Korean J Anesthesiol 9 May; 56(5): 543-5 DOI:.497/kjae.9.56.5.543 Clinical Research Article Desflurane 폐포내농도상승에따른뇌산소포화도반응에미치는 Remifentanil 의효과와뇌혈관의이산화탄소반응성 동국대학교의과대학일산병원마취통증의학교실 이정혁ㆍ이윤석ㆍ인준용ㆍ정승현ㆍ신홍일ㆍ이경진ㆍ김경옥ㆍ조헌 Response of cerebral oximetry to increase in alveolar concentration of desflurane: effect of remifentanil and cerebrovascular CO reactivity Jeoung Hyuk Lee, Younsuk Lee, Junyong In, Seung-Hyun Chung, Hong-il Shin, Kyoungjin Lee, Kyoung Ok Kim, and Hun Cho Department of Anesthesiology and Pain Medicine, Dongguk University College of Medicine, Ilsan Hospital, Goyang, Korea Background: It is known that sympathetic stimulation and increase in cerebral blood flow velocity can be induced by desflurane. Cerebral oxygen balance could be disturbed during desflurane induction. Aim of this study was to elucidate that cerebral oxygen imbalance induced by desflurane mask induction can be reduced by combination of remifentanil and hypocapnia. Methods: Twenty ASA - subjects were allocated randomly into 5 groups divided by concentration of remifentanil (.,.5,.,.5, and. ng/ml). After confirmation of attaining proposed concentration of remifentanil, propofol and vecuronium were administered and mechanical ventilation was done with 8% desflurane with facial mask. Subsequently, changes in regional cerebral oxygen saturation (ΔrSO ), arterial blood pressure, heart rate, cardiac index, estimated alveolar concentration of desflurane (P DESF), and end-tidal concentration of carbon dioxide (PET CO) were recorded for the following minutes. According to concentration of desflurane and remifentanil, ΔrSO and hemodynamic factors were checked. Results: During desflurane induction, changes in cerebral oximetry reached up to +% (6 [first quartile], 3 [third quartile]). Arterial blood pressure, heart rate, and cardiac index were changed within clinical ranges. The ΔrSO showed S-shaped increasing pattern according to increasing P DESF. Hypocapnia and concentration of remifentanil reduced the maximum ΔrSO (P =.46, P =.6). Hypocapnia also shifted the curve to left (P =.). Conclusions: During 8% desflurane induction, regional cerebral oxygen saturation (rso ) increases maximum +5%. Hypocapnia and use of remifentanil can reduce the increase in regional cerebral oxygen saturation. (Korean J Anesthesiol 9; 56: 543~5) Key Words: Cerebral blood flow, Cerebral oximetry, Desflurane, Hypocapnia, Nonlinear mixed model, Remifentanil. 