Anesth Pain Med 2015; 10: 208-213 http://dx.doi.org/10.17085/apm.2015.10.3.208 임상연구 소아간이식동안수액반응성예측인자 : 수축기와이완기시간변이도와맥압변이도의비교 울산대학교의과대학서울아산병원마취통증의학과, * 강릉아산병원마취통증의학과, 울산대학교병원마취통증의학과 문영진ㆍ이화미 * ㆍ김정원ㆍ정형주ㆍ이수호ㆍ허인영 ㆍ황규삼 A comparison of systolic and diastolic time variation with pulse pressure variation as a predictor of fluid responsiveness during pediatric liver transplantation Young-Jin Moon, Hwa-Mi Lee*, Jung-Won Kim, Hyung-Joo Chung, Sooho Lee, In Young Huh, and Gyu-Sam Hwang Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, *Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea Background: In pediatric patients, dynamic preload indices to predict fluid responsiveness remain controversial. Because each beat of blood pressure (BP) waveform contains evidence of a systolic and diastolic time interval (STI, DTI), we compared pulse pressure variation (PPV) with respiratory STI and DTI variation (STV, DTV) as predictors of fluid responsiveness during pediatric liver transplantation. Methods: A total of 61 datasets from 16 pediatric liver transplant patients (age range one month to seven years), before and after an inferior vena cava clamp was applied, were retrospectively evaluated from electronically archived BP and central venous pressure (CVP) waveforms. STI and DTI were separated by a beat-to-beat blood pressure waveform. STV, DTV and PPV were Received: March 19, 2015. Revised: 1st, April 8, 2015; 2nd, April 17, 2015. Accepted: May 7, 2015. Corresponding author: In Young Huh, M.D., Ph.D., Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, 877, Bangeojinsunhwando-ro, Dong-gu, Ulsan 682-714, Korea. Tel: 82-2-250-7246, Fax: 82-2-250-7249, E-mail: inyoung_huh@uuh.ulsan.kr 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. calculated by averaging three consecutive respiratory cycles. Averaged CVP was used as a static preload index. A PPV threshold of 16%, a known cutoff value in pediatric surgery, was used to discriminate fluid responsiveness in the receiver operating characteristic (ROC) curve analysis. Results: PPV showed correlations with STV and DTV (r = 0.65 and 0.57, P < 0.001, respectively), but not with CVP (r = 0.30, P = 0.079). The area under the ROC curves (AUC) of STV, DTV and CVP were 0.834, 0.872, and 0.613, respectively. Cut-off values of STV and DTV were 7.7% (sensitivity/specificity, 