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The use of static and dynamic haemodynamic parameters before volume expansion: A prospective observational study in six French intensive care units
Accepted Manuscript Title: The use of static and dynamic haemodynamic parameters before volume expansion: a prospective observational study in six French intensive care units Author: S´ebastien Preau Florent Dewavrin Vincent Demaeght Arnaud Chiche Benoˆıt Voisin Franck Minacori Julien Poissy Claire Boulle-Geronimi Caroline Blazejewski Thierry Onimus Alain Durocher Fabienne Saulnier PII: DOI: Reference:
S2352-5568(15)00143-5 http://dx.doi.org/doi:10.1016/j.accpm.2015.08.003 ACCPM 88
To appear in: Received date: Accepted date:
27-6-2014 31-8-2015
Please cite this article as: S´ebastien PreauFlorent DewavrinVincent DemaeghtArnaud ChicheBenoˆıt VoisinFranck MinacoriJulien PoissyClaire Boulle-GeronimiCaroline BlazejewskiThierry OnimusAlain DurocherFabienne Saulnier The use of static and dynamic haemodynamic parameters before volume expansion: a prospective observational study in six French intensive care units (2015), http://dx.doi.org/10.1016/j.accpm.2015.08.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The use of static and dynamic haemodynamic parameters before volume expansion: a prospective observational study in six French intensive care units
Évaluation prospective de l’utilisation des paramètres hémodynamiques statiques et dynamiques avant
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remplissage vasculaire dans six réanimations françaises.
Sébastien Preau 1, Florent Dewavrin 2, Vincent Demaeght 2, Arnaud Chiche 3, Benoît Voisin 1, Franck
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Minacori 4, Julien Poissy 1, Claire Boulle-Geronimi 5, Caroline Blazejewski 6, Thierry Onimus 1, Alain
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Durocher 1, Fabienne Saulnier 1.
(1) Intensive Care Unit, Calmette Hospital, University Hospital of Lille, France. (2) Intensive Care
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Unit, General Hospital of Valenciennes, France. (3) Intensive Care Unit, General Hospital of Tourcoing, France. (4) Intensive Care Unit, University Hospital of Lomme, France. (5) Intensive Care
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Hospital of Lille, France.
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Unit, General Hospital of Douai, France. (6) Intensive Care Unit, Salengro Hospital, University
S. Preau: [email protected], F. Dewavrin: [email protected], V. Demaeght: [email protected], A. Chiche: [email protected], B. Voisin: [email protected], F., Minacori: [email protected], J. Poissy: [email protected], C. Boulle-Geronimi: [email protected], C. Blazejewski: [email protected], T. Onimus: [email protected], A. Durocher: [email protected], F. Saulnier: [email protected]
CORRESPONDING AUTHOR
S. Preau (MD, PhD), Critical care centre, University Hospital of Lille, Avenue du Professeur Emile Laine, Lille 59037, France. [email protected]. Telephone: +333 20 44 40 84. Fax: +333 20 44 50 94
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Abbreviations CO, cardiac output. CVP, central venous pressure. GEDV, global end diastolic volume.
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ICU, intensive care unit. IVCV, respiratory variations in inferior vena cava diameter.
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PAOP, pulmonary artery occlusion pressure. PLR, passive leg raising.
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SIRS, systemic inflammatory response syndrome. SV, stroke volume.
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VE, volume expansion. VPP, respiratory variations in systemic pulse pressure.
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ABSTRACT
Objective: The aim of the present study was to determine the use of static and dynamic haemodynamic parameters for predicting fluid responsiveness prior to volume expansion (VE) in intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS). Methods: We conducted a prospective, multicentre, observational study in 6 French ICUs in 2012. ICU physicians were audited concerning their use of static and dynamic haemodynamic parameters before each VE performed in patients with SIRS for 6 consecutive weeks. Results: The median volume of the 566 VEs administered to patients with SIRS was 1,000 ml [5001,000 ml]. Although at least one static or dynamic haemodynamic parameter was measurable before 99% (IC95%, 99% - 100%) of VEs, at least one them was used in only 38% (IC95%, 34% - 42%) of
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cases: static parameters in 11% of cases (IC95%, 10% - 12%) and dynamic parameters in 32% (IC95%, 30% - 34%). Static parameters were never used when uninterpretable. For 15% of VEs (IC95%, 12% - 18%), a dynamic parameter was measured in the presence of contraindications. Among dynamic parameters, respiratory variations in arterial pulse pressure (PPV) and passive leg raising
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(PLR) were measurable and interpretable before 17% and 90% of VEs, respectively. Conclusions: Haemodynamic parameters are underused for predicting fluid responsiveness in current
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practice. In contrast to static parameters, dynamic parameters are often incorrectly used in the presence of contraindications. PLR is more frequently valid than PPV for predicting fluid responsiveness in
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ICU patients.
KEY WORDS: Intensive care; Sepsis; Inflammation; Systemic inflammatory response syndrome;
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INTRODUCTION
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SIRS; Fluid; Preload; Passive leg raising; Respiratory variations.
Fluid loading is a common therapy in intensive care units (ICU) for patients with systemic inflammatory response syndrome (SIRS) and acute circulatory failure (1, 2). Fluid administration compensates for an absolute or relative decrease in circulating volume. Despite positive effects upon cardiac output and tissue perfusion when accurately performed, an inappropriate amount of fluid may be deleterious and is associated with poor outcome. Indeed, excessive fluid loading may lead to pulmonary oedema (3, 4), while insufficient fluid loading fails to prevent global hypo-perfusion, commonly found in SIRS conditions (5, 6).
The rapid and repetitive perfusion of small amounts of crystalloids or colloids, i.e. the so-called volume expansion (VE), is recommended in current practice to optimize fluid therapy (1, 7–9). A VEinduced change in stroke volume (SV) of ≥ 10-15% usually defines a positive response to VE (7). Despite the selection of patients with acute circulatory failure, only half of all ICU patients increase
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their SV in response to VE (10). The repetition of ineffective and possibly deleterious VE may lead to fluid overload and poor outcome. Numerous haemodynamic parameters are currently available for predicting the benefit-risk balance of VE at the bedside. Static parameters such as central venous pressure (CVP), pulmonary artery
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occlusion pressure (PAOP), or global end diastolic volume measured with a PiCCOTM device (GEDV) require pressure or volume measurements. Dynamic parameters such as respiratory variations in
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systemic pulse pressure (PPV), expiratory occlusion test-induced change in pulse pressure, passive leg raising (PLR)-induced change in haemodynamics, or respiratory variations in inferior vena cava
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diameter (IVCV) require pressure, flow or diameter measurements during dynamic procedures. Conflicting recommendations on the use of static and dynamic parameters for predicting or evaluating
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fluid responsiveness in current practice have been published (1, 2, 7–9). In international guidelines, static parameters and fluid challenge are recommended in the early phase of haemodynamic
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resuscitation of patients with shock or severe sepsis (8,9). Conversely, French guidelines recommend
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the early use of dynamic parameters in this setting (1,7).
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To our knowledge, only one study has estimated the current use of static and dynamic haemodynamic parameters in critically ill patients (11). Moreover, as several studies have analysed PPV suitability in current practice (12,13), there is no similar information about other dynamic parameters. The main aim of the study was to determine the use and limitations of static or dynamic parameter measurements prior to VE in ICU patients with SIRS. A secondary aim was to determine physicians’ accordance with guidelines and elucidate perceptions of their own individual practice. MATERIALS AND METHODS
We conducted a prospective, multicentre, observational study in 6 French ICUs in 2012. The study was approved by the regional ethics committee of the North of France and no informed consent was required from patients. Study design
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First part (preliminary questionnaire): The physicians’ agreement with guidelines and their perception of their own practices were evaluated during a 2-week period from 16 to 29 April 2012. All 88 physicians present at the time of the audit were asked to fill out a written anonymous questionnaire concerning their agreement with current recommendations (1, 2, 7–9) and the perception of their own use of static and dynamic haemodynamic parameters to guide VE. The questionnaire consisted of
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multiple-choice questions with 4 levels of answers concerning agreement (total agreement; agreement; disagreement; total disagreement) and frequency (≥ 75%; ≥ 50% to < 75%; ≥ 25% to < 50%; < 25%)
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(Figure 1). All physicians except F. Dewavrin and S. Preau were blinded to incoming evaluations of
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their practice 6 months later.
