low ered a rte r ial PO 2 in in ju red pa tien ts is d iagno stic w hen fo und in con ju nc tion w ith anorm al o r reduced pCO2 .

D efec tive gas transfe r across the a lveo la r/a rte rio lar m em brane is caused by the severed eg ree o f a lveo la r oedem a tha t deve lop s in th is synd rom e . C arbon d iox ide is no t re ta ined

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THE FAT EM BOL ISM SYNDROM E 41 3because it d iffu se s ac ro ss th e m em b rane a t a m uch fa ste r ra te than do es oxygen . L a ter inth e course o f the d iso rde r v en o-ar te ria l sh un tin g p lay s an im portan t ro le (S prou le, B rady andG ilbe rt 19 64) . C h est rad iog raph y is a lso h elp fu l, the sign if ican t pos itiv e fea tu re s b ein g even lyd istr ibu ted , sm a ll fleck -lik e areas o f co nso lida tion , cong es ted h ila r shadow s and a t tim esd ila tatio n o f the rig h t hea rt. R ad iog raphs a lso h elp to ex clu de o the r p u lm ona ry p ath o log y ,such as pneum otho rax (F ig . 4 ).

T h e im portan ce o f a rte r ial hyp ox ia in p rodu cin g the ce reb ra l fea tu re s o f the fat em bo lismsyndrom e h as been stre ssed b y W ertzb erge r and P e ltie r (19 68 ) and by R oss (197 0). In m o stcases rep orted he re con fu sion , d row sin es s and com a appeared to fo llow th e onset o f hyp ox ia .Th ere w ere ten pa tien ts , ale r t and orien ta ted o n adm iss ion , w ho becam e d eep ly com a tosean d in w hom resp ira to ry in vo lv em en t w as m in im a l o r absen t. S ys tem ic fa t em bo lism w herecerebra l fea tu res p red om ina te is less comm on than pu lm on ary fa t em bolism , bu t doesappear to occu r occasiona lly .

Haemorrhage*Hypovo l aem ia*

R elease o f C atecho lam in es/j A ctiv atio n of C oagu la tio n

R eac tIve V asocons tric tion +\ M icro th rom bus Fo rm atio nT issue H ypox iakC I D 0

Activa tion of P ro tea se s+R e lease o f

V asoac tiv e P o lypep tides(Kin ins)SHOCKI an d

LFAT EM BOLISM SYNDROM EF IG . 3

A suggested sch em e of the ra tion ale o f the fa t em bolism syndrom e.

Pe tech ial h aem o rrhages, firs t no ted by B en es tad in 1911 , are a cla ssica l f ind ing , usu allyo n the second to fou rth d ay s afte r in ju ry . In itia lly they o ccu r ac ross the fro n t o f th e ch est,pa r ticu lar ly the an ter io r ax illa ry fo ld , the roo t o f the n eck , the m ucosa o f the m ou th andthe con junc tiva . O n occasio ns pe tech iae can be fou nd a ll o ve r and they w ere ev en no ted o nthe h ands and fee t o f o ne pa tien t in th is se ries . T he rash m ay la st o n ly a few days an d isve ry easily ov e rloo ked un le ss th e pa tien t is s tud ied ca re fu lly eve ry day . B o th P eltie r (1 965 )and B ergen tz (19 68 ) quo te 20 pe r cen t fo r the inc idence o f pe tech iae in d iagn osed cases o ffa t e mbo lism .

