Pulmonary Artery Catheter (PAC) Accuracy and Efficacy Compared with Flow Probe and Transcutaneous Doppler (USCOM): An Ovine Cardiac Output Validation.
ABSTRACT Background. The pulmonary artery catheter (PAC) is an accepted clinical method of measuring cardiac output (CO) despite no prior validation. The ultrasonic cardiac output monitor (USCOM) is a noninvasive alternative to PAC using Doppler ultrasound (CW). We compared PAC and USCOM CO measurements against a gold standard, the aortic flow probe (FP), in sheep at varying outputs. Methods. Ten conscious sheep, with implanted FPs, had measurements of CO by FP, USCOM, and PAC, at rest and during intervention with inotropes and vasopressors. Results. CO measurements by FP, PAC, and USCOM were 4.0 ± 1.2 L/min, 4.8 ± 1.5 L/min, and 4.0 ± 1.4 L/min, respectively, (n = 280, range 1.9 L/min to 11.7 L/min). Percentage bias and precision between FP and PAC, and FP and USCOM was -17 and 47%, and 1 and 36%, respectively. PAC under-measured Dobutamine-induced CO changes by 20% (relative 66%) compared with FP, while USCOM measures varied from FP by 3% (relative 10%). PAC reliably detected -30% but not +40% CO changes, as measured by receiver operating characteristic area under the curve (AUC), while USCOM reliably detected ±5% changes in CO (AUC > 0.70). Conclusions. PAC demonstrated poor accuracy and sensitivity as a measure of CO. USCOM provided equivalent measurements to FP across a sixfold range of outputs, reliably detecting ±5% changes.
- [show abstract] [hide abstract]
ABSTRACT: Maintaining threshold values of cardiac output (CO) and systemic vascular resistance (SVR) when used as part of the American College of Critical Care Medicine (ACCM) haemodynamic protocol improves the outcomes in paediatric septic shock. We observed the evolution of CO and SVR during the intensive care admission of children with fluid-refractory septic shock and report this together with the eventual outcomes. Prospective observational study. Tertiary care Paediatric Intensive Care Unit (PICU) in London. Children admitted in fluid refractory septic shock to the Intensive Care Unit over a period of 36 months were studied. Post liver re-transplant children and delayed septic shock admissions were excluded. A non-invasive ultrasound cardiac output monitor device (USCOM) was used to measure serial haemodynamics. Children were allocated at presentation into one of two categories: (1) hospital-acquired infection and (2) community-acquired infection. Vasopressor, inotrope or inodilator therapies were titrated to maintain threshold cardiovascular parameters as per the ACCM guidelines. Thirty-six children [19 male, mean age (SD) 6.78 (5.86) years] were admitted with fluid-refractory septic shock and studied. At presentation, all 18 children with hospital-acquired (HA) sepsis and 3 from among the community-acquired (CA) sepsis group were in 'warm shock' (SVRI < 800 dyne s/cm(5)/m(2)) whereas 15 of the 18 children with community-acquired sepsis and none in the hospital-acquired group were in 'cold shock' [cardiac index (CI) < 3.3 l/min/m(2)]. All 21 children in 'warm shock' were initially commenced on a vasopressor (noradrenaline). Despite an initial good response, four patients developed low CI and needed adrenaline. Similarly, all 15 children in cold shock were initially commenced on adrenaline. However, two of them subsequently required noradrenaline. Five others needed milrinone as an inodilator. In general, both groups of children had normalised SVRI and CI within 42 h of therapy but required variable doses of vasopressors, inotropes or inodilators in a heterogeneous manner. The overall 28-day survival rate was 88.9 % in both groups. Central venous oxygen saturation (ScvO2) was significantly (p = 0.003) lower in the community-acquired group (mean 51.72 % ± 4.26) when compared to the hospital-acquired group (mean 58.72 % ± 1.36) at presentation but showed steady improvement during therapy. Gram-positive organisms were predominant in blood cultures, 61 % in HA and 56 % in CA groups. In general, we found children with community-acquired septic shock presented in cold shock whereas hospital-acquired septic shock children manifested warm shock. Both types evolved in a heterogeneous manner needing frequent revision of cardiovascular support therapy. However the 28-day survival in both groups was the same at 89 %. Frequent measurements of haemodynamics using non-invasive ultrasound helped in fine tuning cardiovascular therapies.European Journal of Intensive Care Medicine 06/2013; · 5.17 Impact Factor