Second part (prospective observational study): The use of static and dynamic haemodynamic
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parameters prior to VE was determined over a 6-week period from November 5 to December 16, 2012. Physicians were audited for each VE they performed in patients with SIRS hospitalized at the 6
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ICUs participating in the study. The decision to perform VE and the fluid therapy administered were left to the discretion of the individual clinician. SIRS was defined as the presence of at least 2 criteria
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among the following 4: high or low body temperature (> 38°C or < 36°C), elevated heart rate (> 90
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b/min), high respiratory rate (> 20 c/ min) or a low PaCO2 (< 32 mmHg) and significant white blood cell changes (elevated white blood cell count of > 12,000.109 cells.l-1, < 4,000 cells.l-1, or the presence of more than 10% immature neutrophils) (14). VE was defined as any intravenous administration of fluid (crystalloid or colloid) within one hour. Blood product transfusions were not considered to be VE. The written anonymous questionnaire was composed of 4 items: physician’s grade, clinical signs of acute circulatory failure (systemic arterial hypotension, tachycardia, mottled skin and oliguria), static and dynamic haemodynamic parameters measured before VE and VE characteristics (volume and type) (Figure 2). All ICU physicians and nurses were trained and implicated in the study. Questionnaires were combined with fluid loading solutions so that nurses could systematically ask physicians to fill out the forms while they were administering VE. The quantification of prescribed VEs, the number of questionnaires filled out, the availability and lack of contraindications in haemodynamic measurements were checked retrospectively within 48 h by the main investigator at
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each centre (Figure 3). Limitations for static and dynamic parameters were as follows (10,13): irregular cardiac rhythm, spontaneous breathing activity, low tidal volume (< 8 ml / kg of body weight), low ratio: heart rate / respiratory rate (< 3.6), poor pulmonary compliance (≤ 30 ml / cmH2O), low airway driving pressure (≤ 20 cmH2O) and right ventricular dysfunction (peak systolic velocity of tricuspid annular motion assessed by tissue Doppler echocardiography <0.15 m/s) for PPV;
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spontaneous breathing activity for respiratory occlusion test; spontaneous breathing activity and
abdominal compartment syndrome for IVCV; amputation of lower limbs, abdominal compartment
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syndrome and high intracranial pressure for PLR; pressure measurement site not placed in superior
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vena cava or right atrium for CVP; lack of pulmonary artery catheter in place for PAOP; abdominal cava/common iliac vein catheter, aortic aneurysm, intra-cardiac shunt and severe valvular
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insufficiency for GEDV. Because reliable retrospective estimations of respiratory plateau pressure and tissue Doppler echocardiography were not possible in the participating ICUs, the presence of some
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PPV limitations (e.g. poor pulmonary compliance, low airway driving pressure and right ventricular dysfunction) were not recorded. Moreover, the measurement methods for CVP and PAOP (pressure
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transducer location, time of measurement within respiratory and cardiac cycles), GEDV (volume,
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number, temperature, time and length of injections), PPV (automatic or manual, number of cardiac cycles, threshold values), PLR (automatic bed elevation technique, lowering of the head and trunk, SV or CVP measurement) and IVCV (sampling location, TM or bi-dimensional mode, long or short axis view, time of measurement within respiratory and cardiac cycles) were not recorded. Statistical analysis
The statistical unit was a VE. The main judgment criterion was the percentage of VEs preceded by any measurement of static or dynamic parameters. A recent study from the ICU of the Hospital Centre of Valenciennes (France, 23 beds) showed that 509 VEs were performed over a 6 month period (15). We estimated that 35% of VEs were preceded by measurement of static and/or dynamic parameters. From these data, we calculated that 546 VEs were needed for a 4% precision with a risk α ≤ 5%. We estimated that a study period of 6 weeks would be necessary to analyse at least 546 VEs in the 6 ICUs (114 beds) participating in the study. Qualitative variables were expressed as frequencies and
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percentages. Frequencies were compared using a Fisher test. The normality of quantitative variables was tested using a Kolmogorov-Smirnov test. Quantitative variables were expressed as means ± SD if normally distributed, or medians [25 - 75% interquartile range] if not. Differences between two independent means were tested using the Student t-test if normally distributed or the Mann-Whitney test if not. A P-value ≤ 0.05 was considered statistically significant. Statistical analysis was performed
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using SPSS 13.0.1TM software (SPSS, Chicago IL).
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RESULTS
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Between November 5 and December 16, 2012, 566 (75%) VEs were prescribed in patients with SIRS. SIRS was diagnosed by the presence of fever (n = 313, 55%), elevated heart rate (n = 444, 78%),
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tachypnea (n = 457, 81%) and significant white blood cell changes (n = 412, 73%). Nurses did not communicate any refusals to answer a questionnaire during the study and the main investigators
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reported that a questionnaire was filled out for each prescribed VE. The median volume of VE was 1,000 mL [500 - 1,000 mL] and crystalloids were prescribed more frequently than colloids (58%
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versus 42%; P < 0.001) (Table 1). The mean volume of VE was higher with crystalloids, 1,000 mL
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[1,000 - 1,000 mL], than with colloids, 500 mL [500 - 500 mL] (P < 0.0001). Seniors and residents prescribed 57% and 43% of VEs, respectively. Seniors more frequently prescribed colloids than did residents (50% versus 33%; P < 0.001). No VE was prematurely interrupted. VE was always prescribed in the presence of at least one clinical sign of circulatory failure (n = 566, 100%): hypotension, INCLUDING THE NEED FOR CATECHOLAMINES (n = 392, 69%), tachycardia (n = 275, 49%), oliguria (n = 208, 37%) and/or mottled skin (n = 110, 19%). SV, cardiac output (CO), arterial lactate level and venous oxygen saturation measurements were never cited prior to VE. Although at least one static and/or dynamic parameter was measurable before 99% (IC95%, 99 %-100 %) of VEs, at least one static or dynamic parameter was actually used in only 38% (IC95%, 34 % - 42 %) of cases. Seniors measured static parameters more frequently than did residents (15% versus 5%; p < 0.0001). The use of dynamic parameters by seniors and residents was statistically similar (32% versus 31%; P = 0.86). At least one static parameter was used before performing 11% (IC95%, 10% 12%) of VEs and one dynamic parameter was used before carrying out 32% (IC95%, 30% - 34%) of
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VEs. At least one static or dynamic parameter was not used, although measurable and interpretable, in 62% (IC95%, 58% - 66%) of VEs. Conversely, at least one static or dynamic parameter was used, although uninterpretable, in 15% (IC95%, 12% - 18%) of cases (Table 2). Dynamic parameters were not measurable, or were uninterpretable because of the presence of spontaneous breathing activity (n = 252, 45%), low tidal volume (n = 196, 35%), low heart rate/respiratory rate ratio (n = 166, 29%),
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irregular cardiac rhythm (n = 147, 26%), absence of a systemic artery catheter (n = 147, 26%), high
intracranial pressure (n = 27, 5%), amputation of lower limbs (n = 18, 3%) or abdominal compartment
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syndrome (n = 13, 2%) (Figure 4). Static measurements were impossible because of the absence of a
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central venous catheter in the superior vena cava area (n = 161, 28%), absence of a pulmonary artery catheter (n = 558, 99%) or absence of a PiCCOTM (Pulsion) device (n = 530, 95%) (Figure 4). The
echocardiography were never mentioned prior to VE.
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end-expiratory occlusion test (16) and end-diastolic ventricular pressure estimation with
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Among 88 physicians working in the 6 ICUs participating in the study, 84 (95%) of them, including 52 seniors and 32 residents, answered the questionnaire concerning their agreement with the use of
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4).
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static or dynamic parameters to guide VE (Table 3) and the perception of their own practices (Table
DISCUSSION
The main finding of this study was that dynamic parameters are both underused and misused, whereas static parameters have been virtually abandoned in critically ill patients with SIRS. Although PPV is valid in only a very restricted population of ICU patients, it is often misused in the presence of contraindications. Since it is measurable and interpretable before 90% of VEs, PLR is the safest dynamic parameter used in ICU patients. To our knowledge, even though these data are not the first on the use of haemodynamic parameters to guide VE in current practice (11–13), this is the first study that describes both the use and the limitations of such a large range of static and dynamic parameters in ICU patients.
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Our results support the idea that VEs are administered in agreement with most current guidelines, which globally recommend the administration of 250 to 1,000 ml of crystalloids as a first-choice treatment, or 250 to 500 ml of albumin or gelatin as a second-choice treatment, over a 15 to 30 min period (1, 7–9). Moreover, no VE was implemented without a sign of circulatory failure such as tachycardia, hypotension, oliguria or mottling. In accordance with numerous recent guidelines (1, 2, 7,
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9), VE is reserved for haemodynamically unstable patients. Nonetheless, it must be underlined that no VE was prematurely interrupted. Once started, the volume of fluid prescribed was always totally
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perfused. This finding strongly suggests that, whatever the volume prescribed, no safety limit is used
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to stop an ongoing perfusion. This should be taken into account when prescribing VE in current practice. VE of a smaller volume, such as 250 ml, as previously recommended (8), might lead to more
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frequent benefit-to-risk evaluation and may further prevent fluid overload.
Another interesting finding of the present study was that CO and SV measurements were never
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mentioned prior to VE. This result might have been underestimated since CO or SV were not part of preselected items and needed to be spontaneously declared in an open-ended response format.
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Nevertheless, this result is in accordance with the study by Boulain et al. where CO was monitored in
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less than 10% of VEs and no measurements were performed in more than a quarter of the ICUs (11). Although the static analysis of SV or CO before VE is not a specific tool for guiding VE, VE-induced change in SV is the reference standard for estimating VE benefits. An increase in SV of > 10 - 15% is considered a prerequisite for a positive response to VE (7). Thermodilution and echocardiography are the most frequently available techniques for measuring SV or CO in the ICU. Although SV and CO measurements are of great interest for assessing responders to VE, they are recommended only in case of persistent shock (8). Current developments in echocardiography may facilitate SV measurements and may help to improve fluid responsiveness assessment at the bedside. In other situations, VEinduced change in pulse pressure has been proposed as giving a rough estimate of fluid responsiveness (17). Though static or dynamic parameters were measured before only 38% of VEs, over 75% of the physicians estimated using one of them before ≥ 50% of VEs. This overestimation of haemodynamic
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measurements is particularly striking for PPV and PLR. Over 75% of the physicians estimated using PPV and PLR before ≥ 50% of VEs, but they really used them in only 19% and 13% of cases, respectively. These results are in accordance with a previous study where PPV and PLR were used to predict fluid responsiveness in 19% and 27% of patients, respectively (12). Moreover, PPV and PLR were used before less than 10% of VEs in two recent studies (11, 13). Even after 24 hours of
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resuscitation, when haemodynamic monitoring is the most frequent, the use of any static or dynamic
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parameter before VE never exceeds 40% of cases (11).
