Change in cardiac output during Trendelenburg maneuver is a reliable predictor of fluid responsiveness in patients with acute respiratory distress syndrome in the prone position under protective ventilation
Yonis et al. Critical Care
Change in cardiac output during Trendelenburg maneuver is a reliable predictor of fluid responsiveness in patients with acute respiratory distress syndrome in the prone position under protective ventilation
Hodane Yonis 1 4
Laurent Bitker 1 4
Mylène Aublanc 0 1 3 4
Sophie Perinel Ragey 0 1 3 4
Zakaria Riad 0 1 3 4
Floriane Lissonde 1 4
Aurore Louf-Durier 1 4
Sophie Debord 0 1 3 4
Florent Gobert 0 1 3 4
Romain Tapponnier 1 4
Claude Guérin 0 1 2 3 4
Jean-Christophe Richard 0 1 3 4 5
0 Université de Lyon, Université LYON I , Lyon , France
1 Service de Réanimation Médicale, Hôpital De La Croix Rousse, Hospices Civils de Lyon , 103 Grande Rue de la Croix Rousse, 69004 Lyon , France
2 IMRB, INSERM 955Eq13 , Créteil , France
3 Université de Lyon, Université LYON I , Lyon , France
4 Service de Réanimation Médicale, Hôpital De La Croix Rousse, Hospices Civils de Lyon , 103 Grande Rue de la Croix Rousse, 69004 Lyon , France
5 CREATIS INSERM 1044 CNRS 5220 , Villeurbanne , France
Background: Predicting fluid responsiveness may help to avoid unnecessary fluid administration during acute respiratory distress syndrome (ARDS). The aim of this study was to evaluate the diagnostic performance of the following methods to predict fluid responsiveness in ARDS patients under protective ventilation in the prone position: cardiac index variation during a Trendelenburg maneuver, cardiac index variation during an end-expiratory occlusion test, and both pulse pressure variation and change in pulse pressure variation from baseline during a tidal volume challenge by increasing tidal volume (VT) to 8 ml.kg-1. Methods: This study is a prospective single-center study, performed in a medical intensive care unit, on ARDS patients with acute circulatory failure in the prone position. Patients were studied at baseline, during a 1-min shift to the Trendelenburg position, during a 15-s end-expiratory occlusion, during a 1-min increase in VT to 8 ml.kg-1, and after fluid administration. Fluid responsiveness was deemed present if cardiac index assessed by transpulmonary thermodilution increased by at least 15% after fluid administration. Results: There were 33 patients included, among whom 14 (42%) exhibited cardiac arrhythmia at baseline and 15 (45%) were deemed fluid-responsive. The area under the receiver operating characteristic (ROC) curve of the pulse contourderived cardiac index change during the Trendelenburg maneuver and the end-expiratory occlusion test were 0.90 (95% CI, 0.80-1.00) and 0.65 (95% CI, 0.46-0.84), respectively. An increase in cardiac index ≥ 8% during the Trendelenburg maneuver enabled diagnosis of fluid responsiveness with sensitivity of 87% (95% CI, 67-100), and specificity of 89% (95% CI, 72-100). The area under the ROC curve of pulse pressure variation and change in pulse pressure variation during the tidal volume challenge were 0.52 (95% CI, 0.24-0.80) and 0.59 (95% CI, 0.31-0.88), respectively. (Continued on next page)
(Continued from previous page)
Conclusions: Change in cardiac index during a Trendelenburg maneuver is a reliable test to predict fluid
responsiveness in ARDS patients in the prone position, while neither change in cardiac index during end-expiratory
occlusion, nor pulse pressure variation during a VT challenge reached acceptable predictive performance to predict
fluid responsiveness in this setting.
Trial registration: ClinicalTrials.gov, NCT01965574. Registered on 16 October 2013. The trial was registered 6 days after
inclusion of the first patient.
Predicting fluid responsiveness is of paramount
importance to avoid unnecessary fluid administration in
patients with acute respiratory distress syndrome (ARDS),
since a positive fluid balance is strongly associated with
ARDS mortality [1, 2]. Several tests with high reliability
in prediction of fluid responsiveness may help
optimization of fluid administration to achieve a neutral
or negative fluid balance in this condition.
