Variations in burn perfusion over time as measured by portable ICG fluorescence: A case series

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1 Burns & Trum, Otoer 2014, Vol 2, Issue 4 Cse Report Vritions in urn perfusion over time s mesured y portle ICG fluoresene: A se series Shrmil Dissnike, Senn Adul-Hmed, John A. Griswold Deprtment of Surgery, Texs Teh University Helth Sienes Center, Luok, Texs, USA Corresponding uthor: Shrmil Dissnike, Deprtment of Surgery, Milstop 8312, Texs Teh University Helth Sienes Center, th St, Luok, Texs 79430, USA. E-mil: Shrmil.dissnike@ttuhs.edu Reeived: , Revised: , Aepted: ABSTRACT The erly determintion of heling potentil in indeterminte thikness urns my e diffiult to estlish y visul inspetion lone, even for experiened urn prtitioners. This se series explores the use of indoynine green (ICG) fluoresene using portle edside ssessment s potentil tool for erly determintion of urn depth. Three sujets with indeterminte thikness urns hd dily perfusion ssessment using ICG fluoresene ssessment using the SPY mhine (SPY, Lifeell Corp., NJ, USA) in ddition to stndrd urn re. The fluoresene ws quntified s perentge of the perfusion of intt skin, nd res of hypond hyper-perfusion were indited. The study ws onluded when the urn surgeon, linded to the ICG results, mde linil determintion of the need for skin grfting or dishrge. The perfusion in res of differing depth of urn were ompred over the entire study period to determine oth the mgnitude of differene, nd the point in the time ourse of heling when these hnges eme evident. Signifint differenes in perfusion were noted etween urned res of vrying depth. These differenes were evident s erly s the first post-urn dy, nd persisted till the ompletion of the study. ICG fluoresene represents potentil djunt in urn ssessment in this first longitudinl study of its use; however muh more systemti reserh will e required to judge the fesiility of linil implementtion. Key words: Burn depth ssessment, indoynine green, SPY Introdution While it is reltively esy for experiened urn prtitioners to differentite etween urns tht re lmost ertinly going to hel (first degree nd superfiil seond degree urns) nd those tht will lmost ertinly not hel nd insted require exision nd skin grfting (deep seond nd third degree urns), the quest to determine the heling potentil of indeterminte urns hs oupied urn Aess this rtile online Quik Response Code: Wesite: DOI: / speilists for dedes. The erly reognition of urns tht will not hel without srring llows for erlier definitive surgil therpy exision nd split thikness skin grfting, reduing hospitl length of sty s well s improving the finl osmeti nd funtionl result, ompred to delyed surgery. In ttempts to hieve this outome, some enters dvote poliy of erly opertion on most seond degree urns; however this pproh neessrily sujets some ptients to unneessry surgery. A ommon option is wit-nd-see pproh, with dily or otherwise frequent evlution of the urn y the senior urn surgeon, with visul ssessment of likelihood of heling. This proess my involve 5-7 dys of dily ssessment, nd thus my result in dely to definitive surgery in some ptients, nd potentilly unneessry prolongtion of hospitl sty in others. Alterntives to visul inspetion hve een proposed y mny uthors, nd of these, lser Doppler ssessment hs reeived the most ttention. [1-4] 201

2 The use of indoynine green (ICG) fluoresene ws first desried y Sheridn et l., [5] in groundreking tril of 10 ptients sed on suessful preliminry results in porine model. They showed ler differenes in perfusion in deep urns ompred to superfiil urns, thus estlishing proof of priniple. Still et l., susequently orroorted these results with tril in nine ptients in [6] A reent study using n niml model lso onfirmed the potentil for ICG to serve s tool in ssessing urn injury. [7] However oth linil studies only used the imging tehnique t single timepoint fter urn, nd due to limittions of the tehnology t tht time, ould only perform visul ssessment of the fluoresein imges. In ddition, the equipment required to perform the study ment tht this ws usully umersome proess, requiring the ptient to e moved into room with speilized hevy equipment similr to n ngiogrphy suite. The ssessment of ICG fluoresene hs now een inorported