Despite ease of availability, static parameters were used prior to less than 11% of VEs. Moreover,
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CVP is virtually the only static parameter used in current practice. In accordance with previous studies, insertion of a pulmonary artery catheter and PAOP assessments are only marginal in ICU
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patients (11, 18). Despite the fact that extreme values of GEDV enable an accurate prediction of fluid responsiveness and may guide fluid prescriptions at the bedside (19), the use of a specific device, or
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the need for repetitive thermodilution measurements may limit its use in current practice. Eventually, despite its availability and simplicity, the use of CVP for guiding VE is particularly limited and has
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been virtually abandoned among residents. This last finding is consistent with what was recently
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observed in 19 French hospitals, where only 17% of shock patients experienced CVP measurements during their first four days in the ICU (11). These results are probably due to previous studies demonstrating that static parameters fail to predict fluid responsiveness (20) and fluid overload (4). Moreover, although the dynamic use of CVP has been proposed for guiding VE (21), no convincing data exist concerning its advantages in current practice, and no difference has been reported in VEinduced increases in CVP and PAOP between responders and non-responders to VE (17, 20). Thus, new data are needed to demonstrate the advantages of static parameters at the bedside. The reasons why physicians underuse dynamic parameters strongly differ from the reasons why they underuse static parameters. In accordance with French guidelines (1, 7), physicians are convinced of the usefulness of dynamic parameters for guiding fluid therapy. Therefore, low measurement of these parameters may be the consequence of poor feasibility in current practice, rather than being due to the physician’s desire to limit their use. The use of PLR-induced haemodynamic changes and IVCV might
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be limited by the need for echo-Doppler equipment and skills. Although a PLR-induced change in pulse pressure may be used for predicting fluid responsiveness (22), this method presents a demonstrated risk of false-negatives (10). The reference method is based on analysis of PLR-induced changes in SV or CO measured by echocardiography or oesophageal Doppler (10, 22). Thus, current developments in echocardiography may help to improve PLR and IVCV assessment in the ICU.
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Despite the need for SV assessment, PLR limitations concern only 10% of VEs in ICU patients. Thus, PLR is the safest dynamic parameter used in current practice in ICU patients. Among dynamic
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parameters, a sharp distinction should be made between PPV, on the one hand, and PLR or IVCV on
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the other. PPV is the only dynamic parameter that is overused at the bedside, but it has numerous limitations (12, 13, 23–25). According to our study, the complexity of these limitations may lead to
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more than 50% of inappropriate measurements. Although certain limitations of PPV could not be recorded in our study (e.g. low pulmonary compliance, low airway driving pressure and right
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ventricular dysfunction), PPV was considered measurable and interpretable in only 17% of VEs. This result is in accordance with those of two French studies which found that less than 2% of ICU patients
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satisfy all PPV validity criteria (12, 13). Although a tiny proportion of ICU patients satisfied all the
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validity criteria for use of PPV, some of its limitations are still poorly understood. Forty-five to 60% of interviewed physicians considered that PPV could be used in case of low tidal volume or low pulmonary compliance. Moreover, 35% of seniors considered that PPV could be used in case of spontaneous breathing. Accordingly, a recent French study found that none of the surveyed ICU physicians had full knowledge of all the limiting factors required to correctly interpret PPV (26). As suggested in our study, and in accordance with previous results (12, 13, 26), supplementary efforts should be made at improving the knowledge of PPV limits, particularly among seniors. Eventually, even when all validity criteria are satisfied and PPV measurement methods are accurate, there still exists a “grey zone” in which results are uncertain. As described earlier, this grey zone, ranging from 4% to 17%, concerns more than half of PPV measurements (27). Although not explored in our study, this limitation in PPV interpretation might be the source of supplemental diagnostic errors. This grey zone limitation should be kept in mind when treating patients and must be sufficiently emphasized when teaching haemodynamic monitoring.
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Despite fewer limitations than PPV, the respiratory occlusion test was never mentioned prior to VE in our study. Firstly, this dynamic parameter might be less well known than PPV. The respiratory occlusion test has been tested in only a small number of studies, most of them recent (16, 23, 28). Secondly, a lack of mechanical ventilation, non-invasive ventilation or low sedation during mechanical ventilation may be responsible for spontaneous breathing activity in 45% to 74% of ICU
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patients (12). Moreover, 26% to 45% of ICU patients have no arterial lines and some patients without spontaneous breathing activity might not tolerate respiratory occlusion and try breathing (12).
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Although PPV and the respiratory occlusion test should be used with caution in the ICU, they still may
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be easily measurable and interpretable in an anaesthesia setting where patients experience less spontaneous breathing, higher tidal volume and lower prevalence of ARDS or cardiac arrhythmia.
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Our study has certain limitations. First, despite all efforts made to avoid missing questionnaires and the declared completeness of filling out these questionnaires, some VEs might have been overlooked.
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Since physicians less interested in the field of fluid responsiveness prediction were more likely to avoid questionnaires, results may have been embellished, leading to overestimation of the use of static
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and dynamic parameters or the quality of knowledge in the field. Second, detailed patient data were
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not recorded. Our results do not provide such data as the presence of organ failure, mechanical ventilation, the cause of SIRS, the time between circulatory failure and VE or the volume of fluids administered before VE. We were unable to evaluate practice differences according to precise clinical situations in which VE is known to influence outcome, such as severe sepsis and acute respiratory distress syndrome (3, 5, 6). Moreover, we were unable to analyse the influence of fluid balance, or organ failures on the use of static or dynamic parameters to predict fluid responsiveness (3, 4, 29). Third, haemodynamic data after VE were not recorded; thus, fluid responsiveness was not assessed. Although these data would have been of great interest for assessing fluid responsiveness in real life, they were not essential for achieving our main objective, i.e. determining the use of static and dynamic haemodynamic parameters prior to VE in ICU patients with SIRS. Fourth, the availability of certain static or dynamic parameters could not be precisely determined. Since poor pulmonary compliance, low driving pressure and right ventricular dysfunction were not retrospectively assessed by the
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investigators, PPV interpretability may have been overestimated (13, 23–25). Moreover, the presence of extrasystoles or spontaneous breathing at the time of PPV measurement cannot be excluded and may have led to supplementary overestimation of PPV interpretability. Conversely, since intraabdominal pressure could not be consistently and retrospectively estimated, femoro-iliac venous pressure was not considered to be a possible estimate of CVP and CVP measurability may have been
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underestimated (30). Since PPV is clearly overused and CVP is largely underused, such errors would not have changed the conclusions of this study. Fifth, measurement methods were not recorded for
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CVP, PAOP, GEDV, PPV, PLR or IVCV. To our knowledge, there exists no published data on precise
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techniques used in current practice for measuring static and dynamic parameters. Since measurement methods may significantly alter test conclusions, our results may have underestimated both static and
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dynamic parameter misuse. Sixth, this study provides no data on haemodynamic measurements not followed by VE. In the presence of acute circulatory failure or tissue hypo-perfusion, VE might have
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been considered but not administered. To our knowledge, there exists no published data on the frequency of, or reasons why, physicians do not perform VE in haemodynamically unstable patients.
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Finally, the 6 ICUs participating in the study are located in the same region of France and work with
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the same university hospital, i.e. the University Hospital of Lille. Since several physicians from this region and numerous authors of this study have a long experience in the field of fluid responsiveness, practices may differ in other regions or countries. CONCLUSIONS
Despite the well-established impact of controlled fluid resuscitation upon ICU patient outcome, fewer than 40% of VEs are guided by static or dynamic haemodynamic parameters. Dynamic parameters are both underused and misused, whereas static parameters have been virtually abandoned in critically ill patients with SIRS. As PPV is frequently misused because of numerous contraindications, PLR is the safest dynamic parameter used in ICU patients. These findings provide new information that should help to improve future care, teaching and research in the field of fluid resuscitation.
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COMPETING INTERESTS The authors declare that they have no competing interests. ACKNOWLEDGMENTS The authors thank the physicians and nursing staff of the 6 ICUs participating in the study for their
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valuable cooperation. The authors also thank Doctor W. Khaliq for his fruitful comments.
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Mahjoub Y, Lejeune V, Muller L, Perbet S, Zieleskewicz L, Bart F, et al. Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point-prevalence study. Br J Anaesth. 29 2013;
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Fischer M-O, Mahjoub Y, Boisselier C, Tavernier B, Dupont H, Leone M, et al. Arterial pulse pressure variation suitability in critical care: A French national survey. Anaesth Crit Care Pain Med. - 2015;34:23-8.
14.
[No authors listed]. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864-74.
15.