- Pediatric Critical Care Medicine 01/2014; 15(1):84-5. · 2.35 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Supra-sternal Doppler (USCOM Ltd., Sydney, Australia) can be used during anaesthesia to measure cardiac output (CO) and related flow parameters. However, before the USCOM can be used routinely, its utility and limitations need to be fully understood and critical information about its use disseminated. In "Window to the Circulation" we use the example of an elderly man undergoing major urological robotic surgery to highlight the utility and limitations of intra-operative USCOM use. USCOM readings were verified against oesophageal Doppler. Despite the lack of major blood loss (<500 ml in 8-h), significant changes in haemodynamics were recorded. CO ranged from 3.2 to 8.3 l/min. The quality of USCOM scans and reliability of data was initially poor, but improved as CO increased as surgery progressed. When USCOM scans became acceptable the correlation with oesophageal Doppler was R(2) = 8.0 (p < 0.001). Several characteristic features of the supra-sternal Doppler scans were identified: Aortic and pulmonary flow waves, valve closure, E and A waves, false A-wave and aberrant arterial flow patterns. Their identification helped with identifying the main flow signal across the aortic valve. The USCOM has the potential to monitor changes in CO and related flow parameters intra-operatively and thus help the anaesthetist to more fully understand the patient's haemodynamics. However, achieving a good quality scan is important as it improves the reliability of USCOM data. The supra-sternal route is rich in flow signals and identifying the aortic valve signal is paramount. Recognizing the other characteristic waveforms in the signal helps greatly.International Journal of Clinical Monitoring and Computing 08/2013;
Hindawi Publishing Corporation
Critical Care Research and Practice
Volume 2012, Article ID 621496, 9 pages
PulmonaryArteryCatheter (PAC) Accuracy
Doppler(USCOM):An OvineCardiac OutputValidation
Robert A.Phillips,1,2Sally G.Hood,3Beverley M. Jacobson,2Malcolm J. West,1
1School of Medicine, The University of Queensland, Brisbane QLD 3010, Australia
2USCOM Ltd., Department of Clinical Science, Sydney NSW 3010, Australia
3Howard Florey Institute, University of Melbourne, Parkville VIC 3010, Australia
4Department of Pharmacology, University of Melbourne, Parkville VIC 3010, Australia
Correspondence should be addressed to Robert A. Phillips, email@example.com
Received 10 January 2012; Accepted 23 February 2012
Academic Editor: Giuseppe Ristagno
Copyright © 2012 Robert A. Phillips et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
Background. The pulmonary artery catheter (PAC) is an accepted clinical method of measuring cardiac output (CO) despite no
prior validation. The ultrasonic cardiac output monitor (USCOM) is a noninvasive alternative to PAC using Doppler ultrasound
(CW). We compared PAC and USCOM CO measurements against a gold standard, the aortic flow probe (FP), in sheep at varying
outputs. Methods. Ten conscious sheep, with implanted FPs, had measurements of CO by FP, USCOM, and PAC, at rest and
during intervention with inotropes and vasopressors. Results. CO measurements by FP, PAC, and USCOM were 4.0 ± 1.2L/min,
4.8±1.5L/min, and 4.0±1.4L/min, respectively, (n = 280, range 1.9L/min to 11.7L/min). Percentage bias and precision between
FP and PAC, and FP and USCOM was −17 and 47%, and 1 and 36%, respectively. PAC under-measured Dobutamine-induced