into portle ommeril devie (SPY, Lifeell Corp., NJ, USA) tht is in widespred linil use for ssessing the perfusion of intestinl nstomosis nd myofsioutneous flps, thus signifintly reduing the logistil diffiulty of performing the study. Although previous reserhers hve shown tht ICG fluoresene might e helpful in urn depth ssessment, their use of only one mesurement t n ritrry time point from injury signifintly limits the generlizility of their findings. Therefore we performed pilot study using ICG fluoresene to mp the res of n indeterminte urn on dily sis during the ourse of initil hospitliztion, in order to evlute the differene in seline perfusion s well s perfusion hnges in res of different urn depth. In ddition, we used the urrently ville improved tehnology to lulte perfusion s perentge of the perfusion of intt skin, thus providing muh more preise estimte of perfusion thn ws previously possile. The gol of this study ws to identify perfusion differenes etween res of different depth, nd to determine how erly in the post-urn time ourse these differenes eme pprent, thus evluting the potentil of portle ICG perfusion mesurement to determine likelihood of heling in urns. Methods This study ws pproved y the Texs Teh University Helth Sienes Center Institutionl Review Bord. Study ondut Ptients with urns of indeterminte thikness nd less thn 15% TBSA, s determined y n ttending urn surgeon on dmission, were sreened for inlusion in the study. After informed onsent, eh sujet hd dily dressing hnges nd wound re per our stndrd urn enter protool. In ddition, SPY ssessment ws performed during every dily dressing hnge. This involved n intrvenous dose of 5 mg of ICG eing injeted, followed y fluoresene imges eing ptured of the urn. Eh ptient reeived the sme 5 mg dose whih ws not weight-djusted, s per FDA pproved protool when the SPY devie is used for other inditions. While repet doses re routinely used in linil prtie nd doses up to 50 mg t one setting hve een doumented s sfe, the lowest effetive dose ws hosen in order to ensure ptient sfety for the purposes of this study. The SPY mhine ws tivted nd the re to e ssessed pled under the viewer. Digitl photogrphs of the re were ptured using the uilt-in mer on the SPY mhine. One the ICG ws injeted, imges of perfusion egn ppering on sreen within 1-2 min, nd imge pture ws egun s soon s this ourred. Imge pture ontinued until the ICG egn to wshout, proess tht usully is omplete t round 5 min. Quntifition of perfusion ws performed on the sved imges s desried elow. This proess ws repeted dily until determintion of need for skin grfting or rediness for dishrge ws mde. The ttending urn surgeon ws linded to the results of the SPY ssessment until the study ws ompleted, nd thus ll linil deisions were mde sed on stndrd visul ssessment s per usul protool. Quntifition of perfusion The SPY mhine lultes the perfusion in given re s perentge sed on referene re indited y the opertor. Intt, unurned skin ws seleted s the referene for mesurement of perfusion, nd ws therefore set to 100%. This llowed for res of oth hyperemi nd hypoperfusion to e doumented reltive to intt skin. At the onlusion of the study, the perfusion in n re tht ws determined to e superfiil y visul ssessment ws ompred with tht of deeper re nd the differene ws quntified using perfusion perentge. Vlues for these sme res for eh dy of the study were retrospetively ompred s within-sujet omprison with the unurned skin set s the stndrd. Clinil re Wound re ws performed using stndrd urn enter protool, nd onsisted of non-dhesive guze 202

3 impregnted with either Neosporin or Sulfmylon ointment. The urn surgeon, who ws linded to the SPY results, ssessed the urn visully eh dy fter the SPY proedure ws omplete. The SPY results were not used to guide tretment deisions in ny wy, nd the study ws terminted when the surgeon determined tht the urn either required grfting, or ws heling nd the ptient ould e dishrged. Results Cse 1 A 54-yer-old femle ws dmitted with 7% TBSA urn to the left rm nd hnd following ooking-relted flme injury. She underwent dily ssessment for 5 dys, fter whih time it ws determined tht while ertin res of the urn were likely to hel, the mjority of the urn required skin grft, nd the study ws onluded. The perfusion nd photogrphi imges re shown