ORIGINAL ARTICLE 외상성출혈성쇼크환자에게서 O 형적혈구수혈의유용성과안전성 : 예비연구 * 아주대학교의과대학외과학교실외상외과, 인문사회의학교실 강병희 * ㆍ정경원 * ㆍ허윤정 ㆍ이국종 * Safety and Efficacy of Type-O Packed Red Blood Cell Transfusion in Traumatic Hemorrhagic Shock Patients: Preliminary Study Byung Hee Kang, M.D.*, Kyoungwon Jung, M.D*, Yunjung Heo, M.D., John Cook-Jong Lee, M.D.* *Division of Trauma Surgery, Department of Surgery, Department of Medical Humanities and Social Medicine, Ajou University School of Medicine, Suwon, Korea Correspondence to: John Cook-Jong Lee, M.D. Division of Trauma Surgery, Department of Surgery, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtonggu, Suwon 16499, Korea Tel: +82-31-219-7764 Fax: +82-31-219-7781 E-mail: ajoutrauma@gmail.com Purpose: A new unmatched type-o packed red blood cell (UORBC) storage system was established in Ajou University Hospital Trauma Center. This system was expected to deliver faster and more efficient transfusion. Methods: On March 2016, a new blood storage bank was installed in the trauma bay. Sixty patients who received UORBC from March 2016 to August 2016 were compared with 50 traumatic shock patients who received transfusions at the trauma bay in 2015. Time of transfusion, mortality, adverse transfusion reaction and change of systolic blood pressure were reviewed. Results: Transfusion time from arrival at the hospital was significantly shorter in 2016 (14.07±11.14 min vs. 34.72±15.17 min, p<0.001), but 24-hour mortality was not significantly different (13.3% vs. 20.8%, p=0.292). Systolic blood pressure significantly increased after UORBC transfusion (92.49 mmhg to 107.15 mmhg, p=0.002). Of the 60 patients who received UORBC in trauma bay, 47 (78.3%) patients had an incompatible ABO type, but no adverse transfusion reaction was notated. Conclusion: UORBC allows early blood transfusion and improved systolic blood pressure without significant adverse reactions. (J Acute Care Surg 2017;7:50-55) Key Words: Erythrocyte transfusion, Shock, Wound and injuries, ABO blood group system Received January 4, 2017, Revised April 13, 2017, Accepted April 25, 2017 Copyright 2017 by Korean Society of Acute Care Surgery cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ISSN 2288-5862(Print), ISSN 2288-9582(Online) https://doi.org/10.17479/jacs.2017.7.2.50 서론 빠른수혈은출혈성쇼크환자에게필수적이며최근전문외상소생술에서도강조되고있다 [1]. 쇼크환자에게서수혈은심박출 량의증가와조직에서의산소공급을증가시키기때문에산소부채 (oxygen debt) 시간을줄이고더좋은결과를얻는다 [2]. 그러나수혈부작용은드물지않으며 200,000 420,000 단위의수혈마다치명적인부작용이보고된다 [3]. 이러한수혈부작용을방지 50 J Acute Care Surg Vol. 7 No. 2, October 2017