P ath o log ica l chang es m ay be found on re tinoscop y . C lass ica lly , m u ltip le w h ite f lu ffyexu da tes , fine s treaks o f haem o rrhage and m acu la r oedem a are fou nd (N ew m an 1948 , K earns1956 , A dam s 1971 ). S co tom ata m ay occur and usu a lly reso lv e com ple te ly (D uke-E lder 1954 ).O ligu ria is no t uncom m on and com ple te an uria do es o ccu r . R ena l in vo lvem en t is so freq uen tin fa t em bo lism th at S ev itt (196 0) has su ggested n eed le b io psy o f the k id ney as an a id to thed iag nosis o f o bscu re case s. A d eb ah r (19 57) be lieves the sud den d rop in the haem og lob inva lu e, occu rrin g even a fter ad equa te b lood rep lacem en t a t th e tim e o f in ju ry , is d ue topu lm on ary haem orrhage . It is m uch m o re like ly tha t th is anaem ia fo llow s an increasedVOL . 56B , NO . 3, AUGUST 1974

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tendency of red cells to ag grega te, fo llow ed by trapp in g and haem olys is o f the aggrega tedcells (G elin 1 956 ).

P reven tio n o f th e fa t em bo lism synd rom e in fac t m eans the p reven tion o f shock . In m anyhosp itals it h as no t been a rou tine to g ive fractu re pa tien ts p roph y lactic treatm en t o f sh ockin the fo rm of trans fus ions, seda tive s, an a lg esics o r gene ral an aesth es ia (B ergen tz 1 968 ). T h ism ay exp lain w hy fractu re pa tien ts sub jec ted to imm ed ia te in terna l fix atio n appea r to deve lopth e c lin ica l sy ndrom e le ss o ften than pa tien ts trea ted con serva tive ly (S a ikku 1954 , L iljedah land W este rm ark 1 967 ). A d equa te vo lum e substitu tion is es sen tial, u sing ce ll- free co llo ida l

so lu tions o r fre sh b loo d . M ille r,_ _______________ Fonk alsrud , L atta and M alon ey (19 62)

------ w- show ed tha t tran sfu sion of sto red b loodcan re su lt in fa t em bo lism . B erg en tz

. (1 968 ) a ttem pts to keep the p ost-traum atic haem atocrit a ro und 30 to 35 ,w hich g iv es satis fac to ry o xyg en-ca rry in gcapac ity o f the b lood w ith ou t in ter fe ringtoo m uch w ith f low . C orrec tion ofm etabo lic ac id osis is a lso necessa ry , asis ad eq ua te ea rly im m ob ilisatio n of thefractu re.The ro le o f p ro teases in th e p roductionof sho ck-T h is is cu rren tly und er study .P ro tease inh ib ition by the na tu ra llyoccurring en zym e T rasy lo l has b eenused in th irty pa tien ts . U n fortuna te lyit w as no t g iven as pa rt o f a con tro lledtria l and sta tis tica l con clu sion s cann o tye t b e d raw n . It is d ifficu lt to eva lua tespec ific treatm en t am ongst the rou tinem easu re s g iv en to each p atien t b ecausespo n taneou s reco ve ry o ccurs an d isunp red ic tab le . T he o n ly a ttem pt a tana lysis th at can be m ade is to com pare- th e f irs t th irty -th ree pa tien ts , fo r w hom

F I;. 4 o n ly rou tine treatm en t w as av ailab le ,A n an tc ro -pos tc rio r rad iog raph of the lung fie lds sh ow ing and a seco nd rou of s ix t -seven casesth e typ ica l d iffuse pa tchy appearances, com plicated on the g y

le ft side by a pneum oth orax . w here p ro tea se lnh Ib ltlO n therapy w asava ilab le b u t o n ly g iv en to th irty w hen

rou tine m easu re s appea red to b e fa iling . In the f irs t g rou p 60 p er cen t reco ve red fu lly and15 pe r cen t d ied from the fa t em bo lism syndrom e, w h ile in the secon d g rou p reco ve ry w asfu ll in 85 p e r cen t and the m o rta lity on ly 5 pe r cen t (T ab le III) . Z imm erm an (1972), incon tro l led tria ls w ith pro tease in h ib ition in p atien ts w ith th e sh ock lun g syn drom e and th efa t em bo lism syndrom e , has reduced the m o rta lity from a lm ost 7 0 pe r cen t w ith rou tin eth erapy a lone to 3 9 pe r cen t w hen using T rasy lo l in add ition .