in Figure 1. Are 1 ws n re determined to require grfting, while re 2 ws judged likely to hel y linil visul ssessment. The differene in perfusion of res 1 nd 2 is evident on the first dy post-urn, with re 2 hving lmost doule the perfusion of re 1. This mgnitude of differene remined stedy throughout the study period, despite the solute vlues vrying over time. Both res were exised nd grfted t opertion to provide uniformity nd prevent hypertrophi srring long the wound edges. Cse 2 A 72-yer-old femle ws dmitted with 10% TBSA urn to left thigh, left flnk nd left upper hest lso following ooking-relted ident. She ws ssessed dily for 5 dys nd ws dishrged home fter we determined tht her wounds will hel with no surgery. The perfusion nd photogrphi imges re shown in Figure 2. The differene in re 1 nd 2 in this se were smller thn tht in the previous se, likely due to smller mgnitude of differene in urn depth. Unlike Cse 1, this ptient demonstrted spike in perfusion on dy 4, immeditely prior to the ssessment of heling nd dishrge. Cse 3 A 37-yer-old mle ws dmitted with 7% TBSA urn to ilterl upper extremities following motor vehile ident. His wounds were evluted for 7 dys nd the ptient ws sent home fter it ws determined tht no surgil tretment ws indited. The perfusion nd photogrphi imges re shown in Figure 3. Similr to Cse 2, this ptient showed spike in perfusion of oth res on dy 3, whih then returned to level similr to previous vlues on dy 4. The solute differene etween res 1 nd 2 ws of smller mgnitude ompred to the previous ses, nd on dy 2 the vlues were similr enough to e indistinguishle. Neither of the ltter two ptients required susequent skin grfting, suggesting tht the orret surgil deision hd Figure 1: Representtive photogrphs of urn in se 1. () Are 1 shows deeper urn nd re 2 shows the more superfi il urn. () Corresponding perfusion grphs showing perfusion in eh re over the time ourse of the study. Intt, unurned skin is set s the referene t 100%. () Perfusion imges of the res in photogrph. Ares of mesured perfusion re shown in green with orresponding perentges. The perfusion sns re from dy 3 in se 1. Figure 2: Representtive photogrphs of urn in se 2. () Are 1 shows deeper urn nd re 2 shows the more superfi il urn. () Corresponding perfusion grphs showing perfusion in eh re over the time ourse of the study. Intt, unurned skin is set s the referene t 100%. () Perfusion imges of the res in photogrph. Ares of mesured perfusion re shown in green with orresponding perentges. The perfusion sns re from dy 3 in se

4 een mde sed on linil grounds lone. In ll ses the res determined to e deeper y visul ssessment were shown to hve redued perfusion y quntittive ssessment; however s indited ove, the mgnitude of differene nd solute vlues oth vried sustntilly etween ptients nd oth res eventully heled. Disussion This pilot study demonstrtes tht ICG fluoresene ssessment hs the potentil to differentite depth of urn s erly s dy 1, severl dys prior to this eoming pprent to n expert urn surgeon on visul ssessment. It is telling tht these hnges in perfusion re sutle enough tht they re only lerly evident when the omputerized system of lulting perfusion s perentge of seline is used; the hnges in perfusion re diffiult to ppreite on visul inspetion of the fluoresene imges lone. This of ourse reflets the diffiulty urn physiins fe using visul ssessment the differenes in regions of heling re indeed sutle, nd often require tehnologil ids in order to mke this determintion t n erly stge. Erly reports of ICG fluoresene demonstrted the tehnique in urns tht were lerly ovious on visul inspetion to e either very deep or superfiil. [5,6] With omputer-ided mesurement of perfusion, the tehnology ppers to hve evolved to level tht llows detetion of sutle differenes in heling in indeterminte urns, whih inreses the potentil for linil utility. The uthors intend this se series to suggest proof-ofonept, rther thn mke definitive sttement on the linil potentil of this tehnology in urns. Deeper res Figure 3: Representtive photogrphs of urn in se 3. () Are 1 shows deeper urn nd re 2 shows the more superfi il urn. () Corresponding perfusion grphs showing perfusion in eh re over the time ourse of the study. Intt, unurned skin is set s the referene t 100%. () Perfusion