Review Articles

Does the Central Venous Pressure Predict Fluid

Responsiveness? An Updated Meta-Analysis
and a Plea for Some Common Sense*
Paul E. Marik, MD, FCCM1; Rodrigo Cavallazzi, MD2

Background: Despite a previous meta-analysis that concluded 0.56 (95% CI, 0.54–0.58) for those done in the operating room.
that central venous pressure should not be used to make clinical The summary correlation coefficient between the baseline central
decisions regarding fluid management, central venous pressure venous pressure and change in stroke volume index/cardiac index
continues to be recommended for this purpose. was 0.18 (95% CI, 0.1–0.25), being 0.28 (95% CI, 0.16–0.40) in
Aim: To perform an updated meta-analysis incorporating recent the ICU patients, and 0.11 (95% CI, 0.02–0.21) in the operating
studies that investigated indices predictive of fluid responsive- room patients.
ness. A priori subgroup analysis was planned according to the Conclusions: There are no data to support the widespread prac-
location where the study was performed (ICU or operating room). tice of using central venous pressure to guide fluid therapy. This
Data Sources: MEDLINE, EMBASE, Cochrane Register of Con- approach to fluid resuscitation should be abandoned. (Crit Care
trolled Trials, and citation review of relevant primary and review Med 2013; 41:1774–1781)
articles. Key Words: central venous pressure; fluid challenge; hemodynamic
Study Selection: Clinical trials that reported the correlation monitoring; meta-analysis; volume responsive
coefficient or area under the receiver operating characteristic
curve (AUC) between the central venous pressure and change
in cardiac performance following an intervention that altered
cardiac preload. From 191 articles screened, 43 studies met

T
our inclusion criteria and were included for data extraction. The he cornerstone of treating patients with hypotension,
studies included human adult subjects, and included healthy hypoperfusion, and shock remains as it has been for
controls (n = 1) and ICU (n = 22) and operating room (n = 20) decades, that is, IV fluids. A fluid optimization protocol
patients. based on maximizing perioperative stroke volume (SV) and
Data Extraction: Data were abstracted on study characteristics, cardiac output (CO) has been shown to reduce postoperative
patient population, baseline central venous pressure, the correla- complications and length of stay in patients undergoing major
tion coefficient, and/or the AUC between central venous pres- surgery (1–5). Similarly, early aggressive resuscitation of critically
sure and change in stroke volume index/cardiac index and the ill patients may limit and/or reverse tissue hypoxia, progression
percentage of fluid responders. Meta-analytic techniques were to organ failure, and improve outcome (6–8). However, over-
used to summarize the data. zealous fluid resuscitation has been associated with increased
Data Synthesis: Overall 57% ± 13% of patients were fluid complications, increased length of ICU and hospital stay, and
responders. The summary AUC was 0.56 (95% CI, 0.54–0.58) increased mortality (9–13). Fundamentally, the only reason to
with no heterogenicity between studies. The summary AUC was give a patient a fluid challenge is to increase SV (volume respon-
0.56 (95% CI, 0.52–0.60) for those studies done in the ICU and siveness) with an increase in CO and oxygen delivery (6). If the
fluid challenge does not increase SV, volume loading serves the
*See also p. 1823. patient no useful benefit and is likely to be harmful.
1
Division of Pulmonary and Critical Care Medicine, Eastern Virginia Medi- Despite limited scientific data, the central venous pressure
cal School, Norfolk, VA. (CVP) has been used for the last 50 years to guide fluid therapy
2
Division of Pulmonary, Critical Care, and Sleep Disorders, University of (14). In 2008, we published a meta-analysis evaluating the
Louisville, Louisville, KY.
ability of the CVP to guide fluid therapy (15). We demonstrated
The authors have disclosed that they do not have any potential conflicts
of interest. that the CVP was no better than flipping a coin in predicting
For information regarding this article, E-mail: marikpe@evms.edu fluid responsiveness and concluded that the “CVP should not
Copyright © 2013 by the Society of Critical Care Medicine and Lippincott be used to make clinical decisions regarding fluid management.”
Williams & Wilkins Despite this finding, the CVP continues to be recommended to
DOI: 10.1097/CCM.0b013e31828a25fd guide fluid resuscitation (16, 17). Since the publication of our