Pulse pressure variation (PPV) [3–5] and other
related tests exploring intra-tidal cyclic changes in
hemodynamics during mechanical ventilation [6–9]
are highly reliable to detect fluid responsiveness, as
long as the tidal volume (VT) is greater than
8 ml.kg-1, the cardiac rhythm is regular, the ratio of
heart rate to respiratory rate remains high , and
both compliance of the respiratory system and
abdominal pressure stay in the normal range. However,
all these validity criteria are strongly challenged in
patients with ARDS under protective ventilation
[11–13], even more so in the prone position (PP).
Cardiac index variation during an end-expiratory
occlusion (EEO), by transiently suppressing cardiopulmonary
interaction, and hence the cyclic impediment to cardiac
preload during inspiration, is reliable in supine patients
with ARDS to detect fluid responsiveness , but has
been validated with VT slightly higher than 6 ml.kg-1.
Since low respiratory system compliance decreases airway
pressure transmission to intravascular pressure , the
validity of this test may be challenged in patients with
severe ARDS under protective ventilation (VT of 6 ml.kg-1
predicted body weight (PBW) or lower).
Cardiac index variation during passive leg raising is
also a reliable method to identify fluid responsiveness
, free of the limitations of the previously
described tests, but is impracticable in the PP. The
Trendelenburg maneuver may be an interesting
alternative to transiently modify cardiac preload, and
identify fluid responsiveness. None of the previous tests
have been validated in the PP in patients with ARDS,
although this treatment is now a therapeutic standard
in severe ARDS .
The primary aim of this study was to evaluate the
diagnostic performance of cardiac index variation during a
Trendelenburg maneuver to predict fluid responsiveness
in patients with ARDS under protective ventilation in
the PP. Secondary objectives were to evaluate the
diagnostic performance of cardiac index variation during an
EEO, and both PPV and change in PPV from baseline
during a VT challenge from 6 to 8 ml.kg-1 PBW.
This study is a prospective single-center study,
performed between October 2013 and January 2017 in a
15bed medical ICU and registered at ClinicalTrials.gov
(NCT01965574). The study protocol (see Additional file
1) was approved by the local ethics committee (Comité
de Protection des Personnes Sud-Est IV,
ID-RCB-2013A00526-39). Written consent from the patients’ closest
relatives was required for inclusion, and eventually
confirmed by the patient after ARDS resolution.
The subjects had to fulfill all the following inclusion
criteria: ARDS according to the Berlin definition ,
ongoing session of PP under invasive mechanical
ventilation, ongoing monitoring with the PiCCO® device
(Pulsion Medical Systems, Feldkirchen, Germany), and
decision by the attending physician to administer fluids
with at least one criterion of acute circulatory failure
among the following: arterial lactate >2 mmol.L-1, mean
arterial pressure <65 mm Hg, cardiac output decrease,
urine output <0.5 ml.kg.h-1, heart rate >100 min-1 and
Non-inclusion criteria were the following: age
<18 years, contra-indication to the Trendelenburg
position, pregnancy, lower limbs amputation, known
obstruction of inferior vena cava, previous inclusion in
current study, and patient under a legal protection
measure as required by French regulation. Patients
exhibiting respiratory effort detected on the pressure-time
curve displayed on the ventilator during a 15-s EEO
were excluded from the study.
Patients were deeply sedated with a combination of
morphine and midazolam targeting a Ramsay score of 6 ,
and remained in PP with a 13° upward bed angulation
throughout the study, except during the Trendelenburg
maneuver. They were ventilated in volume-controlled
mode with a VT 6 ml.kg-1 PBW. Patients were studied at
baseline (baseline-1), during a 1-min postural change to
the Trendelenburg position with a −13° downward bed
angulation (Fig. 1), during a 1-min VT challenge at
8 ml.kg-1 PBW, during a 15-s EEO maneuver, and after
intravenous infusion (IV) of 500 ml crystalloids over
15 min. Patients were returned to baseline settings for
1 min after each intervention (see Additional file 2). The
following adverse events were prospectively collected
throughout the protocol: drop of systolic arterial
pressure >30 mm Hg, increase in heart rate >10%, decrease
in peripheral oxygen saturation <88%, new onset of
cardiac arrhythmia, or any other adverse event considered
relevant by investigators.