Jouhet J, Dewavrin f, Tavernier B. Remplissage vasculaire par cristalloïdes ou colloïdes: étude comparative de quantité et de durée d’action [résumé]. Réanimation. 2012;21: S271.
16.
Silva S, Jozwiak M, Teboul J-L, Persichini R, Richard C, Monnet X. End-expiratory occlusion test predicts preload responsiveness independently of positive end-expiratory pressure during acute respiratory distress syndrome. Crit Care Med. 2013;41:1692-701.
17.
Lakhal K, Ehrmann S, Perrotin D, Wolff M, Boulain T. Fluid challenge: tracking changes in cardiac output with blood pressure monitoring (invasive or non-invasive). Intensive Care Med. 2013;39:1953-62.
18.
Gershengorn HB, Wunsch H. Understanding changes in established practice: pulmonary artery catheter use in critically ill patients. Crit Care Med. 2013;41:2667•76.
19.
Michard F, Alaya S, Zarka V, Bahloul M, Richard C, Teboul J-L. Global end-diastolic volume as an indicator of cardiac preload in patients with septic shock. Chest. 2003;124:1900-8.
20.
Osman D, Ridel C, Ray P, Monnet X, Anguel N, Richard C, et al. Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med. 2007;35:64-8.
21.
Vincent JL, Weil MH. Fluid challenge revisited. Crit Care Med. 2006;34:1333-7.
22.
Préau S, Saulnier F, Dewavrin F, Durocher A, Chagnon JL. Passive leg raising is predictive of fluid responsiveness in spontaneously breathing patients with severe sepsis or acute pancreatitis. Crit Care Med. 2010;38:819-25.
23.
Monnet X, Bleibtreu A, Ferré A, Dres M, Gharbi R, Richard C, et al. Passive leg-raising and end-expiratory occlusion tests perform better than pulse pressure variation in patients with low respiratory system compliance. Crit Care Med. 2012;40:152-7.
24.
Vallée F, Richard JCM, Mari A, Gallas T, Arsac E, Verlaan PS, et al. Pulse pressure variations adjusted by alveolar driving pressure to assess fluid responsiveness. Intensive Care Med. 2009;35:1004-10.
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an
us
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10.
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Muller L, Louart G, Bousquet P-J, Candela D, Zoric L, de La Coussaye J-E, et al. The influence of the airway driving pressure on pulsed pressure variation as a predictor of fluid responsiveness. Intensive Care Med. 2010;36:496-503.
26.
Fischer M-O, Dechanet F, du Cheyron D, Gérard J-L, Hanouz J-L, Fellahi J-L. Evaluation of the knowledge base of French intensivists and anaesthesiologists as concerns the interpretation of respiratory arterial pulse pressure variation. Anaesth Crit Care Pain Med. 2015;34:29-34.
27.
Biais M, Ehrmann S, Mari A, Conte B, Mahjoub Y, Desebbe O, et al. Clinical relevance of pulse pressure variations for predicting fluid responsiveness in mechanically ventilated intensive care unit patients: the grey zone approach. Crit Care 2014;18:587.
28.
Tavernier B, Makhotine O, Lebuffe G, Dupont J, Scherpereel P. Systolic pressure variation as a guide to fluid therapy in patients with sepsis-induced hypotension. Anesthesiology. 1998;89:1313-21.
29.
Belikova I, Lukaszewicz AC, Faivre V, Damoisel C, Singer M, Payen D. Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis. Crit Care Med. 2007;35:2702-8.
30.
Ait-Oufella H, Boelle P-Y, Galbois A, Baudel J-L, Margetis D, Alves M, et al. Comparison of superior vena cava and femoroiliac vein pressure according to intra-abdominal pressure. Ann Intensive Care. 2012;2:21.
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25.
Figure 1. Preliminary questionnaire: physicians’ agreement with guidelines and their perception of their own practices.
Figure 2. Questionnaire a: physicians’ use of static and dynamic haemodynamic parameters for predicting fluid responsiveness.
Figure 3. Questionnaire b: limitations of static and dynamic haemodynamic parameters.
Figure 4. Identified limitations of static and dynamic haemodynamic parameters before volume expansion. Values are expressed as number (% of the 566 volume expansions). PPV, respiratory variations in systemic pulse pressure. PLR, passive leg raising. IVCV, respiratory variations in inferior vena cava diameter. CVP, central venous pressure measured with a central venous catheter. PAOP, pulmonary artery occlusion pressure. GEDV, global end diastolic volume measured with PiCCOTM device (Pulsion).
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Table 1. The main characteristics of 566 volume expansions prescribed for intensive care unit patients with systemic inflammatory response syndrome. Gelatin
Albumin
Frequency
314 (56%)
14 (3%)
146 (26%)
80 (14%)
Volume (ml)
1000 [1000 - 1000]
875 [500 - 1000]
500 [500 - 500]
500 [200 - 500]
Hydroxyethylstarch
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Isotonic sodium bicarbonate
12 (2%)
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Isotonic sodium chloride
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500 [500 - 500]
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Values are expressed as numbers (% of the 566 volume expansions) or medians and interquartile ranges [25th–75th percentiles].
Measurable and interpretable
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Used
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Table 2. Static and dynamic haemodynamic parameters measured before the 566 volume expansions. Used when uninterpretable
Not used, but measurable and interpretable
Dynamic parameters PPV
110 (19%)
96 (17%)
65 (12%)
51 (9%)
PLR
75 (13%)
508 (90%)
7 (1%)
440 (78%)
IVCV
31 (6%)
252 (45%)
15 (3%)
236 (42%)
CVP
50 (9%)
405 (72%)
0 (0%)
355 (63%)
PAOP
7 (1%)
8 (1%)
0 (0%)
1 (0%)
GEDV
6 (1%)
26 (5%)
0 (0%)
20 (4%)
Static parameters
Values are expressed as numbers (% of the 566 volume expansions). PPV, respiratory variations in systemic pulse pressure. PLR, passive leg raising. IVCV, respiratory variations in inferior vena cava diameter. CVP, central venous pressure measured with a central venous catheter. PAOP, pulmonary artery occlusion pressure. GEDV, global end diastolic volume measured with PiCCOTM device (Pulsion).
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Table 3. Agreement by 84 physicians with use of static and dynamic haemodynamic parameters to guide volume expansion in patients with systemic inflammatory response syndrome. Residents (n = 32)
P
“Measurement of static parameters is recommended for predicting VE response”
13 (25%)
12 (38%)
0.22
“Low values of static parameters indicate VE in patients with shock”
46 (89%)
28 (88%)
1
“Use of dynamic parameters is recommended for predicting VE response”
47 (90%)
27 (84%)
“Use of dynamic parameters improves outcome of highly selected patients”
35 (67%)
23 (72%)
“A VE-induced change in SV or CO ≥ 10 - 15% usually defines a positive response to VE”
39 (75%)
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Seniors (n = 52)
0.81
0.15
3 (6%)
1 (3%)
1
18 (35%)
4 (13%)
0.04
“PPV can be used in case of low tidal volume”
28 (54%)
18 (56%)
0.82
“PPV can be used in case of poor pulmonary compliance”
24 (46%)
15 (47%)
1
“PLR can be used in case of abdominal compartment syndrome”
5 (10%)
2 (6%)
0.7
“PPV can be used in case of irregular cardiac rhythm”
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“PPV can be used in case of spontaneous breathing”
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28 (88%)
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0.30
Both “total agreement” and “agreement” from the preliminary questionnaire 1 (Figure 1) were considered as an agreement with the corresponding sentences in this table. Values are expressed as number (% of 52 seniors or 32 residents). VE, volume expansion. PPV, respiratory variations in systemic pulse pressure. PLR, passive leg raising. SV, stroke volume. CO, cardiac output.
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Residents (n = 32)
P
PPV
39 (75%)
26 (81%)
0.6
PLR
40 (77%)
26 (81%)
IVCV
16 (31%)
13 (41%)
22 (42%)
12 (38%)
0.82
0 (0%)
1
4 (13%)
0.27
1 (2%)
GEDV
12 (23%)
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PAOP
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Static parameters CVP
0.79 0.48
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Dynamic parameters
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Seniors (n = 52)
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Table 4. Declared use by 84 physicians of static and dynamic parameters prior to ≥ 50 % of volume expansions.
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Values are expressed as numbers (% of 52 seniors or 32 residents). PPV, respiratory variations in systemic pulse pressure. PLR, passive leg raising. IVCV, respiratory variations in inferior vena cava diameter. CVP, central venous pressure measured with a central venous catheter. PAOP, pulmonary artery occlusion pressure. GEDV, global end diastolic volume measured with PiCCOTM device (Pulsion).
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S2352-5568(15)00143-5 http://dx.doi.org/doi:10.1016/j.accpm.2015.08.003 ACCPM 88
To appear in: Received date: Accepted date:
27-6-2014 31-8-2015
Please cite this article as: S´ebastien PreauFlorent DewavrinVincent DemaeghtArnaud ChicheBenoˆıt VoisinFranck MinacoriJulien PoissyClaire Boulle-GeronimiCaroline BlazejewskiThierry OnimusAlain DurocherFabienne Saulnier The use of static and dynamic haemodynamic parameters before volume expansion: a prospective observational study in six French intensive care units (2015), http://dx.doi.org/10.1016/j.accpm.2015.08.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
The use of static and dynamic haemodynamic parameters before volume expansion: a prospective observational study in six French intensive care units
Évaluation prospective de l’utilisation des paramètres hémodynamiques statiques et dynamiques avant
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remplissage vasculaire dans six réanimations françaises.