서 Desflurane은현시대에흔하게사용되는흡입마취제의하나로서, 낮은혈액용해도를가지고있음에도불구하고폐포농도의초기상승중에일어나는교감신경계의항진효과 Received: January 9, 9. Accepted: March 3, 9. Corresponding author: Younsuk Lee, M.D., Ph.D., Department of Anesthesiology and Pain Medicine, Dongguk University College of Medicine, Ilsan Hospital, 84, Siksa-dong, Ilsan-gu, Goyang 4-773, Korea. Tel: 8-3-96-787, Fax: 8-3-96-7864, E-mail: ylee@dongguk.ac.kr Copyright c Korean Society of Anesthesiologists, 9 론 는 desflurane의중요한단점이다. Desflurane이유발하는교감신경계의항진은혈압및맥박수의증가, 동공산대로표출되며, 뇌혈류의유속증가도나타난다고하는데뇌혈류의유속증가가교감신경계항진의전신반응의일부로나타나는것인지 desflurane의뇌혈관작용에기인하는것인지에대한보고는미흡하다. 마스크를통한통상적인마취유도과정에서 desflurane 폐포농도가상승하는초기단계부터뇌산소포화도 (rso, regional cerebral oxygen saturation) 가상승한다고하였다 []. 저자들은 desflurane 마취유도과정의 rso 상승은교감신경계활성화에따른전신반응과무관하며 desflurane 자체의뇌혈관확장작용이뇌대사감소작용보다선행함으로써 543
Vol. 56, No. 5, May 9 Korean J Anesthesiol 초래된다고가정하였다. 이와같은 rso 의증가가 desflurane 의폐포농도에대해서표준적인농도-반응곡선에부합할것으로보고 desflurane 유도중에 rso 의상승을예측할수있는비선형혼합모형을개발한뒤에, 임상적인범위의 remifentanil 병용이 rso 상승에미치는교란효과와비항정상태 (non-steady state) 에서측정되는뇌혈관의이산화탄소반응성의존재여부를알아보았다. 대상및방법전신마취로간단한수술을받은미국마취과학회신체등급분류 에해당하는총 명의성인환자를대상으로하였다. 기관임상연구윤리위원회의승인을얻었으며대상환자들로부터서면승낙을얻었다. 심혈관계, 자율신경계, 호흡계, 내분비계, 뇌신경계의질환을가지거나해당약물을복용하고있는자는제외하였다. Remifentanil 농도에 (.,.5,.,.5,. ng/ml) 따라환자들을무작위로다섯군중한군에배정하였다. 각군간에나이, 성별, 체중, 신장은통계적으로유의한차이를보이지않았다 (Table ). 뇌산소포화도변화량을 desflurane 농도에따라비선형으로회귀분석한뒤모형인수에대해두개의공변량 (remifentanil 농도와호기말이산화탄소분압 [PET CO]) 으로선형결합을시행할예정이었으므로, 과잉적합을방지하기위해서제한표본수 (limiting sample size ) 를 명으로선정하였다. 환자가수술실에도착하기전에마취기 (S/5 Avance Carestation R, Datex-Ohmeda, Helsinki, Finland) 와마취회로를미리 % 산소 6 L/min, desflurane 8.% 로포화시킨후회로내 desflurane 농도를검증하였다. 마취전투약은하지않았다. 표준감시장치외에 rso (INVOS 5B, Somanetics R, Troy, USA) 의발광-감지기결합체 (emitter-sensor couplet) 를우측이마에붙이고, 평균동맥혈압 (MBP, mean arterial blood pressure), 심박수 (HR, heart rate), 심박출량지수 (CI, cadiac index) 를지속적으로측정하기위해서 Finometer (Finapres Medical Systems, Amsterdam, Netherland) 의감지기를우측네번째손가락의중간마디 (midphalanx) 에부착하였다. 이상의측정값들은환자가대기중에서호흡하면서약 분간안정을이룬후기록하였다. Remifentanil을지속주입하기시작했으며 (Orchestra, Fresenius Vial, France), 혈장및효과처의추정농도 (estimated plasma and effect-site concentration) 가모두앞서배정된 remifentanil 농도에도달한것을확인하였다. Desflurane의호기분압 (P DESF) 과 PET CO 는마취기에장착된가스모듈 (airway module embedded in S/5 Avance Carestation R ) 을이용해서측정하였다. 마취유도를위해 propofol.5 mg/kg을정주한뒤에의식소실을확인하였고, 별도로준비해둔호흡장치 (bag-valve device) 로용수환기의용이성을평가한뒤에 vecuronium. mg/kg을정주하였다. Desflurane 8.% 로포화시킨마취기의회로를환자의안면마스크와연결하였다. 