Intensive Care Med (2007) 33:11911194 DOI 10.

1007/s00134-007-0640-0

BRIEF REPORT

Pierre Squara Dominique Denjean Philippe Estagnasie Alain Brusset Jean Claude Dib Claude Dubois

Noninvasive cardiac output monitoring (NICOM): a clinical validation

Received: 13 June 2006 Accepted: 26 March 2007 Published online: 26 April 2007 Springer-Verlag 2007 Electronic supplementary material The online version of this article (doi:10.1007/s00134-007-0640-0) contains supplementary material, which is available to authorized users. Support: This study was supported by a grant from Cheetah Med. Inc., Wilmington, DE, USA.

P. Squara (u) D. Denjean P. Estagnasie A. Brusset J. C. Dib C. Dubois Clinique Ambroise Par, CERIC, 27, boulevard Victor Hugo, 92200 Neuilly-sur-Seine, France e-mail: pierre.squara@wanadoo.fr Tel.: +33 1-46418971 Fax: +33-1-46418981

Abstract Objective: To evaluate the clinical utility of a new device for continuous noninvasive cardiac output monitoring (NICOM) based on chest bio-reactance compared with cardiac output measured semicontinuously by thermodilution using a pulmonary artery catheter (PAC-CCO). Design: Prospective, single-center study. Setting: Intensive care unit. Patients: Consecutive adult patients immediately after cardiac surgery. Interventions: Cardiac output measurements obtained from NICOM and thermodilution were simultaneously recorded minute by minute and compared in 110 patients. We evaluated the accuracy, precision, responsiveness, and reliability of NICOM for detecting cardiac output changes. Tolerance for each of these parameters was specied prospectively. Measurements and results: A total of 65,888 pairs of cardiac output measurements were collected. Mean reference values for cardiac output ranged from 2.79 to 9.27 l/min. During periods of stable PAC-CCO

(slope < 10%, 2SD/mean < 20%), the correlation between NICOM and thermodilution was R = 0.82; bias was +0.16 0.52 l/min (+4.0 11.3%), and relative error was 9.1% 7.8%. In 85% of patients the relative error was < 20%. During periods of increasing output, slopes were similar with the two methods in 96% of patients and intra-class correlation was positive in 96%. Corresponding values during periods of decreasing output were 90% and 84%, respectively. Precision was always better with NICOM than with thermodilution. During hemodynamic challenges, changes were 3.1 3.8 min faster with NICOM (p < 0.01) and amplitude of changes did not differ signicantly. Finally, sensitivity of the NICOM for detecting signicant directional changes was 93% and specicity was 93%. Conclusion: Cardiac output measured by NICOM had most often acceptable accuracy, precision, and responsiveness in a wide range of circulatory situations.

Introduction
Until now, continuous monitoring of cardiac output (CO) in the intensive care unit has been achieved only by invasive methods such as continuous thermodilution with a pulmonary artery catheter (PAC-CCO) [1], an arterial catheter for pulse contour analysis [2, 3], an intra-tracheal tube for partial CO2 re-breathing [4], or an intra-esophageal probe for continuous Doppler velocity

ow assessment [5, 6]. A non-invasive method would be useful, especially for low-risk patients in whom CO monitoring is rarely used at present, given the potential side effects of invasive procedures. Thoracic bioimpedance was the rst non-invasive method for CO monitoring [79], but inconsistent accuracy was found in intensive care [10, 11]. A new signal processing method has been developed (NICOM, Cheetah Medical, Inc. Wilmington, DE). In addition to

