04-예성열

대한응급의학회지제 25 권제 1 호 Volume 25, Number 1, February, 2014 원 저 응급의료센터실신위험도평가연구의표준화된보고지침을적용하여시행한 San Francisco Syncope Rule 의외부적타당화연구 경희대학교의학전문대학원응급의학교실 예성열 권오영 이종석 최한성 홍훈표 고영관 External Validation Study of San Francisco Syncope Rule Based on Standardized Reporting Guidelines for Emergency Department Syncope Risk Stratification Research Sung Yeol Ye, M.D., Oh Young Kwon, M.D., Jong Seok Lee, M.D., Han Sung Choi, M.D., Hoon Pyo Hong, M.D., Young Gwan Ko, M.D. Purpose: We validated the performance of the San Francisco Syncope Rule (SFSR) for accurate identification of Korean emergency department (ED) syncope patients who will experience a short term serious outcome. Methods: This retrospective study included patients over 16 years old who fulfilled the inclusion criteria according to the definition of syncope and visited the ED from January 2010 to June 2013. The authors excluded patients with alcohol or illicit drugs use seizure, stroke or transient ischemic attack, head trauma followed by loss of consciousness, or hypoglycemia. The patients were divided into two groups according to the SFSR for the purpose of performing a comparative analysis. The authors calculated sensitivity, specificity, positive predictive value, and negative predictive value of SFSR and analyzed other variables, except five predictor variables of SFSR. Results: Of 1,235 visits screened, 409 were included. The average age of enrolled patients was 55.2±20.1 and male population accounted for 45.0%(n=184). A total of 93 (27.7%) patients experienced serious outcomes; 41 of 287 (14.3%) patients with a serious outcome were not identified 책임저자 : 최한성서울특별시동대문구회기동 1 경희대학교의과대학부속병원응급의학과 Tel: 02) 958-8275, Fax: 02) 958-8746 E-mail: hsg3748@hanmail.net 접수일 : 2013년 9월 16일, 1차교정일 : 2013년 9월 18일게재승인일 : 2013년 10월 6일 23 as high risk according to the rule. The rule performed with a sensitivity of 55.9%, specificity of 77.8%, positive predictive value of 42.6%, and negative predictive value of 85.7%. Conclusion: In this retrospective validation study based on the standardized reporting guidelines for ED syncope risk stratification research, the SFSR performed with significantly lower sensitivity than previously reported. The results suggest that application of the original rule has limited generalizability and conduct of future studies will be needed in order to refine the SFSR. Key Words: Syncope, Risk, Validation, Sensitivity and specificity Department of Emergency Medicine, College of Medicine, Kyung Hee University, Seoul, Korea 서 실신은일시적인의식소식이있으며기간이매우짧고완벽하게신경학적결손없이회복된상태를말한다. 모든인구의약 25% 가량이평생동안실신을경험하며응급의료센터에방문하여입원하는모든환자중 1~2% 를차지한다 1-3). 이중입원하여발생하는의료비용은연간 2천만달러에달한다고보고하였다 4). 실신의원인은대부분심각하지않지만, 드물게생명을위협하는부정맥, 심근경색, 폐색전증, 밝혀지지않은출혈또는사망등과연관이있다. 따라서실신을주소로온환자들의다수가입원하여원인에대한감별과정을시행받게된다 1-4). 그러나이러한과정중에서입원을권유하는기준이모호하며근거가분명하지않은경우가있었고, 입원후진단적감별과정에서도별다른진행없이입원하여보존적치료및관찰만하는경우가많았으며, 진단적감별과정후에도특별한원인이밝혀지지않은경우가많았다 5). 결과적으로이과정에서상당한의료비용이발생하였고이에대해불필요한의료비용을줄여야하며, 비용-효율적인접근이필요하다는주장이제기되었다 6-9). 론

24 / 대한응급의학회지 : 제 25 권제 1 호 2014 이주장을배경으로하여발표된 San Francisco Syncope Rule (SFSR) 은 5가지의예측인자 ( 호흡곤란, 울혈성심부전의병력, 비정상심전도, 초기수축기혈압 <90 mmhg, 혈색소수치 <30%) 중하나라도양성일때 고위험군 으로, 모두음성일때 저위험군 으로분류하여응급의료센터기반으로적용하기쉬우면서동시에단기중증결과를매우민감하게예측하여 ( 민감도 92%, 특이도 53%) 이의사결정도구에따라저위험군으로판정된환자의불필요한입원율을의미있게낮추었다 10-12). 그러나이후 SFSR을사용한타당화연구에서예측및결과변수의차이로인해일관되지않은결과가발생하였다 13-20). 또한축적된연구를기반으로두차례의체계적고찰및메타연구가시행되었으나각연구의 실신 에대한정의가달라예후판정이너무높게평가되거나낮게평가되고, SFSR의중요한예후판정인자인 비정상심전도 의정의가일치하지못하는등의연구수행및보고방식이지나치게달라연구간정확한비교가어렵다고지적하였다 21,22). 이에응급의료센터기반실신연구의향상을위해표준화된보고체계에대한필요성이제기되었고실신에대한기존의지침개발에참여했거나또는기타실신에대한연구를시행했던연구자들이모여전문가합의과정을통해도출한실신연구의새로운표준화된보고지침을제안하였다 23). 이는적합성기준, 결과측정, 심전도결과, 대상자예측변수로각각분류되는총 92가지로구성되었으며동시에향후제반연구를통해부적절한항목을제외하거나, 제시된항목에는포함되지않았지만실신연구에필요한항목을추가할가능성도열어두었다 23). 그러나현재까지새로운표준화된보고체계에따라실신환자의예후및위험도평가연구가보고된예는없다. 따라서저자들은본응급의료센터에서실신또는전실신으로내원한환자를대상으로새로운표준화된보고지침에서권고하는기준을엄격히적용하여조사된자료를바탕으로 SFSR의타당화연구를시행하였다. 대상과방법 1. 연구대상본연구는 2010년 1월1일부터 2013년 6월30일까지일개응급의료센터를내원한 16세이상실신및전실신환자중 30일이내본원으로입원하거나외래추적검사를받은환자를대상으로하였다. 환자의의무기록을기반으로하여응급의료센터를방문한환자정보를확인하였으며의무기록을선택하는방법으로는연속적인표본채취방법 (consecutive sampling method) 을사용하였고입원또는귀가여부와관계없이연속된기간동안의모든환자의의무기록을검토하였다. 대상환자의검색을위해서 ICD-10의진단코드중 syncope, fainting, postural hypotension 을포함한 R558000, R558002, R550000, G900001, T671000, F488005, I951001에해당하는환자의의무기록에대해선별검사를시행하였다. 만 16세이상의성인환자로표준화된보고지침의항목중 연구적합성 에서제시하는실신의정의를만족하는경우를포함하였고배제진단또한가이드라인의정의를적용하였다 23) (Appendix 1). 