연구보조자가양손으로안면마스크를환자에게적용함으로써누출을최소화하였으며, % 산소 6 L/min을유지하며일회호흡량 9 ml/kg, 호흡수 /min의용적제한형기계환기를시작하면서이시점 (T) 을시작으로하여 분간총 회에걸쳐,.,.5,.,.5,.,.5, 3., 4., 5., 7.5,.분째다음측정 Table. Physical and Basic Measurements According to Concentration of Remifentanil (C REMI) Concentration of remifentanil (ng/ml)..5..5. P Age (yrs) Gender (F/M) Weight (kg) Height (cm) Preinduction MBP (mmhg) HR (beat/min) CI (L/min/m ) At T MBP (mmhg) HR (beat/min) CI (L/min/m ) rso (%) 38 (9, 46) 3/ 69 (6, 78) 68 (6, 74) 9 (8, 99) 8 (67, 94) 4. (3., 5.) 85 (75, 95) 75 (66, 85) 3. (., 3.9) 65 (56, 74) 37 (3, 4) 3/ 66 (59, 7) 66 (6, 7) 9 (84, 97) 76 (67, 86) 4. (3.3, 4.7) 8 (75, 89) 73 (66, 8) 3. (.6, 3.9) 67 (6, 73) 35 (3, 4) /3 6 (57, 67) 64 (6, 67) 9 (86, 96) 7 (64, 8) 4. (3.5, 4.6) 79 (73, 85) 7 (65, 76) 3.5 (.9, 4.) 69 (63, 74) 34 (8, 4) / 58 (5, 65) 6 (57, 66) 9 (85, 97) 67 (58, 77) 4. (3.4, 4.8) 76 (69, 84) 68 (6, 75) 3.7 (3., 4.3) 7 (64, 77) 33 (5, 4) 4/ 55 (46, 64) 59 (53, 66) 9 (8, ) 63 (5, 76) 4. (3., 5.) 74 (63, 84) 66 (56, 76) 3.9 (3., 4.8) 7 (63, 8).59.5.536.89.8959.5.85.675.36.83.947 Values are mean (first quartile, third quartile). MBP: mean arterial blood pressure, HR: heart rate, CI: cardiac index, rso : regional cerebral oxygen saturation, T: time. min during desflurane induction. 544
Lee et al:desflurane and rso 값들을반복하여기록하였다 : rso, MBP, HR, CI, P DESF, PET CO. 연구기간동안맥박산소포화도는 99% 이상으로유지되었다. MBP가 55 mmhg 미만, HR가 45 /min 미만으로측정되었을때에는연구를중단한뒤에적절히치료하였다. 연구중단전까지측정된값들은분석에포함하였다. 자료분석 환자들의인구학적, 생리학적지표들은 remifentanil 농도에대해공분산분석으로비교하였다. rso 의환자별상승폭, MBP, HR, CI의변동을이원배치반복측정분산분석 (two-way repeated measures analysis of variance) 으로시간과 remifentanil 농도 (C REMI) 에대해서비교하였으며, 유의한결과를얻은요인에대해서다중비교를시행하였다. ΔrSO 는각반복측정시점의 rso 와 T의 rso 의차이이다. 다중비교는시간 (T) 과 C REMI(. ng/ml) 의대조값을기준으로짝지어분석하였으며 Holm-Sidak의절차에따라보정된유의도를이용하였다. Desflurane 폐포분압의상승에따른 ΔrSO 은표준 3인수로지스틱곡선 (standard 3-parameter logistic curve) 에적합시켰다. P DESF 을폐포분압으로해석하였다. ΔrSO 예측값은다음의식처럼 PDESF와모형인수인 A, LC 5, θ의함수로표현할수있다. A Predicted ΔrSO (%) = A + e (logp DESF LC 5 )/θ ( 식 ) P DESF 는로그값으로치환하여대입하였으며, 인수 A 는 ΔrSO 의최대예측값이며, LC 5 은 ΔrSO 가 A의 5% 에도달했을시점의 P DESF 의로그값이므로로그중간농도 (logarithm of median effect concentration) 로해석할수있으며, θ는가로축요인 (abscissa factor) 으로서 ΔrSO 가 A의 5% 에도달한지점과 73% 에도달한지점의거리이므로간단히말해서기울기의역수로볼수있다. ΔrSO 상승에미치는 PET CO 와 C REMI 의효과는식 처럼모형인수 A, LC 5, θ와의선형결합으로산출한추정값을식 에대입하여인구예측값 (population prediction) 을구하였다. A = A + A (PET CO 4) + A C REMI LC 5 = L + L (PET CO 4) ( 식 ) θ = θ + θ C REMI Remifentanil 농도별이분산성 (heteroscedasticity) 을분산함수 Var(ϵ) = σ δ REMI를적용하여고정하였다. C REMI =. ng/ml의분산을 로 (δ. = ) 조정했다. 