imges of the res in photogrph. Ares of mesured perfusion re shown in green with orresponding perentges. The perfusion sns re from dy 3 in se 3. lerly hd less perfusion thn more superfiil res; however the pttern of vritions in perfusion is intriguing. The two ptients who did not require skin grfting displyed ler spikes in perfusion immeditely efore the time tht the determintion of heling ws mde finding tht ws not seen in the ptient who required skin grfting. The ptients tht heled lso hd more vriility in the perfusion urves of the deeper nd superfiil res, while the first ptient who hd two lerly distint res, one whih required grfting nd one whih would hve otherwise heled, showed nerly prllel lines in perfusion. Lrger studies will e required to onfirm tht these findings represent iologi phenomen rther thn rndom vrition mplified y the smll smple size. One drwk to this method is the need for n intrvenous injetion of the ICG whih inreses the invsiveness of the ssessment. ICG is n FDA pproved nd well-tested drug with inditions for perfusion ssessment in mny other res, nd long trk reord of sfe use; nevertheless this is signifint drwk ompred to ompletely noninvsive methods. While the generi ICG is ville t low ost ($50 per dose from our institutionl phrmy) the proprietry kit tht is sold y the SPY ompny is onsiderly more expensive ($1500 per hospitl ontrt t this institution), nd therefore it likely to e ostprohiitive for routine dily use. Currently the stndrd ontrt etween the ompny nd hospitl require use of the ommeril kit rther thn generi ICG, nd thus the ost per ptient would e signifint. There re severl limittions to the generlizility of these results, esides the ovious limittion of smll desriptive se series. Firstly, while the mesured perfusion lerly vried with depth of urn, this differene ws pprent even when oth res were reltively deep, or reltively superfiil i.e. the perfusion differene ompred to intt skin seems to e reltively liner ontinuous vrile rther thn n ordinl or exponentil vrile. As suh, it is likely to e diffiult to generte ler ut-off point to mke deisions on opertive tretment. There ws no signifint differene in solute perfusion in the se tht required surgery nd the ses tht heled, whih is wrning tht linil ppliility might e limited. The solute vlue of perfusion vried sustntilly etween ses, suggesting tht vriility etween individuls my lso pose prolem with this form of ssessment. Finlly, there ws sustntil vriility in perfusion etween dy 3 nd 4 in the ltter two ses, whih indites tht timing of the intervention will signifintly ffet the results, nd would hve to e stndrdized in order to rete linilly useful ssessment tool. 204

5 Referenes 1. Hoeksem H, Bker RD, Hollnd AJ, Perry T, Jeffery SL, Verelen J, et l. A new, fst LDI for ssessment of urns: A multi-entre linil evlution. Burns Shrm VP, O Boyle CP, Jeffery SL. Mn or mhine? The linimetri properties of lser Doppler imging in urn depth ssessment. J Burn Cre Res 2011;32: Gill P. The ritil evlution of lser Doppler imging in determining urn depth. Int J Burns Trum 2013;3: Hop MJ, Hiddingh J, Stekelenurg C, Kuipers HC, Middelkoop E, Nieuwenhuis MK, et l. LDI study group. Cost-effetiveness of lser Doppler imging in urn re in the Netherlnds. BMC Surg 2013;13:2. 5. Sheridn RL, Shomker KT, Luhin LC, Hurley J, Yin LM, Tompkins RG, et l. Burn depth estimtion y use of indoynine green fluoresene: Initil humn tril. J Burn Cre Rehil 1995;16: Still JM, Lw EJ, Klvuhn KG, Islnd TC, Holtz JZ. Dignosis of urn depth using lser-indued indoynine green fluoresene: A preliminry linil tril. Burns 2001;27: Fourmn MS, Phillips BT, Crwford L, MClin SA, Lin F, Thode HC Jr, et l. Indoynine green dye ngiogrphy urtely predits survivl in the zone of ishemi in urn om model. Burns 2014;40: How to ite this rtile: Dissnike S, Adul-Hmed S, Griswold JA. Vritions in urn perfusion over time s mesured y portle ICG fl uoresene: A se series. Burn Trum 2014;2: Soure of Support: Nil, Conflit of Interest: None delred. Stying in Touh with the Journl (1) Tle of Contents (TOC) emil lert Reeive n emil lert ontining the TOC when new issue of the journl is ville online. To register for TOC lerts go to (2) Connet to the journl on soil medi Users n ontt the editoril offie of Burns & Trum on feook, LinkedIn nd wecht. 205