Sébastien Preau 1, Florent Dewavrin 2, Vincent Demaeght 2, Arnaud Chiche 3, Benoît Voisin 1, Franck
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Minacori 4, Julien Poissy 1, Claire Boulle-Geronimi 5, Caroline Blazejewski 6, Thierry Onimus 1, Alain
an
Durocher 1, Fabienne Saulnier 1.
(1) Intensive Care Unit, Calmette Hospital, University Hospital of Lille, France. (2) Intensive Care
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Unit, General Hospital of Valenciennes, France. (3) Intensive Care Unit, General Hospital of Tourcoing, France. (4) Intensive Care Unit, University Hospital of Lomme, France. (5) Intensive Care
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Hospital of Lille, France.
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Unit, General Hospital of Douai, France. (6) Intensive Care Unit, Salengro Hospital, University
S. Preau: [email protected], F. Dewavrin: [email protected], V. Demaeght: [email protected], A. Chiche: [email protected], B. Voisin: [email protected], F., Minacori: [email protected], J. Poissy: [email protected], C. Boulle-Geronimi: [email protected], C. Blazejewski: [email protected], T. Onimus: [email protected], A. Durocher: [email protected], F. Saulnier: [email protected]
CORRESPONDING AUTHOR
S. Preau (MD, PhD), Critical care centre, University Hospital of Lille, Avenue du Professeur Emile Laine, Lille 59037, France. [email protected]. Telephone: +333 20 44 40 84. Fax: +333 20 44 50 94
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Abbreviations CO, cardiac output. CVP, central venous pressure. GEDV, global end diastolic volume.
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ICU, intensive care unit. IVCV, respiratory variations in inferior vena cava diameter.
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PAOP, pulmonary artery occlusion pressure. PLR, passive leg raising.
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SIRS, systemic inflammatory response syndrome. SV, stroke volume.
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VE, volume expansion. VPP, respiratory variations in systemic pulse pressure.
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ABSTRACT
Objective: The aim of the present study was to determine the use of static and dynamic haemodynamic parameters for predicting fluid responsiveness prior to volume expansion (VE) in intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS). Methods: We conducted a prospective, multicentre, observational study in 6 French ICUs in 2012. ICU physicians were audited concerning their use of static and dynamic haemodynamic parameters before each VE performed in patients with SIRS for 6 consecutive weeks. Results: The median volume of the 566 VEs administered to patients with SIRS was 1,000 ml [5001,000 ml]. Although at least one static or dynamic haemodynamic parameter was measurable before 99% (IC95%, 99% - 100%) of VEs, at least one them was used in only 38% (IC95%, 34% - 42%) of
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cases: static parameters in 11% of cases (IC95%, 10% - 12%) and dynamic parameters in 32% (IC95%, 30% - 34%). Static parameters were never used when uninterpretable. For 15% of VEs (IC95%, 12% - 18%), a dynamic parameter was measured in the presence of contraindications. Among dynamic parameters, respiratory variations in arterial pulse pressure (PPV) and passive leg raising
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(PLR) were measurable and interpretable before 17% and 90% of VEs, respectively. Conclusions: Haemodynamic parameters are underused for predicting fluid responsiveness in current
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practice. In contrast to static parameters, dynamic parameters are often incorrectly used in the presence of contraindications. PLR is more frequently valid than PPV for predicting fluid responsiveness in
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ICU patients.
KEY WORDS: Intensive care; Sepsis; Inflammation; Systemic inflammatory response syndrome;
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INTRODUCTION
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SIRS; Fluid; Preload; Passive leg raising; Respiratory variations.
Fluid loading is a common therapy in intensive care units (ICU) for patients with systemic inflammatory response syndrome (SIRS) and acute circulatory failure (1, 2). Fluid administration compensates for an absolute or relative decrease in circulating volume. Despite positive effects upon cardiac output and tissue perfusion when accurately performed, an inappropriate amount of fluid may be deleterious and is associated with poor outcome. Indeed, excessive fluid loading may lead to pulmonary oedema (3, 4), while insufficient fluid loading fails to prevent global hypo-perfusion, commonly found in SIRS conditions (5, 6).
The rapid and repetitive perfusion of small amounts of crystalloids or colloids, i.e. the so-called volume expansion (VE), is recommended in current practice to optimize fluid therapy (1, 7–9). A VEinduced change in stroke volume (SV) of ≥ 10-15% usually defines a positive response to VE (7). Despite the selection of patients with acute circulatory failure, only half of all ICU patients increase
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their SV in response to VE (10). The repetition of ineffective and possibly deleterious VE may lead to fluid overload and poor outcome. Numerous haemodynamic parameters are currently available for predicting the benefit-risk balance of VE at the bedside. Static parameters such as central venous pressure (CVP), pulmonary artery
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occlusion pressure (PAOP), or global end diastolic volume measured with a PiCCOTM device (GEDV) require pressure or volume measurements. Dynamic parameters such as respiratory variations in
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systemic pulse pressure (PPV), expiratory occlusion test-induced change in pulse pressure, passive leg raising (PLR)-induced change in haemodynamics, or respiratory variations in inferior vena cava
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diameter (IVCV) require pressure, flow or diameter measurements during dynamic procedures. Conflicting recommendations on the use of static and dynamic parameters for predicting or evaluating
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fluid responsiveness in current practice have been published (1, 2, 7–9). In international guidelines, static parameters and fluid challenge are recommended in the early phase of haemodynamic
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resuscitation of patients with shock or severe sepsis (8,9). Conversely, French guidelines recommend
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the early use of dynamic parameters in this setting (1,7).
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To our knowledge, only one study has estimated the current use of static and dynamic haemodynamic parameters in critically ill patients (11). Moreover, as several studies have analysed PPV suitability in current practice (12,13), there is no similar information about other dynamic parameters. The main aim of the study was to determine the use and limitations of static or dynamic parameter measurements prior to VE in ICU patients with SIRS. A secondary aim was to determine physicians’ accordance with guidelines and elucidate perceptions of their own individual practice. MATERIALS AND METHODS
We conducted a prospective, multicentre, observational study in 6 French ICUs in 2012. The study was approved by the regional ethics committee of the North of France and no informed consent was required from patients. Study design
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First part (preliminary questionnaire): The physicians’ agreement with guidelines and their perception of their own practices were evaluated during a 2-week period from 16 to 29 April 2012. All 88 physicians present at the time of the audit were asked to fill out a written anonymous questionnaire concerning their agreement with current recommendations (1, 2, 7–9) and the perception of their own use of static and dynamic haemodynamic parameters to guide VE. The questionnaire consisted of
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multiple-choice questions with 4 levels of answers concerning agreement (total agreement; agreement; disagreement; total disagreement) and frequency (≥ 75%; ≥ 50% to < 75%; ≥ 25% to < 50%; < 25%)
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(Figure 1). All physicians except F. Dewavrin and S. Preau were blinded to incoming evaluations of
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their practice 6 months later.
Second part (prospective observational study): The use of static and dynamic haemodynamic
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parameters prior to VE was determined over a 6-week period from November 5 to December 16, 2012. Physicians were audited for each VE they performed in patients with SIRS hospitalized at the 6
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ICUs participating in the study. The decision to perform VE and the fluid therapy administered were left to the discretion of the individual clinician. SIRS was defined as the presence of at least 2 criteria
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among the following 4: high or low body temperature (> 38°C or < 36°C), elevated heart rate (> 90
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b/min), high respiratory rate (> 20 c/ min) or a low PaCO2 (< 32 mmHg) and significant white blood cell changes (elevated white blood cell count of > 12,000.109 cells.l-1, < 4,000 cells.l-1, or the presence of more than 10% immature neutrophils) (14). VE was defined as any intravenous administration of fluid (crystalloid or colloid) within one hour. Blood product transfusions were not considered to be VE. The written anonymous questionnaire was composed of 4 items: physician’s grade, clinical signs of acute circulatory failure (systemic arterial hypotension, tachycardia, mottled skin and oliguria), static and dynamic haemodynamic parameters measured before VE and VE characteristics (volume and type) (Figure 2). All ICU physicians and nurses were trained and implicated in the study. Questionnaires were combined with fluid loading solutions so that nurses could systematically ask physicians to fill out the forms while they were administering VE. The quantification of prescribed VEs, the number of questionnaires filled out, the availability and lack of contraindications in haemodynamic measurements were checked retrospectively within 48 h by the main investigator at
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each centre (Figure 3). Limitations for static and dynamic parameters were as follows (10,13): irregular cardiac rhythm, spontaneous breathing activity, low tidal volume (< 8 ml / kg of body weight), low ratio: heart rate / respiratory rate (< 3.6), poor pulmonary compliance (≤ 30 ml / cmH2O), low airway driving pressure (≤ 20 cmH2O) and right ventricular dysfunction (peak systolic velocity of tricuspid annular motion assessed by tissue Doppler echocardiography <0.15 m/s) for PPV;
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spontaneous breathing activity for respiratory occlusion test; spontaneous breathing activity and
abdominal compartment syndrome for IVCV; amputation of lower limbs, abdominal compartment
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syndrome and high intracranial pressure for PLR; pressure measurement site not placed in superior
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vena cava or right atrium for CVP; lack of pulmonary artery catheter in place for PAOP; abdominal cava/common iliac vein catheter, aortic aneurysm, intra-cardiac shunt and severe valvular
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insufficiency for GEDV. Because reliable retrospective estimations of respiratory plateau pressure and tissue Doppler echocardiography were not possible in the participating ICUs, the presence of some
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PPV limitations (e.g. poor pulmonary compliance, low airway driving pressure and right ventricular dysfunction) were not recorded. Moreover, the measurement methods for CVP and PAOP (pressure
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transducer location, time of measurement within respiratory and cardiac cycles), GEDV (volume,
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number, temperature, time and length of injections), PPV (automatic or manual, number of cardiac cycles, threshold values), PLR (automatic bed elevation technique, lowering of the head and trunk, SV or CVP measurement) and IVCV (sampling location, TM or bi-dimensional mode, long or short axis view, time of measurement within respiratory and cardiac cycles) were not recorded. Statistical analysis
The statistical unit was a VE. The main judgment criterion was the percentage of VEs preceded by any measurement of static or dynamic parameters. A recent study from the ICU of the Hospital Centre of Valenciennes (France, 23 beds) showed that 509 VEs were performed over a 6 month period (15). We estimated that 35% of VEs were preceded by measurement of static and/or dynamic parameters. From these data, we calculated that 546 VEs were needed for a 4% precision with a risk α ≤ 5%. We estimated that a study period of 6 weeks would be necessary to analyse at least 546 VEs in the 6 ICUs (114 beds) participating in the study. Qualitative variables were expressed as frequencies and
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percentages. Frequencies were compared using a Fisher test. The normality of quantitative variables was tested using a Kolmogorov-Smirnov test. Quantitative variables were expressed as means ± SD if normally distributed, or medians [25 - 75% interquartile range] if not. Differences between two independent means were tested using the Student t-test if normally distributed or the Mann-Whitney test if not. A P-value ≤ 0.05 was considered statistically significant. Statistical analysis was performed
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using SPSS 13.0.1TM software (SPSS, Chicago IL).