T hree case s in th is p re sen t stud y d ied of m assive pu lm on a ry em bo lism w hils t o n pro teaseinh ib ition trea tm en t. In re trosp ec t w e no ted th at T ra sy lo l w as no t com m enced un til the pC O2had b eg un to ris e, w h ich is a bad pro gno stic sign . P ro tea se in h ib ition ough t to be usedprop hy lac tica lly and the refo re g iven as early as p ossib le. Th is , o f cou rse , m akes eva lu atio nev en m ore d iff icu lt as so m any cases recov e r spon tan eo usly . It is o u r clin ica l im pression tha tp ro tea se inh ib ition w ith T rasy lo l h as a p lace in the trea tm en t o f th is syn drom e . N o side -ef fects w ere o bserv ed in th e th irty cases trea ted .

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THE FAT EM BOL ISM SYNDROM E 41 5The es tab lished case -H ere the a im of trea tm en t is to ensure an ad eq ua te a rte ria l P #{176}2 Besidesthe co rrec tion of anaem ia and the low erin g of b loo d v iscos ity , re sp ira to ry ca re m ay in clu detracheostom y and m echan ica l ven tila tion , an d su ch pa tien ts ou gh t to b e in an in tensiv e ca reun it. A n tib io tics are ind ica ted fo r a ll p atien ts w ith m odera te o r severe resp irato ry in vo lvem en t.D igox in m ay be req u ired fo r tachy card ia , a rrhy thm ias o r r igh t hea rt fa ilu re , an d calc iumin traveno usly fo r hyp ocalcaem ia . V o lz (19 66) sugg es ted tha t h ypo ca lcaem ia can b e seve reenough to re su lt in te tan y , b u t th is w as no t observed in any of these case s. A summ ary oftreatm en t is g iven in Tab le IV .

TABLE IIICOM PARAT IVE R ESULTS IIEFORE AND AFTER TH E AD VENT OF TRASYLO L

Morta l i tyN umbe rG roup of T rasy lo l Partia l Fu ll F atcases recovery recovery O vera ll em bolismsynd rome

A 33 0 4 20(6 0#{176}c) 9 5(15# {176 } , )B 67 30 3 57(83 5#{176} 7 3(4 5#{176}, , )

TABLE IVSCHEM E OF TREATMENT

S ho ck p re ve ntio n1 ) R e st o ra ti o n o f c ir cu la ti ng vo l ume a) fresh b lo od

h) phy sio log ica l substitu te2) M ain ten ance of n orm al pH3) P ro tease inh ib ition4) E arly an d adequ ate imm ob ilisation of the in ju red partE stab lish ed sy ndrom eI) M ain ten ance of norm a l ar te ria l P#{176}22) C are of th e unconsc ious p atien t3 ) N on-spec ific d rugs a) antibiotics

h) Digox inc) ca lc ium

SUMMARY1 . A d istinc tion m ust be m ade be tw een th e fa t em bo lism syndrom e , a clin ica l en tity , and fatem bo lism dem onstra ted p a tho lo g ically , w h ich m ay be found a fter death fo llow ing frac tu rew ith no p rio r ev id en ce of th e syn drom e .2 . O ne hund red cases o f the syn drom e en co un te red ove r a p e riod of fo u r yea rs have b eenstud ied in de ta il and th e d iagnos tic c rite ria hav e been defined . T h ese in clud e one m ajo rfeatu re, fou r m in or fea tu res an d fat m acrog lo bu laem ia .3 . S ix teen of th e pa tien ts d ied -e igh t from sev ere p u lm ona ry insu ff ic ien cy o f the sy ndrom e,e igh t from other traum atic cau ses.4 . T he prev en tion o f sho ck is the b es t m easu re fo r p rev en tion o f the syn drom e . T he ro leo f p ro tea se s in th e p ro duc tion o f sho ck an d the p lace o f p ro tea se inh ib ition in trea tm en t o fthe sy ndrom e are b rie f ly d iscussed .5 . For th e estab lish ed case th e a im of trea tm en t is to en su re an adequa te p re ssu re o f a rte r ialoxygen .VOL . 56 B, NO . 3, AUGUST 1974