CO changes by 20% (relative 66%) compared with FP, while USCOM measures varied from FP by 3% (relative 10%). PAC reliably
detected −30% but not +40% CO changes, as measured by receiver operating characteristic area under the curve (AUC), while
USCOM reliably detected ±5% changes in CO (AUC > 0.70). Conclusions. PAC demonstrated poor accuracy and sensitivity as
a measure of CO. USCOM provided equivalent measurements to FP across a sixfold range of outputs, reliably detecting ±5%
Since its introduction in 1970 ,the SwanGanz pulmonary
artery catheter (PAC), using the thermodilution method
(TD), has been accepted as a gold standard for the clinical
measurement of cardiac output (CO). The PAC has been
used to evaluate and guide clinical care, to develop our
understanding of physiology and pathophysiology, and as a
reference standard for evaluation of novel CO measurement
years, it remains essentially without validation and without
clinical outcomes benefit [2–5]. Explanations for the absence
of PAC effectiveness may be the uncertain accuracy of the
method [6–12]. Additionally, PAC TD, using either bolus
injections or continuous thermometric monitoring [1, 13,
14], is invasive, with associated patient risks [15–18], and is
Given the importance of the circulation in clinical
practice, the frequency of clinical interventions, and the
limitations of PAC, there is a need for an improved CO mea-
surement and monitoring method. CO2partial re-breathing
, breath-to-breath pulmonary blood flow measures ,
arterial pulse pressure analysis , and transesophageal
Doppler  have also been used to measure CO. However,
these alternatives have limitations which have precluded
significant adoption. A noninvasive, accurate, and effective
alternative to PAC may improve clinical care and contribute
to our understanding of circulation.
2Critical Care Research and Practice
The Ultrasonic Cardiac Output Monitor, (USCOM)
invasive, morphometrically calibrated, continuous wave
(CW) Doppler ultrasound device which provides an instan-
taneous, beat-to-beat measure of right- and left-sided CO.
CW Doppler is a widely adopted clinical tool with an
accuracy measured by Doppler string phantoms of ±2.3%
in animals , with echocardiography from 0.12L/min in
neonates , in externally driven artificial hearts in ortho-
topic transplantation , with PAC in the postcardiac sur-
gical setting [28–31], and with PAC from 2.14 to 18.7L/min
in liver transplantation [32, 33]. It has acceptable reproduci-
bility in adults and children [34–36], and has been recom-
mended as an alternative to PAC .
The ultrasonic transit-time flow probe (FP) is considered
a true gold standard method for measuring beat-to-beat CO
with an accuracy of ±1 to 2%  but is limited to animal
studies as it requires surgical implantation.
This study compared the two clinical methods of CO
measurement, PAC and USCOM, with measures from an
implanted FP in conscious sheep to evaluate the relative
accuracy and sensitivities of the methods across a range of
outputs at baseline and during pharmacologic interventions.
2.1. Study Design and Data. The study was approved by the
Animal Experimentation Ethics Committee of the Howard
Florey Institute. Prior to experiment, 10 adult Merino ewes
were anaesthetised with intravenous (i.v.) sodium thiopental
(15mg/kg), and, following intubation, anesthesia was main-
tained with 1.5–2.0% isoflurane in oxygen. An incision was
made above the fourth left rib, the periosteum stripped,
and the rib resected. The pericardium was opened, and the
ascending aorta cleared for implantation of a FP (20mm,
Transonic Systems Inc., Ithaca, NY, USA). The pericardium,
periosteum, muscle, and skin were closed in layers. The flow
probe cable was tunnelled superficially and exteriorised near
the thoracic spine. Antibiotic prophylaxis (900mg procaine
penicillin, Troy Laboratories, NSW, Australia) was admin-
istered for three days after surgery. Postsurgical analgesia
was maintained with intramuscular injection of flunixin
meglumine (1mg/kg) (Mavlab, Qld, Australia) at the end
of surgery, then four and sixteen hours after surgery. A
to any study.
