08-정다원

대한응급의학회지제 25 권제 5 호 Volume 25, Number 5, October, 2014 원 저 Resuscitation 저체온치료를받은병원전심정지환자에서비정상이산화탄소분압과예후와의관계 전남대학교의과대학응급의학교실 정다원 이병국 정경운 정용훈 이성민 이동훈 송경환 허 @ 탁 민용일 The Association between Dyscarbia and Outcome in Out-of-hospital Cardiac Arrest Survivors Treated with Therapeutic Hypothermia Da Won Jeong, M.D., Byung Kook Lee, M.D., Kyung Woon Jeung, M.D., Yong Hun Jung, M.D., Sung Min Lee, M.D., Dong Hun Lee, M.D., Kyung Hwan Song, M.D., Tag Heo, M.D., Yong Il Min, M.D. Purpose: There is a lack of clinical evidence in terms of the association between carbon dioxide tension and outcomes in cardiac arrest survivors treated with therapeutic hypothermia (TH). We investigated the association of time-weighted mean carbon dioxide tension (TWMCO 2 ) and outcomes in out-ofhospital cardiac arrest (OHCA) survivors treated with TH. Methods: This was a retrospective cohort study including 177 OHCA survivors. The patients were divided into three groups according to the values of TWMCO 2 (normocarbia, 35~45 mmhg; hypocarbia, <35 mmhg; hypercarbia, >45 mmhg). The primary outcome was in-hospital mortality and the secondary outcome was neurologic outcome at discharge. We assessed neurologic outcome at hospital discharge using the Cerebral Performance Categories (CPC). Neurologic outcome was dichotomized as either good neurologic outcome (CPC1 and CPC2) or poor neurologic outcome (CPC 3 to 5). The odds ratio with 95% confidence interval (CI) was estimated. Results: The median value of PaCO 2 was 38.2 (33.9-43.3) mmhg. Among a total of 1,239 PaCO 2 values, normocarbia, hypocarbia, and hypercarbia were 618 (49.8%), 380 책임저자 : 이병국광주광역시동구제봉로 42 전남대학교의과대학응급의학교실 Tel: 062) 220-6809, Fax: 062) 228-7417 E-mail: bbukkuk@hanmail.net 접수일 : 2014년 5월 31일, 1차교정일 : 2014년 6월 2일게재승인일 : 2014년 8월 21일 557 (30.7%), and 241 (19.5%), respectively. Results of univariate logistic regression analysis showed that hypocarbia had a significantly high odds ratio for in-hospital mortality (2.474 (95% CI, 1.129-5.424), p=0.024) compared with normocarbia. Results of multivariate logistic regression analysis showed that hypocarbia (2.926; 95% CI, 1.212-7.066; p= 0.017) and hypercarbia (4.673; 95% CI, 1.348-16.205; p= 0.015) had a significantly high odds ratio for in-hospital mortality compared with normocarbia. Conclusion: In OHCA survivors treated with TH, dyscarbia (hypocarbia and hypercarbia) was frequent and dyscarbia showed an association with in-hospital mortality. Key Words: Cardiac arrest, Outcome, Carbon dioxide Department of Emergency Medicine, School of Medicine, Chonnam National University, Gwangju, Korea Article Summary What is already known in the previous study Hypocarbia is associated with poor outcome in cardiac arrest survivors. However, the role of hypercarbia in prognostication is controversial. What is new in the current study We built a new parameter of time-weighted mean carbon dioxide (TWMCO 2) under consideration of ischemic-perfusion period. Both hypocarbia (TWMCO 2<35 mmhg) and hypercarbia (TWMCO 2>45 mmhg) showed association with increased odds ratio of in-hospital mortality in out-ofhospital cardiac arrest survivors treated with therapeutic hypothermia. 