USA). Pressure transducers were taped on the thorax at
the phlebostatic reference point (Fig. 1). The following
hemodynamic variables were measured throughout the
study: arterial pressure, central venous pressure (CVP),
pulse contour-derived cardiac index (CCI), heart rate,
Transpulmonary thermodilution measurements were
performed at study onset (baseline-1) and after volume
expansion using the PiCCO® device. Values were
computed as the mean of four consecutive measurements,
using a 15-ml bolus of cold saline serum. ΔCCITREND
was computed as the difference between the maximal
value of CCI during Trendelenburg and baseline-1 CCI,
normalized by baseline-1 CCI. ΔPPV6-8 was computed
as the difference between the maximal value of PPV
during ventilation with VT 8 ml.kg-1 and baseline-2 PPV,
normalized by baseline-2 PPV. ΔCCIEEO was computed
as the difference between the maximal value of CCI
during the EEO maneuver and baseline-3 CCI, normalized
by baseline-3 CCI. Fluid responsiveness was deemed
present if cardiac index assessed by transpulmonary
thermodilution (CITPTD) increased by at least 15% after
volume expansion, as compared to baseline-1 .
Jugular central venous and femoral arterial lines were
connected to an Intellivue MP40 monitor equipped with
a PiCCO® module (Philips Healthcare, Andover, MA,
The study primary endpoint was the diagnostic
performance of ΔCCITREND to predict fluid responsiveness.
Secondary endpoints were diagnostic performance of
ΔCCIEEO to predict fluid responsiveness, and both PPV
Statistical analyses were performed using R . Median
(1st quartile to 3rd quartile) and counts with percentages
are reported for quantitative and categorical variables,
respectively. A p value below 0.05 was chosen for
We calculated that with a sample size of 33 patients,
the study would provide at worst ± 0.15 precision for the
95% confidence interval (CI95%) of the area under the
receiver operating characteristic (ROC) curve (AUC),
assuming a prevalence of fluid responsiveness of 50% [16,
22–24] and an AUC of at least 0.8  (i.e. a lower
bound for the AUC CI95% amounting to at least 0.65).
Comparisons between groups of patients were
performed with the Fisher’s exact test for categorical
variables, and with the t test, Mann-Whitney test or analysis
of variance (ANOVA) for continuous and ordinal
variables when appropriate. Hemodynamic parameters were
compared using a linear mixed effects model [26, 27].
Multiple comparisons between experimental conditions
and baseline-1 were performed using Dunnett’s test .
Diagnostic performance of tests under investigation
was assessed by computation of the AUC . The
CI95% for the AUC was computed using the Delong
method. The optimal cutoffs were computed by
maximizing the Youden index. The CIs for optimal cutoffs
were computed using the gray zone approach (area of
uncertainty of optimal cutoffs) . Response to each
test below the lower or above the higher border of the
gray zone were considered negative and positive,
respectively. Responses to the test within the gray zone
were considered inconclusive. The CI95% for sensitivity,
specificity and medians were computed using
bootstrapping and 10000 replicates [30, 31].
During the study period, 55 patients presented with
inclusion criteria (see Additional file 3) and 33 were
included, whose general characteristics, cardiovascular and
respiratory parameters at inclusion are reported in
Tables 1 and 2. There were 14 patients (42%) who
exhibited cardiac arrhythmia at inclusion and were excluded
in the analyses pertaining to PPV: 15 patients (45%) were
classified as fluid responsive after fluid administration.
The total duration of the study amounted to 26 (
min. None of the variables measured after return to
baseline settings (baseline-2 to baseline-4) were
significantly different from baseline-1 (Table 3). Mean arterial
pressure, CVP, CITPTD, global end-diastolic volume
index and global ejection fraction increased significantly
after fluid administration. No adverse event was
identified throughout the protocol.
CVP increased significantly during Trendelenburg, while
heart rate remained unchanged (Table 3). Median
ΔCCITREND amounted to 6% (CI95%, 3–10%) and was significantly
greater in responders than in non-responders (13% vs. 3%, p
< 0.001, Fig. 2). ΔCCITREND was significantly correlated with
change in CITPTD related to volume expansion (R2 = 0.41,
Fig. 3). ΔCCITREND predicted fluid responsiveness with an
AUC of 0.90 (CI95%, 0.80–1.00, p < 0.001), with sensitivity
of 87% and specificity of 89% at a threshold of 8% (gray
zone, 5–12%) (Table 4, Figs. 4 and 5). Cardiac index
response to volume expansion increased stepwise in patients
with a negative response, those with an inconclusive
response, and those with a positive response to the test (see
Additional file 4). Four patients were misclassified (Fig. 2),
and none of their hemodynamic and respiratory parameters
were significantly different from those of the 29 correctly
classified patients (data not shown).
