Table of Contents  
Year : 2014  |  Volume : 7  |  Issue : 1  |  Page : 19-24

Validity of right ventricular end-diastolic volume as a guide for fluid resuscitation compared with central venous pressure in living donor liver transplantation recipients: a randomized controlled trial

1 Department of Anesthesia and Intensive Care, Liver Transplantation Unit, Gastroenterology Surgical Center, Mansoura University, Mansoura, Egypt
2 Department of Hepatology, Liver Transplantation Unit, Gastroenterology Surgical Center, Mansoura University, Mansoura, Egypt
3 Department of Surgery, Liver Transplantation Unit, Gastroenterology Surgical Center, Mansoura University, Mansoura, Egypt

Date of Submission18-Aug-2013
Date of Acceptance04-Oct-2013
Date of Web Publication31-May-2014

Correspondence Address:
Amr M Yassen
MD, Department of Anesthesia and Intensive Care, Liver Transplantation Unit, Gastroenterology Surgical Center, Mansoura University, Gehan Street, Postal code 35516, Mansoura
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1687-7934.128392

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Fluid transfusion inflects major impact on graft and renal functions in living donor liver transplantation. Major hemodynamic swinging renders intraoperative preload assessment crucial yet difficult task. In this prospective randomized double-blind controlled trial, we examined the validity of right ventricular end-diastolic volume (RVEDV) as a preload indicator compared with central venous pressure (CVP) in recipients of living donor liver grafts.
Patients and methods
A total of 21 patients included in the study were randomly allocated into either the RVEDV group (n = 11) or the CVP group (n = 10) on the basis of the trigger for operative fluid resuscitation. Basal value for both right ventricular end-diastolic volume index (RVEDVI) and CVP was recorded after laparotomy. Fluids (albumin 4% or Voluven) were given in boluses of 250 ml when the triggering parameter decreased by 20% of its basal value. Hemodynamic data were recorded after laparotomy (basal), at the end of hepatectomy, before portal unclamping, 15 min after portal unclamping, and at skin closure. Total fluids infused, blood loss, early graft, and patient's outcomes were also recorded.
Both groups were similar with respect to demographic and operative data. Fluids infused were significantly higher in the RVEDVI group compared with the CVP group. Cardiac output and stroke volume were significantly higher in the RVEDVI than in the CVP group starting at end of hepatectomy and thereafter. Urine output was significantly less in the CVP group compared with the RVEDVI group. Hypotensive episodes were greater in the CVP group compared with the RVEDVI group. RVEDVI and CVP did not correlate at any time point. No intergroup differences were observed with respect to early graft functions, serum creatinine, blood urea, ICU stay, 28th day graft, and patient survival.
RVEDV appears to be a more sensitive preload indicator and a trigger for fluid resuscitation compared with CVP; however, patient monitoring with either parameter did not significantly affect the patient outcome.

Keywords: Fluid therapy, living donor liver transplantation, right ventricular end-diastolic volume, volumetric

How to cite this article:
Yassen AM, Elsarraf WR, Elmorshidy M, Elsadany M, Salah T, Sultan AM. Validity of right ventricular end-diastolic volume as a guide for fluid resuscitation compared with central venous pressure in living donor liver transplantation recipients: a randomized controlled trial. Ain-Shams J Anaesthesiol 2014;7:19-24

How to cite this URL:
Yassen AM, Elsarraf WR, Elmorshidy M, Elsadany M, Salah T, Sultan AM. Validity of right ventricular end-diastolic volume as a guide for fluid resuscitation compared with central venous pressure in living donor liver transplantation recipients: a randomized controlled trial. Ain-Shams J Anaesthesiol [serial online] 2014 [cited 2022 Oct 7];7:19-24. Available from:

  Introduction Top

Liver transplantation is an established line of therapy for patients with end-stage liver disease of any etiology. Recipient operation represents a major anesthetic challenge because of several factors including the pathologic changes associated with end-stage liver disease and the operative nature per se [1]. Major hemodynamic swinging, fluid shifts, mechanical impact of the operative technique on the hemodynamics, length of the operation, and probable use of hemodynamically effective drugs render those patients liable for stormy operative course [2]. Fluid resuscitation during the operative period may be a factor for complicating the operative course with misjudgment of the true needs. Accurate preload assessment is accordingly critical to prevent volume overload or underload induced complications [3],[4],[5]. A literature review in 2008 concluded that central venous pressure (CVP) should not be used to make clinical decisions about fluid management [6]. Volumetric indices for preload assessment, such as right ventricular end-diastolic volume (RVEDV), are gaining more popularity over the traditional pressure indices such as CVP in several operative and intensive care settings [7],[8]. However, the validity of these volumetric indices needs to be validated in complex, multiphasic operative courses such as living donor liver transplantation (LDLT). We hypothesize that the changes inflected on the right side of the heart by the alteration of myocardial compliance as well as the changes in the pulmonary vascular resistance during different phases of the operation might jeopardize the accuracy of the RVEDV measurement during liver transplantation operation. We designed this prospective randomized double-blind controlled trial to examine the validity of RVEDV as a preload indicator compared with CVP in recipients of living donor liver grafts.

  Patients and methods Top

Twenty-four recipients for right lobe LDLT in Mansoura University Liver Transplantation Program were enrolled in this prospective, double-blind, randomized controlled trial from March 2010 to December 2011. Relevant ethical and legal approvals were obtained from the university ethical committee and written informed consent was secured from each patient. Patients between 30 and 60 years of either sex were enrolled in this trial. Patients with preoperative evidence of pulmonary hypertension, right ventricular enlargement (> 20% of reference value), grade II valvular heart disease, or moderate degree mitral valve prolapsed and patients with creatinine clearance less than 60 ml/kg/day were excluded from the study. Random number generator was used to allocate patients in one of the study groups. During the study, massive transfusion (> 10 units of RBCs or plasma) and the use of vassopressors or inotropic drugs were the reasons for excluding patients from the trial. Anesthesia was induced in all patients with intravenous injection of propofol 1-2 mg/kg (propofol 1%; Fresenius, Freseniu Kabi, Hamburg, Germany) and fentanyl 2 μg/kg (fentanyl; Janssen-Cilag, Beers, Belgium). Rocuronium bromide 0.5 mg/kg (Esmeron; Organon, Molenstraat, Netherlands) was used for muscle relaxation. After anesthesia induction, a high-frequency continuous thermal fiberoptic pulmonary artery catheter (CCO/SvO 2 /CEDV; Edwards Life Science, Irvine, California, USA) was inserted in the right internal jugular vein under fluoroscopy for continuous monitoring of right ventricular end-diastolic volume index (RVEDVI) and right ventricular ejection fraction through Vigilance monitor (Edwards Life Science). Datex-Ohmeda AS5 monitor (Microvitec Display Ltd, Bedford, UK) was used for monitoring and calculation of other hemodynamic parameter. Anesthesia was maintained through continuous intravenous infusion of fentanyl 1-2 μg/kg/h and sevoflurane (Abbot, Illinois, USA) in air/oxygen mixture (0.4%). We maintained muscle relaxation through infusion of rocuronium bromide 0.3 μg/kg/h and ventilated the patient to maintain end-tidal carbon dioxide between 30 and 32 mmHg. Positive end-expiratory pressure (PEEP) of 5 cm H 2 O pressure was maintained throughout the whole procedure. Both fentanyl and rocuronium bromide were tapered from portal unclamping until peritoneal closure. On the basis of the fluid resuscitation protocol, we used the parameter used to guide the fluid infusion during the operative course to randomize patients through closed envelopes into either the CVP group or the RVEDVI group. Intraoperative fluid protocol commenced as background continuous infusion of either 10% dextrose or acetated ringer's solution at a rate of 4 ml/kg/h throughout the operative period. Thereafter, 250 ml fluid boluses of either Voluven (Fresenus Kabi, Hamburg, Germany) or 4% albumin were used for fluid resuscitation and were infused over 10 min when the triggering parameters decreased below 20% of its basal (postinduction) value. This is followed by reassessment of the same parameter after 10 min for further fluid needs. Albumin administration was adopted only if the serum albumin decreased below 3.0 mg/dl. A dedicated resident recorded the hemodynamic data 10 min after laparotomy and suction of all ascetic fluid (basal), at the end of hepatectomy, immediately before portal unclamping, 15 min after portal reperfusion, and at skin closure. He also calculated total blood loss, total fluids infused, and urine output at skin closure. Early graft function and renal functions were evaluated through laboratory assessment at days 1 and 7 as well as during ICU stay and on 28th day patient survival. The study aimed at testing the validity of RVEDVI as a guide for fluid therapy compared with CVP. For this, we used end-operative fluid balance as the primary outcome objective in this trial. Secondary objectives included the graft and renal and patients' outcomes.