0.80/0.83) and 7.7% (sensitivity/specificity, 0.70/0.88), respectively. Conclusions: This study demonstrates that STV and DTV from a BP waveform showed the potential to predict fluid responsiveness as a surrogate of PPV during pediatric surgery. (Anesth Pain Med 2015; 10: 208-213) Key Words: Children, Fluid responsiveness, Liver transplantation, Systolic time interval. 서 적절한혈관내용적을평가하는것은마취영역에서중요하지만어려운일중하나이다. 이를위해서주로혈관내용적을증가시켜이에대한반응을봄으로써용적상태를파악하는방법이사용된다. 성인에서는이런수액반응성 (fluid responsiveness) 에대한많은연구를통해유용한인자 (index) 들이알려져있다 [1]. 하지만소아환자의경우, 이러한인자들의용적반응성의결과는다양하게나타난다고보고되고있다 [2-6]. 특히, 동맥파형을기초로하는역동적인자 (dynamic variable) 들은용적반응성을예측하지못하는것으로나타났다 [5,6]. 하지만최근연구에서선천성심장질환을가진소아환자에서수술전후에정적 (static) 인자나역동적인자중에서맥압변이도 (pulse pressure variation, PPV) 는가장정확하게수액반응성을예측할수있다고보고하였다 [2,7]. 수축기시간간격 (systolic time interval, STI) 는좌심실의수축기간을의미하며, 심박수, 일회박출량및좌심실기능등여러인자들과관련성이있다 [8,9]. 일회의호흡주기동 론 208
문영진외 6 인 :Respiratory variation of systolic time 209 안좌심실기능이나심박수는큰변화가없을것으로생각할수있으므로, 호흡에의한 STI의변화는일회박출량의변화와관련성을가진다 [10,11]. 이완기시간간격 (diastolic time interval, DTI) 는이완기의충만 (diastolic filling) 으로써대변되며이는전부하와관련성을가지고있다 [12]. 맥파전달시간 (Pulse transit time, PTT) 은좌심실의탈분극의시작부터좌심실의박출의시작하는시간을의미하며, 심실의전부하을반영한다 [13]. 기계환기를시행받는성인환자에서 PTT의호흡에의한변화도역시수액반응성을예측할수있다고보고되고있다 [14]. 이에저자들은소아간이식을시행받는환자에서혈역학적변화가가장심한시기인하대정맥 (inferior vena cava) 결찰전후에동맥압파형에서 STI, DTI, PTT를추출하여호흡의변화에따른그인자들의변화정도가 PPV와비교하여수액반응성을예측할수있는지보고자하였다. 대상및방법이연구는병원 IRB 승인후에 2007년부터 2011년사이간이식을시행받는소아환자의혈역학적데이터를후향적으로연구하였다. 대상환자중기록자체가불완전하거나동맥파형의이상이있는경우, 수술중부정맥이있는경우, 전기소작등에의한잡음이심한경우등은제외하였다. 이기간소아간이식이진행된총환아 31명중 16명이대상이되었다. 소아간이식마취는본원에서시행되는통상적인방법에의해시행되었다. 간략하게설명하면, 기본적인혈역학적감시를시행한후 thiopental sodium 2 3 mg/kg와 fentanyl 0.5 1 μg/kg 투여후, vercuronium bromide 0.1 mg/kg로근이완후기관내삽관을시행하였다. 마취유지는 sevoflurane 1 2 vol%, fentanyl 3 5 μg/kg/hr로지속주입하였다. 기계환기는일회호흡량 8 10 ml/kg로하여 ETCO 2 35 40 mmhg 사이를유지할정도의호흡수를조정하였다. 마취유도후에우측요골동맥에동맥관을, 초음파를이용하여우측내정정맥에중심정맥관을거치하였다. 모든환자는컴퓨터기반의데이터모집프로그램인 WINDAQ TM (DI-720U, DATAQ Instruments, Inc., Akron, OH, USA) 을이용하여심전도, 동맥압과중심정맥압의박동대박동 (beat-to-beat) 파형을지속적으로기록하였다. 간이식마취기간동안에는하대정맥결찰전과후에환자의혈량상태에큰차이가발생하므로저자들은마취기간동안기록되었던데이터에서하대정맥결찰전후의데이터를선택하였다. 이선택된데이터에서적어도 10분이상떨어진시점에서 3회호흡주기의데이터를각환자에서결찰전, 결찰후각각 2개씩얻었다. 각환아에서총 4번의데이터를수집하였으며, 총 64개의데이터중부적당한 3개의데이터는추가로제외하였다. 저자들은동맥파형의수축기상승 (upstroke) 시작부분 ( 대동맥판막이열리고혈류가요골동맥에도착하기시작한시점 ) 에서중복맥 (dicrotic notch, 대동맥판막이닫히는시점 )) 까지의시간을 STI로, 이완기에해당되는 DTI는중복맥에서다음박동의수축기상승시작시점까지로정의하였다 (Fig. 1). 