환자내에서시간에따른자기상관 (autocorrelation) 을연속성자기상관함수 (continuous autogressive function) 로보정하였다. 개별환자에대응하는모형의인수, 즉 A, LC 5, θ의개별추정값 (individual estimates) 은식 3의행렬연산을전개하여최량선형비편향추정 (best linear unbiased estimation, BLUE) 의형식으로얻을수있으며, 인수별임의효과인 b A, b LC5, b θ 는평균이 이고분산이각각 σ A, σ LC5, σ θ 인정규분포를따르는것으로전제하였다. 개별예측값 (individual prediction) 은개별추정값을식 에대입하여구하였다. BLUE of A LC 5 θ = b A = N (, σ A) b LC5 = N (, σ LC5 ) b θ = N (, σ θ) PET CO 4 C REMI A A A L L θ θ C REMI + PET CO 4 b A b LC5 b θ ( 식 3) 환자개인에따른환자-내 (within-individual), 환자-간 (interindividual) 변이를세모형인수에대해서대칭성양의정부호행렬 (general symmetric positive-definite matrix) 로산출하였다. 모형의안정성을점검하기위해서비모수적자육법 (nonparametric bootstrap) 을이용하여재표집 (resampling) 하였고각모형인수별환자-간임의효과의평균 (mean) 과표준오차 (standard error, SE), 95% 신뢰구간, 편향 (bias) 을구하여관찰추정값과비교하였다. 자육반복횟수는,회로하였다. 모형인수추정값은평균, SE, 95% 신뢰구간으로표기하였으며, 표준화잔차 (standardized residuals) 는중위수 ( 제사분위수, 제3사분위수 ) 로, 이외에따로지정하지않은모든측정값은평균 ( 제사분위수, 제3사분위수 ) 으로표기하였다. 통계분석에 S-PLUS 8. for Windows Enterprise Developer (TIBCO Software Inc., Palo Alto, USA) 를이용하였다. 비선형혼합모형은 S-PLUS에추가로장착된 nlme (nonlinear mixed-effects) 3.3판라이브러리 (Pinheiro and Bates, USA) 를, 비모수적자육은 resample 3.판라이브러리 (TIBCO Software Inc.) 를이용하여구현하였다. 모든추리통계의유의도 P가.5 미만일때통계적으로유의한차이가있다고판정하였다. 545
Vol. 56, No. 5, May 9 Korean J Anesthesiol 결 과 Fig.. Changes in regional cerebral oxygen saturation (ΔrSO ) during desflurane mask induction for individual subject. It is clear that ΔrSO increases during desflurane induction ( a) P <.5 vs. min). Remifentanil-induced changes are not significant (P =.35). 마취유도전 MBP, HR, CI, T 시점에서 MBP, HR, CI, rso 는통계적으로유의한차이를나타내지않았으나 (Table ). C REMI. ng/ml군의한명,. ng/ml군의한명의환자에서각각.분,.5분째에저혈압이발생되어측정을중단하였으며 ephedrine 5 mg 정주로회복되었다. 관찰된 ΔrSO 의최대값은 +5% 이며평균 +% (6, 3) 로서, C REMI 가상승함에따라유의하게감소하는관계를보였다 (r =.533, P =.6). ΔrSO 의시간에따른변동은통계적으로유의한차이를보였으며 (P <.) 모든시간대에서 T와비교하여유의한차이가나타났지만 (P <.5), C REMI 에따른차이, 시간과농도의교차작용은유의하지않았다 (P =.35,.) (Fig. ). MBP의시간에따른차이는통계적으로유의했으나 (P <.) C REMI 에따른차이, 시간과농도의교차작용은유의하지않았다 (P =.55,.653). MBP의시간에따른변동가운데.5분, 4.분, 5.분, 7.5분과.분째에서 T의 MBP와유의한차이를보였다 (P <.5). 546 Fig.. Temporal changes in arterial blood pressure (upper), heart rate (middle), and cardiac index (lower). Despite those significant temporal changes ( a) P <.5) from time., remifentanil-induced changes are not (P =.55,.734, and.57) for arterial blood pressure, heart rate, and cardiac index, respectively.