1774 www.ccmjournal.org July 2013 • Volume 41 • Number 7

 Review Articles

meta-analysis, the concept of fluid responsiveness has become

well accepted, and a number of studies have been published
investigating the role of various techniques to assess fluid
responsiveness (6). Due to the ongoing recommendations in the
Critical Care and Anesthesia literature to use the CVP to guide
fluid therapy, we decided it was important to update our meta-
analysis to include the most recent studies. We were curious
to explore whether any of the more recent studies were able to
demonstrate a role of the CVP in guiding fluid resuscitation.
In addition, in our previous meta-analysis, all the studies
were grouped together. We postulated that in the controlled
environment of the operating room, the CVP may be more
predictive of volume responsiveness than in hemodynamically
unstable critically ill ICU patients. Furthermore, due to
changes in cardiac performance following cardiac surgery, the
CVP may be less reliable in these patients than in those patients
undergoing noncardiac surgery. We therefore decided a priori
to perform subgroup analysis according to the setting the
study was performed (ICU or operating room) and the type
of patient population (cardiac surgery vs noncardiac surgery
patients) to make our finding more clinically relevant.
Figure 1. Flowchart of study selection. ROC = receiver operator
characteristic.
METHODS
Identification of Trials size, study setting, patient population, criteria used to define fluid
Our aim was to identify all relevant clinical trials that inves- responsiveness, type of fluid challenge, the primary technology
tigated the ability of the CVP to predict fluid responsive- being assessed, the correlation coefficients and AUC (including
ness. Fluid responsiveness was defined as an increase in CO 95% CIs) for the CVP and fluid responsiveness, the percentage
or SV following a preload challenge, usually a volume chal- of patients responding to a fluid challenge, as well as the baseline
lenge or passive leg raising (PLR) maneuver. We restricted CVP in the fluid responders and nonresponders.
this analysis to human adults; however, there was no restric-
tion as to the type of patient or the setting where the study Data Analysis
was performed. We used a multimethod approach to identify Studies were subgrouped according to the location where the
relevant studies for this review. Both authors independently study was performed (ICU or operating room) and the type
searched the National Library of Medicine’s MEDLINE data- of patient population (cardiac surgery vs noncardiac surgery
base for relevant studies in any language published from 1966 patients). Summary data are presented as means (± standard
to June 2012, using the following Medical Subject Headings deviations) and percentages as appropriate. Meta-analytic
and keywords: CVP (explode) and fluid therapy or fluid techniques were used to summarize the data. The random
responsiveness. In addition, we searched EMBASE and the effects models using Comprehensive Meta-analysis 2.0 (Biostat,
Cochrane Database of Systematic Reviews. Bibliographies of Englewood, NJ) were used to determine the summary AUC
all selected articles and review articles that included informa- and correlation coefficients. Summary effects estimates are
tion on hemodynamic monitoring were reviewed for other presented with 95% CIs. We assessed heterogeneity between
relevant articles. This search strategy was done iteratively, studies using the Cochran Q statistic (19), with a p value of
until no new potential citations were found on review of the less than or equal to 0.10 indicating significant heterogeneity
reference lists of retrieved articles. We performed this meta- (20), and I2 with suggested thresholds for low (25%–49%),
analysis according to the guidelines proposed by the Quality moderate (50%–74%), and high (> 75%) values (21, 22).
of Reporting of Meta-analyses group (18).