심전도상의 R 파형의정점에서동맥파형의수축기상승부의시작시점까지를 PTT로정의하였다. 심전도의 R파형의정점간의간격을심간격 (cardiac period) 으로정의하였다. 각호흡주기의최대및최소의맥압 (pulse pressure, PP), STI, DTI와 PTT를측정하였다 (PPmax, PPmin, STImax, STImin, DTImax, DTImin, PTTmax, PTTmin). 호흡에따른맥압변이도 (Pulse pressure variation, PPV), 수축기시간변이도 (systolic time variation, STV), 이완기시간변이도 (diastolic time variation, DTV) 및맥파전달시간변이도 (pulse transit time variation, PTTV) 는아래공식을통하여계산하였다. PPV (%) = 100 (PPmax PPmin)/[(PPmax + PPmin)/2] STV (%) = 100 (STImax STImin)/[(STImax + STImin)/2] DTV (%) = 100 (DTImax DTImin)/[(DTImax + DTImin)/2] PTTV (%) = 100 (PTTmax PTTmin)/[(PTTmax + PTTmin)/2] Fig. 1. Schematic illustration of systolic time interval (STI), diastolic time interval (DTI) and pulse transit time (PTT).
210 Anesth Pain Med Vol. 10, No. 3, 2015 STV, DTV와 PTTV는심박수의영향을받으므로각값을해당 RR간격으로나누어서심박수의영향을최소하는과정을거쳤다. PPV, STV, DTV, PTTV와중심정맥압 (CVP) 은 3 회호흡주기동안의값을평균하여사용하였다. 61번의측정된 PPV값각각을 16% 를기준으로두군으로나누었다. PPV 16% 는소아의선천성심장질환의수술적치료전후에수액반응성을예측할수있는인자였다는보고에기초하였다 [7]. 모든값은평균 ± 표준편차로기술하였다. 결찰전후 PPV 값등혈역학적변수의변화는정규분포를따르기때문에 paired t-test, PPV 16% 를기준으로두군간차이는정규분포를따르지않아 Mann-Whitney U test를이용하였다. PPV, STV, DTV, PTTV와 CVP 사이에서 Pearson s correlation coefficient를이용하여상관관계를보았다. PPV 16% 를예측할수있는 STV, DTV, PTTV 및 CVP의 cut off 값을결정하기위해 Receiver operating characteristic (ROC) curve 와 area under the curve (AUC) 를사용하였다. 통계적방법은 MedCalc 10.0.1.0 (MedCalc Inc., Mariakerke, Belgium) 를이용하였다. P < 0.05를통계적으로유의하다고판정하였다. 결 대상이된 16명의환아의나이는평균 8.5개월 (1개월부터 7세 ), 남아와여아는각각 8명이었다. 간이식을시행받는진단명은 biliary atresia가 8명이었고 Child score는 10.3 ± 2.2, pediatric End-stage liver disease (PELD) 20.7 ± 10.1이었다. 인구학적데이터는 Table 1에기술하였다. 대정맥결찰전후의값을평균하여비교하였을때 PPV값은결찰전후각각 10.5 ± 5.9, 14.9 ± 5.8로의미있는변화를보였다. 2명의환아는대정맥결찰전후지속적으로 PPV가 16% 이상이었고, 2명의환아는결찰후 PPV 평균값이감소하였다 ( 환아 1: 8.0 7.7, 환아 2: 15.1 13.4). Table 1. Patients Characteristics Characteristics Male/female 8/8 Age (months) 8.5 ± 24.7 (0.8 84) Weight (kg) 9.7 ± 5.9 Height (cm) 74.2 ± 24.7 Diagnosis (biliary atresia/unknown/others) 8/6/2 CTP grade (A/B/C) 1/8/7 CTP score 10.3 ± 2.2 PELD score 20.7 ± 10.1 Values represent number of patients or mean ± SD (range). CTP: Child-Turcotte-Pugh, PELD: Pediatric End-Stage Liver Disease. 