Lee et al:desflurane and rso Fig. 3. Predicted changes in regional cerebral oxygen saturation (ΔrSO ) for estimated alveolar concentration of desflurane (P DESF) accompanied with computer-estimated concentration of remifentanil (C REMI). Predicted ΔrSO follows 3-parameter logistic curve. Maximum ΔrSO is reduced by increasing C REMI (P =.6) and hypocapnia (P =.46). Curve is shifted to left by hypocapnia (P =.). Slope of the curve is steepened by increasing C REMI (P =.87). PET CO: end-tidal concentration of carbon dioxide (mmhg). 547
Vol. 56, No. 5, May 9 HR의시간에따른차이는통계적으로유의했으나 (P <.) C REMI 에따른차이, 시간과농도의교차작용은유의하지않았다 (P =.734,.736). HR의시간에따른변동가운데 7.5분과.분째에서 T의 HR와유의한차이를보였다 (P <.5). CI의변동의시간에따른차이, C REMI 에따른차이, 시간과농도의교차작용은모두통계적으로유의하지않았다 (P =.57,.75,.97) (Fig. ). Desflurane 마취유도중의 ΔrSO 는 desflurane 폐포농도에대해서 3인수로지스틱모형에잘적합하였다. 모형인수 A의예측값은 PET CO 이상승함에따라통계적으로유의하게상승하였으며 (P =.46) C REMI 가높을수록하강하였다. LC 5 은 PET CO 이상승함에따라유의하게상승하였으므로 (P =.), 곡선은우방으로편위되었다 (P =.6). 가로축요인 θ는 C REMI 가상승할수록유의한하강을보였으므로곡선중심부의기울기는 C REMI 가높을수록가파른양상을보였다 (Fig. 3) (Table ). 인수별임의효과 b A, b LC5, b θ 의분산은각각.8 5, 3. 5,.6 4 으로매우낮았고,,회자육 Korean J Anesthesiol 을통한재표집의결과를표에기술하였다. 환자-내표준화잔차 (standardized residuals) 는.6% (.63,.5) 로나왔다 (Table 3). 비선형혼합모형의진단을위하여환자개별적합값 (individually fitted) 을실제관찰값 (observed) 에대비하여도식하였고, 가중잔차 (weighted residuals) 를개별적합값에대비하여도식하였다 (Fig. 4). 고찰마취유도중 desflurane의폐포농도에비례적으로 rso 가상승한다. 비례형태는 S자형으로서표준적인 3인수로지스틱농도-반응곡선을잘따르며, PET CO 가낮을수록, remifentanil 농도가높을수록 rso 의상승이억제되었다. 근적외선분광측정기 (near infrared spectroscopy, NIRS) 는비침습적이며조직을투과하거나흡수되는근적외선을이용하여, 산소화된혈색소와탈산소화된혈색소의흡광율의차이로뇌국소조직의산소포화도를나타낸다 []. 여러연구자들이 NIRS를이용하여뇌혈류와 [3-5] 뇌혈량을 [6] 추정 Table. Population Estimates of the Final Model Predicted ΔrSO (%) = A A + e (logp DESF LC 5 )/θ Estimates SE 95% CI P A = A + A (PET CO 4) + A C REMI A A A LC 5 = L + L (PET CO 4) L L θ = θ + θ CREMI θ θ 7..3 5.47.5.3.69.3 3.96..96...4. 9.3, 4.94.,.5 9.67,.7.45,.54.,.4.,.7.56,.8 <..46.6 <...55.87 A, LC 5, and θ model parameters, ΔrSO : increase in regional cerebral oxygen saturation (%) from T (time. min during desflurane induction), PET CO: end-tidal concentration of carbon dioxide (mmhg), C REMI: computer-estimated remifentanil concentration (ng/ml), P DESF: estimated alveolar concentration of desflurane (%). Table 3. Inter-individual Variance Component of Random Effects in the Final Model. Observed and Resampled Estimates from, Replicates of Nonparametric Bootstrapping σ A σ LC5 σ θ Observed.8 5 3. 5.6 4 Resampled Mean SE 95% CI Bias. 5 3.3 4.97 4 4.6 6. 4 8.36 4 4.6 6,.4 5 4.98 5, 9.53 4 7.5 5, 4.8 4 5.77 7.78 5 9.54 6 σ A: inter-individual variance of random effects A, σ LC5 : inter-individual variance of random effects LC 5, σ θ: inter-individual variance of random effects θ. 548