On the day of the study, a single experienced operator
inserted a PAC-continuous cardiac output monitor (CCO)
(Baxter Healthcare Corp., Irvine, CA, USA) via the right
jugular vein into the pulmonary artery under 2% lignocaine
local anesthesia and connected it to a Vigilance Monitor
sheep lying on its right side, both the CO measures from the
FP and PAC were captured from the flow meter (Transonics
Systems) and the Vigilance, and recorded to computer using
at a frequency of 100Hz per beat. Ultrasound coupling gel
third and fifth left ribs, and the upper thorax was insonated
by a single experienced operator using a 3.3MHzCW probe
which was manipulated to optimise the transpulmonary
Doppler flow profiles on the USCOM monitor. The USCOM
device requires the pulmonary valve diameter (PV) to calcu-
late flow volumes, for example, CO and stroke volume (SV).
In human subjects this is determined using a proprietary
anthropometric algorithm. An equivalent algorithm is not
available for sheep, so for each subject, the USCOM values
were calibrated to the FP measurements during a calibration
phase prior to experimental measurements, with only post
calibration data analysed. The USCOM investigator was
blinded to the FP and PAC values, and acquired the Doppler
signals and stored the flow profiles to the USCOM hard
drive. Each stored screen recorded 6–12 consecutive Doppler
files were later traced to generate output values for each beat
and stored to the USCOM hard drive for later collation and
comparison with the corresponding FP and PAC measures.
2.2. Measurement of Outcomes. Contemporaneous CO
measurements were made using all methods over a baseline
period of up to 40 minutes, during i.v. infusion of the
inotrope dobutamine (0.2, 0.4 and 1.0mg/min for 40–
(10min), during infusion of the vasopressor arginine vaso-
pressin (AVP) (15ng/min for 15–20min), and during a
5min post vasopressor phase. The order of dobutamine and
AVP infusions was randomised, and a recovery period of 30
minutes between treatments was allowed for CO to return
to control levels. As this study compared two beat-to-beat
methods, USCOM and FP, against a time averaged method,
PAC, 6 to 13 sequential measures of CO by USCOM, and
FP were acquired at each comparison point on each subject,
depending on heart rate, and averaged to represent the mean
CO values at each time point for comparison with PAC
values. Further no time to measurement after intervention
was less than 4 minutes, thus allowing PAC time to respond
to any CO changes.
PAC is an uncalibrated method functioning by detection
of temperature gradients across a known distance so was
not calibrated. However to address any potential for bias, we
FP values to generate a FP-calibrated PAC series (cPAC), for
comparison with FP measures.
as mean and standard deviation (SD) and data were analysed
using SPSS v.16 (SPSS Inc, Chicago, Ill, USA). Analysis
included Bland Altman determination of reliability and
reproducibility , analysis of means, standard deviations
(SD), regression analysis, and Pearson’s correlation coeffici-
ent. Percentage changes during and after interventions and
receiver operator characteristic statistics (ROC) was cal-
culated for PAC and USCOM compared to FP. Area under
the ROC curves (AUC) were calculated for 5% incremental
changes in CO between −40 and +40% CO to determine
the sensitivity to change of both methods [40, 41] with ac-
ceptable sensitivity to change defined as AUC > 0.70 .
Critical Care Research and Practice3
FP versus PACFP versus USCOMFP versus cPAC
Mean (%) difference between methods
Figure 1: Percentage bias and precision for all paired measures for
FP versus PAC (−17.2% and 47%), FP versus USCOM (1% and
36.4%), and FP versus cPAC (−0.2% and 54.4%).
3.1. Baseline Characteristics and Exclusions. A total of 363
CO measures by FP, 370 measures by USCOM and 293 PAC
measures were collected from the 10 adult ewes (39 ± 4kg).
PAC failed in 20% of the experimental acquisitions, while
satisfactory FP and USCOM measurements were obtained
in all animals and at all time points. Statistical analysis
excluded calibration measurements and included only data
from contemporaneous, valid, triplicate measures, leaving
of 29 ±11 triplicate measures were completed on each sheep
(range 5−42 measures). A further 280 cPAC measures were
calculated post hoc by calibrating PAC with baseline FP
reference measures to complete the data set.