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RESULTS
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Between November 5 and December 16, 2012, 566 (75%) VEs were prescribed in patients with SIRS. SIRS was diagnosed by the presence of fever (n = 313, 55%), elevated heart rate (n = 444, 78%),
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tachypnea (n = 457, 81%) and significant white blood cell changes (n = 412, 73%). Nurses did not communicate any refusals to answer a questionnaire during the study and the main investigators
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reported that a questionnaire was filled out for each prescribed VE. The median volume of VE was 1,000 mL [500 - 1,000 mL] and crystalloids were prescribed more frequently than colloids (58%
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versus 42%; P < 0.001) (Table 1). The mean volume of VE was higher with crystalloids, 1,000 mL
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[1,000 - 1,000 mL], than with colloids, 500 mL [500 - 500 mL] (P < 0.0001). Seniors and residents prescribed 57% and 43% of VEs, respectively. Seniors more frequently prescribed colloids than did residents (50% versus 33%; P < 0.001). No VE was prematurely interrupted. VE was always prescribed in the presence of at least one clinical sign of circulatory failure (n = 566, 100%): hypotension, INCLUDING THE NEED FOR CATECHOLAMINES (n = 392, 69%), tachycardia (n = 275, 49%), oliguria (n = 208, 37%) and/or mottled skin (n = 110, 19%). SV, cardiac output (CO), arterial lactate level and venous oxygen saturation measurements were never cited prior to VE. Although at least one static and/or dynamic parameter was measurable before 99% (IC95%, 99 %-100 %) of VEs, at least one static or dynamic parameter was actually used in only 38% (IC95%, 34 % - 42 %) of cases. Seniors measured static parameters more frequently than did residents (15% versus 5%; p < 0.0001). The use of dynamic parameters by seniors and residents was statistically similar (32% versus 31%; P = 0.86). At least one static parameter was used before performing 11% (IC95%, 10% 12%) of VEs and one dynamic parameter was used before carrying out 32% (IC95%, 30% - 34%) of
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VEs. At least one static or dynamic parameter was not used, although measurable and interpretable, in 62% (IC95%, 58% - 66%) of VEs. Conversely, at least one static or dynamic parameter was used, although uninterpretable, in 15% (IC95%, 12% - 18%) of cases (Table 2). Dynamic parameters were not measurable, or were uninterpretable because of the presence of spontaneous breathing activity (n = 252, 45%), low tidal volume (n = 196, 35%), low heart rate/respiratory rate ratio (n = 166, 29%),
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irregular cardiac rhythm (n = 147, 26%), absence of a systemic artery catheter (n = 147, 26%), high
intracranial pressure (n = 27, 5%), amputation of lower limbs (n = 18, 3%) or abdominal compartment
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syndrome (n = 13, 2%) (Figure 4). Static measurements were impossible because of the absence of a
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central venous catheter in the superior vena cava area (n = 161, 28%), absence of a pulmonary artery catheter (n = 558, 99%) or absence of a PiCCOTM (Pulsion) device (n = 530, 95%) (Figure 4). The
echocardiography were never mentioned prior to VE.
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end-expiratory occlusion test (16) and end-diastolic ventricular pressure estimation with
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Among 88 physicians working in the 6 ICUs participating in the study, 84 (95%) of them, including 52 seniors and 32 residents, answered the questionnaire concerning their agreement with the use of
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4).
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static or dynamic parameters to guide VE (Table 3) and the perception of their own practices (Table
DISCUSSION
The main finding of this study was that dynamic parameters are both underused and misused, whereas static parameters have been virtually abandoned in critically ill patients with SIRS. Although PPV is valid in only a very restricted population of ICU patients, it is often misused in the presence of contraindications. Since it is measurable and interpretable before 90% of VEs, PLR is the safest dynamic parameter used in ICU patients. To our knowledge, even though these data are not the first on the use of haemodynamic parameters to guide VE in current practice (11–13), this is the first study that describes both the use and the limitations of such a large range of static and dynamic parameters in ICU patients.
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Our results support the idea that VEs are administered in agreement with most current guidelines, which globally recommend the administration of 250 to 1,000 ml of crystalloids as a first-choice treatment, or 250 to 500 ml of albumin or gelatin as a second-choice treatment, over a 15 to 30 min period (1, 7–9). Moreover, no VE was implemented without a sign of circulatory failure such as tachycardia, hypotension, oliguria or mottling. In accordance with numerous recent guidelines (1, 2, 7,
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9), VE is reserved for haemodynamically unstable patients. Nonetheless, it must be underlined that no VE was prematurely interrupted. Once started, the volume of fluid prescribed was always totally
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perfused. This finding strongly suggests that, whatever the volume prescribed, no safety limit is used
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to stop an ongoing perfusion. This should be taken into account when prescribing VE in current practice. VE of a smaller volume, such as 250 ml, as previously recommended (8), might lead to more
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frequent benefit-to-risk evaluation and may further prevent fluid overload.
Another interesting finding of the present study was that CO and SV measurements were never
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mentioned prior to VE. This result might have been underestimated since CO or SV were not part of preselected items and needed to be spontaneously declared in an open-ended response format.
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Nevertheless, this result is in accordance with the study by Boulain et al. where CO was monitored in
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less than 10% of VEs and no measurements were performed in more than a quarter of the ICUs (11). Although the static analysis of SV or CO before VE is not a specific tool for guiding VE, VE-induced change in SV is the reference standard for estimating VE benefits. An increase in SV of > 10 - 15% is considered a prerequisite for a positive response to VE (7). Thermodilution and echocardiography are the most frequently available techniques for measuring SV or CO in the ICU. Although SV and CO measurements are of great interest for assessing responders to VE, they are recommended only in case of persistent shock (8). Current developments in echocardiography may facilitate SV measurements and may help to improve fluid responsiveness assessment at the bedside. In other situations, VEinduced change in pulse pressure has been proposed as giving a rough estimate of fluid responsiveness (17). Though static or dynamic parameters were measured before only 38% of VEs, over 75% of the physicians estimated using one of them before ≥ 50% of VEs. This overestimation of haemodynamic
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measurements is particularly striking for PPV and PLR. Over 75% of the physicians estimated using PPV and PLR before ≥ 50% of VEs, but they really used them in only 19% and 13% of cases, respectively. These results are in accordance with a previous study where PPV and PLR were used to predict fluid responsiveness in 19% and 27% of patients, respectively (12). Moreover, PPV and PLR were used before less than 10% of VEs in two recent studies (11, 13). Even after 24 hours of
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resuscitation, when haemodynamic monitoring is the most frequent, the use of any static or dynamic
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parameter before VE never exceeds 40% of cases (11).