실신및전실신으로응급의료센터방문이후 30일이내의입원기록및외래추적관찰기록을모두검토하였다. 중증질환의발생여부는응급의료센터에서진료과정중에확인된경우, 방문후 7일이내발생한경우, 방문후 7~30 일사이의기간동안발생한경우, 총 3가지경우로각각나누어조사하였으며, 30일이내퇴원한이후외래추적이이루어지지않았을경우또는응급의료센터에서귀가후 30일이상외래추적이이루어지지않았을경우는 추적손실 (loss of follow up) 로간주하여연구대상에서제외하였다. 단, 추적손실이되었더라도기간내에중증질환이발 Appendix 1. Guideline elements: study eligibility (>80% Panel Consensus). The following components should be included in the definition of syncope for ED-based studies: 1 Transient loss of consciousness (LOC) 2 Inability to maintain postural tone 3 Immediate recovery 4 Spontaneous recovery without medical intervention 5 Complete recovery (to pre-existing mental status and neurological function) The following patients should be excluded from syncope risk stratification studies: 6 Alcohol or illicit drugs as presumptive cause of LOC 7 Seizure as presumptive cause of LOC 8 Stroke/ transient ischemic attack as presumptive cause of LOC 9 Head trauma followed by LOC 10 Hypoglycemia as presumptive cause of LOC

예성열외 : 응급의료센터실신위험도평가연구의표준화된보고지침을적용하여시행한 San Francisco Syncope Rule 의외부적타당화연구 / 25 생한경우는연구에포함하였다. 중증질환은보고가이드라인의정의를따랐으며사망률에서 2가지항목 (cardiac death, syncope-related death), 부정맥에서 8가지항목 (ventricular fibrillation, ventricular tachycardia >30 seconds, symptomatic ventricular tachycardia <30 seconds, sick sinus syndrome with alternating sinus bradycardia and tachycardia, sinus pause >3 seconds, Mobitz type II atrioventricular heart block, complete heart block, pacemaker or implantable cardioverter-defibrillator Appendix 2. Guideline elements: outcomes (>80% Panel Consensus). An ED-based risk stratification tool should: 11 Identify serious outcomes that are recognized during the ED evaluation 12 Identify serious outcomes occurring within 7 days after the ED visit 13 Identify serious outcomes occurring 7~30 days after the ED visit Clinically important serious outcomes that should be predicted by a risk stratification tool include: Mortality 14 Cardiac death 15 Syncope-related death Arrhythmias 16 Ventricular fibrillation 17 Ventricular tachycardia > 30 seconds 18 Symptomatic ventricular tachycardia < 30 seconds 19 Sick sinus syndrome with alternating sinus bradycardia and tachycardia 20 Sinus pause > 3 seconds 21 Mobitz type II atrioventricular heart block 22 Complete heart block 23 Pacemaker or implantable cardioverter-defibrillator malfunction with cardiac pauses. Structural/ Ischemic Heart Disease 24 Aortic stenosis with valve area 1 cm 2 25 Hypertrophic cardiomyopathy with outflow tract obstruction 26 Left atrial myxoma or thrombus with outflow tract obstruction 27 Myocardial infarction 28 Pulmonary embolus Other Outcomes 29 Aortic dissection 30 Internal hemorrhage or anemia requiring transfusion 31 Recurrent syncope or fall resulting in major traumatic injury (trauma that requires admission or procedural/surgical intervention) 32 Permanent pacemaker or defibrillator placement 33 Cardiopulmonary resuscitation ED: emergency department Appendix 3. Guideline elements: electrocardiogram (>80% consensus). ECG Findings The following ECG findings should be considered abnormal: 34 Non-sinus rhythms (includes paced rhythm) 35 Sinus bradycardia 40 per minute 36 Complete left bundle branch block 37 Delta waves (e.g. Wolff-Parkinson-White) 38 Prolonged QRS (>120 ms) 39 Prolonged QTc (> 450 ms) 40 Brugada pattern 41 Q/ST/T changes consistent with acute or chronic ischemia ECG Interpretation: 42 Report who is interpreting the ECG (e.g. emergency physician, cardiologist, research team, etc.) ECG: electrocardiogram

26 / 대한응급의학회지 : 제 25 권제 1 호 2014 Appendix 4. Guideline element: candidate predictors (>80% consensus). Data on the following elements should be collected and reported: Demographic characteristics 43 Age 44 Sex Historical features 45 Exertion 46 While driving 47 Time of syncope event 48 Supine position 49 Sitting position 50 Lack of warning symptoms 51 Chest discomfort 52 Shortness of breath 53 Palpitations 54 Traumatic injury (laceration, fracture, intracranial bleed, thoraco-abdominal injury) 55 Lightheadedness 56 Standing from supine/ sitting position 57 Post-prandial (within 1 hour of meal) 58 Nausea/ vomiting 59 Feeling of warmth 60 Diaphoresis 61 Blurred vision 62 Any prodromes lasting greater than 5 seconds 63 Triggered by painful/ emotionally distressing stimulus 64 Triggered by turning