3.2. Main Outcomes. Mean CO by FP, PAC, USCOM and
cPAC across all measures was 4.0 ± 1.2L/min (range 1.9 to
11.7/min), 4.8 ± 1.5L/min (range 2.5 to 10.1L/min), 4.0 ±
2.4 to 7.8L/min), respectively (n = 280). CO varied across
a sixfold range (1.9 to 11.7L/min) during the experiment.
The mean percentage bias and precision between paired
measures for FP and PAC were −17.2% and 47.0% (Limits of
agreement (LOA) −64.2 to 29.9), for FP and USCOM these
were1.0%and 36.4% (LOA −35.3to37.4),andFPandcPAC
−0.2% and 54.4% (LOA −53.6 to 53.1) (Table 1, Figures 1, 2,
3, and 4). Calibration of PAC to the FP, cPAC, improved the
bias when compared with FP from −17.2% to −0.2%, but
the error in precision increased from 47.0% to 54.4%.
Regression analysis demonstrated a correlation between
FP and PAC of y = 0.780x + 1.679L/min, compared with
correlations of y = 0.927x+0.308L/min for FP and USCOM
and y = 0.634x + 1.521L/min for FP and cPAC. Pearson
correlation across all CO measurements by FP and PAC was
FP versus PAC
Mean CO (L/min)
Figure 2: Bland Altman plots of FP versus PAC showing bias
(−17.2%) and LOAs (−64.2% and 29.8%).
Mean CO (L/min)
FP versus USCOM
Figure 3: Bland Altman plots of FP versus USCOM showing bias
(1%) and LOAs (−35.3% and 37.4%).
r = 0.604, while for FP and USCOM it was r = 0.813, and
for FP and cPAC r = 0.588.
measured by FP was 35% (3.85 ± 0.93 to 5.13 ± 1.31L/min)
while for PAC the measured dobutamine changes were15%
ment of 20% compared to FP, or a relative under measure-
ment of 56%. USCOM measured a 39% change (3.67 ± 0.96
to 5.04 ± 1.43L/min), an absolute difference of 4%, or a
relative difference of 10% from FP. For cPAC the change was
13% (3.79±1.23 to 4.30±1.26L/min), a 22% absoluteunder
measurement or a relative under measurement of 63%.
4Critical Care Research and Practice
Table 1: Summary of comparison of methods for all paired measures and all sheep as absolute values and % values (n = 280).
Mean (l/min) Bias (l/min)LOAs (L/min)
FP versus PAC4.4 ±1.3
FP versus cPAC4.0 ±1.1
−64.2 to 29.9
−35.3 to 37.4
−54.7 to 54.2
−3.3 to 1.7
−1.6 to 1.6
−3.0 to 1.8
FP versus cPAC
Mean CO (L/min)
Figure 4: Bland Altman plots of FP versus cPAC showing bias
(0.2%) and LOAs (−54.7% and 54.2%).
The decrease in CO induced by AVP was 13.7±7.35% for FP,
9.5±10.5% forPAC, 5.3±17.5% forUSCOM,and 4±13.5%
for cPAC (Table 2).
Reliable sensitivity to CO change, ROC AUC > 0.70, was
achieved by PAC for changes in excess of −30% but not
+40%, with AUC values for ±5% changes being 0.524 and
0.496, respectively, indicating random values (Figures 5 and
6). USCOM reliably detected all incremental CO changes
down to ±5%, where AUC values were 0.708 and 0.715.
USCOM was more sensitive to CO change than PAC for all
values from −40% to +40% (Table 3).
but not the precision nor sensitivity of the method (Table 1).
The FP calibration of USCOM allowed calculation of
sheep PV from a regression equation relating sheep weight
(kg), where PV = 0.0132 weight + 1.0329cm.