Lee et al:desflurane and rso Fig. 4. Diagnostic plots of the fitted model. Individually fitted changes in cerebral oximetry (ΔrSO ) vs. observed ΔrSO (upper) and weighted residuals vs. individually fitted ΔrSO (lower). Individual fits have a tendency to underestimate the observed ΔrSO (upper), which is resulted from an extreme outlier (lower). 한바있으나아직은임상적유효성을완전하게입증하지는못하였다. rso 는전체가아닌전두엽일부분의산소포화도만을반영할뿐이지만반복적이고지속적인감시가가능하여동적인뇌산소측정에널리사용되고있다 [7]. 뇌관류압과 rso 의상관관계는뇌혈관자동조절능력의상실을민감하게반영하며 [8,9], 뇌관류압과 rso 는확실한연관관계가있고, 외상성뇌손상환자의뇌관류압의감시나침습적인뇌압감시를위한지침으로사용할수있으며 [] 뇌허혈을유발할정도의뇌혈류의변화측정시신뢰도를높여준다 [4]. 본연구에서는 rso 에영향을미칠수있는맥박산소포화도는 99% 이상으로유지하였으며혈색소농도 [,] 또한모두정상범위였으며, 모든측정이마취유도중의단 분동안이루어졌으므로한환자내에서는혈색소농도가변동되지않았음을확신할수있다. 실제분석에서는 rso 의절대값이아닌증가폭을적용함으로써혈색소농도에따른 rso 의환자-간변이를최소화하였다. rso 는뇌혈류의증가를직접적으로나타내지는못하고단지뇌산소요구량과공급량의균형을나타낸다. Desflurane 의폐포농도상승에따른 rso 의상승의의미는명확히밝혀져있지는않지만이는 desflurane에의한뇌혈관의자동조절능력의상실과 [3-5] 그로인한뇌혈류의증가에의하여 rso 가증가한것으로추정된다. 또한이연구의결과에서산출된 PET CO 변화에대한 rso 의반응은, 8% 의 desflurane 마취에서도뇌혈관의이산화탄소반응성이보존되어있음을나타낸다. 이결과는 MAC의 desflurane 마취에서이산화탄소에대한뇌혈관의반응성이잘보존된다는다른연구자들의결과와잘부합된다 [6-8]. Fassoulaki 등은 [9] 항정상태 (steady state) 의 desflurane 마취중에측정한 rso 의증가는 desflurane 폐포농도에비례 하며뇌산소대사율 (CMRO ) 의감소즉, 뇌산소요구량의감소를반영한다고하였다. Desflurane의경우에는폐포농도가동맥농도와평형에도달한뒤에도약 4분에거쳐뇌의 desflurane 섭취가일어난다는보고가있듯이 [] 강제로유지한항정상태에서측정된결과를매일만나는임상상에바로적용하는데에는어려움이있다. 이연구의주요관심사처럼마취유도중에언제나거치게되는비항정상태, 즉 desflurane의폐포농도와동맥농도는평형에도달하였으나뇌세포내의 desflurane 분압은충분히항정상태를이루기전까지의상태에서측정된 rso 이므로임상적가치가더욱높다. 본연구는임상적인마취유도환경을완전히동일하게모사하기위해서항정상태를기다리지않은채급격히증가되는 desflurane의폐포농도에서 rso 를측정하였다. 항정상태와달리저자들의모사한비항정상태에서증가한 rso 는 desflurane에의한뇌산소요구량의감소효과에기인한다기보다는뇌혈관의확장과뇌혈류의증가가뇌산소요구량의감소를상회했기때문에벌어졌을것으로추정하는것이타당하다. 다른아편제제와달리 remifentanil은사람과동물에서뇌산소대사율을감소시키며 [,] 개에게서는대뇌피질, 해마, 꼬리 (caudate) 의뇌혈류를 4 5% 까지감소시킨다 [3]. Propofol과같이사용하면뇌혈류의자동조절능력을보존한다 [4]. 본연구에서낮은폐포농도의 desflurane에서는 remifentanil의농도가높을수록 rso 의증가속도를줄이며높은폐포농도의 desflurane에서는 rso 의최대증가폭을줄였다. 이는 desflurane에의한뇌혈류의자동조절능력손상이 remifentanil 병용에의해완충될수있는가능성을암시하며 sevoflurane과 remifentanil을사용한마취에서뇌혈류의자동조절능력이보존된다고했던과거의연구와일치한다 [5]. 549