서 이산화탄소분압은대뇌혈류를조절하는기능이있는데, 론

558 / 대한응급의학회지 : 제 25 권제 5 호 2014 자발순환이회복된심정지환자에게도저탄산혈증은혈관수축을유도하여대뇌혈류를감소시키고, 고탄산혈증은그반대의작용을하는것으로알려져있다 1,2). 즉, 심정지이후에발생하는허혈-재관류손상으로부터신경보호를위해서이산화탄소농도를적정함으로써대뇌혈류를조절하는것은필수적인조치이다. 따라서, 미국심장협회 (American heart association, AHA) 2010 가이드라인은심정지후치료에있어이산화탄소분압의목표치를 40~45 mmhg로권고하고있다 3). 저체온치료를받은병원전심정지환자에서이산화탄소분압의분포를확인한최근의한연구는내원후 48시간이내의동맥혈가스분석결과에서 35 mmhg 이하의저탄산혈증이 34% 였고, 45 mmhg 이상의고탄산혈증이 12% 로나타나비정상탄산혈증의빈도가높음을보고하였고, 비정상탄산혈증으로인해대뇌혈류에심각한영향을미칠수있으므로환기조절의필요성을강조하였다 4). 하지만, 이들의연구에서는예후와의연관성을밝히지는않았다. 심정지환자를대상으로이산화탄소분압과예후와의관계를분석한연구가많지는않지만, 대체적으로저탄산혈증이사망률이나나쁜신경학적예후와관련이있음을보고하고있고, 고탄산혈증의예후와의관련성은연구에따라이견이있다 5-8). Schneider 등 5) 의연구는가장많은수의환자를대상으로하였지만, 저체온치료를받은환자의수가적고중환자실에입원한지 24시간이내에측정된이산화탄소분압들중한개의값만을이용하여분석하였다. Pynnonen 등 6) 의연구는저체온치료를적용한환자들을대상으로하였지만총 8명의환자만을포함한예비연구였다. Roberts 등 7) 에의한연구는자발순환회복후 24시간동안시행된동맥혈가스분석의결과중저탄산혈증이나고탄산혈증의노출여부에따라군을구분하였기때문에정량적인이산화탄소분압에따른구분이라고하기어렵다. 자발순환이회복되더라도심정지증후군은수시간이상지속되며, 환기상태또한자주변하기때문에실제로도동맥혈가스분석은자주시행하게된다 9). 그러므로환자의환기상태를반영하기위해서는여러시점에서측정된이산화탄소분압을이용하는것이타당하다. 또한, 가스분압은저체온치료자체에의해영향을받기때문에저체온치료를받은환자는그렇지않은환자와는구분하여분석해야한다 10). 따라서본연구에서는저체온치료를받은병원전심정지환자들을대상으로자발순환이후부터저체온치료가종료되는시점까지여러시점에서측정된이산화탄소분압을이용하여시간을반영한이산화탄소분압값을구하고이들을구분하여이산화탄소분압과예후와의관계를확인하고자한다. 대상과방법본연구는전남대학교병원연구윤리심의위원회의허가 (CNUH-2013-101) 를받고진행되었다. 1. 연구대상 2008년 1월부터 2012년 12월까지전남대학교병원응급의료센터로내원한환자중병원전심정지후자발순환이회복되어저체온치료를포함한소생후치료를받았던 16세이상의환자들을대상으로하였다. 자발순환회복후의식이회복되거나, 말기질환자, 혈역학적으로불안정한환자, 위장관출혈이있는환자, 그리고보호자가저체온치료를거부한환자를제외하고저체온치료를시행하였다. 저체온치료치료도중치명적인부정맥이발생하거나혈역학적으로불안정하여저체온치료가중단된경우, 체외순환보조 (extracorporeal membrane oxygenation, ECMO) 를받았던경우, 저체온치료유지기간이나목표체온이달랐던경우 ( 목표체온이 <32 C 이거나 >34 C, 유지기간이 48시간혹은 72시간 ), 동맥혈가스분석자료가누락된경우는연구대상에서제외되었다. 2. 저체온치료 33 C 의목표체온에도달하기위하여 4 생리식염수의정주와얼음팩등의고식적인방법과함께온도조절냉각요 (Blanketrol II, Cincinnati Subzero Products, USA), 냉각용중심정맥카테터 (COOLGARD 3000 Thermal Regulation System, Alsius Corporation, USA), 또는온도조절패드 (Artic Sun Energy Transfer Pads TM, Medivance Corp, Louisville, USA) 를이용하여저체온치료유도를시작하였다. 목표체온에도달하면 24시간동안 32~34 C 의저체온치료를유지하고, 이후에는시간당 0.25~0.5 C 의속도로재가온을실시하였다. 저체온치료를실시하는동안진정과떨림의방지를위해 fentanyl 혹은 remifentanyl과, midazolam을투여하였다. 떨림을조절하기위해필요에따라서 atracurium도투여하였다. 이산화탄소분압과산소분압을적정하기위해여러차례동맥혈가스분석을시행하였다. 채혈은자발순환후, 저체온치료시작, 목표체온에도달하였을때, 목표체온도달후매 6시간마다시행하였고, 임상의가필요에따라추가적으로실시하였다. 3. 연구방법 의무기록지를후향적으로조사하였다. 연령, 성별, 기저