Despite no history of validation or efficacy, PAC has been a
clinical standard for hemodynamic measurement, diagnosis
and monitoring, and applied as a research method and refer-
ence standard against which new CO measurement methods
have been compared. This study found that PAC was an
inaccurate measure of CO and was unreliable for detec-
tion of CO changes less than 30–40%. These findings may
Detection of 5% decrease in CO
1 0.90.8 0.70.60.5 0.40.3 0.20.10
Figure 5: ROC curve for 70% certainty of detection of 5% decrease
in CO from baseline with PAC in red (AUC = 0.496), USCOM in
blue (AUC = 0.715). Random values are represented by the dotted
line (AUC = 0.50) and clinical effectiveness AUC ≥ 0.70.
explain the absence of reported outcomes benefit associated
with PAC use and raises questions as to its continued use
as a gold standard hemodynamic monitor. USCOM demon-
strated equivalence to FP measures across COs from 1.9 to
11.7L/min, and reliably detected ±5% changes in CO.
to have acceptable agreement with PAC but good agreement
with proven CO measures such as FPs and external cardiac
pumps. Prior comparisons of USCOM with PAC in post-
cardiac surgical critical care patients have reported bias’s of
study. While mean errors in precision reported for USCOM
PAC comparisons in a variety of clinical groups averaged
30% [28–33, 37, 43–46], the recommended acceptable cut-
off value . However, comparisons between USCOM and
non-PAC methods have demonstrated superior agreement.
Critchley et al. compared USCOM with FPs in dogs and
found a bias of less than 1% and an error in precision of 13%
across 319 paired measures . In heart failure patients
USCOM CO measures demonstrated a bias of less than 1%
and an error in precision of less than 10% when compared
with values from external circulatory pumps driving trans-
planted artificial hearts . The results from the current
side-by-side study demonstrate that PAC compares poorly
Critical Care Research and Practice5
Table 2: Mean percentage change of CO from baseline (0%) at each intervention and recovery time-point in all sheep by each method.
Table3:ROCareaunderthecurve(AUC)valuesfordetectionofincreasedanddecreasedpercentagechangesofCOrelativetoFPwhere P is
significance of difference between the two measures. An AUC of 1 represents perfect sensitivity, 0.7 represents clinically acceptable sensitivity
to change, while 0.5 is a random relationship.
1 0.9 0.80.7 0.60.50.40.30.20.10
Detection of 5% increase in CO
Figure 6: ROC curve for 70% certainty of detection of 5% increase
in CO from baseline with PAC in red (AUC = 0.524), USCOM in
blue (AUC = 0.708). Random values are represented by the dotted
line (AUC = 0.50) and clinical effectiveness AUC ≥ 0.70.
with both FP and USCOM as a measure and monitor of CO,
findings consistent with the prior studies.
The Bland Altman method is the standard statistical
method for comparison of two clinical methods , and
PAC has been the preferred reference method for validation
studies. However, PAC coefficient of variation (COV), an
index of repeatability, is high, being on average 28% in 8 hu-
man comparison studies with USCOM [28, 30, 32, 33, 37,
43, 44, 46]. Therefore it is almost mathematically impossible
for even a perfect reference method to achieve less than a
30% error of precision compared with PAC . This limi-
tation of bias and precision analysis was noted by Bland
and Altman  and confirms that the poor reproducibility
of PAC limits its performance as a reference standard for
CO method comparisons. In this study FP versus USCOM
errors in precision were smaller than those of FP versus PAC,
36% versus 47%, suggesting that, as the variability of FP is
a constant, the increased error in precision reflects the in-
creased variability of PAC alone. In clinical practice this poor
intrinsic repeatability of PAC is acknowledged by the aver-
aging of 3 measurements that fall within 10% of each other
to achieve a clinically acceptable measure . This meth-
odological bias may reject 3 or more PAC measures which
would otherwise contribute to true PAC variability and in-
crease the underlying COV.
tion of hemodynamic monitoring, with detection of 15%
changes in CO considered to be clinically desirable [46, 49].