head/ cough/ micturation/ defecation Co-morbidities 65 Premature (<50 years) sudden death in sibling or parents 66 Congestive heart failure 67 Coronary artery disease (past MI/ PTCA/ CABG) 68 Congenital heart disease 69 Structural heart disease- aortic stenosis 70 Structural heart disease- outflow tract disease, excluding aortic stenosis (e.g. idiopathic hypertrophic subaortic stenosis) 71 Structural heart disease- ejection fraction <40% by objective testing (e.g. echocardiogram, cardiac catheterization) within one year 72 Structural heart disease- pulmonary hypertension 73 Structural heart disease- valve disease, excluding aortic stenosis and mitral prolapse 74 Arrhythmia- ventricular tachycardia/ ventricular fibrillation/ sudden death 75 Arrhythmia- SVTs, including PSVT, atrial fibrillation, atrial flutter 76 Arrhythmia- sick sinus syndrome, Mobitz II or complete heart block, junctional rhythm 77 Implanted permanent pacemaker 78 Implanted defibrillator 79 Hypertension requiring medication 80 Syncope in the prior year Medications 81 Diuretics 82 Beta-blockers 83 Nitrates 84 Other antiarrhythmics not listed above (e.g. amiodarone, sotalol) Physical Exam Findings 85 Triage systolic blood pressure 86 Lowest systolic blood pressure measured in ED 87 Triage pulse 88 Lowest pulse measured in ED 89 Orthostatic vital signs (blood pressure and pulse measured lying and standing) 90 Heart murmur 91 New neurologic deficits Laboratory Tests 92 Hematocrit or Hemoglobin MI: myocardial infarction, PTCA: percutaneous transluminal coronary angioplasty, CABG: coronary artery bypass graft, SVT: supraventricular tachycardia, ED: emergency department, PSVT: paroxysmal supraventricular tachycardia

예성열외 : 응급의료센터실신위험도평가연구의표준화된보고지침을적용하여시행한 San Francisco Syncope Rule 의외부적타당화연구 / 27 malfunction with cardiac pauses), 구조적또는허혈성심장질환에서 4가지항목 (aortic stenosis with valve area 1 cm 2, hypertrophic cardiomyopathy with outflow tract obstruction, left atrial myxoma or thrombus with outflow tract obstruction, myocardial infarction), 기타결과에서 6가지항목 (pulmonary embolus, aortic dissection, internal hemorrhage or anemia requiring transfusion, recurrent syncope or fall resulting in major traumatic injury, permanent pacemaker or defibrillator placement, cardiopulmonary resuscitation) 이었다. 표준화된보고가이드라인에서권고하는대로 4가지가이드라인의요소, 즉연구적합성기준 10가지항목, 결과 23가지항목, 심전도소견 9가지항목, 예측변수 50가지항목총 92개항목에대한변수를각각조사하였다 23) (Appendix 1-4). 연구기간동안응급의료센터에처음방문한경우와첫방문후 30일후내원할경우 초회방문 (initial visit) 으로정의하였고, 처음방문후 30일이내다시내원할경우 재방문 (revisit) 으로정의하였다. 응급의료센터의무기록을전문의와 3년차이상전공의가검토하였고각진료기록에차이가있을경우해당진료의사의기록중가장정확한것을이용하였다. 초기자료수집과정에서연구자의관측편향의가능성을낮추기위해맹검법을통해의무기록사항중병력과진찰부분만볼수있게하였다. 환자의중증질환여부에관한결과는따로수집하였고, 추후각각따로조사된초기자료 ( 병력및진찰, 검사결과 ) 와통합하는과정을거쳤다. 자료추출과수집하는과정후무작위숫자발생기를이용하여 15% 의의무기록 (409명중 61명 ) 을선정후각변수들을다시조사하여관찰자내일치도 (intraobserver agreement) 를평가하였고불일치가발생할경우제 3의연구자와상의후합의된결과를반영하였다. 2. 연구방법및자료의분석조사된항목중연속형변수의경우평균 ± 표준편차로, 범주형변수의경우건 (%) 으로제시하였다. 중증질환양성군과중증질환음성군간의예측변수를비교하기위한통계분석에서는연속형자료에대해서 Student s t-test 또는 Mann-Whitney U test, 범주형자료에대해서 χ² test 또는 Fisher s exact test 를시행하였다. 단변량분석에서의미있는결과가나온변수들을대상으로다중로지스틱회귀분석을시행하였다. 각각의결과는 p값이 0.05 미만인경우를통계적으로유의한것으로판단하였다. 그리고중증질환발생에대한 SFSR의예측률을평가하기위해민감도 (sensitivity), 특이도 (specificity) 를계산하였다. 모든통계분석은 SPSS 18.0 package for window (SPSS Inc., Chicago, USA) 를이용하였다. 결과 1. 추출편향 (abstraction bias) 과관찰자내일치도추출편향의가능성을염두에두고일차적으로조사된자료의관찰자내일치도를평가한결과전체항목간의 κ값은 0.836으로나타나일치하는경향을보였다 (95% 신뢰구간 0.74-0.90). 개별항목에서는, 앙와위 (supine), 외상성손상 (traumatic injury), 식후한시간이내 (post-prandial <1-hour) 의세항목에서는낮은일치도를보였으나나머지의항목에서는높은일치도를보였다. 2. 일반적인특성과중증결과발생여부에따른비교총 1,235명의의무기록을선별하였고, 실신및전실신의정의에합당하지않은 285명, 스캔된차트를확인할수없는 16명, 추적관찰이충분하게이루어지지못한 277명등총 578명은이번연구에서제외되었다. 포함기준에합당한 657명중 248명은배제기준 ( 알코올또는약물, 실신, 뇌졸중및일과성뇌허혈, 두부외상, 저혈당 ) 에해당되어연구에서제외되었다. 최종적으로 409명의환자를통해연구가진행되었다 (Fig. 1). 연구가진행된 409명의환자중 93명 (22.7%) 의환자에서응급의료센터방문후 30일이내에중증결과가확인되었다. 이중 60명 (64.5%) 은응급의료센터진료과정중, 30명 (32.2%) 은응급의료센터방문 7일이내, 6명 (6.4%) 은방문후 7~30일이내에중증결과가확인되었다. 중증질환발생군중사망은총 3명, 부정맥은총 11명, 구조적또는허혈성심장질환은총 21명, 그외다른결과는총 67 명이었다 (Table 1, 2). 전체환자의평균연령은 55.2±20.1세였고중증결과발생군은 57.96±21.0세, 중증결과가발생하지않은군은 54.38±19.8세로두군간유의한차이는없었다 (p=0.132). 호흡곤란을보인환자는중증결과양성군에서 9명 (9.7%), 음성군에서 8명 (2.5%) 이었고 (p=0.015), 혈색소 30% 미만을나타낸환자는중증결과양성군에서 13명 (14.0%), 음성군에서 6명 (1.9%) 이었다 (p<0.001). 비정상심전도를보인환자는중증결과양성군에서 33명 (35.5%), 음성군에서 47명 (14.9%) 이었고 (p<0.001), 위의세항목은모두유의한차이를보였다. 비정상심전도중에서는 QTc간격연장 항목만유의한차이를보였다.

