대한수혈학회지 : 제 24 권제 2 호, 2013 The Korean Journal of Blood Transfusion Vol. 24, No. 2, 121-127, August 2013 ISSN 1226-9336 Original Article 수혈전예비투약실태조사 : 단일기관연구 김보람ㆍ최재림ㆍ김지은ㆍ우광숙ㆍ김정만ㆍ한진영ㆍ김경희 동아대학교의과대학진단검사의학교실 Transfusion Premedication: A Single Center Study Bo-Ram Kim, Jae-Lim Choi, Ji-Eun Kim, Kwang-Sook Woo, Jung-Man Kim, Jin-Yeong Han, Kyeong-Hee Kim Department of Laboratory Medicine, Dong-A University College of Medicine, Busan, Korea Background: Acute transfusion reaction occurs during or within a few hours of transfusion with 0.5 3% of blood transfusion. Febrile non-hemolytic transfusion reactions (FNHTRs) and allergic transfusion reactions (ATRs) are the most common transfusion reactions. Premedication with acetaminophen and diphenhydramine has been used to prevent these reactions in 50 80% of transfusions. The purpose of this study was to describe the frequency of premedication and FNHTRs and ATRs according to premedication in Korea. Methods: Between January 1 and 31, 2013, analysis of the first transfusion was performed retrospectively with chart review. A total of 549 cases were analyzed with regard to product of blood, care area, premedication, and FNHTRs and ATRs. Results: Premedication was administered in 88.2% (484/549) of transfusions; 4 mg chlorphenamine, a well-known antihistamine, was used as premedication in all cases. Occurrence of FNHTRs was 7.7% without premedication and 3.7% with premedication. Occurrence of ATRs was 0% without premedication and 0.8% with premedication. The frequency of premedication was related to care area but not blood products. Conclusion: Premedication use was more frequent than previously reported. However, the sample size in this study is small; therefore, conduct of further prospective multicenter studies is needed. (Korean J Blood Transfus 2013;24:121-127) Key words: Premedication, Transfusion reaction, Febrile non-hemolytic transfusion reaction, Allergic transfusion reaction 서론 급성수혈반응은수혈도중또는수혈후몇시 간이내에발생하는부작용으로전체수혈의 0.5 3% 에서발생한다. 1) 이중비용혈성발열반응과알레르기반응이가장흔히접할수있는수혈부 Received on July 25, 2013. Revised on August 19, 2013. Accepted on August 19, 2013 Correspondence to: Kyeong-Hee Kim Department of Laboratory Medicine, Dong-A University College of Medicine, 1 Dongdaesin-dong 3-ga, Seo-gu, Busan 602-715, Korea Tel: 82-51-240-2850, Fax: 82-51-255-9366, E-mail: progreen@dau.ac.kr This study was supported by research funds from Dong-A University. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright C 2013 The Korean Society of Blood Transfusion - 121 -
