Eur J Anaesthesiol 2015; 32:5–12
ORIGINAL ARTICLE
Calibrated versus uncalibrated arterial pressure waveform analysis in monitoring cardiac output with transpulmonary thermodilution in patients with severe sepsis and septic shock An observational study Cornelis Slagt, Mochamat Helmi, Ignacio Malagon and A.B. Johan Groeneveld BACKGROUND Cardiac output (CO) measurement is often required in critically ill patients. The performances of newer, less invasive techniques require evaluation in patients with severe sepsis and septic shock. OBJECTIVES To compare calibrated arterial pressure waveform analysis-derived CO (COap, VolumeView/EV1000) and the uncalibrated form (COfv, FloTrac/Vigileo) with transpulmonary thermodilution derived CO (COtptd). DESIGN A prospective, observational, single-centre study. SETTING ICU of a general teaching hospital. PATIENTS Twenty consecutive patients with severe sepsis or septic shock requiring haemodynamic monitoring by VolumeView/EV1000 and receiving mechanical ventilation. INTERVENTION Connection of FloTrac/Vigileo to radial artery catheter already in situ. MAIN OUTCOME MEASURES Radial (COfv) and femoral (COap) arterial waveform-derived CO measurements were compared with COtptd with respect to bias, precision, limits of agreement and percentage error, and the percentage error in the course of time since the last calibration of COap by COtptd.
RESULTS In comparing COap with COtptd (n ¼ 267 paired measurements), the bias was 0.02 and limits of agreement were 2.49 to 2.52 l min1, with a percentage error of 31%. The percentage error between COap and COtptd remained less than 30% until 8 h after calibration. In comparing COfv with COtptd (n ¼ 301), the bias was 0.86 l min1 and limits of agreement were 4.48 to 2.77 l min1, with a percentage error of 48%. The biases of COap and COfv correlated with systemic vascular resistance [r ¼ 0.13 (P ¼ 0.029) and r ¼ 0.42 (P < 0.001), respectively]. Clinically significant changes in COap and COfv correlated positively with COtptd at r ¼ 0.51 (P < 0.001) and r ¼ 0.64 (P < 0.001), respectively. CONCLUSION There was moderate agreement when measuring CO with either arterial waveform analysis technique. Compared with the uncalibrated COfv, the recently introduced calibrated arterial pressure waveform analysisderived COap was more accurate and less dependent on vascular tone for up to 8 hours after callibation when monitoring CO in patients with severe sepsis and septic shock. The COap and COfv methods have poor to moderate CO-tracking abilities. Published online 9 November 2014
This article is accompanied by the following Invited Commentary: Crossingham I, Columb M. Moderate agreement for cardiac output monitors. Moderately good or moderately bad? Eur J Anaesthesiol 2015; 32:1–2.
From the Department of Anesthesiology and Intensive Care, Zaans Medical Centre, Zaandam (CS), Department of Intensive Care, Erasmus Medical Centre, Rotterdam, The Netherlands (MH, ABJG), NIHR Respiratory and Allergy Clinical Research Facility, University Hospital South Manchester NHS Foundation Trust, Manchester, UK (IM) Correspondence to Cornelis Slagt, MD, PhD, Department of Anaesthesiology and Intensive Care, Zaans Medical Centre, Koningin Julianaplein 58, 1502 DV Zaandam, The Netherlands Tel: +31756507359; fax: +31756501929; e-mail: [email protected] 0265-0215 ß 2014 Copyright European Society of Anaesthesiology