28 / 대한응급의학회지 : 제 25 권제 1 호 2014 나머지 울혈성심부전의과거력, 수축기혈압 90 mmhg 미만 은통계적으로유의한차이를보이지않았다. SFSR의예측변수외의 노력시발생 (p=0.040), 경고증상의결핍 (p=0.004) 항목에서두군간의유의한차이가있었다 (Table 3). 3. 중증결과발생예측에대한 SFSR의타당성평가 SFSR의 5가지예측변수에대해표준화된보고지침의정의를이용하여조사한자료를기반으로 SFSR의중증결과예측률을평가하였다. SFSR을사용하여응급의료센터에방문한실신및전실신환자중중증결과를예측할때, 민감도는 55.9%, 특이도는 77.8% 로측정되었다. 또한양성예측도, 음성예측도는각각 42.6%, 85.7% 였다 (Table 4). 4. 중증결과양성군에서 SFSR이예측하지못한경우 SFSR을사용하여모든사망 (n=3) 은예측할수있었으 나저위험군으로판정된 287명중 41명 (14.3%) 에게중증결과가발생하는것을예측하지못하였다. 상세내역으로 반복되는실신또는실신으로인해주요외상성손상이발생한경우 가 29명 (70.7%) 으로가장많았고다음이 심근경색 으로 5명 (12.2%), 내출혈또는수혈이필요한빈혈 4 명 (9.7%) 순이었다. 고찰실신을주소로응급의료센터를방문하는환자는초기증상이나생체징후또는심전도이상등에따라안정적또는불안정한환자로분류된다. 불안정한실신환자는약 70% 이상심근경색, 부정맥, 출혈등의중증임상결과를보인다 12,13). 반면안정적인실신환자의경우대부분방문당시특별한증상및징후를나타내지않고, 목격자또한없는경우가많아의료진이치료의방향및환자의예후에대해정확히판단하기매우어렵다 11). 또한실신의원인으로경 Fig. 1. Flow of study patients.

예성열외 : 응급의료센터실신위험도평가연구의표준화된보고지침을적용하여시행한 San Francisco Syncope Rule 의외부적타당화연구 / 29 증부터생명을위협할수있는질병이다양하므로, 의료진은진단되지않은심근경색이나일시적이어서확인되지못한부정맥을우려하여불필요한입원을시키기도한다 6-9). 한편응급의료센터에서는실신의원인을밝히고처치하기위한시간과검사방법에제약이있어현실적으로진단을목표로하기보다임상적인지표를기반으로한위험도평가를한다 24). 폐색전증에대한 Wells score, Ottawa ankle rules 에서보듯이병력청취, 신체진찰및기본적인진단검사를바탕으로얻어낸중요한예측인자를포함한임상적의사결정도구 (clinical decision rule) 를도출하여환자위험도예측에이용하기도한다 25-26). SFSR의경우도실신환자의병력청취, 신체진찰및기본적인진단검사등을이용하여위험도를평가하고중증질환의발생가능성을예측하는도구이며, 이를이용하여추가적인검사나처치를결정함으로써실신환자의치료방향을결정할수있다. Quinn 등 10,12) 은도출연구와전향적타당화연구에서도중증질환의발생에대한높은예측률을나타내었다. 하지만다른인구집단에적용했을때 Quinn 등 10,12) 의연구와같이높은예측률을보이지않았고, 가장큰원인의하나로각연구마다 SFSR을형성하는항목들의정의가일치하지않기때문으로지적하고있어표준화된보고지침을따른실신환자연구가요구되었다. 본연구는응급의료센터기반실신위험도연구의표준화된보고지침을 SFSR의타당성평가에처음으로적용한사례임에의의가있다. 그러나연구의결과는 Quinn 등 10,12) 이 SFSR의도출연구 (96%, 95% CI 92-100) 와타당화연구 (98%, 95% CI 89-100) 에서보고한결과에비해차이가난다 10-12). 기존의여러타당도연구에서도 Quinn 등 10,12) 의연구와차이가나는보고는다수존재한다. 미국에서 Sun 등 13) ( 민감도 89%, 특이도 42%), Birbaum 등 14) ( 민감도 74%, 특이도 57%), Schladenhaufen 등 15) ( 민감도 76.5%, 특이도 36.8%) 이결과를보고하였고, 캐나다에서 Thiruganasambandamoorthy 등 16) 이민감도 90%, 특이도 33% 를보고하였다. 오스트레일리아에서 Cosgriff 등 17) ( 민감도 90%, 특이도 57%), 영연방에서 Reed 등 18) ( 민감도 100%), 이탈리아에서 Dipaola 등 19) ( 민감도 81%, 특이도 63%), 그리고한국에서 Shin 등 20) ( 민감도 71.4%, 특이도 69.8%) 이결과를보고하였다. 이번연구의결과가기존연구들에서보인 SFSR의타당성연구결과와차이를보이는이유는다음과같이생각된다. 첫째, 중증결과항목중기존연구에서모두포함되었던 뇌졸중 과 지주막하출혈 이새로운보고지침에서제외되었다. 오히려배제진단에뇌졸중및일과성뇌허혈이추가되었고따라서이항목에해당하는환자는자료수집단계에서배제되었다. 실제로본연구에서배제진단에포함되었으나제외된이유가뇌졸중및일과성뇌허혈인환자는 657명중 71명 (10.8%) 에이른다. 둘째, 예측변수중 비정상심전도 와결과변수중 부정맥 이표준화된새로운보고지침에서엄격하게정의되었기때문이다. 이두가지항목은과거다수의타당도연구에서결과차이의원인으로지적된항목이다. Quinn 등 10-12) 의 SFSR 연구에서사용된정의인심전도항목의 모든이상 (any abnormality) 또는 증상과관련된부정맥 처럼광범위한정의에비해본연구에서는심전도항목에서단 8가지의구체적인사례, 그리고결과변수에서도단 8가지의구체적인사례로만정의하였다 23) (Appendix 2, 3). SFSR을사용하여모든사망 (n=3) 은예측할수있었으나저위험군으로판정된 287명중 41명 (14.3%) 에게중증결과가발생하는것을예측하지못하였다. 반복되는실신또는실신으로인해주요외상성손상이발생한경우 는실신의원인질환의중증도및기전과관계없이적용된결과항목이다. SFSR의 5가지예측변수와관계없는심각하지않은질병또는상황이많았고실제로 41 명중가장많은 12명의최종진단이미주신경성실신이었다. 따라서이결과항목은좀더세분화되거나변형될필요가있다고생각된다. 심근경색 의경우에는 SFSR을적용하여예측하지못했으나대부분다른임상증상과징후및부가적인진단방법 ( 흉통, 심장표지자, 심초음파등 ) 를통해진단할수있었던사례이고, 내출혈또는수혈이필요한빈혈 의경우는대부분초기의증상및징후와생체징후가감지하기힘든애매한경우여서 SFSR에서 low risk로판정된경우가많은것으로확인되었다. 본연구를통해표준화된실신연구의보고지침을적용함에따라중증결과의발생에대한 SFSR의예측률이더낮아짐을확인하였고이를일반화하여국내인구에그대로적용하기는어려워보인다. 중증결과발생을예측하는의미있는변수를포함시켜기존 SFSR에서예측변수의범위를확장하거나심장표지자및심초음파등비침습적인검사항목을보완하는시도가필요할것으로생각된다. 이번연구는의무기록검토를통해시행한후향적연구의공통적인한계점을가지고있다. 첫째는자료수집과정에서발생하는편향의가능성이다. 자료수집과정에서편향을줄이기위해본연구는표준화된보고지침의권고대로실신의정의를엄격히적용하여실신이아닌대상을배제하였다. 연구에사용한실신의정의는 American College of Emergency Physician, American College of Physician, American Heart Association, European Society of Cardiology에서공식적으로사용하는정의들을전문가합의과정에의해도출한것이다. 실제로본연구의의무기록검토과정에서는실신관련진단코드를사용한대상군을선별한후실신의정의를엄격히적용하여 1,235 명중 285명 (23.1%) 이실신의정의에합당하지않아배제되었다.