Byung Hee Kang, et al: Type-O Blood Transfusion in Traumatic Shock 하기위하여수혈전에교차시험을거치고있으나이는시간이소요되기때문에응급한상황에적합하지않다. 따라서응급한상황에서는 ABO type만확인을하고교차시험을거치지않은농축적혈구 (unmatched ABO type specific packed red blood cell, UtypeRBC) 가주로사용된다. 그렇지만이방법도환자에게샘플을시행하고, ABO 혈액형을확인하고, 피를이송하는데에시간이많이소요된다. O형혈액은적혈구에 A 또는 B 항원이없으며, 혈청에항A 및항B 항체가존재한다. 그렇지만농축적혈구에는혈청이 10 ml 이하가들어있기때문에, 응급상황에서교차시험을거치지않은 O형농축적혈구 (unmatched type-o packed RBC, UORBC) 는혈액형에관계없이빠르게투여될수있다. 이미많은연구에서 UORBC의투여가안전하다고보고하였으며, UORBC 의사용으로 UtypeRBC보다빠른수혈을가능하게해주었다 [4-6]. 더욱신속한수혈을위해서는병원내혈액은행위치도고려돼야하는데, 응급실과혈액은행의거리가멀수록, 혈액을운반할인력이필요할수록수혈에필요한시간이오래걸리기마련이다. 이러한점들을고려하여최근에새로운혈액저장장치가본원의외상소생구역내에설치되었으며, UORBC를바로사용할수있도록저장되어있다. 이는외상환자에게서빠른수혈을가능케하기위함이며여기에 UORBC 를사용한효과와안정성에대한초기연구를보고하고자한다. 대상및방법 이있는경우등 ) 에게 UORBC를사용하였으나, 타병원을경유하여전원을온환자도있으므로반드시활력징후에만의존하지않고의사의판단에의하여수혈이결정되었다. 대규모수혈이필요한경우에는농축적혈구, 신선동결혈장, 혈소판을 1:1:1의비율로입원하여사용하였다. 2015년에내원한환자들중수혈이급하게필요한환자를구분하기위하여내원당시수축혈압이 100 mmhg 이하의환자를모집하였다. 외상성출혈환자에게서혈압은많은양의실혈이후에감소하기시작하므로심한저혈압환자군을모집하지않고혈압이떨어지기시작하는시점을생각하여기준을정하였으며, 100 mmhg 이하의환자군의의무기록을확인하였을때수혈이이루어진경우는모두급한수혈 (Utype 또는 UORBC 수혈 ) 이이루어졌었다. 모든환자는외상으로내원하였으며, 18세미만의환자, 병원도착시맥박이만져지지않는환자, 외부병원에서수혈을받고온환자는제외하였다. 환자가병원에도착하여수혈을받는데까지걸리는시간을비교하였으며, 수혈의효용성을알기위하여수혈전후의혈압의변화및출혈로인한사망을반영할수있는 24시간내사망률을조사하였다. 급성수혈부작용을확인하기위하여혈압, 체온, 피부상태를수혈전, 수혈중, 수혈후확인하였다. 지연부작용을확인하기위하여전체혈구계산, 간접빌리루빈, 간효소수치, 요검사, 흉부방사선검사및활력징후를주기적으로시행하였으며입원이후환자가사망한경우진료기록부를확인하여수혈과관련성을조사하였다. 본연구는아주대학교병원의기관연구윤리위원회의심의를통과하였다 (AJIRB-MED-MDB-17-077). 2016년 3월본원외상센터에새로운혈액저장장치가설치되었으며여섯단위의 UORBC가항상구비되어있다 (Fig. 1). 한국에서는 Rh 음성혈액형의비율이약 0.15% 로낮게알려져있기때문에 Rh 양성혈액을저장하여사용하였다 [7]. 새로운혈액저장장치가설치된 2016년 3월부터 8월까지외상소생구역에서 UORBC를수혈받은환자를후향적으로조사하였으며, 2015년 1월부터 12월까지외상소생구역에혈액저장장치가없을때외상소생구역에서수혈을받은환자와비교하였다. 2016년내원한환자들중에불안정한활력징후 ( 수축기혈압 <100 mmhg, 심박동수 >110/min 또는체온 <35 C) 를지니고있으면서 1 L 이상의수액요법에반응이없는경우, 또한다량의출혈이의심되는환자 ( 개방성상처에서급성출혈이심한경우, 복부팽만또는 Focused Assessment with Sonography in Trauma 양성인경우, 진찰에서불안정골반골절 Fig. 1. Blood refrigerator for O-type red blood cell in traumatic bay. www.jacs.or.kr 51
J Acute Care Surg Vol. 7, No. 2, Oct. 2017 통계적분석연속성변수의검정을위하여독립표본 t검정이사용되었으며범주형변수의검정을위하여카이제곱검정이사용되었다. 통계적분석은 SPSS 23.0 (IBM Co., Armonk, NY, USA) 이사용되었으며 p<0.05인경우통계적으로유의하다고정의하였다. 결과 총 113명의환자를분석하였으며평균연령은 52세였고남자가 83명 (73.5%) 이었다. 60명의환자가 2016년혈액저장장치가설치되고난이후수혈을받았으며 2015년수혈을받은외상성쇼크환자는 53명이었다. 양그룹간에 injury severity score에는차이가없었으나최초혈압은 2015년수혈을받은그룹에서통계적으로유의하게낮았다. 저장장치가설치된이후총 145 단위의 UORBC를수혈하였으며, 2015년빠른수혈이필요한 53명의환자중 7명의환자에게서 14 단위의 UORBC를수혈하였다 (Table 1). 새로운저장장치가생기고난이후수혈이통계적으로 Table 1. Patient characteristics (n=113) Characteristic 2016 (n=60) 2015 (n=53) p-value Age (y) 52.02±18.47 52.17±19.19 0.963 Gender 0.976 Male 44 39 Female 16 14 Injury severity score 26.72±11.98 29.60±17.11 0.307 Initial systolic blood 94.43±29.01 80.51±21.42 0.004* pressure Initial heart rate 102.43±23.91 106.57±27.24 0.392 Glasgow coma scale 9.18±5.07 8.58±5.21 0.538 UORBC transfusion 145 (2 [2 3]) 14 (2 [2 2]) in trauma