DOI:10.1097/EJA.0000000000000173
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
6 Slagt et al.
Introduction The VolumeView/EV1000 (Edwards Lifesciences, Irvine, California, USA) is a new transpulmonary thermodilution (TPTD) device that has recently been introduced to monitor cardiac output (CO). It utilizes TPTD to calculate CO (COtptd) and, using this result, calibrates the system which estimates cardiac output from the arterial pressure waveform (COap). Thereafter, arterial pressure waveform analysis is used to estimate continuous CO (CCO), similar to the technique embedded in the FloTrac/Vigileo (Edwards Lifesciences) monitor (COfv). With each TPTD measurement, the COap is recalibrated.1 There is a single validation study in relatively haemodynamically stable patients, suggesting that COap is as accurate as the TPTD reference and superior to pulse contour-derived (PiCCO2; Pulsion Medical Systems, Munich, Germany).1 Both techniques (PiCCO2 and VolumeView) use TPTD with the Stewart-Hamilton equation to calculate CO. We previously suggested2,3 that even with the most recent third-generation FloTrac/Vigileo software, the calculated (uncalibrated) CO is still too inaccurate in vasodilated and septic patients to allow for clinically meaningful CO monitoring and therapeutic decision making. The aim of the current prospective, observational, singlecentre study was to compare calibrated COap and uncalibrated COfv with COtptd in critically ill patients with severe sepsis or septic shock in the ICU. We hypothesised that calibrated would outperform uncalibrated CO measurement in this setting.
arterial cannula already in situ and then connected to the Vigileo monitor. After placement of the TPTD catheter (VolumeView/EV1000 system; Edwards Lifescience) in the femoral artery, all time clocks from the Spacelab monitor (Spacelabs Medical Inc, Issaquah, Washington, USA), VolumeView/EV1000 and FloTrac/Vigileo monitors were synchronised. The TPTD measurement was performed in sets of three to five bolus injections of 20 ml iced isotonic saline through the central venous catheter irrespective of the ventilator cycle. All individual bolus measurements had to be validated before being averaged. The mean value was recorded and regarded as the COtptd. At the start of each TPTD CO measurement, the COfv was measured and the mean value was recorded. All haemodynamic data stored in the EV1000 computer and FloTrac/Vigileo monitor were downloaded for analysis. All paired COap and COtptd measurements were also analysed in relation to the time after the last calibration to establish the calibration- free period in which COap remains clinically acceptable with a percentage error less than 30%.4 The mean arterial pressure (MAP) was monitored using the femoral arterial catheter and the central venous pressure (CVP) from a central venous catheter (internal jugular or subclavian vein), inserted for clinical reasons. The systemic vascular resistance (SVRtptd) was calculated from (MAP - CVP) x 80/COtptd, dyne s cm5. The electrocardiogram was monitored throughout and heart rate (HR) was recorded.
Materials and methods
Description of techniques
After Medical Ethics Review Committee approval (Ethics Committee, Noord-Holland, Alkmaar, The Netherlands No. M011-019; 26 April 2011) and written informed consent, 20 consecutive patients were included in this observational study. All patients with severe sepsis or septic shock (as defined by the American College of Chest Physicians/Society of Critical Care Medicine consensus conference) requiring vasoactive therapy along with monitoring of CO, radial arterial pressure and central venous pressure (CVP) were eligible for this study. Additional inclusion criteria that had to be met were the use of norepinephrine, organ failure and mechanical ventilation. The study was performed in the ICU of a general teaching hospital from June 2011 to April 2013. Exclusion criteria were age less than 18 years, contraindications for a femoral artery catheter and known severe tricuspid or aortic valvular regurgitation. The study did not otherwise alter the standard of care provided.
The TPTD measurement using the VolumeView/ EV1000 system uses a bolus injection through a central venous catheter situated above the diaphragm and a femoral arterial catheter with a specific thermistor tip subsequently measures the thermodilution curve. This method provides CO measurements as well as volumetric indices such as global end-diastolic volume (GEDV), intrathoracic blood volume (ITBV), extravascular lung water (EVLW), global ejection fraction and pulmonary vascular permeability index.5 The CO is estimated from the bolus TPTD measurements using the Stewart– Hamilton equation.1 For the CCO measurements, the VolumeView/EV1000 monitor combines the area under the systolic part of the arterial pressure waveform and waveform analysis as used in the FloTrac/Vigileo system. The exact method of how both algorithms are integrated into the COap measurement has not been disclosed at this time. After each intermittent bolus TPTD measurement, the COap is recalibrated.1
Protocol
The FloTrac/Vigileo system estimates CO by using the standard deviation of the pulse pressure, incorporating actual vascular tone based on waveform analysis and patient characteristics.6 The arterial waveform is analysed over 20 s with a frequency of 100 Hz. The thirdgeneration software version (3.02) includes two separate
Patient characteristics were recorded, including disease severity scores. Paired CO measurements were performed as clinically required, at least once every shift and with any changes to therapy with fluids and vasoactive agents. A FloTrac sensor was connected to the 20-guage radial
Eur J Anaesthesiol 2015; 32:5–12 Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
Less invasive versus invasive cardiac output in sepsis 7
Table 1
Patient characteristics at ICU admission
Age (years) Sex (male/female) Weight (kg) Height (cm) Cause of sepsis Pneumonia Abdominal Urogenital Others APACHE II score SAPS II Length of ICU stay (days) Mortality at 28 days
63.3 (11) 16/4 88.6 (22) 178.1 (7) 9 8 1 2 31.0 (8) 58.3 (17) 15 (6 to 46) 4/20
Data are displayed as mean (SD), number (%) or median (range) as appropriate. APACHE, acute physiology and chronic health evaluation; SAPS, simplified acute physiology score.