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41 6 A . R . GURD AND R . I. W ILSONW e w ish to thank our o rtho paed ic co lleagues fo r perm ission to s tudy p a tien ts under th eir ca re , and D r R . C .G ray , D r D . L . C oppe l and D r W . F . K . M o rrow of the R esp ira to ry In tensive C are Un it, R oya l V ic to riaH osp ita l. B e lfas t, fo r the ir in va lu ab le he lp .

REFERENCESADAMS , C . B . T . (1971 ): T h e re tina l m an ifesta tion offa t em bo lism . In ju ry , 2 , 2 21 -2 24 .ADEBAHR , G . ( I 957) : B lu tun gen in d er L ung e be i F ettem bolie . Zen tra lb la tt f ir a ilgem ein e P ath okg ie iu ,d

p a th o log isc lze Ana tom ie , 9 6 , 267-274 .ADK INS , R . B ., FOSTER , J. H ., and OSAILE , D . (1962 ): E xperim en ta l s tu dy of th e g en es is o f fa t em bolism .

A ,zn a ls o f Su rg en , 15 6 , 51 5 -5 27 .BENESTAD . G . ( I 91 1 ) : D re i F fllle v on F e ttem bolie m it pun k tfo rm igen B lu tun gen in der H au t. D e ut sc he Z eit sc hr ,f t

fir C hiru rg ie , 1 12 , 19 4-2 05 .BERGENTZ , S . -E . (1961) : S tud ies on the genes is o f pos t-traum atic fa t em bolism . A da ch iru rg ica S ca nd ina iic a,

Supp lem en tum 282 .BERGENTZ , S .-E . (1 968 ): Fa t em bo lism . Progress iii Surger j , 6 , 8 5-1 20 .BERGENTZ , S.-E .. GEL IN , L.-E ., RUDENSTAM , C .-M ., and ZEDERFELDT , B . (1 96 1) : Ind ica tio ns fo r the use of low

v iscous dex tran in su rgery . A cta c hiru rg ic a Scand inav ica , 1 22 , 3 43 -3 57 .BRADFORD , D . S. , FOSTER , R . R ., and NOSSEL , H . L . (19 70): C oagu la tio n a lte ra tion s, hyp oxem ia , and fa t

em bo lism in frac tu re p a tien ts . Jou r na l o fTrauma , 1 0, 3 07 -3 21 .BRYANS , W ., an d E ISEMAN , B . (1955 ): T he inc idence of fa t g lob u lem ia fo llow ing sof t tissue and orthop ed ic

opera t ions . S urg ica l Fo rum , 6, 28-32 .DUKE -ELDER , S ir W . S . (1954) : T ex tb oo k o fO ph th alm o lo gy . Vo lum e V I. In ju rie s. L ond on : H enry K im p ton .GEuN , L .-E . (1956) : S tud ies in an em ia ofin ju ry . Acta c hfr ur gic a S ca nd in av ic a, Supp lemen tum 210 .GURD , A . R . (197 0): F a t em bolism : an a id to d iagnos is. Journa lo fBone andJo in t Surge ry , 52 -B , 732-737 .KEARNS , T . P . ( I 9 5 6) : Fa t em bolism of the re tina : dem on stra ted by fla t retina l p rep aration . A mer ica ,z Journa l

o f O p ht ha lm o lo g y, 41 , 1-2 .L IUEDAHL , S .-O ., and WESTERMARK , L . ( 19 67 ): Aetio logy and treatm en t o f fa t em bo lism . A ct a a na es th es io lo g ic a