However, 15% sensitivity is rarely achieved by current moni-
toring methods, with PAC sensitivity reported to be in the
order of 30% , similar to the 30–40% found in this
study. Walker et al. found CW Doppler sensitivity in hemo-
dynamics models to be 2.3% , while trans-aortic CW
Doppler measured minute distance (MD), a cross-sectional
area independent measure of output, has a reported sensi-
tivity of 11% and 20% [50, 51]. In this study USCOM was
found to reliably detect ±5% changes in CO 70% of the
time while 15% changes were detected with 80 to 85% cer-
tainty (Table 3). This high sensitivity is predicted by Moulin-
ier et al.  who identified an 11% sensitivity of a single
repeated Doppler CO/SV measure. Further Moulinier de-
monstrated that with repeated observations this sensitivity
was increased by a function of 1/√n, where n is the number
of repeated observations averaged to constitute the reference
measure. The mean number of repeated observations in this
study was 9 (range 6–12), meaning the predicted sensitivity
of USCOM, using generalizability theory and 9 repeated
measures, is 11% × 1/√9 or 4%, a value similar to the sen-
sitivity determined by the ROC AUC statistic of 5% found
in this study. PAC, using the same AUC > 0.70 to define ac-
ceptable sensitivity, detected a −30% change in CO but not a
+40% change relative to the FP (Table 3), a value broadly in
line with prior studies. Boyle et al, in a PAC USCOM com-
parison in ICU patients, found an AUC of 67% for detection
6Critical Care Research and Practice
of 15% changes , while in a similar comparison Thom
et al. found a 50% sensitivity for detecting 15% changes
. However, these comparisons with PAC as the reference
standard prove only that one of the methods, PAC or
USCOM, is insensitive to change and not which method is
inaccurate. The current study suggests that the insensitivity
of PAC is the source of this disagreement and not, as Boyle
and Thom hypothesised, the unreliability of USCOM.
The current data also demonstrate that PAC under meas-
ured the CO change associated with inotropic intervention,
a critical and common intervention in the deranged circu-
lation, by 20% (relative 66%) compared with the FP, while
USCOM differed by 4% (relative 10%). The differences be-
tween measured CO changes associated with vasopressors,
where the hemodynamic changes were smaller, were less
marked (Table 2). This study of normal sheep determined
that the mean inotropic reserve associated with a standard
weight indexed dobutamine dose was approximately 35%,
and that a normal vasopressor dose reduced CO by approxi-
mains the test of effectiveness of a method, and a number of
studies have been conducted to establish the clinical utility of
Connors et al. in a multicentre RCT demonstrated a rela-
tive increase in mortality of 26% and an increase in hospital
costs by 38% associated with PAC use in 5,735 critically ill
patients . Shah et al. in a meta-analysis of 13 randomised
controlled trials (RCT) between 1985 and 2005 studying
PAC use in 5,051 critically ill patients found no mortality
benefit or reduced in hospital stay despite an increased
use of inotropes and vasodilators  in PAC patients. The
ESCAPE trial, a 26 centre prospective RCT of PAC use in
433 acute heart failure patients was prematurely halted when
the National Heart, Lung, and Blood Institute Data Safety
and little likelihood of a positive outcome . The American
Society of Anesthesiology in a literature review identified an
associated mortality of 0.2 to 1.5% with PAC use, and an
incidence of catheter tip infection in excess of 19% and an
attributable sepsis rate of 0.7 to 3% .
A commonly cited benefit of PAC is that it provides
filling pressures which can be used to identify fluid respon-
siveness and guide fluid administration. However, these fil-
ing pressures have been found to be neither uniformly ac-
curate , nor effective [2, 42, 52] for fluid guidance with
Marick et al. demonstrating an AUC of 0.56 . USCOM-
measured SV changes with autologous physiologic chal-
lenges have been shown to detect fluid responsiveness with
a positive predictive value of 91% in a patient group that in-
cluded subjects in atrial fibrillation, on and off mechanical
ventilation, and on vasopressors . In the same study
the invasively measured central venous pressure (CVP) and
mean arterial pressure (MAP) were not significantly predict-
ive of fluid responsiveness with ROC AUC values of 0.52
and 0.62, respectively. Further Sturgess et al.  in a
study of septic subjects identified a correlation of 0.81 be-
tween USCOM measured corrected flow time (FTc) with
fluid responsiveness, while CVP and brain natriuretic pep-
tide (BNP) showed no significant correlation with fluid res-
ponsiveness, r = 0.4 and 0.3, respectively. Both of these stud-
ies relied on the sensitive detection of small incremental
changes in flow volume (CO/SV) using USCOM to describe
responsiveness, a utility which remains unproven in PAC.