정다원외 : 저체온치료를받은병원전심정지환자에서비정상이산화탄소분압과예후와의관계 / 559 질환 ( 관상동맥질환, 심부전, 고혈압, 당뇨, 폐질환, 신질환, 뇌혈관질환, 간질환 ) 의여부, 심정지의목격여부, 초기심율동, 심정지의원인 ( 심인성혹은비심인성 ), 심정지로부터자발순환회복까지의시간, 자발순환회복으로부터저체온치료유도까지의시간, 저체온치료의시작으로부터목표체온까지도달시간, 재가온기간, 퇴원시생존여부를조사하였다. 질환의중증도를반영하기위하여내원후첫 24시간동안의 sequential organ failure assessment (SOFA) 점수를측정하였다 11). 또한퇴원시의신경학적예후판정을위하여 cerebral performance category scale (CPC) 를측정하였다 12). CPC 1, 2점은예후우량군으로 CPC 3~5점은예후불량군으로정의하였다. 일차결 과 (primary outcome) 는병원내사망으로, 이차결과 (secondary outcome) 는신경학적예후로정의하였다. 여러차례동맥혈가스분석이시행되었기때문에, 각환자마다시간을반영한이산화탄소분압과산소분압을제시하기위하여시간가중평균이산화탄소분압과시간가중평균산소분압을계산하였다. 각환자마다총 7회 ( 자발순환회복후, 저체온치료시작, 저체온치료유지기의시작, 유지기시작후 6시간째, 12시간째, 18시간째, 24시간째 ) 의동맥혈가스분석결과와자발순환회복후부터재가온이완료되는저체온치료의종료까지총 7 구간의시간간격을이용하였다. 매동맥혈가스분석시점의사이시간과가스분압을곱한총합을전체시간으로나누어각각의시간가중평균이산 Table 1. Patient demographics and clinical characteristics. In-hospital mortality Neurologic outcome Survivors Nonsurvivors p Favorable Unfavorable p (n=127) (n=50) (n=59) (n=118) Age, yr, median (IQR) 53.0 (43.0-68.0) 63.0 (50.3-71.0) <0.042 48.0 (37.0-57.0) 63.0 (48.0-72.0) <0.001 Male gender, n (%) 094 (74.0) 33 (66.0) <0.286 44 (74.6) 083 (70.3) <0.555 Pre-existing illness, n (%) Coronary artery disease 020 (15.7) 08 (16.0) <0.967 09 (15.3) 019 (16.1) <0.884 Heart failure 011 (08.7) 05 (10.0) <0.775 05 (08.5) 011 (09.3) <0.853 Hypertension 043 (33.9) 24 (48.0) <0.081 12 (20.3) 055 (46.6) <0.001 Diabetes 034 (26.8) 14 928.0) <0.869 07 (11.9) 041 (34.7) <0.001 Pulmonary disease 011 (08.7) 05 (10.0) <0.775 02 (03.4) 014 (11.9) <0.064 Renal impairment 008 (06.3) 04 (08.0) <0.742 00 (00.0) 012 (10.2) <0.011 Cerebrovascular accident 011 (08.7) 03 (06.0) <0.760 02 (03.4) 012 (10.2) <0.146 Hepatic disease 004 (03.1) 01 (02.0) <1.000 01 (01.7) 004 (03.4) <0.666 Witness of collapse, n (%) 104 (81.9) 32 (64.0) <0.011 51 (86.4) 085 (72.0) <0.032 First monitored rhythm, n (%) <0.001 <0.001 Shockable 045 (35.4) 04 (08.0) 36 (61.0) 0013 (11.0) Non-shockable 082 (64.6) 46 (92.0) 23 (39.0) 105 (89.0) Aetiology, n (%) <0.015 <0.001 Cardiac 086 (67.7) 24 (48.0) 52 (88.1) 058 (49.2) Non-cardiac 041 (32.3) 26 (52.0) 07 (11.9) 060 (50.8) Time from collapse to ROSC, min, median (IQR) 29.0 (20.0-40.0) 35.0 (24.5-45.0) < 0.043 25.0 (15.0-34.0) 32.0 (25.0-41.5) <0.001 Time from ROSC to initiation of TH, min, median (IQR) 230 (163-300) 185 (150-300) < 0.377 213 (160-300) 210 (160-300) < 0.833 Time from initiation of TH to achieving target temperature, 3.0 (2.0-5.0) 2.0 (1.0-3.1) <0.001 3.5 (2.0-5.5) 2.0 (1.4-4.0) <0.001 h, median (IQR) Rewarming duration, h, median (IQR) 11.0 (7.0-12.0) 10.0 (5.5-13.0) < 0.723 10.5 (6.5-12.0) 11.0 (7.0-13.0) < 0.658 SOFA score 9 (7-11) 10 (9-12) <0.005 8 (6-10) 10 (8-12) <0.001 TWMO 2, mmhg, median (IQR) 143.9 (125.0-160.0) 126.9 (106.8-155.4) < 0.023 149.1 (129.0-160.6) 135.1 (117.8-155.5) < 0.039 TWMCO 2, mmhg, median (IQR) 39.0 (36.6-41.6) 37.4 (34.3-42.1) < 0.198 38.6 (36.7-41.2) 38.9 (35.3-42.2) < 0.796 IQR: interquartile range, ROSC: restoration of spontaneous circulation, TH: therapeutic hypothermia, SOFA: sequential organ failure assessment, TWMO 2: time-weighted mean oxygen tension, TWMCO 2: time-weighted mean carbon dioxide tension