models for the arterial tone factor: first, an arterial tone model that was developed predominantly from patients who did not have a hyperdynamic circulation (this is the same model used in the previous version 1.10); and second, an arterial tone model that was developed predominantly from patients who had a hyperdynamic circulation. The need for using two separate models is because of the differences in relating peripheral arterial pressure to flow during nonhyperdynamic and hyperdynamic circulations.7 The switching between the two models is automated using an algorithm that analyses 14 parameters of the arterial pressure waveform to detect the occurrence of hyperdynamic circulation. Statistical analyses
After confirming normal distribution of data using the Kolmogorov–Smirnov test, data were pooled and Table 2
summarised as mean (SD) and parametric analyses were performed. Pearson correlation coefficients of pooled data were estimated using Statistical Package for Social Sciences (SPSS) version 21 (SPSS Inc, Chicago, Illinois, USA). To assess agreement, a Bland-Altman analysis8 was performed and adjusted for repeated measurements (Medcalc software version 12.2.1.0; Mariakerke, Belgium). Bias was defined as the mean difference between CO derived from two methods. Limits of agreement were calculated from 1.96 SD of the bias. The percentage error (1.96 SD/mean CO) was calculated with 30% taken as clinically acceptable.9 The precision of the reference COtptd was calculated using the method proposed by Cecconi et al.4 to calculate the precision of the test methods. Polar plots (SigmaPlot software version 11, San Jose, California, USA) were also used to analyse the agreement in CO trend monitoring between methods.10 In the polar plot, the changes of CO data are converted to a radial vector wherein the degree of agreement between two devices becomes the angle between radial vector and horizontal axis (i.e. the polar axis). If agreement is perfect, the radial vector lies along the polar axis and the angle is zero; the angle between the vector and the horizontal axis represents disagreement. Agreement for trending is acceptable when points lie between either 1508 and 2108 or 308 and 3308. The distance from the centre of the plot (vector) represents the mean changes in CO. Concordances of clinically significant changes in CO measurements are reported. As COap is recalibrated with COtptd, we analysed the effect of time on the difference between the two methods. A P value less than 0.05 was considered statistically significant.