Pulse pressure variation
PPVBASELINE-1, PPVVT8 and ΔPPV6-8 did not significantly
differ between fluid responders and non-responders
(Fig. 2). None of the three PPV-derived diagnostic tests
were statistically significant for AUC (Table 4, Fig. 4).
ΔPPV6-8 exhibited the greatest sensitivity (100% (CI95%,
100–100%)) at a threshold of 29%, but with a very low
specificity (40% (CI95%, 10–70%)).
False positive patients with the PPVBASELINE-1 test had
significantly greater driving pressure while true negative
had significantly lower PaO2/FiO2 ratio (data not
shown). CITPTD at inclusion was significantly lower in
the 5 false positive patients as assessed by PPVVT8.
CVP decreased slightly but significantly from 7 (
) mm Hg during EEO, while CCI remained
unchanged (Table 3). ΔCCIEEO was not significantly different
in responders and non-responders (Fig. 2). The AUC of
ΔCCIEEO to predict fluid responsiveness amounted to 0.65
(CI95%, 0.46–0.84), and was not significantly different from
0.5 (Table 4, Fig. 4). ΔCCIEEO had sensitivity of 33%
(CI95%, 13–60%) and specificity of 100% (CI95%, 100–
100%) at a threshold of 10% (gray zone, –4% to 11%) to
predict fluid responsiveness (Table 4, Fig. 5).
In the 14 patients with change in CVP (ΔCVP) ≥0 mm
Hg, the AUC of ΔCCIEEO amounted to 0.89 (CI95%, 0.70–
1.00) (p < 0.05), while it was not statistically different
from 0.5 in the 19 patients with ΔCVP <0 mm Hg (see
Additional files 5 and 6).
This study is the first to evaluate the diagnostic
performance of several diagnostic tests to predict fluid
responsiveness in patients with ARDS in the PP under
protective ventilation. The main findings are that: (
change in cardiac index during the Trendelenburg
maneuver is a highly reliable test to predict fluid
responsiveness, with both sensitivity and specificity approximating
) change in PPV during a transient increase in
VT from 6 to 8 ml.kg-1 is highly sensitive to predict fluid
Table 2 Cardiovascular and respiratory parameters at inclusion
Parameters Overall population (n = 33) Fluid non-responders (n = 18) Fluid responders (n = 15) p
Norepinephrine administration 28 (85%) 17 (94%) 11 (73%) 0.15
Norepinephrine dose (μg.kg-1.min-1) 0.98 (0.41–1.50) 0.68 (0.35–1.04) 1.32 (0.71–1.97) 0.12
Dobutamine administration 7 (21%) 4 (22%) 3 (20%) 1
Dobutamine dose (μg.kg-1.min-1) 10.0 (7.5–14.8) 11.4 (8.8–13.8) 10.0 (5.2–14.9) 0.86
Heart rate (min-1) 100 (93–115) 102 (92–117) 100 (93–112) 0.69
MAP (mm Hg) 69 (64–72) 67 (62–71) 70 (68–72) 0.14
PPV (%)a 7 (
) 7 (
) 7 (
CVP (mm Hg) 7 (
) 7 (
) 7 (
CITPTD (L.min-1.m-2) 2.75 (2.06–3.50) 2.94 (2.26–3.50) 2.70 (2.04–3.04) 0.48
GEDVI (ml.m-2) 701 (587–854) 697 (586–866) 701 (614–773) 0.89
ELWI (ml.kg-1 PBW) 14.6 (11.8–20.4) 15.8 (12.6–20.9) 13.7 (10.1–18.3) 0.23
Global ejection fraction (%) 16 (
) 16 (
) 16 (
Respiratory rate (min-1) 30 (
) 30 (
) 30 (
Heart rate/respiratory rate ≤3.6 20 (61%) 10 (56%) 10 (67%) 0.72
Tidal volume (ml.kg-1 PBW) 6.0 (5.9–6.1) 6.0 (6.0–6.1) 6.0 (5.9–6.0) 0.31
PEEP (cm H2O) 8 (
) 8 (
) 8 (
PEEPt,rs (cm H2O) 9 (
) 9 (
) 10 (
Pplat,rs (cm H2O) 22 (
) 22 (
) 22 (
Driving pressure (cm H2O) 12 (
) 13 (
) 11 (
Cst,rs (mL.cm H2O-1) 30 (
) 28 (
) 31 (
pH 7.33 (7.27–7.38) 7.31 (7.27–7.36) 7.38 (7.28–7.42) 0.20
PaO2/FiO2 (Torr) 158 (120–208) 155 (120–167) 207 (109–241) 0.17
PaCO2 (Torr) 41 (
) 46 (
) 38 (
Arterial lactate (mmol.L-1) 2.5 (1.9–6.4) 2.5 (1.9–6.3) 2.5 (1.8–5.8) 0.94
Data are median (1st quartile to 3rd quartile) or count (percentage)
CITPTD cardiac index assessed by transpulmonary thermodilution, Cst,rs static compliance of the respiratory system, CVP central venous pressure, ELWI extravascular
lung water index, FiO2 inspired oxygen fraction, GEDVI global end-diastolic volume index, MAP mean arterial pressure, PaO2 partial pressure of arterial oxygen,