Statistical analysis

Data were analyzed using statistical package for social sciences (SPSS, version 17; SPSS Inc., Chicago, Illinois, USA). Data were tested for normality using the Kolmogorov-Smirnov test. Two-tailed independent sample Student's t-test assuming equal variance was used to compare the parametric values in both groups, whereas the Mann-Whitney U-test was performed to compare the nonparametric values. Serial changes in hemodynamic data were analyzed using repeat measures analysis of variance. Data were expressed as mean ± SD or number and percentage as appropriate. Pearson's correlation was used to test the association between CVP and RVEDVI through the study time points. A value of P less than 0.05 was considered to represent statistical significance. Preliminary data collected in our program from previous ICU study were used to conduct a prior power analysis using bivariate linear regression, indicating that 12 patients in each group would be sufficient to detect a 30% difference in fluid balance, with a type I error of 0.05 and a power of 90%.

  Results Top

We recruited 31 patients for this trial; seven of them were excluded and we enrolled 24 recipients into the two study groups (12 patients each). Ten patients in the CVP group and 11 patients in the RVEDVI group completed the study. Two patients were excluded in the CVP group because of noradrenaline administration and massive transfusion (13 l of blood products), whereas we only excluded one patient in the RVEDVI group because of protocol violation (unblinded) [Figure 1]. Patient's characteristics, operative data, and outcome parameters did not significantly differ between both groups [Table 1]. A significantly positive fluid balance was demonstrated in the RVEDV group compared with the CVP group (CI = 524.65) [Figure 2]. The volume of fluids infused and urine output during the operative period were both significantly lower in the CVP group compared with the RVEDVI group [Figure 3]. [Table 2] demonstrates the hemodynamic data for the studied groups. Only stroke volume index was significantly higher in the RVEDVI group compared with the CVP group from the end of hepatectomy until the end of operation, whereas hypotensive episodes (mean arterial pressure <90 mmHg) were significantly less frequent in the RVEDVI group compared with the CVP group [Figure 4]. Neither graft functions nor renal functions at the first and seventh postoperative days showed any significant difference between both groups [Table 3].
Table 1: Patient characteristics, operative data, and outcome parameters in the central venous pressure group (n = 10) and in the right ventricular end-diastolic volume index group (n = 11)

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Table 2: Hemodynamic data of the studied groups: the central venous pressure group (n = 10) and the right ventricular end-diastolic volume index group (n = 11)

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Table 3: Postoperative day 1 and day 7 laboratory data in the central venous pressure group (n = 10) and in the right ventricular end-diastolic volume index group (n = 11)

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Figure 1:

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Figure 2:

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Figure 3:

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Figure 4:

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  Discussion Top

This trial demonstrated that the use of RVEDVI as a guide for fluid resuscitation during LDLT was not superior to the use of CVP with respect to neither intraoperative course nor outcome parameters. A significantly positive fluid balance was achieved in this trial when we used RVEDVI as a guide for fluid infusion compared with CVP.

Unnecessary volume infusion inducing volume overload will have deleterious effects on several systems including the pulmonary and gastrointestinal systems, on overall tissue oxygenation, on increased infection rates, on increased intensive care, and on hospital stays as well as patient outcome [3],[4],[9].

A parameter that will truly predict the precise fluid needs will protect this overload-sensitive patient group from these hazards. Both pressure indices and volume indices have been tested as preload indicators under different clinical settings, with discrepant results in different clinical trials [7],[8],[10],[11],[12].

In uncomplicated operative course in liver transplantation, the sensitivity of both CVP and RVEDV to reflect the real fluid needs is jeopardized by acute changes in the vascular volume, pulmonary artery pressure, systemic vascular resistance, myocardial compliance, and intrathoracic pressure, particularly with blood loss or portal and vena cava clamping and unclamping [13].

For testing the impact of these hemodynamic parameters, we compared the hemodynamic profile both before and after portal unclamping, which is the major turn point for pulmonary and systemic circulation, and found that the changes in these parameters after portal unclamping did not significantly differ compared with those before the unclamping profile. Subsequently, we excluded changes in the pulmonary circulation and the right ventricular performance as a sole or major contributor in the sensitivity of RVEDV or CVP.