Despite ease of availability, static parameters were used prior to less than 11% of VEs. Moreover,
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CVP is virtually the only static parameter used in current practice. In accordance with previous studies, insertion of a pulmonary artery catheter and PAOP assessments are only marginal in ICU
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patients (11, 18). Despite the fact that extreme values of GEDV enable an accurate prediction of fluid responsiveness and may guide fluid prescriptions at the bedside (19), the use of a specific device, or
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the need for repetitive thermodilution measurements may limit its use in current practice. Eventually, despite its availability and simplicity, the use of CVP for guiding VE is particularly limited and has
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been virtually abandoned among residents. This last finding is consistent with what was recently
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observed in 19 French hospitals, where only 17% of shock patients experienced CVP measurements during their first four days in the ICU (11). These results are probably due to previous studies demonstrating that static parameters fail to predict fluid responsiveness (20) and fluid overload (4). Moreover, although the dynamic use of CVP has been proposed for guiding VE (21), no convincing data exist concerning its advantages in current practice, and no difference has been reported in VEinduced increases in CVP and PAOP between responders and non-responders to VE (17, 20). Thus, new data are needed to demonstrate the advantages of static parameters at the bedside. The reasons why physicians underuse dynamic parameters strongly differ from the reasons why they underuse static parameters. In accordance with French guidelines (1, 7), physicians are convinced of the usefulness of dynamic parameters for guiding fluid therapy. Therefore, low measurement of these parameters may be the consequence of poor feasibility in current practice, rather than being due to the physician’s desire to limit their use. The use of PLR-induced haemodynamic changes and IVCV might
Page 10 of 20
be limited by the need for echo-Doppler equipment and skills. Although a PLR-induced change in pulse pressure may be used for predicting fluid responsiveness (22), this method presents a demonstrated risk of false-negatives (10). The reference method is based on analysis of PLR-induced changes in SV or CO measured by echocardiography or oesophageal Doppler (10, 22). Thus, current developments in echocardiography may help to improve PLR and IVCV assessment in the ICU.
ip t
Despite the need for SV assessment, PLR limitations concern only 10% of VEs in ICU patients. Thus, PLR is the safest dynamic parameter used in current practice in ICU patients. Among dynamic
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parameters, a sharp distinction should be made between PPV, on the one hand, and PLR or IVCV on
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the other. PPV is the only dynamic parameter that is overused at the bedside, but it has numerous limitations (12, 13, 23–25). According to our study, the complexity of these limitations may lead to
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more than 50% of inappropriate measurements. Although certain limitations of PPV could not be recorded in our study (e.g. low pulmonary compliance, low airway driving pressure and right
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ventricular dysfunction), PPV was considered measurable and interpretable in only 17% of VEs. This result is in accordance with those of two French studies which found that less than 2% of ICU patients
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satisfy all PPV validity criteria (12, 13). Although a tiny proportion of ICU patients satisfied all the
Ac ce pt e
validity criteria for use of PPV, some of its limitations are still poorly understood. Forty-five to 60% of interviewed physicians considered that PPV could be used in case of low tidal volume or low pulmonary compliance. Moreover, 35% of seniors considered that PPV could be used in case of spontaneous breathing. Accordingly, a recent French study found that none of the surveyed ICU physicians had full knowledge of all the limiting factors required to correctly interpret PPV (26). As suggested in our study, and in accordance with previous results (12, 13, 26), supplementary efforts should be made at improving the knowledge of PPV limits, particularly among seniors. Eventually, even when all validity criteria are satisfied and PPV measurement methods are accurate, there still exists a “grey zone” in which results are uncertain. As described earlier, this grey zone, ranging from 4% to 17%, concerns more than half of PPV measurements (27). Although not explored in our study, this limitation in PPV interpretation might be the source of supplemental diagnostic errors. This grey zone limitation should be kept in mind when treating patients and must be sufficiently emphasized when teaching haemodynamic monitoring.
Page 11 of 20
Despite fewer limitations than PPV, the respiratory occlusion test was never mentioned prior to VE in our study. Firstly, this dynamic parameter might be less well known than PPV. The respiratory occlusion test has been tested in only a small number of studies, most of them recent (16, 23, 28). Secondly, a lack of mechanical ventilation, non-invasive ventilation or low sedation during mechanical ventilation may be responsible for spontaneous breathing activity in 45% to 74% of ICU
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patients (12). Moreover, 26% to 45% of ICU patients have no arterial lines and some patients without spontaneous breathing activity might not tolerate respiratory occlusion and try breathing (12).
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Although PPV and the respiratory occlusion test should be used with caution in the ICU, they still may
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be easily measurable and interpretable in an anaesthesia setting where patients experience less spontaneous breathing, higher tidal volume and lower prevalence of ARDS or cardiac arrhythmia.
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Our study has certain limitations. First, despite all efforts made to avoid missing questionnaires and the declared completeness of filling out these questionnaires, some VEs might have been overlooked.
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Since physicians less interested in the field of fluid responsiveness prediction were more likely to avoid questionnaires, results may have been embellished, leading to overestimation of the use of static
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and dynamic parameters or the quality of knowledge in the field. Second, detailed patient data were
Ac ce pt e
not recorded. Our results do not provide such data as the presence of organ failure, mechanical ventilation, the cause of SIRS, the time between circulatory failure and VE or the volume of fluids administered before VE. We were unable to evaluate practice differences according to precise clinical situations in which VE is known to influence outcome, such as severe sepsis and acute respiratory distress syndrome (3, 5, 6). Moreover, we were unable to analyse the influence of fluid balance, or organ failures on the use of static or dynamic parameters to predict fluid responsiveness (3, 4, 29). Third, haemodynamic data after VE were not recorded; thus, fluid responsiveness was not assessed. Although these data would have been of great interest for assessing fluid responsiveness in real life, they were not essential for achieving our main objective, i.e. determining the use of static and dynamic haemodynamic parameters prior to VE in ICU patients with SIRS. Fourth, the availability of certain static or dynamic parameters could not be precisely determined. Since poor pulmonary compliance, low driving pressure and right ventricular dysfunction were not retrospectively assessed by the
Page 12 of 20
investigators, PPV interpretability may have been overestimated (13, 23–25). Moreover, the presence of extrasystoles or spontaneous breathing at the time of PPV measurement cannot be excluded and may have led to supplementary overestimation of PPV interpretability. Conversely, since intraabdominal pressure could not be consistently and retrospectively estimated, femoro-iliac venous pressure was not considered to be a possible estimate of CVP and CVP measurability may have been
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underestimated (30). Since PPV is clearly overused and CVP is largely underused, such errors would not have changed the conclusions of this study. Fifth, measurement methods were not recorded for
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CVP, PAOP, GEDV, PPV, PLR or IVCV. To our knowledge, there exists no published data on precise
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techniques used in current practice for measuring static and dynamic parameters. Since measurement methods may significantly alter test conclusions, our results may have underestimated both static and
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dynamic parameter misuse. Sixth, this study provides no data on haemodynamic measurements not followed by VE. In the presence of acute circulatory failure or tissue hypo-perfusion, VE might have
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been considered but not administered. To our knowledge, there exists no published data on the frequency of, or reasons why, physicians do not perform VE in haemodynamically unstable patients.
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Finally, the 6 ICUs participating in the study are located in the same region of France and work with
Ac ce pt e
the same university hospital, i.e. the University Hospital of Lille. Since several physicians from this region and numerous authors of this study have a long experience in the field of fluid responsiveness, practices may differ in other regions or countries. CONCLUSIONS
Despite the well-established impact of controlled fluid resuscitation upon ICU patient outcome, fewer than 40% of VEs are guided by static or dynamic haemodynamic parameters. Dynamic parameters are both underused and misused, whereas static parameters have been virtually abandoned in critically ill patients with SIRS. As PPV is frequently misused because of numerous contraindications, PLR is the safest dynamic parameter used in ICU patients. These findings provide new information that should help to improve future care, teaching and research in the field of fluid resuscitation.
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COMPETING INTERESTS The authors declare that they have no competing interests. ACKNOWLEDGMENTS The authors thank the physicians and nursing staff of the 6 ICUs participating in the study for their
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valuable cooperation. The authors also thank Doctor W. Khaliq for his fruitful comments.
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REFERENCES
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Tenner S, Baillie J, DeWitt J, Vege SS, American College of Gastroenterology. American College of Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013;108:1400-15; 1416.
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National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, Bernard GR, Thompson BT, Hayden D, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006;354:2564-75.
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Boyd JH, Forbes J, Nakada T, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011;39:259-65.
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Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-77.
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Jansen TC, van Bommel J, Schoonderbeek FJ, Sleeswijk Visser SJ, van der Klooster JM, Lima AP, et al. Early lactate-guided therapy in intensive care unit patients: a multicenter, open-label, randomized controlled trial. Am J Respir Crit Care Med. 2010;182:752-61.
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Teboul J, et le groupe d'experts de la Srlf. Recommandations d’experts de la SRLF «Indicateurs du remplissage vasculaire au cours de l’insuffisance circulatoire». Réanimation. 2004;13:255-63.
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Antonelli M, Levy M, Andrews PJD, Chastre J, Hudson LD, Manthous C, et al. Hemodynamic monitoring in shock and implications for management. International Consensus Conference, Paris, France, 27-28 April 2006. Intensive Care Med. 2007;33:575-90.
9.
Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39:165-228.
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Guerin L, Monnet X, Teboul JL. Monitoring volume and fluid responsiveness: from static to dynamic indicators. Best Pract Res Clin Anaesthesiol. 2013;27:177-85.
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Boulain T, Boisrame-Helms J, Ehrmann S, Lascarrou J-B, Bouglé A, Chiche A, et al. Volume expansion in the first 4 days of shock: a prospective multicentre study in 19 French intensive care units. Intensive Care Med. - 2015;41-:248-56.