30 / 대한응급의학회지 : 제 25 권제 1 호 2014 Table 1. Character and distribution of the outcome variables in the study patients. Characteristics Patient visits, Serious outcome, Non-serious outcome, Odd ratio N=409 (%) N=93 (%) N=316 (%) (95% CI) p value Demographic characteristics Age, y, mean (SD) 55.2 (20.1) 57.96 (21.0) 54.38 (19.8). <0.132 Range, y 16-95 16-89 16-90.. Sex (male) 184 (45.0) 47 (50.5) 137 (43.4) 1.335 (0.840-2.122) <0.221 Historical features Exertion 018 (04.4) 08 (08.6) 010 (03.2) 02.88 (1.102-7.524) <0.039 While driving 001 (00.2) 0 (0)0. 001 (00.3) 1 Supine position 006 (01.5) 04 (04.3) 002 (00.6) 07.056 (1.272-39.155) <0.026 Sitting position 093 (22.7) 19 (20.4) 074 (23.4) 0.840 (0.476-1.481) <0.577 Lack of warning symptoms 072 (17.6) 26 (28.0) 046 (14.5) 2.278 (1.314-3.949) <0.004 Chest discomfort 053 (13.0) 19 (20.4) 034 (10.8) 2.130 (1.149-3.947) <0.021 Shortness of breath* 017 (04.2) 09 (09.7) 008 (02.5) 04.125 (1.544-11.018) <0.005 Palpitations 019 (04.7) 01 (01.1) 018 (05.7) 0.179 (0.024-1.357) <0.089 Traumatic injury 003 (00.7) 0 (0)0. 003 (00.9) 1 Lightheadedness 241 (58.9) 41 (44.1) 200 (63.3) 0.457 (0.286-0.731) <0.001 Standing from supine/sitting position 137 (33.5) 25 (26.9) 112 (35.4) 0.670 (0.401-1.119) <0.135 Post prandial (within 1 hour of meal) 006 (01.5) 0 (0)0. 006 (01.9) <0.344 Nausea/vomiting 075 (18.4) 09 (09.8) 066 (20.9) 0.411 (0.196-0.860) <0.021 Feeling of warmth 005 (01.2) 01 (01.1) 004 (01.3) 0.848 (0.094-7.679) 1 Diaphoresis 045 (11.0) 02 (02.2) 043 (13.6) 0.140 (0.33-0.587)0 <0.002 Blurred vision 052 (12.7) 09 (09.8) 043 (13.6) 0.688 (0.322-1.471) <0.379 Any prodromes lasting greater than 5 seconds 217 (53.2) 37 (39.8) 180 (57.1) 0.496 (0.309-0.794) <0.004 Triggered by painful/ emotionally distressing stimulus 042 (10.3) 01 (01.1) 041 (13.0) 0.074 (0.010-0.543) <0.002 Triggered by turning head/ cough/ micturition/defecation 026 (06.4) 06 (06.5) 020 (06.3) 1.021 (0.397-2.621) 1 Co-morbidities Premature (<50 years) sudden death in sibling or parents 0 (0). 0 (0)0. 0 (0)... *Congestive heart failure 007 (01.7) 04 (04.3) 003 (00.9) 04.689 (1.030-21.340) <0.050 Coronary artery disease (past MI/PTCA/CABG) 048 (11.7) 16 (17.2) 032 (10.1) 1.844 (0.962-3.535) <0.068 Congenital heart disease 002 (00.5) 01 (01.1) 001 (00.3) 03.424 (0.212-55.274) <0.403 Structural heart disease Aortic stenosis 001 (00.2) 0 (0)0. 001 (00.3) 1 Outflow tract disease, excluding aortic stenosis 0 (0). 0 (0)0. 0 (0)... Ejection fraction <40% by objective testing within 1 year 001 (00.2) 01 (01.1) 0 (0). <0.227 Pulmonary hypertension 001 (00.2) 01 (01.1) 0 (0). <0.229 Valve disease, excluding aortic stenosis and mitral prolapse 003 (00.7) 01 (01.1) 002 (00.6) 01.720 (0.154-19.182) <0.537 Arrhythmia Ventricular tachycardia/ ventricular fibrillation/sudden death 0 0 (0)0. 0 (0)... SVTs, including PSVT, atrial fibrillation, atrial flutter 017 (04.2) 03 (03.3) 014 (04.4) 0.727 (0.204-2.587) <0.773 Sick sinus syndrome, Mobitz type II or complete heart block, junctional rhythm 003 (00.7) 03 (03.2) 0 (0). <0.012 (continue)