Vol. 56, No. 5, May 9 흡입마취제의용량의존적인뇌혈관확장은두개내유순도가감소한환자에서더욱문제가될수있는데, 이럴경우에라도 remifentanil을병용함으로써 desflurane의뇌혈관작용을상쇄할수있음을시사한다. 저자들의결과에서 remifentanil이 rso 의변화에미치는효과가시간을기준으로분석하였을때에는유의하게나타나지않았던점은별도로주목할필요가있다. 이와같은차이점은 desflurane 마취유도중 rso 증가가시간에직접적으로연관된현상이아니라 desflurane 농도에연관된현상이기때문에비롯되었을것이다. 게다가반복측정자료의분석에서통상적으로시행하는반복측정분산분석은단위요인당여러개의관찰값을필요로하므로다양한값으로측정된 desflurane 농도를반복측정분산분석의요인으로적용할수없었다. 이와같은자료에서는비선형회귀모형을적용하는것이필수적이며, 비선형회귀모형은반복측정자료의설명변수와반응변수간의함수관계까지규명할수있으므로추가적인이점이있다. 결론적으로 8% 의 desflurane으로마취를유도할때 rso 는 desflurane의폐포농도에비례적으로 S자형태로상승한다. 상승곡선은표준적인 3인수로지스틱농도-반응곡선을잘따르며, 병용한 remifentanil의농도에의존적으로 rso 의상승폭이감소한다. rso 의이산화탄소반응성은 desflurane 폐포농도와 remifentanil 농도에무관하게잘유지된다. ACKNOWLEDGEMENT Granted by Dongguk University research fund. REFERENCES. Lee Y, Lee JH, Yoon DI, Lee Y, Kim KO, Chung S, et al. Hypocapnia attenuates, and nitrous oxide disturbs the cerebral oximetric response to the rapid introduction of desflurane. J Korean Med Sci ; 5: [in press].. Smith M. Perioperative uses of transcranial perfusion monitoring. Neurosurg Clin N Am 8; 9: 489-5. 3. Elwell CE, Cope M, Edwards AD, Wyatt JS, Delpy DT, Reynolds EO. Quantification of adult cerebral hemodynamics by near-infrared spectroscopy. J Appl Physiol 994; 77: 753-6. 4. Gora F, Shinde S, Elwell CE, Goldstone JC, Cope M, Delpy DT, et al. Noninvasive measurement of cerebral blood flow in adults using near-infrared spectroscopy and indocyanine green: a pilot study. J Neurosurg Anesthesiol ; 4: 8-. 5. Roberts IG, Fallon P, Kirkham FJ, Kirshbom PM, Cooper CE, Elliott MJ, et al. Measurement of cerebral blood flow during cardiopulmonary bypass with near-infrared spectroscopy. J Thorac Cardiovasc Surg 998; 5: 94-. Korean J Anesthesiol 6. Hopton P, Walsh TS, Lee A. Measurement of cerebral blood volume using near-infrared spectroscopy and indocyanine green elimination. J Appl Physiol 999; 87: 98-7. 7. Ndubuizu O, LaManna JC. Brain tissue oxygen concentration measurements. Antioxid Redox Signal 7; 9: 7-9. 8. Brady KM, Lee JK, Kibler KK, Smielewski P, Czosnyka M, Easley RB, et al. Continuous time-domain analysis of cerebrovascular autoregulation using near-infrared spectroscopy. Stroke 7; 38: 88-5. 9. DeWitt DS, Prough DS. Rate of change in brain tissue PO: a novel index of cerebral pressure autoregulation. Crit Care Med 3; 3: 33-3.. Dunham CM, Sosnowski C, Porter JM, Siegal J, Kohli C. Correlation of noninvasive cerebral oximetry with cerebral perfusion in the severe head injured patient: a pilot study. J Trauma ; 5: 4-6.. Lee Y, Lee S, In J, Chung SH, Yon JH. Prediction of plasma hemoglobin concentration by near-infrared spectroscopy. J Korean Med Sci 8; 3: 674-7.. Yoshitani K, Kawaguchi M, Iwata M, Sasaoka N, Inoue S, Kurumatani N, et al. Comparison of changes in jugular venous bulb oxygen saturation and cerebral oxygen saturation during variations of haemoglobin concentration under propofol and sevoflurane anaesthesia. Br J Anaesth 5; 94: 34-6. 