Korean J Blood Transfus Vol. 24, No. 2, 121-127, Aug. 2013 작용이다. 비용혈성발열반응은수혈도중또는수혈후 4시간이내에구강온도가 38도이상이거나체온이 1도이상상승한경우로, 용혈이없어야하며오한이동반될수있다. 적혈구제제수혈시 0.3 6%, 혈소판제제수혈시 1 38% 에서발생하며, 보관전백혈구제거혈액제제를수혈할경우 0.2% 로그빈도가감소한다. 2-5) 알레르기반응은수혈시 0.4 3% 의빈도로발생하며백혈구제거혈액제제를사용으로도그빈도를감소시킬수없다. 3,6) 급성수혈반응은그자체로는환자의생명을위협하는문제는아니나다른심각한수혈부작용의초기증상인경우도있어이를위한평가, 치료지연, 비용의증가, 환자의불편등을야기하므로, 이를예방하고자하는노력이있어왔다. 수혈전 acetaminophen과 diphenhydramine 등의예비투약은비용혈성발열반응과알레르기반응을예방하거나개선할수있다고알려져 50 80% 의수혈에서행하여지고있다. 5,7-14) The American Association of Blood Banks (AABB) Technical Manual도비용혈성수혈반응의예방과치료를위해항히스타민제를투여할것을권고하고있다. 3) 하지만아직까지도수혈전예비투약의유효성에대한명백한결론은없으며, 그동향에대한연구또한제한적이다. 현재까지한국에서의수혈전예비투약의빈도, 그약제, 유효성에대한연구는부족하므로그를연구하고자하였다. 대상및방법 2013년 1월 1일부터 1월 31일까지 1개월동안수혈받은환자의첫번째수혈만을대상으로혈액제제, 수혈처방과, 예비투약, 비용혈성발열반응, 알레르기반응을환자의진료기록을토대로조사하였다. 비용혈성발열반응과알레르기반응은 NHSN Biovigilance Component Protocol에따라정의하였다. 3) 수혈전예비투약은수혈전 2시간이내에투약되는약물로정의하였다. 예비투약과비용혈성발열반응, 알레르기반응의상관성은 Chisquared test를이용하였다. 결과상기기간동안총 576건의첫번째수혈이이루어졌다. 이중폐기 5건, 진료기록미비 8건, 자가수혈 10건, 세척적혈구 4건을제외한 549건을진료기록을토대로조사하였다. 총 549건중 484 건 (88.2%) 에서수혈전예비투약을하였고이때사용한약제는모두 chlorphenamine이었다. 전반적인비용혈성발열반응의빈도는 4.2%, 알레르기반응의빈도는 0.7% 였다. 혈액제제별예비투약의빈도는백혈구여과제거적혈구에서 94.1%, 농축적혈구 89.0%, 농축혈소판 87.3%, 백혈구여과제거성분채혈혈소판 77.8%, 신선동결혈장 75.0% 순이었다 (Table 1). 수혈처방과별예비투약의빈도는 Table 2와같 Table 1. Premedication according to blood products RBC (n=419) PLT (n=55) F RBC (n=34) FFP (n=32) A PLT (n=9) Total (n=549) Premedication 373/419 (89.0%) 48/55 (87.3%) 32/34 (94.1%) 24/32 (75.0%) 7/9 (77.8%) 484/549 (88.2%) Non premedication 46/419 (11.0%) 7/55 (12.7%) 2/34 (5.9%) 8/32 (25.0%) 2/9 (22.2%) 65/549 (11.8%) Abbreviations: F RBC, prestorage leukoreduced RBC; A PLT, apheresis PLT. - 122 -
김보람외 : 수혈전예비투약실태조사 : 단일기관연구 Table 2. Premedication according to care area Pediatric medicine Pediatric surgery Medicine Hematooncology Surgery ICU ER Cardiology medicine Cardiology surgery RBC Premedication 88 (85.4%) 90 (88.2%) 101 (99.0%) 17 (100%) 57 (98.3%) 12 (66.7%) 8 (61.5%) Non premedication 6 (100%) 15 (14.5%) 12 (11.8%) 1 (1.0%) 0 1 (1.7%) 6 (33.3%) 5 (38.5%) PLT Premedication 2 (100%) 9 (90.0%) 17 (85.0%) 4 (80.0%) 2 (100%) 4 (80.0%) 3 (100%) 7 (87.5%) Non premedication 0 1 (10.0%) 3 (15.0%) 1 (20.0%) 0 1 (20.0%) 0 1 (12.5%) F RBC Premedication 3 (100%) 27 (93.1%) 1 (100%) 1 (100%) Non premedication 0 2 (6.9%) 0 0 FFP Premedication 0 5 (62.5%) 1 (100%) 4 (100%) 6 (100%) 4 (100%) 1 (50.0%) 3 (50.0%) Non premedication 1 (100%) 3 (37.5%) 0 0 0 0 1 (50.0%) 3 (50.0%) A PLT Premedication 7 (87.5%) 0 Non premedication 1 (12.5%) 1 (100%) Total 12 0 121 160 111 25 69 24 27 Premedication 5 (41.7%) 102 (84.3%) 142 (88.8%) 109 (98.2%) 25 (100%) 66 (95.7%) 17 (70.9%) 18 (66.7%) Non premedication 7 (58.3%) 19 (15.7%) 18 (11.2%) 2 (1.8%) 3 (4.3%) 7 (29.2%) 9 (33.3%) - 123 -
Korean J Blood Transfus Vol. 24, No. 2, 121-127, Aug. 2013 Table 3. FNHTR and ATR according to premedication RBC (n=419) PLT (n=55) F RBC (n=34) FFP (n=32) A PLT (n=9) Total Premedication 373/419 (89.0%) 48/55 (87.3%) 32/34 (94.1%) 24/32 (75%) 7/9 (77.8%) FNHTR 14/373 (3.8%) 3/48 (6.3%) 1/32 (3.1%) 0/24 (0.0%) 0/7 (0.0%) 14/484 (3.7%), P=0.26 ATR 1/373 (0.3%) 1/48 (2.1%) 1/32 (3/1%) 0/24 (0.0%) 1/7 (14.3%) 4/484 (0.8%), P=0.95 Non premedication 46/419 (11.0%) 7/55 (12.7%) 2/34 (5.9%) 8/32 (25%) 2/9 (22.2%) FNHTR 2/46 (4.3%) 2/7 (28.6%) 1/2 (50.0%) 0/8 (0.0%) 0/2 (0.0%) 5/65 (7.7%) ATR 0/46 (0.0%) 0/7 (0.0%) 0/2 (0.0%) 0/8 (0.0%) 0/2 (0.0%) 0/65 (0.0%) 다. 수혈처방과는 9개의영역으로분리하였다. 소아과는소아내과와소아외과로구분하여그빈도를살펴보았다. 응급실은환자의진료분야가정해지기전이므로구분하였으며, 중환자실은각진료과의구분없이중환자실에입원해있는환자를기준으로하였다. 환자를크게외과환자와내과환자로구분하였으며, 수혈의빈도가높은혈액종양내과와순환기내과와흉부외과는구분하였다. 중환자실에서 100%, 외과에서 98.2%, 응급실 95.7%, 혈액종양내과 88.8%, 내과 84.3%, 순환기내과 70.9%, 흉부외과 66.7%, 소아과 41.7% 순으로, 소아과에서특히낮은빈도를보였다. 비용혈성발열반응의빈도는수혈전예비투약을하였을경우 3.7% (18/484) 로예비투약을하지않은경우의 7.7% (5/65) 보다그빈도가절반가량감소하였다. 알레르기반응은예비투약을하였을경우 0.8% (4/484), 예비투약을하지않은경우 0.0% (0/65) 였다 (Table 3). 예비투약과비용혈성발열반응 (P=0.26) 과알레르기반응 (P=0.95) 간의유의성은없었다. 고찰본연구에서수혈전예비투약의빈도는 88.2% 로이전에보고된 50 80% 에비하여높은빈도를보였다. 이러한연구들의대부분이수혈을자 주받는혈액종양환자들을대상으로하였고, 발열성수혈부작용을감소시킨다고알려진보관전백혈구제거혈액제제가널리이용되기전에발표된연구들이었다. 5,7-14) 따라서저자들은수혈전예비투약의빈도가이전보고보다낮을것으로기대하였으나오히려이전연구에비해높은빈도를보였다. 혈액제제별로수혈전예비투약의빈도는적혈구제제에서 89.4%, 혈소판제제에서 85.9%, 신선동결혈장에서 75.0% 로차이가존재하였다. 비용혈성발열반응은혈소판제제수혈할때그발생빈도가적혈구제제수혈시의빈도보다높으므로혈소판제제를수혈할때예비투약을많이할것으로예상하였으나오히려적혈구제제의수혈시높은빈도로예비투약을하고있었다. 최근 Fry 등은 2% 이하의수혈전예비투약의빈도를보고하였는데, 이전보고에비해낮은빈도의원인을보관전백혈구제거혈액제제의사용으로보고하였다. 15) 하지만본연구에서는백혈구제거적혈구수혈의 94.1% 에서예비투약이시행되어지고농축적혈구수혈의 89.0% 에서예비투약이시행되어지는것으로보아, 보관전백혈구제거혈액제제가예비투약을선택하는데영향을주지않음을알수있었다. 그러나동아대학교병원의혈액관리전산시스템으로는수혈당시의필터사용여부를알수없다는제한점이존재하므 - 124 -