bay (unit) a) Injury mechanism Vehicle accident 34 (56.7) 29 (54.7) Motocycle accident 7 (11.7) 2 (3.8) Bike accident 3 (5.0) 4 (7.5) Fall down 10 (16.7) 11 (20.8) Struck 0 4 (7.5) Slip down/roll 0 2 (3.8) Machine 3 (5.0) 1 (1.9) Penetration 3 (5.0) 0 Values are presented as mean±standard deviation, number only, or number (%). UORBC: unmatched type-o packed red blood cell. a) Amount of transfusion for individual, this value is presented as median [interquartile range]. *p<0.05. 유의하게빨랐으며 24시간내사망률이나원내사망률은통계적으로유의한차이를보이지않았다. 2015년에 UORBC를수혈받은 7명의환자는 2016년 UORBC를수혈받은환자들과내원이후수혈에걸리는시간이통계적으로유의하게차이가났으며 (33.43±14.25분 vs. 14.07±11.14분, p<0.001), 2015년에 UtypeRBC 를받은그룹과유의한차이를보이지않았다 (33.43±14.25분 vs. 34.91±15.44분, p=0.812) (Table 2). 2016년 UORBC를수혈한 60명의환자들중 47명 (78.3%) 은 O형이아닌다른혈액형을지니고있었으나급성또는지연성수혈부작용은나타나지않았다 (Table 3). 또한저장장치설치이후 UORBC 수혈을받은환자들은수혈이진행되면서혈압이통계적으로유의하게상승하였다 (p=0.002) (Fig. 2). Table 2. Results of transfusion before and after blood storage system established Table 3. Blood type of patients who were received UORBC transfusion Blood type UORBC (n=60) 2016 (n=60) 2015 (n=53) p-value Any prbc transfusion 14.07±11.14 34.72±15.17 <0.001* from visit hospital (min) a) UORBC transfusion 14.07±11.14 33.43±14.25 b) <0.001* from visit hospital (min) UtypeRBC transfusion NA 34.91±15.44 NA from visit hospital (min) 24-hour mortality 8 (13.3) 11 (20.8) 0.292 In hospital mortality 17 (28.3) 18 (34.0) 0.518 Values are presented as mean±standard deviation or number (%). prbc: packed red blood cell, UPRBC: unmatched type-o packed RBC, UtypeRBC: unmatched ABO type specific packed, NA: not available. a) Any prbc includes UPRBC and UtypeRBC. b) Seven patients received UORBC transfusion in 2015. *p<0.05. Amount of UORBC Adverse reaction A 22 (36.7) 54 0 B 17 (28.3) 39 0 AB 8 (13.3) 17 0 O 13 (21.7) 35 0 Values are presented as number (%) or number only. UORBC: unmatched type-o packed red blood cell. 52 www.jacs.or.kr
Byung Hee Kang, et al: Type-O Blood Transfusion in Traumatic Shock Fig. 2. Change of systolic blood pressure during unmatched type-o packed red blood cell transfusion (mmhg). 고찰 혈압이떨어지는 III 단계이상의출혈성쇼크환자는대부분수혈을필요로한다 [8]. 그렇기때문에최근에는수혈시점을더빠르게하기위한노력들이보고되고있다. Brown 등 [9] 은사고현장에서부터외상센터로헬기를통하여이송이되는병원전단계의응급한환자에게이송중농축적혈구의수혈이사망률을낮추는데도움이된다고하였다. O Reilly 등 [10] 도전투중에다친군인을대상으로병원으로이송중수혈이사망률을낮추는데기여를했다고보고하였다. 최근에는 Powell 등 [11] 은수혈장소가아닌수혈에걸리는시간이생존율에영향을미친다고강조하였으며, 10분씩수혈이지연될때마다사망률이올라간다고하였다. 여러연구결과를종합하여볼때수혈이필요한환자에게서최단시간내에수혈이이루어지는것은합리적이라판단된다 [12]. 이러한빠른수혈을가능케하기위해서는 UORBC 사용이필수적이었으며, 이번연구에서도새로운혈액저장장치는이전보다 20분정도빠른수혈을가능하게하였다. 20분이라는시간이짧아보일수있으나 Golen Hour 가중요한외상환자에게서 20분은큰의미를지니고있다 [13]. 또한 2015년 UORBC를수혈받는데걸리는시간은 UtypeRBC 수혈을받는군과유의한차이를보이지않았으므로 UORBC의수혈뿐만아니라혈액저장장치의위치도중요하다. 