Haemodynamic data at enrollment and drugs used during the study
N
COtptd
COfv
SVR
GEDI
ITBI
ELWI
HR
MAP
CVP
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
12.6 5.2 9.0 9.6 11.1 7.7 9.7 9.4 5.1 7.7 9.5 10.0 6.8 5.0 7.3 8.9 8.3 7.9 9.4 4.2
9.4 6.3 4.4 5.2 7.0 7.3 11.9 5.8 3.3 4.5 9.5 11.3 6.2 5.2 4.9 8.7 9.6 6.7 13.1 5.6
196 1078 418 483 438 636 452 638 1070 1133 406 618 760 1124 825 749 554 864 888 490
805 561 920 832 1162 557 694 768 978 633 656 483 1027 771 954 538 834 1110 681 494
1011 692 1159 1053 1488 692 875 958 1240 785 825 598 1315 962 1155 658 1057 1421 850 600
17.4 6.0 11.9 7.8 16.4 7.1 10.0 8.8 12.1 8.5 9.7 11.5 18.6 18.7 11.5 6.8 13.3 18.1 6.2 8.8
143 99 80 81 116 90 91 95 116 106 104 105 101 75 90 109 109 123 100 99
35 82 53 69 75 71 67 94 82 120 62 95 91 90 87 98 68 99 119 46
5 12 6 11 14 10 12 19 14 11 14 18 27 21 12 14 10 17 16 20
Drugs nor, nor nor, nor, nor, nor, nor, nor, nor, nor, nor, nor nor, nor, nor, nor, nor, nor, nor, nor,
eno eno dop, eno eno eno, ket eno eno eno, ket eno eno eno, ket eno eno, ket, ter eno dop, eno, ket, ter eno eno, ket dop, eno
COfv, cardiac output FloTrac/Vigileo system (l min1); COtptd, cardiac output transpulmonary thermodilution (l min1); CVP central venous pressure (mmHg); dop, dopamine; ELWI, extravascular lung water index (ml kg1); eno, enoximone; GEDI, global end-diastolic volume index (ml m2); HR, heart rate (bpm); ITBI, intrathoracic blood volume index (ml m2); ket, ketanserin; MAP, mean arterial pressure (mmHg); nor, norepinephrine; SVRtptd, systemic vascular resistance by transpulmonary thermodilution (dyne s cm5); ter, terlipressin.
Eur J Anaesthesiol 2015; 32:5–12 Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
8 Slagt et al.
Fig. 1
(a)
(b) 8 6
COap-COtptd (l min–1)
COap(l min–1)
15
10
5
4 +1.96 SD 2
2.52
0
Mean 0.02
–2
-1.96 SD -2.49
–4 0
–6 0
5
10
2
15 –1
4
6
8
10
12
14
16
18
–1
COtptd(l min )
Average of COap + COtptd (l min )
(c)
(d)
6
15
4 –1 COfv-COtptd (l min )
COfv (l min–1)
13
10
8
5
+1.96 SD 2.77
2 0
Mean –0.86
–2 –4
–1.96 SD –4.48
–6 3 –8 0
5
10
15
–1
COtptd(l min )
0
5
10
15
–1 Average of COap + COtptd (l min )
20
Calibrated arterial pressure cardiac output and uncalibrated arterial pressure cardiac output versus transpulmonary thermodilution measurements. (a) The correlation of CO measurements between COap and COtptd (r ¼ 0.86, P < 0.001); (b) Bland–Altman plot; (c) The correlation of CO measurements between COfv and COtptd (r ¼ 0.72, P < 0.001); (d) Bland–Altman plot. Each symbol represents a patient. COap, arterial pressure cardiac output (VolumeView/EV1000) (l min1); COfv, cardiac output FloTrac/Vigileo system (l min1); COtptd, cardiac output transpulmonary thermodilution (VolumeView/EV1000) in (l min1).
Results The characteristics of the 20 patients included in the study are summarised in Table 1. The haemodynamic data at inclusion are given in Table 2. A total of 301 paired measurements were obtained, with the number of paired measurements per patient ranging from 5 to 24. The COap, COfv and COtptd were 8.2 (2.5), 7.3 (3.6) and 8.2 (2.3) l min1, respectively, and the SVRtptd was 636 (246) dyne s cm5. Eighty-five percent of the intermittent measurements were performed during norepinephrine infusions at a median (range) dose of 0.20 (0.02 to 1.70) mg kg1 min1. As the first COtptd measurement in each patient was used to calibrate COap (so not used for analysis) and with
Table 3 Overall results of comparisons between arterial pressure cardiac output and cardiac output FloTrac/Vigileo system with cardiac output transpulmonary thermodilution
Bias (precision) Limits of agreement Percentage error Correlation coefficient (r) Correlation coefficient for changes in CO (r)
COap - COtptd