김보람외 : 수혈전예비투약실태조사 : 단일기관연구 로백혈구제거가예비투약의선택에있어서영향을주었는지는알수없다는한계가있다. 본연구에서는처방과별에따라예비투약의빈도차이를보였다. 중환자실은모든수혈에있어서수혈전예비투약을하였고, 외과에서도 98.2% 로높은예비투약처방률을보였다. 중환자실에서수혈을받은 25명의환자중 23명 (92%) 이낮은의식상태로환자가불편증상을호소할수없는것이중환자실에서의수혈전예비투약의높은처방률과연관이있을것으로생각되어진다. 또한본연구에포함되어진외과환자들은모두수술중수혈을받은환자들로이들또한증상호소를할수없는특수상황이높은예비투약빈도의원인이되었을것으로생각되어진다. 소아과의수혈전예비투약률은 41.7% 로평균 88.2% 에비해매우낮은빈도를보였다. 또한소아과에서는혈소판제제수혈시 100% 예비투약률을보였고, 적혈구제제수혈시 33.3% 의예비투약률을보여전반적인혈액제제별예비투약빈도와도차이를보였다. 비용혈성발열반응의빈도는수혈전예비투약을하였을경우 3.7%, 예비투약을하지않은경우 7.7% 로그빈도가감소하는경향을보였으나예비투약과비용혈성발열반응간의유의성은없었다 (P=0.26). 알레르기반응의빈도는예비투약을하였을경우 0.8% 로, 예비투약을하지않은경우보다오히려빈도가높았으나, 예비투약과알레르기반응사이에도유의성이발견되지않았다 (P=0.95). 최근에발표되어진 6개의연구중다섯연구에서수혈전예비투약이비용혈성발열반응과알레르기반응의빈도를감소시키지못한다고결론지었다. 7-11) Ezidiegwu 등은수혈전예비투약이비용혈성발열반응을빈도를감소시킨다고보고하였으나비용효과적인측면에서는유용하지못하다고보고한바있다. 14) 또한예비투약으로 흔히쓰이는 acetaminophen은다른심각한수혈부작용으로인한발열과수혈과관련없는발열의발현을감출수있어치료를어렵게할수있으며, diphenhydramin의진정효과로인해환자의불편을야기할수있으며, 환자상태판정에영향을미칠수있다. 현재까지수혈전예비투약의유용성에대한명백한결론이없음에도불구하고예비투약의빈도는 88.2% 로높았다. 비록단일기관의소규모연구결과이기는하나, 이는수혈전예비투약의유용성에대한국가적인대규모연구가필요함을보여주는것이며, 그에따른수혈전예비투약의적응증에대한정립이필요할것이다. 요약배경 : 급성수혈반응은수혈도중또는수혈후몇시간이내에발생하는부작용으로전체수혈의 0.5 3% 에서발생한다. Premedication은비용혈성발열반응과, 알레르기반응을예방하거나개선시킬수있다고알려져전체수혈의 50 80% 에서사용한다. 현재까지한국에서의수혈전예비투약의빈도, 그약제, 유효성에대한연구는부족하므로그를연구하고자하였다. 방법 : 2013년 1월 1일부터 1월 31일까지 1개월동안수혈받은환자의첫번째수혈만을대상으로하여조사하였다. 혈액제제, 수혈처방과, 예비투약, 비용혈성발열반응, 알레르기반응을환자의진료기록을토대로조사하였다. 결과 : 549건중 484건 (88.2%) 에서수혈전예비투약이시행되었고, 처방된약은모두 4 mg chlorphenamine이었다. 비용혈성발열반응의빈도는수혈전예비투약을하였을경우 3.7% (18/484), 예비투약을하지않은경우 7.7% (5/65) 이었다. 알레르기반응은예비투약을하였을경우 0.8% - 125 -
Korean J Blood Transfus Vol. 24, No. 2, 121-127, Aug. 2013 (4/484), 예비투약을하지않은경우 0.0% (0/65) 였다. 예비투약의빈도는처방과에따라차이를보였으나, 혈액제제의종류는예비투약의선택에영향이없었다. 결론 : 수혈전예비투약의빈도는이전연구결과들에비해높은빈도를보였다. 하지만본연구는단일기관의단기간의연구결과로전향적인다기관연구가필요할것이다. References 1. Public Health Agency of Canada. Transfusion transmitted injuries. http://www.phac-aspc. gc.ca/hcai-iamss/tti-it/[online] (last visited on 16 August 2013) 2. National Healthcare Safety Network (NHSN) Biovigilance component. NHSN Biovigilance Component Protocol v1.3.1. The National Healthcare Safety Network (NHSN) Manual. www.cdc.gov/nhsn [Online] (last visited on 8 May 2013) 3. Brecher ME. Technical manual. 