예성열외 : 응급의료센터실신위험도평가연구의표준화된보고지침을적용하여시행한 San Francisco Syncope Rule 의외부적타당화연구 / 31 Table 1. Character and distribution of the outcome variables in the study patients. Characteristics Patient visits, Serious outcome, Non-serious outcome, Odd ratio N=409 (%) N=93 (%) N=316 (%) (95% CI) p value Implanted permanent pacemaker 003 (00.7) 02 (02.2) 001 (00.3) 06.923 (0.621-77.217) <0.131 Implanted defibrillator 0 0 (0)0. 0 (0)... Hypertension requiring medication 188 (46.0) 45 (48.4) 143 (45.3) 1.134 (0.714-1.802) <0.637 Syncope in the prior year 076 (18.6) 21 (22.6) 055 (17.4) 1.384 (0.786-2.439) <0.289 *Electrocardiogram 080 (19.6) 33 (35.5) 047 (14.9) 3.148 (1.861-5.326) <0.001 Non-sinus rhythm (includes paced rhythm) 004 (01.0) 02 (02.2) 002 (00.6) 03.451 (0.479-24.837) <0.224 Sinus bradycardia 40 per minute 009 (02.2) 03 (03.2) 006 (01.9) 1.722 (0.422-7.023) <0.431 Complete left bundle branch block 002 (00.5) 01 (01.1) 001 (00.3) 03.424 (0.212-55.274) <0.403 Delta waves (e.g. Wolff-Parkinson-White) 0 (0). 0 (0)0. 0 (0)... Prolonged QRS (>120 ms) 005 (01.2) 03 (03.2) 002 (00.6) 05.233 (0.861-31.802) <0.080 Prolonged QTc (>450 ms) 040 (09.8) 18 (19.4) 022 (07.0) 3.207 (1.637-6.284) <0.001 Brugada pattern 0 (0). 0 (0)0. 0 (0)... Q/ST/T changes consistent with acute or chronic ischemia 038 (09.3) 16 (17.2) 022 (07.0) 2.777 (1.391-5.543) <0.005 Medications Diuretics 026 (06.4) 10 (10.8) 016 (05.1) 2.259 (0.988-5.163) <0.055 Beta-blockers 067 (16.4) 18 (19.4) 049 (15.5) 1.308 (0.719-2.378) <0.425 Nitrates 021 (05.1) 09 (09.7) 012 (03.8) 2.714 (1.106-6.659) <0.032 Other antiarrhythmics not listed above 008 (02.0) 04 (04.3) 004 (01.3) 03.506 (0.859-14.298) <0.083 Physical Exam Findings *Triage SBP <90mmHg 027 (06.6) 10 (10.8) 017 (05.4) 2.119 (0.935-4.802) <0.093 Triage SBP, mmhg (SD). 117.72 (29.1) 122.5 (26.1). <0.129 Lowest SBP, mmhg (SD). 102.66 (22.9) 103.73 (20.7)0. <0.672 Triage pulse, per min (SD). 080.67 (19.0) 78.22 (15.1). <0.258 Lowest pulse, per min (SD). 070.74 (17.2) 67.87 (11.8). <0.137 Heart murmur 002 (00.5) 01 (01.3) 001 (00.3) 03.910 (0.242-63.215) <0.369 New neurologic deficits 0. 0 (0)0. 0 (0)... Laboratory Tests *Hematocrit <30% 019 (04.6) 13 (14.0) 006 (01.9) 08.396 (3.095-22.778) <0.001 * The predictors of San Francisco Syncope Rule Statistical significant by Fisher s exact test CI: confidence interval, SD: standard deviation, MI: myocardial infarction, PTCA: percutaneous transluminal coronary angioplasty, CABG: coronary artery bypass graft, SVT: supraventricular tachycardia, PSVT: paroxysmal supraventricular tachycardia 또한추출오류의위험을낮추기위해현재통용되는의무기록검토에대한방법론적인표준지침을충실히따라자료를검토, 수집하였다 27-30). 환자의의무기록을검토하여중요한임상적인예측변수들을추출하는과정에서정보간내용이충돌하거나, 모호하거나누락되는등의이유로부정확하게추출될가능성이존재하므로관찰자내일치도를평가하여높은일치도를보였다. 둘째는연구대상의추적손실과누락된데이터가많다는점이다. 이번연구에서 277명 (29.6%) 의추적손실이발생하여선택편향을일으킬수있어큰제한점으로작용하였다. 또한최종적으로연구대상에선정된 409명가운데에서도, 표준화된실신연구의보고지침의 92개항목중자료수집과정에서누락된자료가존재하였다. 이는각각예측 변수항목에서 23명 (5.62%), 심전도항목에서 3명 (0.73%), 결과항목에서 20명 (4.89%) 으로발생하여마찬가지로본연구의제한점으로작용하였고후속연구에서는이에대한보완이필요하다. 결론응급의료센터실신위험도평가연구의표준화된보고지침을적용한 SFSR은단기중증결과를예측하는데낮은민감도를보여이를인구집단에일반화하여적용하기는어려울것으로생각된다.

32 / 대한응급의학회지 : 제 25 권제 1 호 2014 Table 2. Details in patients with serious outcomes. During ED Within 7 days 7~30 days All, Serious outcomes evaluation, after ED visit, after ED visit, n=93 (%) n=60 (%) n=30 (%) n=9 (%) Mortality (n=3) Cardiac death 02 (02.1) 01 (01.7) 01 (03.0) 0 Syncope-related death 01 (01.1) 01 (01.7) 01 (03.0) 0 Arrhthmias (n=11) Ventricular fibrillation 0 0 0 0 Ventricular tachycardia >30 seconds 01 (01.1) 0 01 (03.0) 0 Symptomatic VT <30 seconds 01 (01.1) 01 (01.7) 01 (03.0) 1 (11.1) Sick sinus syndrome with alternating sinus bradycardia and tachycardia 0 1 ( 0 1.1) 0 0 1 ( 0 3.0) 0 Sinus pause >3 seconds 03 (03.2) 01 (01.7) 02 (06.1) 0 Mobitz type II atrioventricular heart block 01 (01.1) 01 (01.7) 0 0 Complete heart block 02 (02.1) 01 (01.7) 0 1 (11.1) Pacemaker or implantable cardioverter-defibrillator malfunction with cardiac pauses 0 2 ( 0 2.1) 0 2 ( 0 3.3) 0 0 Structural/ Ischemic heart disease (n=21) Aortic stenosis with valve area 1 cm² 01 (01.1) 0 0 1 (11.1) Hypertrophic cardiomyopathy with outflow tract obstruction 03 (03.2) 0 02 (06.1) 1 (11.1) Left atrial myxoma or thrombus with outflow tract obstruction 0 (0) 0 0 0 Myocardial infarction 17 (18.3) 02 (03.3) 14 (42.4) 1 (11.1) Other outcomes (n=67) Pulmonary embolus 0 (0) 0 0 0 Aortic dissection 02 (02.1) 01 (01.7) 0 1 (11.1) Internal hemorrhage or anemia requiring transfusion 20 (21.5) 16 (26.7) 05 (15.1) 0 Recurrent syncope or fail resulting in traumatic injury 39 (53.4) 35 (58.3) 05 (15.1) 1 (11.1) Permanent pacemaker or defibrillator placement 03 (03.2) 0 03 (09.1) 0 Cardiopulmonary resuscitation 03 (03.2) 01 (01.7) 02 (06.1) 2 (22.2) ED: emergency department, VT: ventricular tachycardia Table 3. Risk factors correlated with serious outcomes which determined by multiple logistic regression. Variables Odd ratio Low 95% CI High p-value* Exertion 02.980 1.051 08.446 0.040 Lack of warning symptom 02.403 1.333 04.331 0.004 Shortness of breath 03.784 1.297 11.035 0.015 Prolonged QTc >450 seconds 02.533 1.216 05.274 0.013 Hematocrit <30% 10.155 3.639 28.343 0.000 CI: confidence interval * Statistical significant by multiple logistic regression Table 4. Performance of the SFSR to predict patients with serious outcomes. Serious Serious Positive Negative outcome (+) outcome (-) Sensitivity Specificity predictive predictive (n=93) (n=316) value value SFSR High risk 52 070 SFSR Low risk 41 246 SFSR: San Francisco Syncope Rule, CI: confidence interval 55.90% 77.80% 42.60% 85.70%

예성열외 : 응급의료센터실신위험도평가연구의표준화된보고지침을적용하여시행한 San Francisco Syncope Rule 의외부적타당화연구 / 33 참고문헌 01. Wolfe TR, Allen TL. Syncope as an emergency department presentation of pulmonary embolism. J Emerg Med 1998;16:27-31. 02. Bass EB, Elson JJ, Fogoros RN, Peterson J, Arena VC, Kapoor WN. Long-term prognosis of patients undergoing electrophysiologic studies for syncope of unknown origin. Am J Cardiol 1988;62:1186-91. 03. Georgeson S, Linzer M, Griffith JL, Weld L, Selker HP. Acute cardiac ischemia in patients with syncope: importance of the initial electrocardiogram. J Gen Intern Med 1992;7:379-86. 04. Sun BC, Emond JA, Camargo CA Jr. Direct medical costs of syncope-related hospitalizations in the United States. Am J Cardiol 2005;95:668-71. 05. Schillinger M, Domanovits H, Müllner M, Herkner H, Laggner AN. Admission for syncope: evaluation, cost and prognosis. Wien Klin Wochenschr 2000;112:835-41. 06. Crane SD. Risk stratification of patients with syncope in an accident and emergency department. Emerg Med J 2002;19:23-7. 07. Zaidi AM, Fitzpatrick AP. Investigation of syncope: increasing the yield and reducing the cost. Eur Heart J 2000;21:877-80. 08. von Dohlen TW, Frank MJ. Presyncope and syncope: how to find the cause and avoid staggering costs. Postgrad Med 1989;86:85-8, 91, 94-6. 09. Bartoletti A, Fabiani P, Gianni R, Cappelletti C, Santoro GM, Fortini A, et al. After the 2001 European Society of Cardiology guidelines: is it possible to reduce the number of patients with syncope to be hospitalized? Minerva Med 2004;95:451-60. 10. Quinn JV, Stiell IG, McDermott DA, Sellers KL, Kohn MA, Wells GA, et al. Derivation of the San Francisco Syncope Rule to predict patients with short-term serious outcomes. Ann Emerg Med 2004;43:224-32. 11. Quinn JV, Stiell IG, McDermott DA, Kohn MA, Wells GA. The San Francisco Syncope Rule vs physician judgment and decision making. Am J Emerg Med 2005;23: 782-6. 