과 PPV 16% 미만 (n = 41) 과 16% 이상 (n = 20) 으로나누어진두군에서 CVP는양군간에차이를보이지않았지만, PPV, STV, DTV와 PTTV는양군간에유의한차이를보였다 (Table 2). PPV는 STV (r = 0.65, P < 0.001), DTV (r = 0.57, P < 0.001) 및 PTTV (r = 0.60, P < 0.001)) 와상관관계를보였으나, CVP (r = 0.30, P = 0.079) 는상관관계를보이지않았다 (Fig. 2). ROC curve을통한분석에서 STV, DTV와 PTTV는소아간이식환자에서 PPV > 16% 를예측할수있는것으로나타났다. 각각의 AUC는 0.834 (95% confidence interval 0.708 0.918, P < 0.001), 0.872 (95% confidence interval 0.691 0.904, P < 0.001), 0.832 (95% confidence interval 0.657 0.885, P < 0.001) 이었다 (Fig. 3). PPV 16% 를예측하는각각의 cut-off 값은 STV 7.7% (80% sensitivity, 83% specificity), DTV 7.7% (70% sensitivity, 88% specificity), PTTV 8.7% (67% sensitivity, 100% specificity) 이었다 (Table 3). 고 소아환자에서수액반응성과관련있다고알려진 PPV 16% 을예측할수있는인자를조사한본연구에서 STV, DTV와 PTTV가 PPV 16% 를예측할수있었다. 따라서기계환기를시행받는환아에서동맥파형에서유추할수있는 STV, DTV와 PTTV가수액반응성을예측할수있는유용한인자로여겨진다. 하지만정적인자인 CVP는 PPV 16% 를예측하지는못하였다. 마취중적절한혈량상태의유지는혈역학적안정성과밀접한관련을가지며, 이를유지하는것은마취통증의학과의사에게중요한일이다. 성인의경우 PPV를포함한다양한인자들이수액반응성을예측한다고보고되었으나 [1], 소아환자의경우각인자에대한연구결과가다양하며아직유용한인자가제한되어있다 [2-7]. 즉 CVP를포함한정적인자는성인과마찬가지로소아에서도수액반응성을 Table 2. Comparison of Hemodynamic Variables for Each Group PPV 16% (N = 20) PPV < 16% (N = 41) P value PPV (%) 20.8 ± 3.3 10.1 ± 3.4 < 0.0001 STV (%) 9.4 ± 3.2 5.5 ± 1.9 < 0.0001 DTV (%) 8.3 ± 3.5 5.5 ± 1.7 < 0.0001 PTTV (%) 10.1 ± 2.3 7.8 ± 2.6 < 0.0001 CVP (mmhg) 4.5 ± 6.7 5.7 ± 2.1 0.533 Values represent mean ± SD. PPV: pulse pressure variation, STV: systolic time variation, DTV: diastolic time variation, PTTV: pulse transit time variation, CVP: central venous pressure. 찰
문영진외 6 인 :Respiratory variation of systolic time 211 Fig. 2. Scatter diagram with linear regression line between systolic time variation (STV), diastolic time variation (DTV), pulse transit time variation (PTTV), central venous pressure (CVP) and pulse pressure variation (PPV). Fig. 3. Receiver operating characteristic (ROC) curves for systolic time variation (STV), diastolic time variation (DTV), pulse transit time variation (PTTV) and central venous pressure (CVP) as predictors for pulse pressure variation (PPV) 16%. 예측할수없으나, 동맥파형에서유래하는여러역동적인자인수축기압변이도 (systolic pressure variation) 나일회박출량변이도 (stroke volume variation) 등은소아의수액반응성예측에서다양한결과를보인다 [2-4,6,7]. 성인과다른결과를보이는이유로는소아가성인에비해혈관확장성이좋으며, 심근의유순도가낮고, 심박수가빠르고, 낮은평균 압과맥압등이영향을미친것으로사료된다 [2,15]. 본연구에서사용된 PPV의경우도소아환자에서연구자에따라결과에차이가있다 [2,7]. 그러나, Renner 등의 [7] 결과에서유래된 PPV 16% 값을본연구에서사용한이유는비슷한연령대이며, 좌-우단락이있는심장질환을가진환자에서특히수술후더좋은 AUC, 특이성및민감성을보이므로이값을사용하였다. 