PaCO2 partial pressure of arterial carbon dioxide, PBW predicted body weight, PEEP positive end-expiratory pressure, PEEPt,rs total PEEP of the respiratory system,
Pplat,rs plateau pressure of the respiratory system
aFor patients without cardiac arrhythmia
responsiveness, but with low specificity; and (
in cardiac index during EEO has low sensitivity, but high
specificity to predict fluid responsiveness in this clinical
Reliability of the Trendelenburg maneuver to predict fluid responsiveness
In the present study, ΔCCITREND amounted to 6%
(CI95%, 3–13%), and was in the range of the 9% increase
observed in a recent systematic review , although
performed in subjects in the supine position, with
various degrees of head-down tilt angulation. An important
issue in the reliability of the Trendelenburg maneuver to
predict fluid responsiveness is related to baroreflex
activation in this position, leading to systemic vasodilation,
decreased heart rate and myocardial contractility.
However, we did not observe a significant change in heart
rate in the Trendelenburg position as compared to
baseline, in keeping with the results of the aforementioned
systematic review . While baroreflex activation is
Fig. 3 Relationship between change in continuous cardiac index
during the Trendelenburg maneuver (ΔCCITREND) and change in
transpulmonary thermodilution-cardiac index by volume expansion
(ΔCIVE). The black line is the regression line. The shaded area is the
95% confidence interval of the regression line. There are 33 data
points presented although some data points are overlapping
immediately evident after carotid declamping in patients
who were awake and undergoing carotid surgery, the
maximal effect on heart rate is observed 10 min later .
Opposite to this, in healthy volunteers, midazolam has been
shown to dose-dependently blunt the fast parasympathetic
efferent pathway of the baroreflex [34, 35]. Taken together,
these data suggest that the 1-min duration of the maneuver
may not have been long enough to significantly activate the
baroreflex in deeply sedated patients with ARDS.
Reliability of PPV to predict fluid responsiveness
The present study confirmed the lack of predictive
ability of PPV to predict fluid responsiveness in patients
with ARDS under protective ventilation [11–13]. This
finding is not unexpected since cardiopulmonary
interactions under mechanical ventilation (the underlying
physiological mechanism behind PPV) are dependent on
both ventilatory settings and transmission of airway
pressure to cardiac filling pressures. This transmission is
inversely related to respiratory system elastance ,
and linearly related to the ratio of chest wall to
respiratory system elastances . In conditions combining low
VT and low respiratory system elastance as observed in
patients with ARDS under protective ventilation, a high
rate of false negative patients is expected.
Performing a VT challenge did not significantly
enhance the reliability of the PPV test, since sensitivity
increased at the expense of specificity. While this VT
challenge increased the reliability of the PPV test in one
study performed on 22 ICU patients in the supine
position (9% with ARDS) , our data suggest that this
finding should not be extrapolated to patients with
ARDS on PP. Previous studies have shown that false
positive patients for PPV may occur in the context of
right ventricular failure [7, 37], and the higher driving
pressure in this group of the present study favors this
Reliability of EEO to predict fluid responsiveness
The EEO test has been shown to accurately predict fluid
responsiveness in the supine position in four studies [12,
14, 39, 40] including one restricted to patients with
ARDS ventilated with VT slightly greater than 6 ml.kg-1
. However, its predictive performance was poor in a
recent study in which 6 ml.kg-1 VT was first applied, but
was restored during a VT challenge at 8 ml.kg-1 .