12.
Mahjoub Y, Lejeune V, Muller L, Perbet S, Zieleskewicz L, Bart F, et al. Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point-prevalence study. Br J Anaesth. 29 2013;
13.
Fischer M-O, Mahjoub Y, Boisselier C, Tavernier B, Dupont H, Leone M, et al. Arterial pulse pressure variation suitability in critical care: A French national survey. Anaesth Crit Care Pain Med. - 2015;34:23-8.
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[No authors listed]. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20:864-74.
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Jouhet J, Dewavrin f, Tavernier B. Remplissage vasculaire par cristalloïdes ou colloïdes: étude comparative de quantité et de durée d’action [résumé]. Réanimation. 2012;21: S271.
16.
Silva S, Jozwiak M, Teboul J-L, Persichini R, Richard C, Monnet X. End-expiratory occlusion test predicts preload responsiveness independently of positive end-expiratory pressure during acute respiratory distress syndrome. Crit Care Med. 2013;41:1692-701.
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Lakhal K, Ehrmann S, Perrotin D, Wolff M, Boulain T. Fluid challenge: tracking changes in cardiac output with blood pressure monitoring (invasive or non-invasive). Intensive Care Med. 2013;39:1953-62.
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Gershengorn HB, Wunsch H. Understanding changes in established practice: pulmonary artery catheter use in critically ill patients. Crit Care Med. 2013;41:2667•76.
19.
Michard F, Alaya S, Zarka V, Bahloul M, Richard C, Teboul J-L. Global end-diastolic volume as an indicator of cardiac preload in patients with septic shock. Chest. 2003;124:1900-8.
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Osman D, Ridel C, Ray P, Monnet X, Anguel N, Richard C, et al. Cardiac filling pressures are not appropriate to predict hemodynamic response to volume challenge. Crit Care Med. 2007;35:64-8.
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Vincent JL, Weil MH. Fluid challenge revisited. Crit Care Med. 2006;34:1333-7.
22.
Préau S, Saulnier F, Dewavrin F, Durocher A, Chagnon JL. Passive leg raising is predictive of fluid responsiveness in spontaneously breathing patients with severe sepsis or acute pancreatitis. Crit Care Med. 2010;38:819-25.
23.
Monnet X, Bleibtreu A, Ferré A, Dres M, Gharbi R, Richard C, et al. Passive leg-raising and end-expiratory occlusion tests perform better than pulse pressure variation in patients with low respiratory system compliance. Crit Care Med. 2012;40:152-7.
24.
Vallée F, Richard JCM, Mari A, Gallas T, Arsac E, Verlaan PS, et al. Pulse pressure variations adjusted by alveolar driving pressure to assess fluid responsiveness. Intensive Care Med. 2009;35:1004-10.
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Muller L, Louart G, Bousquet P-J, Candela D, Zoric L, de La Coussaye J-E, et al. The influence of the airway driving pressure on pulsed pressure variation as a predictor of fluid responsiveness. Intensive Care Med. 2010;36:496-503.
26.
Fischer M-O, Dechanet F, du Cheyron D, Gérard J-L, Hanouz J-L, Fellahi J-L. Evaluation of the knowledge base of French intensivists and anaesthesiologists as concerns the interpretation of respiratory arterial pulse pressure variation. Anaesth Crit Care Pain Med. 2015;34:29-34.
27.
Biais M, Ehrmann S, Mari A, Conte B, Mahjoub Y, Desebbe O, et al. Clinical relevance of pulse pressure variations for predicting fluid responsiveness in mechanically ventilated intensive care unit patients: the grey zone approach. Crit Care 2014;18:587.
28.
Tavernier B, Makhotine O, Lebuffe G, Dupont J, Scherpereel P. Systolic pressure variation as a guide to fluid therapy in patients with sepsis-induced hypotension. Anesthesiology. 1998;89:1313-21.
29.
Belikova I, Lukaszewicz AC, Faivre V, Damoisel C, Singer M, Payen D. Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis. Crit Care Med. 2007;35:2702-8.
30.
Ait-Oufella H, Boelle P-Y, Galbois A, Baudel J-L, Margetis D, Alves M, et al. Comparison of superior vena cava and femoroiliac vein pressure according to intra-abdominal pressure. Ann Intensive Care. 2012;2:21.
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25.
Figure 1. Preliminary questionnaire: physicians’ agreement with guidelines and their perception of their own practices.
Figure 2. Questionnaire a: physicians’ use of static and dynamic haemodynamic parameters for predicting fluid responsiveness.
Figure 3. Questionnaire b: limitations of static and dynamic haemodynamic parameters.
Figure 4. Identified limitations of static and dynamic haemodynamic parameters before volume expansion. Values are expressed as number (% of the 566 volume expansions). PPV, respiratory variations in systemic pulse pressure. PLR, passive leg raising. IVCV, respiratory variations in inferior vena cava diameter. CVP, central venous pressure measured with a central venous catheter. PAOP, pulmonary artery occlusion pressure. GEDV, global end diastolic volume measured with PiCCOTM device (Pulsion).
Page 16 of 20
Table 1. The main characteristics of 566 volume expansions prescribed for intensive care unit patients with systemic inflammatory response syndrome. Gelatin
Albumin
Frequency
314 (56%)
14 (3%)
146 (26%)
80 (14%)
Volume (ml)
1000 [1000 - 1000]
875 [500 - 1000]
500 [500 - 500]
500 [200 - 500]
Hydroxyethylstarch
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Isotonic sodium bicarbonate
12 (2%)
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Isotonic sodium chloride
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500 [500 - 500]
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Values are expressed as numbers (% of the 566 volume expansions) or medians and interquartile ranges [25th–75th percentiles].
Measurable and interpretable
Ac ce pt e
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Used
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Table 2. Static and dynamic haemodynamic parameters measured before the 566 volume expansions. Used when uninterpretable
Not used, but measurable and interpretable
Dynamic parameters PPV
110 (19%)
96 (17%)
65 (12%)
51 (9%)
PLR
75 (13%)
508 (90%)
7 (1%)
440 (78%)
IVCV
31 (6%)
252 (45%)
15 (3%)
236 (42%)
CVP
50 (9%)
405 (72%)
0 (0%)
355 (63%)
PAOP
7 (1%)
8 (1%)
0 (0%)
1 (0%)
GEDV
6 (1%)
26 (5%)
0 (0%)
20 (4%)
Static parameters
Values are expressed as numbers (% of the 566 volume expansions). PPV, respiratory variations in systemic pulse pressure. PLR, passive leg raising. IVCV, respiratory variations in inferior vena cava diameter. CVP, central venous pressure measured with a central venous catheter. PAOP, pulmonary artery occlusion pressure. GEDV, global end diastolic volume measured with PiCCOTM device (Pulsion).
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Table 3. Agreement by 84 physicians with use of static and dynamic haemodynamic parameters to guide volume expansion in patients with systemic inflammatory response syndrome. Residents (n = 32)
P
“Measurement of static parameters is recommended for predicting VE response”
13 (25%)
12 (38%)
0.22
“Low values of static parameters indicate VE in patients with shock”
46 (89%)
28 (88%)
1
“Use of dynamic parameters is recommended for predicting VE response”
47 (90%)
27 (84%)
“Use of dynamic parameters improves outcome of highly selected patients”
35 (67%)
23 (72%)
“A VE-induced change in SV or CO ≥ 10 - 15% usually defines a positive response to VE”
39 (75%)
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Seniors (n = 52)
0.81
0.15
3 (6%)
1 (3%)
1
18 (35%)
4 (13%)
0.04
“PPV can be used in case of low tidal volume”
28 (54%)
18 (56%)
0.82
“PPV can be used in case of poor pulmonary compliance”
24 (46%)
15 (47%)
1
“PLR can be used in case of abdominal compartment syndrome”
5 (10%)
2 (6%)
0.7
“PPV can be used in case of irregular cardiac rhythm”
Ac ce pt e
“PPV can be used in case of spontaneous breathing”
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28 (88%)
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0.30
Both “total agreement” and “agreement” from the preliminary questionnaire 1 (Figure 1) were considered as an agreement with the corresponding sentences in this table. Values are expressed as number (% of 52 seniors or 32 residents). VE, volume expansion. PPV, respiratory variations in systemic pulse pressure. PLR, passive leg raising. SV, stroke volume. CO, cardiac output.
Page 19 of 20
Residents (n = 32)
P
PPV
39 (75%)
26 (81%)
0.6
PLR
40 (77%)
26 (81%)
IVCV
16 (31%)
13 (41%)
22 (42%)
12 (38%)
0.82
0 (0%)
1
4 (13%)
0.27
1 (2%)
GEDV
12 (23%)
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PAOP
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Static parameters CVP
0.79 0.48
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Dynamic parameters
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Seniors (n = 52)
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Table 4. Declared use by 84 physicians of static and dynamic parameters prior to ≥ 50 % of volume expansions.
Ac ce pt e
d
Values are expressed as numbers (% of 52 seniors or 32 residents). PPV, respiratory variations in systemic pulse pressure. PLR, passive leg raising. IVCV, respiratory variations in inferior vena cava diameter. CVP, central venous pressure measured with a central venous catheter. PAOP, pulmonary artery occlusion pressure. GEDV, global end diastolic volume measured with PiCCOTM device (Pulsion).
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