Scand ina c a , 1 1, 1 77 -1 94 .MILLER , J . A ., FONKALSRUD , E . W ., LATTA , H . L ., an d MALONEY , J. V . F . (1 96 2): Fat em bolism assoc ia ted w ith

ex tracorporea l circu la tion and b lood transfusion . Surgery , 51 , 448-451 .N EWMAN , P . H . (1 948 ): T he cl in ic al d iagn os is of fa t embo l i sm . Journa l o f B one and Jo in t Surge r y , 30 -B ,

290-297 .NOLTE , W . J ., OLOF 5 SON , T. , SCHERSTEN , T. , an d LEW IS , D . H . (19 74): E v alua tion of th e Gurd test fo r fa t

embol ism. Jou r na l of B oze an d Jo in t Surge r y , 56-B , 417 -42 0 .PELT IER , L . F . (19 65): T he d iag nosis o f fa t em bolism . S urg ery , G yneco logy a nd O bs te tr ic s, 12 1, 371 -37 9.PORTER , W . T . (1 91 7): F at em bolism . A cau se of sho ck . Bos ton M ed ica l an d Su rg ica l J ou rna l, 176 , 248 .R oss, A . P . J . (1970 ): Th e fa t em bolism syndrom e: w ith spec ia l re fe rence to the im po rtan ce of h ypox ia in the

syndrome. Aii izals the R oya l C o lleg e o f S u rg eo ns o f En g land , 46 , 159-171 .SA IKKU , L. A . (195 4) : F at em bolism in co nnection w ith tre atm en t of fractures. Acta c hir iirg ic a S ca nd iiz aric a,

108 , 275-282 .SALDEEN , T. (19 70): Fa t em bolism and sign s of in travascu la r coagu la tion in p ost-traum atic au to psy m ate ria l.

Journa l o f T raum a, 10 , 273-286 .SCULLY , R . E . (1 956): F a t em bolism in K ore an b att le ca su alties. Am erican Journa l o f P a th o logy , 32 , 379-403 .SEVI r r , S . ( 19 57 ): Burns . P atho log y and Th erapeu t ic A pp lic a tion s . L ondo n: B utte rw orth & Co . (Pub lishers) L td .SEvrrr , S. (1960) : T he sign if icance and c lassifica tion of fa t-embolism. Lancea , 2 , 8 25 -8 28 .SEVITT , S. (1962) : F at E mb olism . L ond on : B utte rw orths .SOLOWAY , H . B ., an d ROB INsON , E. F. (19 72): T h e coagu la tio n m ech an ism in experim en ta l p u lm onary fa t

embo l i sm . Jou rna l o f T raum a , 1 2, 6 30 -6 31 .SPROULE , B. J. , BRADY, J . L ., and G ILBERT , J. A . L . (19 64 ): S tud ies o n the sy nd rom e o f fat em bo liza tio n .

C an ad ia n M ed ica l A ssoc ia tio ,z Jou r na l , 90 , 1243-1247 .TEDESCH I . C . G ., CA5TELL I , W ., KROPP , G. , and TE DE SCH I, L. G . (19 68) : Fat m acro g lo bu linem ia and fat

embol ism. Su rge ry , G yn eco lo gy an d O bste tr ics , 126 , 83-90 .VOLZ , R . G . (1 96 6): Curre nt c oncepts o f fa t e mb olis m. Rocky M oun ta in M ed ica l J ou rn a l, 63 , 39-43 .WARREN , S . (1946): F at e mb olis m. Am er ica ,, Jo u rna l o f P ath o log y , 22 , 69-88 .WERTZBERGER , J . J. T. , an d PELT IER , L. F. (19 68): F at embol ism: the impor tance of arteria l hy pox ia . Surger i ,

63 , 626-629 .Z IMMERMAN , W . E . (197 2): Pape r read at a sym po sium on sh ock he ld at B uenos A ires, S ou th A m eric a in

Octo b e r 1972 .

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