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Data were available from 110 patients with 65,888 pairs of CO values (599 341 min per patient), age 68 11 years, left ventricular ejection fraction 47 12%. Inotropic agents were used in 12 patients, vasodilators in 24 patients, and vasopressors in 9 patients. Six patients Methods had chronic obstructive pulmonary diseases. Postoperative pulmonary hypertension (systolic pressure > 40 mmHg) Patients occurred in 23 patients. Time-averaged thermodilution CO ranged from 2.79 to 9.27 l/min (mean 4.74 1.08) The protocol was approved by our institutional review and 65% of the data was obtained when patients were board. Informed consent was obtained from each patient. mechanically ventilated. The database segmentation and We studied 119 consecutive patients requiring PAC in the complete results are given in the ESM. immediate postoperative period following cardiac surgery. Connecting the NICOM to the patient requires four double electrode stickers placed on the thorax. A PACCCO catheter was used (Edwards Life Sciences, Irvine, CA). Bias PAC-CCO and NICOM were automatically recorded using a computer data logger on a minute-by-minute basis. The regression coefcients between thermodilution and Nine patients were excluded because there was clear NICOM values including 9,004 points during 40 perievidence of a situation leading to unrealistic results: three ods of stable CO were R = 0.64, slope = 0.71 (95%CI interferences between an implanted pace-maker and the 0.700.72). Bias was +0.06 0.71 l/min (+3.0 16.9%). NICOM, two severe tricuspid regurgitation leading to er- The proportion of points with acceptable bias (< 20%) roneous thermodilution (dened as a Doppler regurgitation was 80.4% and 98.6% of the patients were inside the limits > 2+ and a systolic wave > 5 mmHg on the right atrial pressure curve), and four early NICOM disconnections due to agitation. Data analysis CO values were compared using linear regressions analysis. The bias was calculated and illustrated by the BlandAltman approach. However, this traditional approach did not allow dealing with our predetermined criteria of clinical acceptability. In particular, precision is affected by natural CO changes and by the large variability and the low time responsiveness of CO monitoring using thermodilution [13]. To address these issues, we developed an original method (detailed in the Electronic Supplementary Material). Basically, it was necessary to distinguish periods of stable, increasing and decreasing CO using thermodilution trend slopes. Periods of rapid CO increase or decrease following acute hemodynamic challenges were also analyzed independently. We prospectively dened clinically acceptable tolerances for the performance parameters: (1) 20% for bias, (2)

the amplitude-modulation recorded by old systems, the NICOM signal is based on the frequency-modulation and phase-modulation of the output voltage. This advanced bioreactance technology yields a signal to noise ratio improved 100-fold. The purpose of this study was to test the clinical acceptability of NICOM in critically ill patients, using PAC-CCO as reference. Clinical acceptability was prospectively dened as: (1) small bias of measurement (accuracy), (2) small random error of measurements around the true value (precision), (3) good responsiveness (time and amplitude), and (4) reliable detection of directional changes in CO [12].

20% for precision and (3) same responsiveness. Finally, we evaluated (4) reliability for CO directional changes. Unacceptable discordances in directional changes were dened as a difference > 20% between the two slopes or as a negative intra-class correlation. All values were reported as mean SD; p < 0.05 was considered signicant.

Results

Fig. 1 Regression PAC-CCO vs. NICOM (each point represents the mean CO value during a period of stable CO). R = 0.82. Slope = 0.82 (95%CI = 0.641.0) not signicantly different from the identity line (red dotted line)

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Table 1 CO changes after hemodynamic challenges Negative CO challenge (n = 14) Lag time (min) Amplitude (l/min) Amplitude (%) Positive CO challenge (n = 23) Lag time (min) Amplitude (l/min) Amplitude (%)