COfv - COtptd
0.02 (1.27) 2.49 to 2.52 31 0.86 0.52
0.86 (1.85) 4.48 to 2.77 48 0.72 0.64
Bias, mean of all the differences; Precision, standard deviation of the bias; Percentage error, 1.96 (SD)/mean CO; Bias, precision and limits of agreement expressed in l min1; correlation coefficient for changes in CO after exclusion of clinically unimportant CO changes (
ORIGINAL ARTICLE
Calibrated versus uncalibrated arterial pressure waveform analysis in monitoring cardiac output with transpulmonary thermodilution in patients with severe sepsis and septic shock An observational study Cornelis Slagt, Mochamat Helmi, Ignacio Malagon and A.B. Johan Groeneveld BACKGROUND Cardiac output (CO) measurement is often required in critically ill patients. The performances of newer, less invasive techniques require evaluation in patients with severe sepsis and septic shock. OBJECTIVES To compare calibrated arterial pressure waveform analysis-derived CO (COap, VolumeView/EV1000) and the uncalibrated form (COfv, FloTrac/Vigileo) with transpulmonary thermodilution derived CO (COtptd). DESIGN A prospective, observational, single-centre study. SETTING ICU of a general teaching hospital. PATIENTS Twenty consecutive patients with severe sepsis or septic shock requiring haemodynamic monitoring by VolumeView/EV1000 and receiving mechanical ventilation. INTERVENTION Connection of FloTrac/Vigileo to radial artery catheter already in situ. MAIN OUTCOME MEASURES Radial (COfv) and femoral (COap) arterial waveform-derived CO measurements were compared with COtptd with respect to bias, precision, limits of agreement and percentage error, and the percentage error in the course of time since the last calibration of COap by COtptd.
RESULTS In comparing COap with COtptd (n ¼ 267 paired measurements), the bias was 0.02 and limits of agreement were 2.49 to 2.52 l min1, with a percentage error of 31%. The percentage error between COap and COtptd remained less than 30% until 8 h after calibration. In comparing COfv with COtptd (n ¼ 301), the bias was 0.86 l min1 and limits of agreement were 4.48 to 2.77 l min1, with a percentage error of 48%. The biases of COap and COfv correlated with systemic vascular resistance [r ¼ 0.13 (P ¼ 0.029) and r ¼ 0.42 (P < 0.001), respectively]. Clinically significant changes in COap and COfv correlated positively with COtptd at r ¼ 0.51 (P < 0.001) and r ¼ 0.64 (P < 0.001), respectively. CONCLUSION There was moderate agreement when measuring CO with either arterial waveform analysis technique. Compared with the uncalibrated COfv, the recently introduced calibrated arterial pressure waveform analysisderived COap was more accurate and less dependent on vascular tone for up to 8 hours after callibation when monitoring CO in patients with severe sepsis and septic shock. The COap and COfv methods have poor to moderate CO-tracking abilities. Published online 9 November 2014
This article is accompanied by the following Invited Commentary: Crossingham I, Columb M. Moderate agreement for cardiac output monitors. Moderately good or moderately bad? Eur J Anaesthesiol 2015; 32:1–2.
From the Department of Anesthesiology and Intensive Care, Zaans Medical Centre, Zaandam (CS), Department of Intensive Care, Erasmus Medical Centre, Rotterdam, The Netherlands (MH, ABJG), NIHR Respiratory and Allergy Clinical Research Facility, University Hospital South Manchester NHS Foundation Trust, Manchester, UK (IM) Correspondence to Cornelis Slagt, MD, PhD, Department of Anaesthesiology and Intensive Care, Zaans Medical Centre, Koningin Julianaplein 58, 1502 DV Zaandam, The Netherlands Tel: +31756507359; fax: +31756501929; e-mail: [email protected] 0265-0215 ß 2014 Copyright European Society of Anaesthesiology