560 / 대한응급의학회지 : 제 25 권제 5 호 2014 화탄소분압과시간가중평균산소분압으로정의하였다. 4. 통계분석범주형변수들은빈도 ( 백분율 ) 로표현하였고, 두군간의비교를위해서조건에따라카이제곱검정이나 Fisher의정확검정을이용하였다. 연속변수는정규성분포검정결과모두비정규분포를보였기때문에중앙값 ( 사분위값 ) 으로표현하였고, 두군의비교를위해서 Mann-Whitney U 검정법을이용하였다. 시간에따른이산화탄소분압의변화를비교하기위하여 Friedman 검정법을이용하였고, Wilcoxon Signed Ranks 검정법과함께 Bonferroni 보정법을이용하여사후검정하였다. 시간가중평균이산화탄소분압은정상탄산상태 (35~45 mmhg), 저탄산혈증 (<35 mmhg), 그리고고탄산혈증 (> 45 mmhg) 으로구분한후단변량로지스틱분석을이용하여승산비 (95% 신뢰구간 ) 를구하였다. 신경학적예후와병원내사망에관련이있는독립적인변수를찾기위해이분형다변량로지스틱회귀분석을이용하였다. 다변량로지스틱회귀분석에는단변량분석에서 p<0.10의결과를나타냈던변수들만을포함하였고, 변수들간의다중공선성의여부를진단하여포함여부를결정하였다. 시간가중평균이산화탄소분압과일차및이차결과와의관계를도시화하기위하여 locally weighted scatterplot smoothing (LOWESS) curve를생성하였다. 통계분석은 PASW/SPSS TM software, version 18 (IBM Corp. NY. USA) 를사용하였으며, p값이 0.05 미만인경우를통계학적으로유의하게판정하였다. 결 1. 연구대상의일반적인특성및일차목적과이차목적에따른비교 연구기간동안에 476명의환자가병원전심정지후자발순환을회복하였으며이들중저체온치료를시도한환자는 261례였지만, 저체온치료의방법이표준프로토콜 ( 목표체온은 33±1 C, 유지기간은 24시간 ) 과달랐던 57례, 저체온치료가중지된 19례를제외한 185례가저체온치료를완료하였다. 또한체외순환보조요법 3례, 동맥혈가스분석결과가누락된 5례를제외하여, 177례가분석에포함되었다. 생존여부와신경학적예후에따른두군의비교는 Table 1 에기술되었다. 50 (28.2%) 례가병원내에서사망하였고 59 (33.3%) 례가예후우량군에해당하였다. 생존군과예후우량군을사망군과예후불량군과각각비교하였을때, 연령, 심정지목격의여부, 초기심율동, 심정지의원인, 목표체온까지의시간, SOFA 점수에서유의한차이를나타냈다 (Table 1). 예후불량군에비해예후우량군의고혈압, 당뇨, 콩팥질환의빈도가유의하게낮았다 (Table 1). 2. 이산화탄소분압의분포와시간가중평균이산화탄소분압 전체 1,239개이산화탄소분압값의중앙값은 38.2 (33.9-43.3) mmhg의분포를나타냈고, 정상탄산상태 과 A B Fig. 1. (A) Distribution of arterial partial pressure of carbon dioxide, (B) Distribution of arterial partial pressure of carbon dioxide according to the time point of blood sampled. Friedman test showed significant change of PaCO 2 over time (p<0.001) and post-hoc test using Wilcoxon signed ranks test with Bonferroni correction revealed that PaCO 2 changed significantly between the time point of return of spontaneous circulation and start of therapeutic hypothermia. PaCO 2: arterial partial pressure of carbon dioxide, ROSC: return of spontaneous circulation, TH: therapeutic hypothermia, M0: initiation of maintenance phase, M6: 6 hrs after initiation of maintenance phase, M12: 12 hrs after initiation of maintenance phase, M18: 18 hrs after initiation of maintenance phase, M24: 24 hrs after initiation of maintenance phase. * p<0.05 (Wilcoxon signed ranks test with Bonferroni correction)