본연구에서 PPV는대정맥결찰전후 PPV값이유의하게증가되었고, 두명의환아를제외하고 PPV는대정맥결찰후에증가되었다. 대정맥결찰후 PPV값이감소한이유에대해서는추가연구가필요할것으로생각되나다른환아에비해변화정도는크지않았다 (39.1% 증가, 환아 1: 8.0 7.7, 환아 2: 15.1 13.4). 그러므로 PPV가간이식을시행받는소아환자에서전부하와연관성을가지고있다고여겨진다. STI은심실의전기적자극이시작되는시점에서기계적으로대동맥판막이닫히는시점으로, 좌심실구혈전기 (preejection period, PEP), 박출시간 (ejection time, ET) 와 PEP/ET비를포함하고있다 [11,16]. 본연구에서는말초동맥인요골동맥파형에서좌심실의박출시점에서대동맥판막이닫히는중복맥까지의시간을 STI로정의하였고, 동맥파형의전체시간 (interbeat time) 에서 STI를제외한시점을 DTI로정의하였다. 즉기존연구에서정의된수축기시간대신저자들은마취과영역에서흔히접할수있는동맥파형에서대동맥
212 Anesth Pain Med Vol. 10, No. 3, 2015 Table 3. Values of ROC Curve Analysis for Predicting PPV 16% AUC 95% CI Sensitivity Specificity Cut-off value P value STV 0.834 0.708 0.918 0.80 0.83 7.7 < 0.001 DTV 0.872 0.691 0.904 0.70 0.88 7.7 < 0.001 PTTV 0.832 0.657 0.885 0.67 1.00 8.7 < 0.001 CVP 0.613 0.469 0.751 0.50 0.85 3.1 0.527 ROC: receiver operating characteristic, PPV: pulse pressure variation, STV: systolic time variation, DTV: diastolic time variation, PTTV: pulse transit time variation, CVP: central venous pressure (mmhg), AUC: area under the ROC curve. 95% CI: 95% confidence interval. 판막이열리고혈류가말초혈관에도달하는부분이동맥파형의상승기에해당되며박출이진행되고대동맥판막이닫히는시점은동맥파형에서중복맥과상응하므로이를본연구에서수축기시간으로정의하였다. STI는심박수, 말초혈관저항, 심장의충만정도, 동맥의순응도, 대동맥판막의질환이나심박출량과관련성을가진다 [8-11,16]. STI는정상이나질병상태의심장에서사용되는약제에대한반응성등을볼수있는방법으로써연구에주로사용되었다 [11,16]. DTI는일회심장주기에서 STI를제외한시점으로, 심박수나심근의수축기의변화에영향을받는다. 이완기시간은관상동맥의관류와밀접한관련을가지고있으며, 이완기충만정도와연관성이있다 [12]. 두인자모두심박수에의한영향을받으므로 [10], 심박수에의한영향을최소화하기위해본연구에서 RR간격으로나눈값을사용하였다. 따라서, 말초혈관의동맥파형에서얻어지는 STI와 DTI는마취과영역에서쉽게얻을수있는인자로써임상적유용성이있을것으로생각된다. 하지만아직 STV와 DTV를혈량상태와관련된연구에사용한예는없었다. 본연구에서소아환자에서 Renner 등이 [7] 보고한유아에서수액반응성을예측한다고알려진 PPV 16% 를 STV와 DTV가잘예측하는것으로나타났다. 따라서 STV와 DTV는일회호흡주기에서다른인자보다는전부하의변화와관련성이있을것으로사료되며, 본연구에서 STV와 DTV는 PPV 16% 을예측하는것으로나타났다. PTT는심전도의 R파형에서말초혈관에도착하는시간으로동맥관의강직도 (arterial stiffness) 나심박출량과같은심혈관의반응성을반영하는인자로알려져있고동맥압에대한감시자로써유용하다 [13,17]. PTT가심실의전기적활동도가나타나고난후심실의실제박출이일어나는시점의연기가존재하며, 이전기기계적연기 (electromechanical delay) 는 PEP와관련되어있다 [18,19]. Bendjelid 등은 [14] 심장수술후기계환기를시행받는환자에서호흡에의한 PEP의변화가환자의수액반응성을예측할수있다고보고하였다. 그러므로 PTTV는수액반응성을예측할수있는유용한인자로여겨지며, 본연구에서도 PTTV는소아환자에서유용한수액반응성의예측지표로써나타났다. 중심 정맥압은정적인자로써본연구에서도다른연구와비슷하게수액반응성을예측하지는못하였다 [1,6]. 본연구는여러제한점을가지고있다. 첫째로, 대상환자에서수액반응성을예측하기위해 PPV 16% 를기준점으로정하였지만, 여러연구에서소아환자에서 PPV는수액반응성을예측하는데유용하지않다고보고되고있다 [2,6]. 그이유로소아가성인에비해동맥의탄성도가크며, 혈관의탄성도가큰경우호흡에의한혈압의변화정도가작게된다 [6,15]. 