Della Rocca et al. [14] investigated the effect of RVEDVI and CVP among other parameters on the generated stroke volume index in patients undergoing liver transplantation. They constructed a multivariate model and concluded that RVEDVI is a better predictor of the actual circulatory state than CVP, with an obvious contradiction to our results.

Intrathoracic pressure reflects the major changes on thoracic venous inflow as well as a direct effect on the atrial pressures, and variation in the intrathoracic pressure affects the CVP readings [15],[16]. In this study, we applied 5 cm H 2 O PEEP throughout the operative procedure. This pressure is capable of increasing the recorded CVP, which is in accordance with several previous trials that reported a significant influence of the level of positive intrathoracic pressure and CVP [16-19]. We adopted the baseline value measured at the initiation of the operation to be the benchmark for detecting the need for fluid boluses in this study. This baseline value was recorded before the application of PEEP. Thereafter, PEEP created a persistent elevation in the CVP value above the baseline and consequently, the trigger for fluid boluses in this protocol was reduced. Previous investigators, in an echocardiographic study, recorded a constant RVEDV during mechanical ventilation, thus nullifying the impact of minor changes of intrathoracic pressure on RVEDV when compared with CVP [20]. This mechanical effect can explain the reduced fluid requirements in the CVP group compared with the RVEDV group and justifies the difference between our results and the results of Della Rocca and colleagues, as they did not use PEEP during their operative course. The differential impact of the mechanical effect of PEEP, which mainly affect the low-pressure CVP readings rather than the RVEDVI readings, accounted for the total absence of any correlation between the CVP and RVEDVI readings recorded throughout the study period. Other investigators reported the absence of significant correlation between those two parameters in other clinical settings [21]. In our trial, hypotensive episodes were more frequent in the CVP group compared with the RVEDVI group. Again, the PEEP effect resulted in false impression of adequate preload state during the study; hence, as a consequence, the liability of reducing the cardiac output was more probable in the CVP group leading to more frequent hypotensive episodes compared with the adequately preloaded RVEDVI group. This finding was in consistence with the recorded stroke volume values that were lower in the CVP group compared with the RVEDVI group at the end of hepatectomy.

However, the recorded reduction in fluid intake, urine output, and the more frequent hypotensive episodes in this trial was not negatively reflected neither on the graft outcome nor on the renal functions. The observed safety in the use of CVP on organ and patient outcomes in this trial is in favor of adoption of this simple parameter as a monitor during liver transplantation, whereas we can postulate that RVEDVI is not a cost-effective monitoring modality in such patients. However, our results cannot be extrapolated to all liver transplant recipients. The trial was conducted on patients with preoperative good renal functions who can handle any possible short-term reduction in preload and cardiac output, but the safety of applying our methodology on patients with hepatorenal syndrome or with pre-existing renal dysfunction cannot be justified by our results. A clinically observed elevation in the serum creatinine was found in the CVP group compared with the RVEDVI group on both day 1 and day 7, although not statistically significant, and a recorded onset of delayed (after 3 weeks) renal dysfunction in some patients involved in this trial is inviting for more research to answer an important question about a possible medium-term impact of such intraoperative practice. We could conclude that the use of CVP as a simple parameter to guide fluid resuscitation in liver transplant recipients may be a considerable alternative to RVEDV. A fair preoperative renal function is a critical prerequest for using CVP as significantly less positive fluid balance is expected with its use.

  Acknowledgements Top

Conflicts of interest

There are no conflicts of interest.

  References Top

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12.12 Lichtwarck-Aschoff M, Beale R, Pfeiffer UJ. Central venous pressure, pulmonary artery occlusion pressure, intrathoracic blood volume and right ventricular end-diastolic volume as an indicator of cardiac preload. J Crit Care 1996; 11:180-188.  Back to cited text no. 12
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21.21 Kumar A, Anel R, Bunnell E, Habet K, Zanotti S, Marshall S, et al. Pulmonary artery occlusion pressure and central venous pressure fail to predict ventricular filling volume, cardiac performance, or the response to volume infusion in normal subjects. Crit Care Med 2004; 32:691-699.  Back to cited text no. 21


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3]


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