DOI:10.1097/EJA.0000000000000173
Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
6 Slagt et al.
Introduction The VolumeView/EV1000 (Edwards Lifesciences, Irvine, California, USA) is a new transpulmonary thermodilution (TPTD) device that has recently been introduced to monitor cardiac output (CO). It utilizes TPTD to calculate CO (COtptd) and, using this result, calibrates the system which estimates cardiac output from the arterial pressure waveform (COap). Thereafter, arterial pressure waveform analysis is used to estimate continuous CO (CCO), similar to the technique embedded in the FloTrac/Vigileo (Edwards Lifesciences) monitor (COfv). With each TPTD measurement, the COap is recalibrated.1 There is a single validation study in relatively haemodynamically stable patients, suggesting that COap is as accurate as the TPTD reference and superior to pulse contour-derived (PiCCO2; Pulsion Medical Systems, Munich, Germany).1 Both techniques (PiCCO2 and VolumeView) use TPTD with the Stewart-Hamilton equation to calculate CO. We previously suggested2,3 that even with the most recent third-generation FloTrac/Vigileo software, the calculated (uncalibrated) CO is still too inaccurate in vasodilated and septic patients to allow for clinically meaningful CO monitoring and therapeutic decision making. The aim of the current prospective, observational, singlecentre study was to compare calibrated COap and uncalibrated COfv with COtptd in critically ill patients with severe sepsis or septic shock in the ICU. We hypothesised that calibrated would outperform uncalibrated CO measurement in this setting.
arterial cannula already in situ and then connected to the Vigileo monitor. After placement of the TPTD catheter (VolumeView/EV1000 system; Edwards Lifescience) in the femoral artery, all time clocks from the Spacelab monitor (Spacelabs Medical Inc, Issaquah, Washington, USA), VolumeView/EV1000 and FloTrac/Vigileo monitors were synchronised. The TPTD measurement was performed in sets of three to five bolus injections of 20 ml iced isotonic saline through the central venous catheter irrespective of the ventilator cycle. All individual bolus measurements had to be validated before being averaged. The mean value was recorded and regarded as the COtptd. At the start of each TPTD CO measurement, the COfv was measured and the mean value was recorded. All haemodynamic data stored in the EV1000 computer and FloTrac/Vigileo monitor were downloaded for analysis. All paired COap and COtptd measurements were also analysed in relation to the time after the last calibration to establish the calibration- free period in which COap remains clinically acceptable with a percentage error less than 30%.4 The mean arterial pressure (MAP) was monitored using the femoral arterial catheter and the central venous pressure (CVP) from a central venous catheter (internal jugular or subclavian vein), inserted for clinical reasons. The systemic vascular resistance (SVRtptd) was calculated from (MAP - CVP) x 80/COtptd, dyne s cm5. The electrocardiogram was monitored throughout and heart rate (HR) was recorded.
Materials and methods
Description of techniques
After Medical Ethics Review Committee approval (Ethics Committee, Noord-Holland, Alkmaar, The Netherlands No. M011-019; 26 April 2011) and written informed consent, 20 consecutive patients were included in this observational study. All patients with severe sepsis or septic shock (as defined by the American College of Chest Physicians/Society of Critical Care Medicine consensus conference) requiring vasoactive therapy along with monitoring of CO, radial arterial pressure and central venous pressure (CVP) were eligible for this study. Additional inclusion criteria that had to be met were the use of norepinephrine, organ failure and mechanical ventilation. The study was performed in the ICU of a general teaching hospital from June 2011 to April 2013. Exclusion criteria were age less than 18 years, contraindications for a femoral artery catheter and known severe tricuspid or aortic valvular regurgitation. The study did not otherwise alter the standard of care provided.
The TPTD measurement using the VolumeView/ EV1000 system uses a bolus injection through a central venous catheter situated above the diaphragm and a femoral arterial catheter with a specific thermistor tip subsequently measures the thermodilution curve. This method provides CO measurements as well as volumetric indices such as global end-diastolic volume (GEDV), intrathoracic blood volume (ITBV), extravascular lung water (EVLW), global ejection fraction and pulmonary vascular permeability index.5 The CO is estimated from the bolus TPTD measurements using the Stewart– Hamilton equation.1 For the CCO measurements, the VolumeView/EV1000 monitor combines the area under the systolic part of the arterial pressure waveform and waveform analysis as used in the FloTrac/Vigileo system. The exact method of how both algorithms are integrated into the COap measurement has not been disclosed at this time. After each intermittent bolus TPTD measurement, the COap is recalibrated.1
Protocol
The FloTrac/Vigileo system estimates CO by using the standard deviation of the pulse pressure, incorporating actual vascular tone based on waveform analysis and patient characteristics.6 The arterial waveform is analysed over 20 s with a frequency of 100 Hz. The thirdgeneration software version (3.02) includes two separate
Patient characteristics were recorded, including disease severity scores. Paired CO measurements were performed as clinically required, at least once every shift and with any changes to therapy with fluids and vasoactive agents. A FloTrac sensor was connected to the 20-guage radial
Eur J Anaesthesiol 2015; 32:5–12 Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
Less invasive versus invasive cardiac output in sepsis 7
Table 1
Patient characteristics at ICU admission
Age (years) Sex (male/female) Weight (kg) Height (cm) Cause of sepsis Pneumonia Abdominal Urogenital Others APACHE II score SAPS II Length of ICU stay (days) Mortality at 28 days
63.3 (11) 16/4 88.6 (22) 178.1 (7) 9 8 1 2 31.0 (8) 58.3 (17) 15 (6 to 46) 4/20
Data are displayed as mean (SD), number (%) or median (range) as appropriate. APACHE, acute physiology and chronic health evaluation; SAPS, simplified acute physiology score.