12. Quinn J, McDermott D, Stiell I, Kohn M, Wells G. Prospective validation of the San Francisco Syncope Rule to predict patients with serious outcomes. Ann Emerg Med 2006;47:448-54. 13. Sun BC, Mangione CM, Merchant G, Weiss T, Shlamovitz GZ, Zargaraff G, et al. External validation of the San Francisco Syncope Rule. Ann Emerg Med 2007; 49:420-7. 14. Birnbaum A, Esses D, Bijur P, Wollowitz A, Gallagher EJ. Failure to validate the San Francisco Syncope Rule in an independent emergency department population. Ann Emerg Med 2008;52:151-9. 15. Schladenhaufen R, Feilinger S, Pollack M, Benenson R, Kusmiesz AL. Application of San Francisco Syncope Rule in elderly ED patients. Am J Emerg Med 2008;26:773-8. 16. Thiruganasambandamoorthy V, Hess EP, Alreesi A, Perry JJ, Wells GA, Stiell IG. External validation of the San Francisco Syncope Rule in the Canadian setting. Ann Emerg Med 2010;55:464-72. 17. Cosgriff TM, Kelly AM, Kerr D. External validation of the San Francisco Syncope Rule in Australian context. CJEM 2007;9:157-61. 18. Reed MJ, Newby DE, Coull AJ, Jacques KG, Prescott RJ, Gray AJ. The Risk stratification Of Syncope in the Emergency department (ROSE) pilot study: a comparison of existing syncope guidelines. Emerg Med J 2007;24: 270-5. 19. Dipaola F, Costantino G, Perego F, Borella M, Galli A, Cantoni G, et al. San Francisco Syncope Rule, Osservatorio Epidemiologico sulla Sincope nel Lazio risk score, and clinical judgment in the assessment of shortterm outcome of syncope. Am J Emerg Med 2010;28: 432-9. 20. Shin MO, Kang TK, Kim HJ, Oh SC, Cho SJ, Lee SL, et al. Retrospective Validation of the San Francisco Syncope Rule for Predicting Serious Outcomes in a Korean Emergency Department. J Kor Soc Emerg Med 2012;23: 235-41. 21. Serrano LA, Hess EP, Bellolio MF, Murad MH, Montori VM, Erwin PJ, et al. Accuracy and quality of clinical decision rules for syncope in the emergency department: a systematic review and meta-analysis. Ann Emerg Med 2010;56:362-73. 22. Saccilotto RT, Nickel CH, Bucher HC, Steyerberg EW, Bingisser R, Koller MT. San Francisco Syncope Rule to predict short term serious outcomes: a systematic review. CMAJ 2011;183:E1116-26. 23. Sun BC, Thiruganasambandamoorthy V, Cruz JD; Consortium to Standardize ED Syncope Risk Stratification Reporting. Standardized reporting guidelines for emergency department syncope risk-stratification research. Acad Emerg Med 2012;19:694-702. 24. Maisel WH. Specialized syncope evaluation. Circulation 2004;110:3621-3. 25. Stiell IG, Greenberg GH, McKnight RD, Nair RC, McDowell I, Worthington JR. A study to develop clinical decision rules for the use of radiography in acute ankle injuries. Ann Emerg Med 1992;21:384-90. 26. Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, et al. Derivation of a simple clinical model to

34 / 대한응급의학회지 : 제 25 권제 1 호 2014 categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D- dimer. Thromb Haemost 2000;83:416-20. 27. Gilbert EH, Lowenstein SR, Koziol-McLain J, Barta DC, Steiner J. Chart reviews in emergency medicine research: Where are the methods? Ann Emerg Med 1996;27:305-8. 28. Worster A, Bledsoe RD, Cleve P, Fernandes CM, Upadhye S, Eva K. Reassessing the methods of medical record review studies in emergency medicine research. Ann Emerg Med 2005;45:448-51. 29. Badcock D, Kelly AM, Kerr D, Reade T. The quality of medical record review studies in the international emergency medicine literature. Ann Emerg Med 2005;45:444-7. 30. Lowenstein SR. Medical record reviews in emergency medicine: the blessing and the curse. Ann Emerg Med 2005;45:452-5.