Study Selection and Data Extraction RESULTS

Only studies that reported the correlation coefficient or the area A flow diagram outlining the search strategy and study selec-
under the receiver operating characteristic curve (AUC) between tion is illustrated in Figure 1. Forty-three studies met the inclu-
the CVP and change in cardiac performance following a fluid sion criteria for this meta-analysis (23–65). The details of these
challenge, PLR maneuver/postural change, or positive end-expi- studies are provided in Table 1. Overall 2,105 fluid responsive-
ratory pressure challenge were included in this analysis. Both ness maneuvers were performed in 1,802 patients. Twenty-two
authors independently abstracted data from all studies using a studies were performed in ICU patients (four cardiac surgery
standardized form. Data were abstracted on study design, study patients), and 20 studies (13 cardiac surgery patients) were

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Marik and Cavallazzi

Table 1. Characteristics of the Studies Included in Meta-Analysis

No. of
Author Year Patients Patients Method
ICU
  Calvin et al (23) 1981 Various 28 PAC
  Reuse et al (24) 1990 Various 41 PAC
  Wagner and Leatherman (25) 1998 Various 25 PAC
  Michard et al (26) 2000 Sepsis 40 PAC
  Reuter et al (27) 2002 CABG 20 PiCCO
  Barbier et al (28) 2004 Sepsis 20 TEE
  Kramer et al (29) 2004 CABG 21 PAC
  Marx et al (30) 2004 Sepsis 10 PAC, PiCCO
  Perel et al (31) 2005 Vascular surgery 14 TEE
  De Backer et al (32) 2005 Various 60 PAC
  Osman et al (33) 2007 Septic 96 PAC
  Magder and Bafaqeeh (34) 2007 CABG 66 PAC
  Wyffels et al (35) 2007 CABG 32 PAC
  Auler et al (36) 2008 CABG 59 PAC
  Muller et al (37) 2008 Various 35 PiCCO
  Huang et al (38) 2008 ARDS 22 PAC, PiCCO
  Garcia et al (39) 2009 Various 38 Flotrac (Edwards
Life-Sciences, Irvine, CA)
  Thiel et al (40) 2009 Various 89 Doppler
  Garcia et al (41) 2009 Various 30 Flotrac
  Moretti and Pizzi (42) 2010 SAH 29 PiCCO
  Muller et al (43) 2011 Various 39 TTE
  Lakhal et al (44) 2011 ARDS 65 PAC/PiCCO
Operating room
  Berkenstadt et al (45) 2001 Neurosurg 15 PiCCO
  Rex et al (46) 2004 CABG 14 PiCCO/TEE
  Preisman et al (47) 2005 CABG 18 TEE, PiCCO
  Hofer et al (48) 2005 CABG 40 PAC, PiCCO
  Wiesenack et al (49) 2005 CABG 20 PiCCO
  Solus-Biguenet et al (50) 2006 Hepatic 8 PAC, TEE
  Cannesson et al (51) 2006 CABG 18 TEE
  Lee et al (52) 2007 Neurosurg 20 TEE, Doppler
  Cannesson et al (53) 2007 CABG 25 PAC
  Belloni et al (54) 2008 CABG 19 PAC, TEE
  Biais et al (55) 2008 OTLTx 35 PAC, TEE

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 Review Articles

Area Under the

Receiver
Operator
Inclusion Mechanical Other Characteristic
Criteria Ventilation Comparator Challenge r-ΔSV Curve

SV N — 250 cc Colloid 0.16 —

CI Y RVEDVI 300 cc Colloid 0.21 —
SV > 10% Y RVEDVI 500 cc Colloid 0.44 —
CI > 15% Y PPV 500 cc Colloid — 0.51
SVI > 15% Y SVV 500 cc Colloid — 0.42
CI > 15% Y IVC-collapse 7 mL/kg Colloid 0.17 0.57
CI > 12% Y PPV 500 cc Colloid 0.13 0.49
CI Y SVV, ITBVI 500 cc Colloid 0.41 —
CI > 15% Y SVV 7 mL/kg colloid 0.27 —
CI > 15% Y SVV 500 cc Colloid — 0.54
CI > 15% Y — 500 cc Colloid — 0.58
CI > 0.3% Y — 350 cc Colloid 0.36 —
CI > 15% Y PPV 500 cc Colloid 0.16 0.6
CI > 15% Y PPV 20 mL/kg LR — 0.58
SVI > 15% Y ITBVI 500 cc Colloid — 0.68
CI > 15% Y SVV, PPV 500 cc Colloid — 0.42
SVI > 15% Y Brachial artery 500 cc Colloid — 0.64
velocity
SV > 15% Y PLR PLR — 0.52
SVI > 15% N Valsalva 500 cc Colloid — 0.51
CI > 15% Y SVV, IVC-collapse 7 mL/kg Colloid — 0.66
VTI > 15% Y PPV/VTI 500 cc Colloid — 0.61
CO > 10% Y PPV 500 cc Colloid — 0.63