Our results are in line with this study, and the high rate
of false negative patients in our study (30%) suggests
that the decrease in the cyclic stress applied to the
cardiovascular system during ARDS under protective
ventilation (due to both low VT and decreased respiratory
system compliance) is not sufficient to generate a
detectable effect on cardiac index in some patients. We
therefore hypothesized that the PP-induced increase in
intraabdominal pressure  could generate an impediment
to venous return, promoting a zone-2 condition in the
inferior vena cava in some patients  (and hence a
Table 4 Diagnostic performance of five diagnostic tests to predict fluid responsiveness
Tests Number of AUC (CI95%) Optimal Gray zone of optimal threshold Patients in gray Sensitivity (CI95%) Specificity (CI95%) PLR NLR
patients analyzed threshold zone, (number (%))
ΔCCITREND 33 0.90* (0.80–1.00) 8% (5–12%) 10 (30%) 87% (67–100%) 89% (72–100%) 7.90 0.15
PPVBASELINE-1 19 0.49 (0.21–0.77) 10% (–Inf to Inf) 19 (100%) 33% (0–67%) 80% (50–100%) 1.65 0.84
PPVVT8 19 0.52 (0.24–0.80) 9% (–Inf to Inf) 19 (100%) 78% (44–100%) 40% (10–70%) 1.30 0.56
ΔPPV6-8 19 0.59 (0.31–0.88) 29% (17%–Inf) 16 (84%) 100% (100–100%) 40% (10–70%) 1.67 0
ΔCCIEEO 33 0.65 (0.46–0.84) 10% (−4% to 11%) 26 (79%) 33% (13–60%) 100 (100–100%) Inf 0.67
AUC area under ROC curve. CI95% 95% confidence interval, ΔCCIEE change in continuous cardiac index during end-expiratory occlusion, ΔCCITREND change in
continuous cardiac index during the Trendelenburg maneuver, ΔPPV6-8 change in pulse pressure variation between ventilation with 6 and 8 ml.kg-1 predicted body
weight tidal volume, Inf infinity, NLR negative likelihood ratio, PLR positive likelihood ratio, PPVBASELINE-1 pulse pressure variation at baseline-1, PPVVT8 pulse pressure
variation during ventilation with 8 ml.kg-1 tidal volume
*p < 0.001 vs. an AUC of 0.5
pressure gradient between the inferior vena cava and the
right atrium), and could explain the high false negative
rate in our study. The slight decrease in CVP during the
EEO in 53% of the patients, combined with the low
predictive value of ΔCCIEEO in this subpopulation favors
this hypothesis, although the lack of direct measurement
of intra-abdominal pressure and venous return precludes
any definite conclusion. Finally, it should be emphasized
that the EEO remains a highly specific test in patients
with ARDS under protective ventilation in PP.
Some limitations of the present study should be
acknowledged. First, the monocentric feature of this study
questions the generalizability of its results. Second,
amplifying the postural change during the Trendelenburg
maneuver (beyond 13° and −13°) could have maximized
the blood transfer from the lower body parts towards
the central circulation and may have further increased
the sensitivity of this test. Third, the high number of
patients with cardiac arrhythmia (therefore excluded from
PPV analyses) makes the study strongly underpowered
for all analyses pertaining to this test. Fourth, the lack of
blinding precludes control of a potential evaluation bias.
Fifth, cardiac output assessed from pulse contour
analysis may be inaccurate in relation to change in resistive
and elastic characteristics of the vascular system,
although its reliability is acceptable during the hour
following calibration . Finally, the lack of
randomization between the three maneuvers performed
to predict fluid responsiveness (namely Trendelenburg
maneuver, VT challenge and EEO) could have hampered
a reliable evaluation of the latter two tests.