is dependent on the accuracy of the prediction of the valve
area and any error in this calculation will convert directly to
an error in CO/SV. Two studies have reported poor agree-
(PV) diameter compared with the morphometrically deter-
mined USCOM values. These studies consequently reported
poor agreement of echocardiographic, and PAC determined
CO values [54, 55]. USCOM’s morphometrically calibrated
Doppler method is based on height and weight determined
the algorithm derived from normal 2D echocardiographic
data . While the 2D echocardiographic measurement of
valve diameters requires meticulous methodology for accu-
rate results  and has significant associated errors, Capps
et al. made direct measurement of the AV and PV diameters
of 6801 cardiac donors using Hegar dilators and derived
morphometric regression equations with values which
approximate those of the USCOM algorithms . Alterna-
tively, the AV or PV diameter, measured by another method
such as echocardiography or MRI, can be manually input to
over ride the USCOM algorithm and preserve reliability, or a
CSA-independent method such as MD, can be used to track
changes and monitor central circulation changes.
The outcomes benefits of hemodynamic optimization
seem intuitive and are the rationale for circulatory interven-
tions with fluid, inotropes, and vaso-active therapies. In
in overall mortality (7.6%) and morbidity . While the
impact of circulatory optimization in septic shock has an
even greater impact with a reported reduction in mortality
of 16% (relative 34%) in adults, and 27.4% (relative 70%)
in children [60, 61]. A noninvasive device which can rapidly
and accurately provide physiologically rational goals such as
SV and SVR for guidance of fluid, inotropes and vasoactive
therapies may increase the adoption of effective hemody-
namic strategies across a variety of clinical applications and
take advanced hemodynamics beyond the critical care.
4.1. Limitations. The PAC is used for CO measurement
in sheep and as a cardiovascular research tool, while the
USCOM algorithms were developed in human subjects. To
compensate the USCOM device was calibrated to baseline
FP measures, and this may have conferred some benefit to
the FP/USCOM bias comparison. However, calibration data
were excluded from analysis and 76% of all measurements
were made after interventions which altered CO across a six-
fold range (1.9 to 11.7L/min), thus mitigating any conferred
benefits from calibration. Additionally the interventional
component of the study, designed to assess sensitivity to CO
Critical Care Research and Practice7
change, involved calibrating all methods to a nominal zero
baseline, thus removing any advantage for any method. As a
further precaution a calibrated PAC series, cPAC, was gene-
rated post hoc to address any methodological bias in the
We found a 20% failure rate of PAC during the monitor-
body temperature of sheep is 39◦to 39.9◦C , higher than
However, we have no explanation for this high PAC failure
rate which may be a limitation of this study.
This study was of a continuous CO iteration of PAC,
CCO, and so some of the observations may not be inter-
changeable with bolus thermodilution. However, CCO is a
thermodilution method and has been adopted on the basis
of very good to excellent agreement with iced bolus thermo-
The FP was implanted around the ascending aorta meas-
uring left heart CO while both PAC and USCOM measured
coronary flow, the values should equate and the comparison
The PAC was sited in the pulmonary artery throughout
the studies, and would have caused some disturbance to the
flow characteristics measured by USCOM. This limitation
of the catheter measurements cannot be overcome in the
current preparation, and would also be a confounding factor
in clinical practice.
may explain the apparent ineffectiveness of PAC in clinical
practice. This study also found that USCOM provided equi-
valent CO measurements to FP and is a noninvasive and ac-
curate alternative to PAC reliably detecting ±5% changes in
An USCOM 1A device was lent to the Howard Florey In-
stitute for the purposes of this study. R. A. Phillips and B.
M. Jacobson are shareholders and employees of Uscom Ltd.
Thanks are due to Simon Parker for statistical support, and
Brendan Smith, Joe Brierley, David Bennett, Darryl Burstow,
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