정다원외 : 저체온치료를받은병원전심정지환자에서비정상이산화탄소분압과예후와의관계 / 561 (35~45 mmhg) 는 618 (49.8%) 개, 저탄산혈증 (<35 mmhg) 은 380 (30.7%) 개, 고탄산혈증 (>45 mmhg) 은 241 (19.5%) 개였다 (Fig. 1). 매시기마다측정된이산화탄소분압의분포는시간이흐름에따라유의한차이를보였는데, 자발순환회복직후와저체온치료시작직전에측정한이산화탄소분압사이에유의한차이가있었다 (Fig. 1). 시간가중평균이산화탄소분압의전체중앙값은 38.8 (35.7-41.7) mmhg였으며, 세군으로구분하면저탄산혈증군은 36 (20.3%) 례, 정상탄산상태군은 125 (70.6%) 례, 고탄산혈증군은 16 (9.1%) 명이었다. 생존군과예후우량군에서는각각 39.0 (36.6-41.6) mmhg와 38.6 (36.7-41.2) mmhg이었고, 사망군과예후불량군에서는각각 37.4 (34.3-42.1) mmhg와 38.9 (35.3-42.2) mmhg로유의한차이는없었다 (Table 1). 3. 시간가중평균이산화탄소분압의신경학적예후와병원내사망과의관계 시간가중평균이산화탄소분압을연속변수로단변량로지 스틱회귀분석을이용하여사망군과예후불량군에대해승산비를구하면, 각각 0.999 (95% 신뢰구간, 0.943-1.059, p=0.980), 0.991 (95% 신뢰구간, 0.932-1.055, p=0.787) 로유의하지않았다. 그러나시간가중평균이산화탄소분압을세군으로나누어정상탄산상태를기준으로비교하였을때, 저탄산혈증은정상탄산상태에비해병원내사망의승산비가 2.474 (95% 신뢰구간, 1.129-5.424, p=0.024) 로유의하게나타났다 (Table 2). 단변량분석에서유의수준이 0.1 미만으로나타난변수들과시간가중평균이산화탄소분압의예후와의관계를분석하기위하여다변량로지스틱회귀분석을이용하였다 (Table 3). 병원내사망과유의한관계를나타낸변수는목격여부, 초기심율동, SOFA 점수, 그리고시간가중평균이산화탄소분압이었는데정상탄산상태에비해저탄산혈증과고탄산혈증은각각 2.926 (95% 신뢰구간, 1.212-7.066, p=0.017) 과 4.673 (95% 신뢰구간, 1.348-16.205, p=0.015) 의유의하게높은승산비를보였다. 신경학적예후와유의한관계를나타낸변수들은연령, 심정지의원인, 초기심율동, 자발순환회복까지의시간이었으 Table 2. Univariate association between time-weighted mean carbon dioxide tension and outcomes. In-hospital mortality OR (95% CI) p Neurologic outcome OR (95% CI) p Degree of TWMCO 2 Nomocapnia, 35~45 mmhg reference (1.000) reference (1.000) Hypocapnia, <35 mmhg 2.474 (1.129-5.424) 0.024 1.630 (0.704-3.771) 0.254 Hypercapnia, >45 mmhg 2.694 (0.921-7.883) 0.070 0.905 (0.308-2.657) 0.905 TWMCO 2: time-weighted mean carbon dioxide tension, OR: odds ratio, CI: confidence interval Table 3. Multivariate logistic regression for outcomes. In-hospital mortality OR (95% CI) p Witness 0.306 (0.130-0.720) <0.007 Shockable rhythm 0.194 (0.062-0.614) <0.005 SOFA 1.256 (1.089-1.449) <0.002 Degree of TWMCO2 Nomocapnia, 35~45 mmhg reference (1.000) Hypocapnia, <35 mmhg 2.926 (1.212-7.066) <0.017 Hypercapnia, >45 mmhg 04.673 (1.348-16.205) <0.015 Unfavorable neurologic outcome OR (95% CI) p Age 1.078 (1.045-1.112) <0.001 Non-cardiac etiology 07.164 (2.108-24.344) <0.002 Shockable rhythm 0.095 (0.031-0.290) <0.001 Time from collapse to ROSC 1.070 (1.033-1.107) <0.001 Degree of TWMCO 2 Nomocapnia, 35~45 mmhg reference (1.000) Hypocapnia, <35 mmhg 2.171 (0.577-8.172) <0.252 Hypercapnia, >45 mmhg 1.119 (0.172-7.286) <0.906 SOFA: sequential organ failure assessment, TWMCO 2: time weighted mean carbon dioxide tension, ROSC: restoration of spontaneous circulation, OR: odds ratio, CI: confidence interval

562 / 대한응급의학회지 : 제 25 권제 5 호 2014 며, 시간가중평균이산화탄소분압은유의하지않았다. LOWESS curve는정상탄산상태의범위에서저탄산혈증이나고탄산혈증보다낮은병원내사망위험과예후불량위험을나타냈다 (Fig. 2). 탄소분압은예후와유의한관계가없었다. 다만, 저체온치료시작직전에측정한동맥혈가스분석결과, 저탄산혈증인경우정상탄산상태에비해신경학적예후와유의한관계가있는것으로나타났다. 4. 체온에따른이산화탄소분압의신경학적예후와병원내사망과의관계 (Table 4) 고 찰 저체온치료동안에는체온이변하므로자발순환회복후, 저체온치료시작직전과저체온치료유지기간의세시점으로구분하여이산화탄소분압과예후와의관계를추가분석하였다. 자발순환회복후나저체온치료유지시간의이산화 측정된이산화탄소분압 1,239개중정상탄산상태 (35~45 mmhg) 는 618 (49.8%) 개, 저탄산혈증 (<35 mmhg) 은 380 (30.7%) 개, 고탄산혈증 (>45 mmhg) 은 241 (19.5%) 개로비정상탄산상태의빈도가높았다. 