SV > 5% Y SVV 100 cc Colloid 0.05 0.493

SVI > 5% Y PPV, ITBVI Head up-down 0.3 —
SV > 15% Y SVV 250 cc Colloid — 0.61
SVI > 25% Y SVV, GEDV 10 mL/kg Colloid 0.02 0.54
SVI > 20% Y PPV 7 mL/kg Colloid 0.34 —
SVI > 10% Y PPV, LVEDA 250 cc Colloid — 0.63
CO > 15% Y LVSA PLR 0.23 0.27
SVI > 10% Y PPV, Doppler 7 mL/kg Colloid — 0.54
CI > 15% Y PVI, PPV 500 cc Colloid 0.28 0.57
CI > 15% Y PPV 7 mL/kg Colloid 0.08 —
CO > 15% Y SVV 20 mL × BMI colloid — 0.64
(Continued)

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Table 1. (Continued). Characteristics of the Studies Included in Meta-Analysis

Type of No. of
Author Year Patients Patients Method­
  Hofer et al (56) 2008 CABG 40 PAC, Flotrac
  de Waal et al (57) 2009 CABG 18 PiCCO
  Cannesson et al (58) 2009 CABG 25 PAC
  Zimmerman et al (59) 2010 Ab-surg 20 Flotrac
  Desebbe et al (60) 2010 CABG 21 PAC
  Desgranges et al (61) 2011 CABG 28 PAC
  Shin et al (62) 2011 OTLTx 33 PAC, Flotrac
  Broch et al (63) 2011 CABG 81 PiCCO
  Cannesson et al (64) 2011 Various 413 PAC/PiCCO
Volunteers
  Kumar et al (65) 2007 Healthy volunteer 12 Echocardiography
SV = stroke volume, PAC = pulmonary artery catheter, RVEDVI = right ventricular end-diastolic volume index, PPV = pulse pressure variation, CABG = coronary
artery bypass graft, PiCCO = transpulmonary thermodilution, Pulsion Medical Systems (Feldkirchen, Germany), SVI = stroke volume index, SVV = stroke volume
variation, TEE = trans-esophageal echocardiography, IVC = inferior vena cava, ITBV = intrathoracic blood volume index, ARDS = acute respiratory distress
syndrome, PLR = passive leg raise, SAH = subarachnoid hemorrhage, CI = cardiac index, TTE = trans-thoracic echocardiography, VTI = velocity time integral,
CO = cardiac output, GEDV = global end-diastolic volume, LVEDA = left ventricular end diastolic area, LVSA = left ventricular surface area, PVI = pleth
variability index, PEEP = positive end-expiratory pressure, OTLTx = orthotopic liver transplant.