소아환자에서수액반응성을예측하는인자에대한체계적재검토에서호흡에의한대동맥혈류의최대속도의변화 (deltap peak) 가수액반응성을예측하는데있어서가장일관적이라고보고하였고, 이는혈압이나혈량측정법 (plethysmography) 에기초한인자와달리동맥의유순도나긴장도의변화에영향을받지않고혈류를직접측정하는방법이기때문인것으로추정하였다 [6]. 그러므로, 일회박출량의변화나 deltap peak 과같은다른인자와 STV, DTV 및 PTTV과의관계에대한평가가추가로필요할것으로생각된다. 두번째제한점은본연구에서 STI, DTI와 PTT가요골동맥파형에서측정하였고, 이자체는실제심장주기를반영하지않는다. 동맥파형에여러인자들이영향을미치며특히혈관의유순도는나이에따라빠른변화를보이므로 [15], 본연구와같이연령의범위가큰경우 (SD 24.7개월, 0.8개월 7세) 결과에영향을미쳤을것으로생각된다. 또한동맥압측정변환기나연결관의길이나순응도등도동맥파형에영향을주었을것으로여겨지며이에의한잡음이나파형변화여부에대해서도충분히고려할필요가있을것으로여겨진다. 비슷한연령대를대상으로하는추가연구가더필요할것으로사료된다. 세번째는연구가후향적으로진행되었고, 대상환아 31명에서 16명의환아가선택되었고, 총 64개의데이터에서 3개의데이터를다시제외되었다. 요골동맥파형의중복맥이명확하지못하거나전기소작기사용등에따른잡음으로인해 STI, DTI, 및 PTT의측정이어려운경우에연구에영향을미치므로제외비율이높았던것으로생각된다. 특히중복맥은혈관의저항과같은혈관상태나환자의혈역학적인자등에영향을받으므로이런부분에대한고려가필요할것으
문영진외 6 인 :Respiratory variation of systolic time 213 로생각된다. 넷째로 PPV를포함한데이터가한환자에서대정맥결찰전후각각 2회씩총 4회반복측정에의해나타난결과이므로, 이결과에대한해석에주의가필요할것으로여겨진다. 또한간이식이란특수한상황에서 STV, DTV, PTTV와 PVV의관계를다른소아환자에게확대하여적용하기위해서는추가연구가필요할것으로생각되며, 본연구는실제로수액을투여한연구가아니므로향후이에대한추가연구가필요할것으로사료된다. 결론적으로 STV, DTV, 및 PTTV가소아간이식환자에서수액반응성을예측하는유용한인자로여겨진다. 또한마취통증의학과의사가흔히접할수있는말초동맥파형에서 STI와 DTI 인자를얻어내는첫연구로써소아마취영역에서용이하게사용될수있을것으로생각된다. REFERENCES 1. Kwak YL. Monitoring for fluid management: dynamic guide and fluid responsiveness. Anesth Pain Med 2013; 8: 1-8. 2. Byon HJ, Lim CW, Lee JH, Park YH, Kim HS, Kim CS, et al. Prediction of fluid responsiveness in mechanically ventilated children undergoing neurosurgery. Br J Anaesth 2013; 110: 586-91. 3. Choi DY, Kwak HJ, Park HY, Kim YB, Choi CH, Lee JY. Respiratory variation in aortic blood flow velocity as a predictor of fluid responsiveness in children after repair of ventricular septal defect. Pediatr Cardiol 2010; 31: 1166-70. 4. Julien F, Hilly J, Sallah TB, Skhiri A, Michelet D, Brasher C, et al. Plethysmographic variability index (PVI) accuracy in predicting fluid responsiveness in anesthetized children. Paediatr Anaesth 2013; 23: 536-46. 5. Tran H, Froese N, Dumont G, Lim J, Ansermino JM. Variation in blood pressure as a guide to volume loading in children following cardiopulmonary bypass. J Clin Monit Comput 2007; 21: 1-6. 6. Gan H, Cannesson M, Chandler JR, Ansermino JM. Predicting fluid responsiveness in children: a systematic review. Anesth Analg 2013; 117: 1380-92. 7. Renner J, Broch O, Duetschke P, Scheewe J, Hocker J, Moseby M, et al. Prediction of fluid responsiveness in infants and neonates undergoing congenital heart surgery. Br J Anaesth 2012; 108: 108-15. 