단변 A Fig. 2. Locally weighted scatterplot smoothing (LOWESS) curves according to the probability of outcomes. LOWESS curves showed V-shaped relationship between the time-weighted mean PaCO 2 and outcomes (A: in-hospital mortality, B: poor neurologic outcome), with the lowest probability of in-hospital mortality and poor neurologic outcome between 35 and 45 mmhg B Table 4. Adjusted odds ratio of carbon dioxide tension for outcomes. In-hospital mortality OR (95% CI) p Neurologic outcome OR (95% CI) PaCO 2 after ROSC Nomocapnia, 35~45 mmhg reference (1.000) reference (1.000) Hypocapnia, <35 mmhg 1.652 (0.668-4.085) 0.277 0.967 (0.295-3.165) 0.956 Hypercapnia, >45 mmhg 1.775 (0.603-5.228) 0.298 0.684 (0.125-3.735) 0.661 PaCO 2 at initiation of TH Nomocapnia, 35~45 mmhg reference (1.000) reference (1.000) Hypocapnia, <35 mmhg 1.568 (0.681-3.611) 0.291 03.737 (1.119-12.480) 0.032 Hypercapnia, >45 mmhg 0.724 (0.277-1.891) 0.509 2.189 (0.649-7.381) 0.206 Mean PaCO 2 during maintenance phase Nomocapnia, 35~45 mmhg reference (1.000) reference (1.000) Hypocapnia, <35 mmhg 1.501 (0.582-3.870) 0.401 02.630 (0.692-10.000) 0.156 Hypercapnia, >45 mmhg 1.947 (0.643-5.897) 0.238 0.735 (0.188-2.882) 0.659 ROSC: return of spontaneous circulation, TH: therapeutic hypothermia, OR: odds ratio, CI: confidence interval p

정다원외 : 저체온치료를받은병원전심정지환자에서비정상이산화탄소분압과예후와의관계 / 563 량분석결과정상탄산상태군에비해저탄산혈증군의병원내사망에대한승산비가유의하게높았으며, 다변량분석결과정상탄산상태군에비해저탄산혈증군과고탄산혈증군모두병원내사망에대한승산비는유의하게높았으나, 신경학적예후와는유의한관계를보이지않았다. 심정지후증후군환자에서이산화탄소분압분포에대한한연구결과정상탄산상태가 40.5%, 저탄산혈증이 18.2%, 고탄산혈증이 41.3% 로고탄산혈증의빈도가가장높고저탄산혈증의빈도는가장낮은것으로나타났다 5). 하지만, 이들의연구에서이산화탄소분압값의선택기준은이산화탄소분압의상태가아니라가장낮은산소분압상태를나타내는동맥혈가스분석결과였기때문에이산화탄소분압의분포를반영한다고보기어렵고, 저체온치료를시행받은환자의비율이낮아서본연구의결과와비교하기어렵다. 저체온치료는그것자체로이산화탄소분압에영향을미칠수있다. 저체온치료로인해산소의이용이감소하여결과적으로이산화탄소의생성이감소한다 13). 또한온도가낮아지면혈액으로이산화탄소의용해도가증가하므로같은이산화탄소농도에서라도이산화탄소분압은감소하게된다 10). 따라서저체온치료의적용여부에따라이산화탄소분압의분포는다를수있다. 저체온치료환자들을대상으로이산화탄소분압의분포를확인한한연구에서는정상탄산상태는 55%, 저탄산혈증은 34%, 고탄산혈증은 12% 로보고하였다 4). 정상탄산상태가가장많기는하지만저탄산혈증이나고탄산혈증의분포도높아서본연구와유사한결과를보였으며, 저체온치료를받는심정지환자에게환기조절이반드시필요함을강조하였다. 동물실험모델과외상성뇌손상환자에서저탄산혈증이신경손상과연관이있음은이미보고되었다 14,15). 심정지후환자를대상으로이산화탄소분압과예후와의관계를확인한대부분의연구들역시저탄산혈증은나쁜예후와관련이있음을보고하였다 5-8). 본연구에서도저탄산혈증은단변량분석과다변량분석모두에서정상탄산상태에비하여병원내사망의승산비가유의하게높은것으로나타나기존의연구들과같은결과를나타냈다. 하지만, 고탄산혈증의예후와의관계는기존연구들에서도차이가있다 5-8). 자발순환이회복되더라도심정지이후에는혈관저항이증가하므로대뇌혈류가감소되어있는상태이다 16,17). 그런데, 동물실험에서경도의고탄산혈증을유도하면대뇌혈관의확장을일으켜대뇌로의관류를개선시키는효과가있는것으로나타났다 18-20). Schneider 등 5) 의연구에서는고탄산혈증이정상탄산상태에비하여생존자들중집으로퇴원가능성이높은것으로나타나고탄산혈증이신경학적예후개선과관련이있음을시사하였다. 하지만, Roberts 등 7) 과 Del Castillo 등 8) 의연구에서는저탄산혈증뿐만아니라고탄산혈증또한사망이나예후불량군과유의한관계가있음을보고하였다. 본연구또한다변량분석결과저탄산혈 증과고탄산혈증모두정상탄산상태에비하여병원내사망과유의한관련이있는것으로나타났다. 고탄산혈증이대뇌관류를향상시키는효과가있는반면에, 폐혈관수축, 더나아가서는우심실기능저하, 두개내압증가를유도할수있기때문에고탄산혈증이무작정좋은효과만있는것은아니다 21). 저체온치료를받은심정지환자 8명을대상으로한예비연구에서도고탄산혈증을유발한것이아니라고탄산혈증에가까운정상탄산상태의이산화탄소분압을유도한상태에서대뇌혈류증가와대뇌젖산이감소함을보고하였기때문에고탄산혈증이신경보호효과가있다고단정지어말하기는어려울것으로생각한다 6). 