15th ed. Bethesda: American Association of Blood Banks, 2005:633-65 4. Federowicz I, Barrett BB, Andersen JW, Urashima M, Popovsky MA, Anderson KC. Characterization of reactions after transfusion of cellular blood components that are white cell reduced before storage. Transfusion 1996; 36:21-8 5. Paglino JC, Pomper GJ, Fisch GS, Champion MH, Snyder EL. Reduction of febrile but not allergic reactions to RBCs and platelets after conversion to universal prestorage leukoreduction. Transfusion 2004;44:16-24 6. Domen RE, Hoeltge GA. Allergic transfusion reactions: an evaluation of 273 consecutive reactions. Arch Pathol Lab Med 2003;127:316-20 7. Patterson BJ, Freedman J, Blanchette V, Sher G, Pinkerton P, Hannach B, et al. Effect of premedication guidelines and leukoreduction on the rate of febrile nonhaemolytic platelet transfusion reactions. Transfus Med 2000;10: 199-206 8. Sanders RP, Maddirala SD, Geiger TL, Pounds S, Sandlund JT, Ribeiro RC, et al. Premedication with acetaminophen or diphenhydramine for transfusion with leucoreduced blood products in children. Br J Haematol 2005;130: 781-7 9. Szelei-Stevens KA, Narvios A, Al-Sammak M. Transfusion reactions: to premedicate or not to premedicate?: SP181. Transfusion 2006;46(Suppl 9S):95A 10. Wang SE, Lara PN Jr, Lee-Ow A, Reed J, Wang LR, Palmer P, et al. Acetaminophen and diphenhydramine as premedication for platelet transfusions: a prospective randomized double-blind placebo-controlled trial. Am J Hematol 2002;70:191-4 11. Kennedy LD, Case LD, Hurd DD, Cruz JM, Pomper GJ. A prospective, randomized, doubleblind controlled trial of acetaminophen and diphenhydramine pretransfusion medication versus placebo for the prevention of transfusion reactions. Transfusion 2008;48:2285-91 12. Geiger TL, Howard SC. Acetaminophen and diphenhydramine premedication for allergic and febrile nonhemolytic transfusion reactions: good prophylaxis or bad practice? Transfus Med Rev 2007;21:1-12 13. Tobian AA, King KE, Ness PM. Transfusion premedications: a growing practice not based on evidence. Transfusion 2007;47:1089-96 14. Ezidiegwu CN, Lauenstein KJ, Rosales LG, Kelly KC, Henry JB. Febrile nonhemolytic transfusion reactions. Management by pre- - 126 -
김보람외 : 수혈전예비투약실태조사 : 단일기관연구 medication and cost implications in adult patients. Arch Pathol Lab Med 2004;128:991-5 15. Fry JL, Arnold DM, Clase CM, Crowther MA, Holbrook AM, Traore AN, et al. Transfusion premedication to prevent acute transfusion reactions: a retrospective observational study to assess current practices. Transfusion 2010; 50:1722-30 - 127 -