본연구에서 UORBC 수혈이후통계적으로유의하게혈압이상승하였으며정상혈압근처까지회복할수있었다. 24시간내사망률이나원내사망률은양그룹간에통계적인차이를보이지않았으나새로운저장장치가설치된이후사망률이낮게나타났다. 이는예비연구에서긍정적인성과이며앞으로 더많은자료가모이면통계적인차이를기대할수있겠다. UORBC를사용하는데있어서가장큰위험요소는수혈부작용이다. 특히용혈성수혈부작용은치명적이며동종면역에의하여일어나는것으로알려져있고, ABO 혈액형불일치는동종면역을일으키는가장잘알려진요소이다 [14]. 그렇지만 O형적혈구는 A 및 B 항원이없으므로동종면역을잘일으키지않는다 [15]. 또한 O형혈액에미량이지만항A- 및항B- 항체가포함되어있어수혈부작용에대한우려가있음에도불구하고, 미국과같은선진국에서는전쟁과같은특별한상황에서이미 O형전혈혈액을사용하고있다 [16]. 더군다나이미출혈성쇼크환자에게 UORBC 를사용한연구들이있으며이번연구와같이치명적인부작용은보고되지않았다 [5,17,18]. Mulay 등 [19] 은 UORBC의투입에서급성용혈성수혈부작용은 0.02% 에서만나타나며다른수혈부작용이일어날확률도 0.3% 이하라고보고하였다. Goodell 등 [20] 은혈액형과관련없는용혈성수혈부작용이 0.3% 에서나타난다고보고하였으므로이는 Mulay 등 [19] 이 UORBC에서나타난 0.02% 보다도높은수치이다. 그밖에수혈과관련된아나필락시스반응이나과용혈반응, 수혈연관폐손상이나감염등도치명적인결과를가져온다 [14]. 그렇지만이러한반응들은예측할수없거나혈액형을맞춘다고예방할수있는문제가아니므로주의깊은관찰이필요하다. 결론적으로 UORBC 사용으로인한치명적인수혈부작용이생길확률은매우낮으며혈액형을맞춘다고하더라고비슷한확률로치명적인수혈부작용이일어날수있다. 다만 UORBC 수급에문제가있을수있으므로 UtypeRBC 사용이가능하면 UtypeRBC를사용하는것이좋으며, UORBC는 UtypeRBC 사용이가능할때까지시간을벌어주는다리 (bridge) 역할을수행할수있다. 실제로본연구의경우 UORBC를투여하면서혈액샘플을시행하였으며, UtypeRBC가사용이가능하면 UtypeRBC를사용하고아직준비가어려운경우에는 UORBC를사용하여효과적으로수혈을할수있었다. 그렇지만 UORBC 사용시고려해야할점들중에하나는이러한 UORBC 수급과관련하여혈액은행의전반적인운영상황을항상주목하여야하며, 본원의외상외과의료진들도혈액수급을운영하는 수혈관리위원회 의운영진으로서참여하고있다. 비록본원외상소생구역에혈액저장장치가설치되었지만혈액보관에관한전문가가외상소생구역에상주하지는않았다. 농축적혈구는 4 C 정도로냉장고안에보관되며만기날짜만간호사에의하여점검되었다. 또한사용되지않은농축적혈구를다른병동의환자에게투입하는것은행정적으로어려운일이어 www.jacs.or.kr 53
J Acute Care Surg Vol. 7, No. 2, Oct. 2017 서외상소생구역혈액은행에는여섯단위의농축적혈구만을보관하고있었다. 그렇지만다량의수혈이필요한경우 UORBC 는 UtypeRBC이준비될때까지다리역할을해주었기때문에적은농축적혈구로도충분하였고다행히혈액의보관기간이만료되어폐기되는일은없었다. 최근에는중증외상환자에게서 UORBC뿐만아니라 O혈전혈이나다른혈액제제의사용대한연구가많이진행되고있다 [21-23]. 현재본원외상센터의혈액은행으로는농축적혈구이외에다른혈액제제에대한보관이어려운상태이며이에대하여더발전된혈액관리체계가필요할수있다. 이번연구는몇가지한계점이있다. 첫째로, 총 UORBC 수혈단위가적기때문에수혈부작용이나타나지않았을수있다. 둘째로, 2016년에내원한불안정한활력징후를가진환자들이모두 UORBC 수혈을받았기때문에, 결정질용액으로도혈압상승효과가똑같이나타날지에대하여확인할수가없다. 셋째로, 아직연구에포함된환자가적기때문에통계적인결론을내기에는무리가있다. 마지막으로중증외상환자의특성상무작위연구가어려우므로후향적연구에의존할수밖에없다는점이다. 결론적으로 UORBC는빠른수혈을가능하게하며혈압의상승에효과가있다. 수혈부작용에대한우려가있으나부작용이나타날확률은적고외상성쇼크환자에게서빠른소생이중요하므로중증외상환자에게 UORBC 수혈을고려해야한다. 또한더나은효과를보기위해서는혈액저장장치가응급실이나외상소생구역등에위치하여야한다. 그리고이번예비연구에이어빠른수혈이생존율상승에영향을미치는지, 대량수혈과의연관성에대해서앞으로연구해보아야하겠다. Conflicts of Interest No potential conflict of interest relevant to this article was reported. References 1. ATLS Subcommittee; American College of Surgeons Committee on Trauma; International ATLS working group. Advanced trauma life support (ATLS R ): the ninth edition. J Trauma Acute Care Surg 2013;74:1363-6. 2. Bjerkvig CK, Strandenes G, Eliassen HS, Spinella PC, Fosse TK, Cap AP, et al. Blood failure time to view blood as an organ: how oxygen debt contributes to blood failure and its implications for remote damage control resuscitation. Transfusion 2016;56 Suppl 2:S182-9. 3. Bolton-Maggs PH. Bullet points from SHOT: key messages and recommendations from the Annual SHOT Report 2013. Transfus Med 2014;24:197-203. 