본연구결과를바탕으로생성한 LOWESS 곡선을보면정상탄산상태일때저탄산혈증이나고탄산혈증에비해병원내사망과예후불량군에대한가능성이확연히떨어짐을관찰할수있다. 이는저탄산혈증이나고탄산혈증모두정상탄산상태보다위험한상태임을의미한다. 본연구의제한점으로는첫째, 본연구는일개의료기관에서적은수의환자를대상으로시행되었기때문에연구결과의적용여부나통계적인분석력에있어서제한점이있다. 또한후향적연구이기때문에이산화탄소분압과예후의인과관계라기보다는단순관계의여부만을파악할수있었다. 향후다기관에서저체온치료의치료프로토콜을동일화하여이에대한추가연구가필요하다. 둘째, 이산화탄소분압은체온에영향을받지만본연구에서는체온에따른교정을하지않은이산화탄소분압값을그대로이용하였다. 체온에따른이산화탄소분압의변화를교정하지않고그대로적용하는방법을 alpha-stat, 체온에따른변화를교정하여적용하는방법을 ph-stat이라고한다. phstat을이용한치료는 alpha-stat을이용한경우보다대뇌산소포화도가높고, 속목정맥의산소불포화도가더낮게나타나는반면, alpha-stat을이용하면대뇌혈류의자동조절력이더좋은것으로알려져있어서궁극적으로두가지방법중어떤방법이더나은지는여전히이견이있다 22,23). 본연구에포함된환자들은 alpha-stat을기준으로기계환기를적용받았던환자들이므로, 분석또한체온에따른교정을하지않은이산화탄소분압을이용하는것이적절한분석법으로생각된다. 셋째, 본연구는여러변수들중유의한변수를찾기위해다변량분석을시행하였다. 예후에영향을미치지만연구자들이기대하지못한혼란변수혹은교란변수들이다변량분석에서누락되었을가능성이있다. 결론저체온치료를시행받은심정지후증후군환자에서저탄산혈증은 30.7% 고탄산혈증은 19.5% 로비정상탄산상태

564 / 대한응급의학회지 : 제 25 권제 5 호 2014 의비율이비교적높았다. 정상탄산상태군을기준으로비정상탄산상태 ( 저탄산혈증군, 고탄산혈증군 ) 는병원내사망에대한승산비가유의하게높았다. LOWESS 곡선은정상탄산상태일때병원내사망과예후불량군에대한위험률이가장낮게나타났다. 참고문헌 01. Brian JE Jr. Carbon dioxide and the cerebral circulation. Anesthesiology. 1998;88:1365-86. 02. Buunk G, van der Hoeven JG, Meinders AE. Cerebrovascular reactivity in comatose patients resuscitated from a cardiac arrest. Stroke. 1997;28:1569-73. 03. Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, et al. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122:S768-86. 04. Falkenbach P, Kamarainen A, Makela A, Kurola J, Varpula T, Ala-Kokko T, et al. Incidence of iatrogenic dyscarbia during mild therapeutic hypothermia after successful resuscitation from out-of-hospital cardiac arrest. Resuscitation. 2009;80:990-3. 05. Schneider AG, Eastwood GM, Bellomo R, Bailey M, Lipcsey M, Pilcher D, et al. Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest. Resuscitation. 2013;84:927-34. 06. Pynnonen L, Falkenbach P, Kamarainen A, Lonnrot K, Yli-Hankala A, Tenhunen J. Therapeutic hypothermia after cardiac arrest - cerebral perfusion and metabolism during upper and lower threshold normocapnia. Resuscitation. 2011;82:1174-9. 07. Roberts BW, Kilgannon JH, Chansky ME, Mittal N, Wooden J, Trzeciak S. Association between postresuscitation partial pressure of arterial carbon dioxide and neurological outcome in patients with post-cardiac arrest syndrome. Circulation. 2013;127:2107-13. 08. Del Castillo J, Lopez-Herce J, Matamoros M, Canadas S, Rodriguez-Calvo A, Cechetti C, et al. Hyperoxia, hypocapnia and hypercapnia as outcome factors after cardiac arrest in children. Resuscitation. 2012;83:1456-61. 09. Polderman KH. Induced hypothermia and fever control for prevention and treatment of neurological injuries. Lancet. 2008;371:1955-69. 10. Kofstad J. Blood gases and hypothermia: some theoretical and practical considerations. Scand J Clin Lab Invest. 