models for the arterial tone factor: first, an arterial tone model that was developed predominantly from patients who did not have a hyperdynamic circulation (this is the same model used in the previous version 1.10); and second, an arterial tone model that was developed predominantly from patients who had a hyperdynamic circulation. The need for using two separate models is because of the differences in relating peripheral arterial pressure to flow during nonhyperdynamic and hyperdynamic circulations.7 The switching between the two models is automated using an algorithm that analyses 14 parameters of the arterial pressure waveform to detect the occurrence of hyperdynamic circulation. Statistical analyses
After confirming normal distribution of data using the Kolmogorov–Smirnov test, data were pooled and Table 2
summarised as mean (SD) and parametric analyses were performed. Pearson correlation coefficients of pooled data were estimated using Statistical Package for Social Sciences (SPSS) version 21 (SPSS Inc, Chicago, Illinois, USA). To assess agreement, a Bland-Altman analysis8 was performed and adjusted for repeated measurements (Medcalc software version 12.2.1.0; Mariakerke, Belgium). Bias was defined as the mean difference between CO derived from two methods. Limits of agreement were calculated from 1.96 SD of the bias. The percentage error (1.96 SD/mean CO) was calculated with 30% taken as clinically acceptable.9 The precision of the reference COtptd was calculated using the method proposed by Cecconi et al.4 to calculate the precision of the test methods. Polar plots (SigmaPlot software version 11, San Jose, California, USA) were also used to analyse the agreement in CO trend monitoring between methods.10 In the polar plot, the changes of CO data are converted to a radial vector wherein the degree of agreement between two devices becomes the angle between radial vector and horizontal axis (i.e. the polar axis). If agreement is perfect, the radial vector lies along the polar axis and the angle is zero; the angle between the vector and the horizontal axis represents disagreement. Agreement for trending is acceptable when points lie between either 1508 and 2108 or 308 and 3308. The distance from the centre of the plot (vector) represents the mean changes in CO. Concordances of clinically significant changes in CO measurements are reported. As COap is recalibrated with COtptd, we analysed the effect of time on the difference between the two methods. A P value less than 0.05 was considered statistically significant.