8. Cybulski G, Michalak E, Kozluk E, Piatkowska A, Niewiadomski W. Stroke volume and systolic time intervals: beat-to-beat comparison between echocardiography and ambulatory impedance cardiography in supine and tilted positions. Med Biol Eng Comput 2004; 42: 707-11. 9. Cheng HM, Yu WC, Sung SH, Wang KL, Chuang SY, Chen CH. Usefulness of systolic time intervals in the identification of abnormal ventriculo-arterial coupling in stable heart failure patients. Eur J Heart Fail 2008; 10: 1192-200. 10. Oh JK, Tajik J. The return of cardiac time intervals: the phoenix is rising. J Am Coll Cardiol 2003; 42: 1471-4. 11. Hamada M, Hiwada K, Kokubu T. Clinical significance of systolic time intervals in hypertensive patients. Eur Heart J 1990; 11 Suppl I: 105-13. 12. Boudoulas H, Rittgers SE, Lewis RP, Leier CV, Weissler AM. Changes in diastolic time with various pharmacologic agents: implication for myocardial perfusion. Circulation 1979; 60: 164-9. 13. Smith RP, Argod J, Pepin JL, Levy PA. Pulse transit time: an appraisal of potential clinical applications. Thorax 1999; 54: 452-7. 14. Bendjelid K, Suter PM, Romand JA. The respiratory change in preejection period: a new method to predict fluid responsiveness. J Appl Physiol (1985) 2004; 96: 337-42. 15. Avolio AP, Chen SG, Wang RP, Zhang CL, Li MF, O'Rourke MF. Effects of aging on changing arterial compliance and left ventricular load in a northern Chinese urban community. Circulation 1983; 68: 50-8. 16. Boudoulas H. Systolic time intervals. Eur Herat J 1990; 11 Suppl I: 93-104. 17. Naschitz JE, Bezobchuk S, Mussafia-Priselac R, Sundick S, Dreyfuss D, Khorshidi I, et al. Pulse transit time by R-wave-gated infrared photoplethysmography: review of the literature and personal experience. J Clin Monit Comput 2004; 18: 333-42. 18. Payne RA, Symeonides CN, Webb DJ, Maxwell SR. Pulse transit time measured from the ECG: an unreliable marker of beat-to-beat blood pressure. J Appl Physiol (1985) 2006; 100: 136-41. 19. Middleton PM, Chan GS, O'Lone E, Steel E, Carroll R, Celler BG, et al. Changes in left ventricular ejection time and pulse transit time derived from finger photoplethysmogram and electrocardiogram during moderate haemorrhage. Clin Physiol Funct Imaging 2009; 29: 163-9.