1996;224:21-6. 11. Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/ failure. On behalf of the Working Group on Sepsis- Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707-10. 12. Booth CM, Boone RH, Tomlinson G, Detsky AS. Is this patient dead, vegetative, or severely neurologically impaired? Assessing outcome for comatose survivors of cardiac arrest. JAMA. 2004;291:870-9. 13. Tokutomi T, Morimoto K, Miyagi T, Yamaguchi S, Ishikawa K, Shigemori M. Optimal temperature for the management of severe traumatic brain injury: effect of hypothermia on intracranial pressure, systemic and intracranial hemodynamics, and metabolism. Neurosurgery. 2003;52:102-11. 14. Muizelaar JP, Marmarou A, Ward JD, Kontos HA, Choi SC, Becker DP, et al. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg. 1991;75:731-9. 15. Ohyu J, Endo A, Itoh M, Takashima S. Hypocapnia under hypotension induces apoptotic neuronal cell death in the hippocampus of newborn rabbits. Pediatr Res. 2000;48:24-9. 16. Buunk G, van der Hoeven JG, Frolich M, Meinders AE. Cerebral vasoconstriction in comatose patients resuscitated from a cardiac arrest? Intensive Care Med. 1996;22: 1191-6. 17. Lemiale V, Huet O, Vigue B, Mathonnet A, Spaulding C, Mira JP, et al. Changes in cerebral blood flow and oxygen extraction during post-resuscitation syndrome. Resuscitation. 2008;76:17-24. 18. Hare GM, Kavanagh BP, Mazer CD, Hum KM, Kim SY, Coackley C, et al. Hypercapnia increases cerebral tissue oxygen tension in anesthetized rats. Can J Anaesth. 2003; 50:1061-8. 19. Hino JK, Short BL, Rais-Bahrami K, Seale WR. Cerebral blood flow and metabolism during and after prolonged hypercapnia in newborn lambs. Crit Care Med. 2000;28: 3505-10. 20. Vannucci RC, Towfighi J, Heitjan DF, Brucklacher RM. Carbon dioxide protects the perinatal brain from hypoxicischemic damage: an experimental study in the immature rat. Pediatrics. 1995;95:868-74. 21. Mekontso Dessap A, Charron C, Devaquet J, Aboab J, Jardin F, Brochard L, et al. Impact of acute hypercapnia and augmented positive end-expiratory pressure on right ventricle function in severe acute respiratory distress syndrome. Intensive Care Med. 2009;35:1850-8. 22. Hoover LR, Dinavahi R, Cheng WP, Cooper JR Jr, Marino MR, Spata TC, et al. Jugular venous oxygenation during hypothermic cardiopulmonary bypass in patients at risk for abnormal cerebral autoregulation: influence of alpha-stat versus ph-stat blood gas management. Anesth

정다원외 : 저체온치료를받은병원전심정지환자에서비정상이산화탄소분압과예후와의관계 / 565 Analg. 2009;108:1389-93. 23. Henriksen L, Hjelms E, Lindeburgh T. Brain hyperperfusion during cardiac operations. Cerebral blood flow measured in man by intra-arterial injection of xenon 133: evidence suggestive of intraoperative microembolism. J Thorac Cardiovasc Surg. 1983;86:202-8.