Risk minimization is an important issue in fluid
administration in patients with severe ARDS, given the potential
for harm of unnecessary fluid bolus. Using the
Trendelenburg test, 70% of the patients could be classified
outside the gray zone, meaning that fluid responsiveness
was assessed with near certainty in the majority of the
patients. Regarding the 30% of patients within the gray
zone of the Trendelenburg test, fluid administration may
be considered, although response to fluid therapy may
be less intense in this group. Finally, whether guiding
fluid therapy using indices of fluid responsiveness
improve ARDS prognosis remains unknown, although it
may help to decrease fluid administration in patients
with septic shock .
This study suggests that the Trendelenburg maneuver is
reliable to predict fluid responsiveness in patients with
ARDS under protective ventilation in the prone position.
Pulse pressure variation or change in pulse pressure
variation from baseline during a tidal volume challenge,
and the end-expiratory occlusion test, although reliable
in other clinical settings, did not reach acceptable
predictive performance for fluid responsiveness.
Additional file 1: Study protocol. Study protocol as it was submitted to
ethics committee and French heath regulation authorities. (DOC 330 kb)
Additional file 2: Figure S1. Protocol description. (DOCX 71 kb)
Additional file 3: Figure S2. Study flow chart. (DOCX 397 kb)
Additional file 4: Figure S3. Change in transpulmonary
thermodilution-cardiac index by volume expansion (ΔCIVE) as function of
response to five diagnostic tests. (DOCX 314 kb)
Additional file 5: Table S1. Diagnostic performance of end-expiratory
occlusion to predict fluid responsiveness as a function of change in CVP
(ΔCVP) during the test as compared to baseline. (DOCX 14 kb)
Additional file 6: Figure S4. Receiver operating characteristics curves
of end-expiratory occlusion to predict fluid responsiveness as a function
of change in CVP (ΔCVP) during the test as compared to baseline.
(DOCX 67 kb)
Additional file 7: Dataset. (XLSX 53 kb)
ARDS: Acute respiratory distress syndrome; AUC: Area under the receiver
operating characteristic curve; CCI: Pulse contour-derived cardiac index;
CI95%: 95% Confidence interval; CITPTD: Transpulmonary thermodilution;
CVP: Central venous pressure; EEO: End-expiratory occlusion; PBW: Predicted
body weight; PP: Prone position; PPV: Pulse pressure variation; ROC: Receiver
operating characteristic; VT: Tidal volume; ΔCCITREND: Difference between
the maximal value of CCI during Trendelenburg and baseline-1 CCI,
Normalized by baseline-1 CCI; ΔPPV6-8: Difference between the maximal value of
PPV during ventilation with tidal volume 8 ml.kg-1 and baseline-2 PPV,
normalized by baseline-2 PPV; ΔCCIEEO: Difference between the maximal value
of CCI during the EEO maneuver and baseline-3 CCI, normalized by
Availability of data and materials
All data generated or analyzed during this study are included in this published
article and its supplementary information files (see Additional file 7).
HY made substantial contributions to data acquisition, study analysis, and
interpretation of data; AND revised the manuscript for important intellectual
content; AND approved the version to be published; AND agreed to be
accountable for all aspects of the work in ensuring that questions related to
the accuracy or integrity of any part of the work are appropriately
investigated and resolved. LB made substantial contributions to study
analysis, and interpretation of data. MY made substantial contributions to
study analysis and interpretation of data. SPR made substantial contributions
to study analysis, and interpretation of data. ZR made substantial
contributions to study analysis, and interpretation of data. FL made
substantial contributions to study analysis, and interpretation of data. ALD
made substantial contributions to study analysis, and interpretation of data.
SD made substantial contributions to study design, data acquisition, study
analysis, and interpretation of data. FG made substantial contributions to
study analysis, and interpretation of data. RT made substantial contributions
to study analysis, and interpretation of data. CG made substantial
contributions to study analysis, and interpretation of data. JCR made
substantial contributions to study design, data acquisition, study analysis, and
interpretation of data. AND agreed to be accountable for all aspects of the
work in ensuring that questions related to the accuracy or integrity of any
part of the work are appropriately investigated and resolved. All authors read
and approved the final manuscript.
Ethics approval and consent to participate
The study protocol was approved by the local ethics committee (Comité de
Protection des Personnes Sud-Est IV, ID-RCB-2013-A00526-39). Written consent
from the patients’ closest relatives was required for inclusion, and eventually
confirmed by the patient after ARDS resolution.
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in
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