performed in the operating room. In addition, a single study clinical settings. A review of cardiac physiology would lead
that evaluated the hemodynamic response to fluid loading in one to the same conclusion as the premise that the CVP (or
healthy volunteers was also included. Most of the studies used pulmonary artery occlusion pressure) is a measure of preload
an increase of stroke volume index (SVI) or cardiac index (CI) responsiveness is seriously flawed. The CVP is believed to be
of 15% following a 500 cc fluid challenge (usually a tetrastarch) an indicator of right ventricular end-diastolic volume index
to define fluid responsiveness. (RVEDVI). The RVEDVI in turn is believed to be an indica-
AUC data were available for 33 studies and correlation tor of preload responsiveness. Both of these assumptions are
data for 20 studies. Overall 57% ± 13% of patients were fluid incorrect, resulting in a cascading error of logic. Due to the
responders, with 52% ± 11% of ICU patients being fluid curvilinear shape of the ventricular pressure-volume curve,
responders as compared to 63% ± 15% of patients in the oper- there is a poor relationship between ventricular filling pressure
ating room. The mean baseline CVP was 8.2 ± 2.3 mm Hg in the and ventricular volume (preload). This relationship is further
fluid responders and 9.5 ± 2.2 mm Hg in the nonresponders. disturbed by diastolic dysfunction and altered ventricular com-
The summary AUC was 0.56 (95% CI, 0.54–0.58), with no het- pliance that is characteristic of critical illness. Furthermore,
erogenicity between studies (Q statistic p = 0.9, I2 = 0%). The clinical studies have clearly demonstrated that ventricular vol-
summary AUC was 0.56 (95% CI, 0.52–0.60) for those studies umes (RVEDVI, left ventricular end-diastolic area, global end-
done in the ICU and 0.56 (95% CI, 0.54–0.58) for those done diastolic volumes) are unable to predict fluid responsiveness
in the operating room. Similarly, the summary AUC was 0.56 (25, 46, 52, 54, 66).
(95% CI, 0.51–0.61) for the cardiac surgery patients and 0.56 The origins of CVP monitoring can be traced back to
(95% CI, 0.54–0.58) for the noncardiac surgery patients. The Hughes and Magovern (14), who in 1959 described a com-
summary correlation coefficient between the baseline CVP plicated technique for right atrial pressure monitoring. These
and the delta SVI/CI was 0.18 (95% CI, 0.1–0.25), being 0.28 authors intermittently measured blood volume (using radio-
(95% CI, 0.16–0.40) in the ICU patients, and 0.11 (95% CI, active serum albumin) and hourly urine output, blood pres-
0.02–0.21) in the operating room patients. sure, respiratory rate, and pulse rate in 25 postthoracotomy
patients. Without providing any summary data or statistical
testing, they made the remarkable conclusion that “right atrial
DISCUSSION pressure is an accurate and sensitive recording of the effective
This study confirms and extends the findings of our previous circulating blood volume” and that “the adequacy and rate of
meta-analysis, namely, that the CVP is unable to predict fluid treatment are accurately reflected by the right atrial pressure
responsiveness among a broad range of patients in various monitor, and two cases are presented to substantiate the same.”

1778 www.ccmjournal.org July 2013 • Volume 41 • Number 7

 Review Articles

Area Under the

Receiver
Operator
Inclusion Mechanical Other Characteristic
Criteria Ventilation Comparator Challenge r-ΔSV Curve
SV > 25% Y SVV, PPV Head up-down — 0.29
SVI > 12% Y PPV, SVV 10 mL/kg Colloid — 0.57
CI > 15% Y SVV 500 cc Colloid — 0.53
SVI > 15% Y SVV/PVI 7 mL/kg Colloid 0.18 0.55
CI < 15% Y PVI 10 cm PEEP — 0.25
CI > 15% Y PVI 500 cc Colloid — 0.48
CI > 15% Y SVV 10 mL/kg Colloid 0.11 0.57
SVI > 15% Y PVI, PPV PLR 0.12 0.6
CO > 15% Y PPV 500 cc Colloid — 0.57

N Various 3,000 Crystalloid 0.32 —

The technique of CVP monitoring was further popularized by 7. Shapiro NI, Howell MD, Talmor D, et al: Implementation and out-
comes of the Multiple Urgent Sepsis Therapies (MUST) protocol. Crit
Wilson and Grow (67) and soon became routine in patients Care Med 2006; 34:1025–1032
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in the operating room and then in the ICU and emergency septic shock. Crit Care Med 2004; 32:1825–1831
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shock: A positive fluid balance and elevated central venous pres-
In conclusion, there are no data to support the widespread sure are associated with increased mortality. Crit Care Med 2011;
practice of using CVP to guide fluid therapy. This approach to 39:259–265
fluid resuscitation is without a scientific basis and should be 10. Maitland K, Kiguli S, Opoka RO, et al; FEAST Trial Group: Mortality
abandoned. after fluid bolus in African children with severe infection. N Engl J Med
2011; 364:2483–2495
11. de-Madaria E, Soler-Sala G, Sánchez-Payá J, et al: Influence of fluid
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