4. Blumberg N, Bove JR. Un-cross-matched blood for emergency transfusion. One year s experience in a civilian setting. JAMA 1978;240:2057-9. 5. Dutton RP, Shih D, Edelman BB, Hess J, Scalea TM. Safety of uncrossmatched type-o red cells for resuscitation from hemorrhagic shock. J Trauma 2005;59:1445-9. 6. Unkle D, Smejkal R, Snyder R, Lessig M, Ross SE. Blood antibodies and uncrossmatched type O blood. Heart Lung 1991;20:284-6. 7. Kim KH, Kim KE, Woo KS, Han JY, Kim JM, Park KU. Primary anti-d immunization by DEL red blood cells. Korean J Lab Med 2009;29:361-5. 8. Townsend CM Jr, Beauchamp RD, Evers BM, Mattox KL. Sabiston textbook of surgery: the biological basis of modern surgical practice. 19th ed. Philadelphia: Elsevier Saunders; 2012. 9. Brown JB, Sperry JL, Fombona A, Billiar TR, Peitzman AB, Guyette FX. Pre-trauma center red blood cell transfusion is associated with improved early outcomes in air medical trauma patients. J Am Coll Surg 2015;220:797-808. 10. O Reilly DJ, Morrison JJ, Jansen JO, Apodaca AN, Rasmussen TE, Midwinter MJ. Prehospital blood transfusion in the en route management of severe combat trauma: a matched cohort study. J Trauma Acute Care Surg 2014;77(3 Suppl 2): S114-20. 11. Powell EK, Hinckley WR, Gottula A, Hart KW, Lindsell CJ, McMullan JT. Shorter times to packed red blood cell transfusion are associated with decreased risk of death in traumatically injured patients. J Trauma Acute Care Surg 2016; 81:458-62. 12. Smith IM, James RH, Dretzke J, Midwinter MJ. Prehospital blood product resuscitation for trauma: a systematic review. Shock 2016;46:3-16. 13. Alarhayem AQ, Myers JG, Dent D, Liao L, Muir M, Mueller D, et al. Time is the enemy: Mortality in trauma patients with hemorrhage from torso injury occurs long before the golden hour. Am J Surg 2016;212:1101-5. 14. Delaney M, Wendel S, Bercovitz RS, Cid J, Cohn C, Dunbar NM, et al. Transfusion reactions: prevention, diagnosis, and treatment. Lancet 2016;388:2825-36. 15. Branch DR. Anti-A and anti-b: what are they and where do they come from? Transfusion 2015;55 Suppl 2:S74-9. 16. Auten JD, Lunceford NL, Horton JL, Galarneau MR, Galindo RM, Shepps CD, et al. The safety of early fresh, whole blood transfusion among severely battle injured at US Marine Corps forward surgical care facilities in Afghanistan. J Trauma Acute Care Surg 2015;79:790-6. 17. Radkay L, Triulzi DJ, Yazer MH. Low risk of hemolysis after transfusion of uncrossmatched red blood cells. Immunohematology 2012;28:39-44. 18. Schwab CW, Shayne JP, Turner J. Immediate trauma resusci- 54 www.jacs.or.kr
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