Haemodynamic data at enrollment and drugs used during the study
N
COtptd
COfv
SVR
GEDI
ITBI
ELWI
HR
MAP
CVP
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
12.6 5.2 9.0 9.6 11.1 7.7 9.7 9.4 5.1 7.7 9.5 10.0 6.8 5.0 7.3 8.9 8.3 7.9 9.4 4.2
9.4 6.3 4.4 5.2 7.0 7.3 11.9 5.8 3.3 4.5 9.5 11.3 6.2 5.2 4.9 8.7 9.6 6.7 13.1 5.6
196 1078 418 483 438 636 452 638 1070 1133 406 618 760 1124 825 749 554 864 888 490
805 561 920 832 1162 557 694 768 978 633 656 483 1027 771 954 538 834 1110 681 494
1011 692 1159 1053 1488 692 875 958 1240 785 825 598 1315 962 1155 658 1057 1421 850 600
17.4 6.0 11.9 7.8 16.4 7.1 10.0 8.8 12.1 8.5 9.7 11.5 18.6 18.7 11.5 6.8 13.3 18.1 6.2 8.8
143 99 80 81 116 90 91 95 116 106 104 105 101 75 90 109 109 123 100 99
35 82 53 69 75 71 67 94 82 120 62 95 91 90 87 98 68 99 119 46
5 12 6 11 14 10 12 19 14 11 14 18 27 21 12 14 10 17 16 20
Drugs nor, nor nor, nor, nor, nor, nor, nor, nor, nor, nor, nor nor, nor, nor, nor, nor, nor, nor, nor,
eno eno dop, eno eno eno, ket eno eno eno, ket eno eno eno, ket eno eno, ket, ter eno dop, eno, ket, ter eno eno, ket dop, eno
COfv, cardiac output FloTrac/Vigileo system (l min1); COtptd, cardiac output transpulmonary thermodilution (l min1); CVP central venous pressure (mmHg); dop, dopamine; ELWI, extravascular lung water index (ml kg1); eno, enoximone; GEDI, global end-diastolic volume index (ml m2); HR, heart rate (bpm); ITBI, intrathoracic blood volume index (ml m2); ket, ketanserin; MAP, mean arterial pressure (mmHg); nor, norepinephrine; SVRtptd, systemic vascular resistance by transpulmonary thermodilution (dyne s cm5); ter, terlipressin.
Eur J Anaesthesiol 2015; 32:5–12 Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited.
8 Slagt et al.
Fig. 1
(a)
(b) 8 6
COap-COtptd (l min–1)
COap(l min–1)
15
10
5
4 +1.96 SD 2
2.52
0
Mean 0.02
–2
-1.96 SD -2.49
–4 0
–6 0
5
10
2
15 –1
4
6
8
10
12
14
16
18
–1
COtptd(l min )
Average of COap + COtptd (l min )
(c)
(d)
6
15
4 –1 COfv-COtptd (l min )
COfv (l min–1)
13
10
8
5
+1.96 SD 2.77
2 0
Mean –0.86
–2 –4
–1.96 SD –4.48
–6 3 –8 0
5
10
15
–1
COtptd(l min )
0
5
10
15
–1 Average of COap + COtptd (l min )
20
Calibrated arterial pressure cardiac output and uncalibrated arterial pressure cardiac output versus transpulmonary thermodilution measurements. (a) The correlation of CO measurements between COap and COtptd (r ¼ 0.86, P < 0.001); (b) Bland–Altman plot; (c) The correlation of CO measurements between COfv and COtptd (r ¼ 0.72, P < 0.001); (d) Bland–Altman plot. Each symbol represents a patient. COap, arterial pressure cardiac output (VolumeView/EV1000) (l min1); COfv, cardiac output FloTrac/Vigileo system (l min1); COtptd, cardiac output transpulmonary thermodilution (VolumeView/EV1000) in (l min1).
Results The characteristics of the 20 patients included in the study are summarised in Table 1. The haemodynamic data at inclusion are given in Table 2. A total of 301 paired measurements were obtained, with the number of paired measurements per patient ranging from 5 to 24. The COap, COfv and COtptd were 8.2 (2.5), 7.3 (3.6) and 8.2 (2.3) l min1, respectively, and the SVRtptd was 636 (246) dyne s cm5. Eighty-five percent of the intermittent measurements were performed during norepinephrine infusions at a median (range) dose of 0.20 (0.02 to 1.70) mg kg1 min1. As the first COtptd measurement in each patient was used to calibrate COap (so not used for analysis) and with
Table 3 Overall results of comparisons between arterial pressure cardiac output and cardiac output FloTrac/Vigileo system with cardiac output transpulmonary thermodilution
Bias (precision) Limits of agreement Percentage error Correlation coefficient (r) Correlation coefficient for changes in CO (r)
COap - COtptd
COfv - COtptd
0.02 (1.27) 2.49 to 2.52 31 0.86 0.52
0.86 (1.85) 4.48 to 2.77 48 0.72 0.64
Bias, mean of all the differences; Precision, standard deviation of the bias; Percentage error, 1.96 (SD)/mean CO; Bias, precision and limits of agreement expressed in l min1; correlation coefficient for changes in CO after exclusion of clinically unimportant CO changes (