NICOM 3.4 1.3 1.7 1.0 28 14 4.0 2.2 1.5 0.9 40 26

PAC-CCO 7.1 3.1 1.7 1.2 34 20 6.8 3.2 1.7 1.3 50 33

p 0.01 0.25 0.25 0.003 0.07 0.07

of agreement of the BlandAltman plot. The proportion of blanks (no values) given by the PAC-CCO was 3.9%. When CO was averaged for each of the 40 periods of stable CO, the relationship between NICOM and thermodilution improved (Fig. 1). Bias was +0.16 0.52 l/min (+4.1 11.3%). The proportion of patients with acceptable bias (< 20%) was 85%, and 95% were inside the limits of agreement. Bias was independently and inversely related to PAC-CCO values (p < 0.0001) and body surface area (p < 0.02). Bias was not correlated with the duration of the experiment and was not changed by mechanical ventilation or when any drugs were used. Precision During periods of stable CO, the thermodilution and NICOM slopes were comparable: 0% 6% vs. 1% 9% (NS). The precision of PAC-CCO measurements around the slope (2SD/mean) was 14% 4%, vs. 12% 7% for the NICOM respectively, p = 0.08. When CO changed, precision was better with NICOM than PAC-CCO: 16% 10% vs. 23% 9% (p < 0.0001) for increasing CO and 16% 10% vs. 20% 7% (p = 0.002) for decreasing CO. Responsiveness A rapid increase in CO was expected in 23 patients (7 rapid uid challenge, 6 dobutamine challenge, 6 high PEEP stops, and 4 adrenaline infusions). In all of the 23 challenges, both NICOM and PAC-CCO increased (Table 1). A rapid decrease in CO was expected in 18 patients (14 PEEP challenges, 3 stops in dobutamine infusion). In 16 of these 18 patients, a fall in PAC-CCO was observed. In the 2 other patients, a fall in PAC-CCO was not documented but probably occurred, as decreases were noted in both SvO2 and blood pressure. Also, in 16 patients, NICOM decreased was expected. In the other two patients, NICOM was unchanged, although PAC-CCO was signicantly decreased. For the 14 patients whose CO values fell with both methods, the averaged response is shown in Table 1.

Reliability for detecting directional changes We identied 236 periods of time with unchanged (n = 82), increasing (n = 74) and decreasing (n = 80) CO. During periods of increasing output, slopes were similar in 96% of patients and intra-class correlation was acceptable in 96%. Corresponding values during periods of decreasing output were 90% and 84%, respectively. Overall, the number of true-positive detections of directional changes in CO was 143, the number of true negatives was 76, the number of false positives was 6, and the number of false negatives was 11. Therefore, sensitivity for signicant directional changes was 93% and specicity was 93%.

Discussion
This validation of NICOM demonstrated that a totally non-invasive method of CO monitoring is possible in intensive care medicine. The bias was negligible when averaged and was acceptable in 85% of cases. NICOM precision was always better than thermodilution. The averaged-time responsiveness of the NICOM was 3 min faster than thermodilution and the amplitude responsiveness was not signicantly different. Finally, sensitivity and specicity for detecting clinically relevant PAC-CCO changes were both 93%. PAC-CCO was taken as reference because we have no better reference for continuous CO monitoring [1, 1315]. Fick [16] or bolus thermodilution methods [17] are considered more robust references for CO snapshot measurements, but we were interested in comparing the NICOM with another automatic and continuous monitoring tool. Using either of these two methods, it would have been impossible to compare precision and responsiveness because they require too much time due to manual data acquisition and averaging of several measurements. Moreover, it would have been impossible to collect enough data to identify statistically eventual factors associated with bias. There are no hard rules for tolerance, but our criteria are restrictive. A 30% limit of acceptability has been empirically proposed for cardiac output [18]. We consider here the reference method variability as limit of acceptability. Reported PAC bias values (either CCO or bolus CO) range from 5% to 15% [13, 17, 19, 20]. Since thermodi-

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lution measures right ventricular output and disregards the bronchial circulation compared with NICOM, we considered that a 20% bias and precision was acceptable. Although unacceptable results were infrequent, it is obvious that several factors increased their number articially. First, even when CO is globally stable, the lag-time difference between NICOM and thermodilution created transient disagreements in the minute-to-minute comparison. Second, there were no blanks in the NICOM response versus 3.9% of blanks in PAC-CCO. Some of the NICOM data were altered by artifacts resulting from nurses interventions and/or from patient movements. The absence of a NICOM response after a PEEP test

in two patients was probably attributable to agitation induced by discomfort associated with high PEEP. Third, although we observed no signicant time-drift in the results, a loss in the quality of the patch adhesive may have occurred in a few patients. Lastly, although tricuspid regurgitation and/or intra-cardiac shunts were exclusion criteria, we cannot exclude transient occurrence of these situations, resulting in transient error in the reference method. In summary, we demonstrated that the NICOM system had most often acceptable accuracy, precision, and responsiveness for CO monitoring in patients experiencing a wide range of circulatory situations.

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