3. Bedforth NM, Girling KJ, Skinner HJ, Mahajan RP. Effects of desflurane on cerebral autoregulation. Br J Anaesth ; 87: 93-7. 4. Holmstrom A, Akeson J. Desflurane induces more cerebral vasodilation than isoflurane at the same A-line autoregressive index level. Acta Anaesthesiol Scand 5; 49: 754-8. 5. Strebel S, Lam AM, Matta B, Mayberg TS, Aaslid R, Newell DW. Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia. Anesthesiology 995; 83: 66-76. 6. Lee Y, Kwon T, In J, Woo S, Yon J, Kim J, et al. Reliability of rso to measure CO reactivity of cerebral vasculatures during desflurane-n O anesthesia Korean J Anesthesiol ; 43: 88-93. 7. Luginbuehl IA, Karsli C, Bissonnette B. Cerebrovascular reactivity to carbon dioxide is preserved during hypocapnia in children anesthetized with. MAC, but not with.5 MAC desflurane. Can J Anesth 3; 5: 66-7. 8. Mielck F, Stephan H, Buhre W, Weyland A, Sonntag H. Effects of MAC desflurane on cerebral metabolism, blood flow and carbon dioxide reactivity in humans. Br J Anaesth 998; 8: 55-6. 9. Fassoulaki A, Kaliontzi H, Petropoulos G, Tsaroucha A. The effect of desflurane and sevoflurane on cerebral oximetry under steady-state conditions. Anesth Analg 6; : 83-5.. Lu CC, Tsai CS, Ho ST, Chueng CM, Wang JJ, Wong CS, et al. Pharmacokinetics of desflurane uptake into the brain and body. Anaesthesia 4; 59: 6-.. Pietrini D, Zanghi F, Pusateri A, Tosi F, Pulitano S, Piastra M. Anesthesiological and intensive care considerations in children undergoing extensive cerebral excision procedure for congenital epileptogenic lesions. Childs Nerv Syst 6; : 844-5.. Tipps LB, Coplin WM, Murry KR, Rhoney DH. Safety and feasi- 55
Lee et al:desflurane and rso bility of continuous infusion of remifentanil in the neurosurgical intensive care unit. Neurosurgery ; 46: 596-6. 3. Hoffman WE, Cunningham F, James MK, Baughman VL, Albrecht RF. Effects of remifentanil, a new short-acting opioid, on cerebral blood flow, brain electrical activity, and intracranial pressure in dogs anesthetized with isoflurane and nitrous oxide. Anesthesiology 993; 79: 7-3. 4. Engelhard K, Werner C, Mollenberg O, Kochs E. Effects of remifentanil/propofol in comparison with isoflurane on dynamic cerebrovascular autoregulation in humans. Acta Anaesthesiol Scand ; 45: 97-6. 5. Vavilala MS, Lee LA, Lee M, Graham A, Visco E, Lam AM. Cerebral autoregulation in children during sevoflurane anaesthesia. Br J Anaesth 3; 9: 636-4. 55