Reviewer's report
Title:Circulatory effects of albumin infusion and assessment of fluid
responsiveness of cardiac index by transpulmonary thermodilution in patients
with advanced cirrhosis of the liver and impaired renal function. A prospective
interventional study.
Version: 1Date:11 March 2008
Reviewer: Georg Auzinger
Reviewer's report:
This is in essence an interesting study into the haemodynamic effects of volume
loading with hyperoncotic albumin in patients with advanced cirrhosis at risk of
renal failure. The authors attempted to assess fluid responsiveness with the aid
of the transpulmonary thermodilution technique.
The study can’t be accepted in its present form and major compulsory revisions
are suggested.
1. The title of the study is misleading as only static variables of pre- and afterload
were studied. The conclusion that the studied parameters are poor predictors of
volume responsiveness is understandable, the wrong parameters were studied.
To assess fluid responsiveness dynamic indices are required. The authors
comment in their discussion that this was not possible given that none of the
patients underwent positive pressure ventilation; however fluid responsiveness
can be assessed in spontaneously breathing patients with the use of passive leg
raising manouvers as previously shown by Teboul as well as Lamia et al., or by
assessing respiratory variations in CVP see Magder et al. In essence the authors
are in fact reporting on markers of preload rather than predictors of preload
dependency or fluid responsiveness.
2. The fact that it is difficult to augment central blood volume in cirrhotics does
not invalidate the value of intra thoracic blood volume as a marker of preload as
suggested in the background section on page 4.
3. Did the authors measure intraabdominal pressures (IAP) in this cohort of
patients? The incidence of IAH is significant in patients with decompensated
cirrhosis and ascites. If this data is available it should be reported as it may have
influenced CVP readings. Presence of IAH makes CVP a poor marker of preload.
IAP readings should be correlated with CVP and GEDV to assess its influence on
the measured parameters.
4. What was the indication for fluid loading? Fluid responsiveness does not mean
that the patients needs volume. Less than 50% of “volume challenges” resulted
in an >10% increase in CI. The patients were as per inclusion criteria free of
sepsis, not receiving vasopressors or inotropic agents and not actively bleeding.
The sole presence of renal dysfunction in the absence of hypovolemia or
hypotension does not necessarily justify volume loading. Was there any
suggestion of imbalance between oxygen delivery and consumption? Is data on
central venous saturation or arterial lactate available?
5. Were any of the patients receiving terlipressin during the study period? If yes
the comment that none of the patients received vasopressor medication is
factually incorrect.
6. The authors stipulate in the discussion that SVRI as an indicator of afterload
was the best predictor of fluid responsiveness. Generally speaking afterload is
not thought to influence the immediate hemodynamic response to a volume
challenge. The authors quote an interesting study by Kumar et al in support of
their findings, alluding to preload independent mechanisms of fluid
responsiveness (change in contractility and afterload). I would contest this notion
for various reasons: In the cited study only healthy volunteers were studied. The
incidence of occult cardiac dysfunction in cirrhosis is substantial, including both
systolic and diastolic dysfunction which will result in different response to volume
loading. There was no significant increase of preload (EDV) seen with fluid
loading in Kumar’s study, which contrasts the findings of the present study. Use
of SVRI as an indicator of afterload is too simplistic without knowledge of cardiac
chamber diameter and wall thickness all of which determine myocardial wall
tension or afterload (Laplace’s law). Finally there is a potential flaw with the use
of SVRI as a marker of fluid responsiveness due to mathematical coupling in the
calculation of SVRI and its dependence on CI.
7. Why did the authors wait for an hour prior to performing repeat haemodynamic
measurements? This practice contrasts usual practice of testing for volume
responsiveness with rapid infusion of volume and assessment of the immediate
haemodynamic response. Was there a concern of some of the patients being
volume overloaded?
8. The last sentence in the conclusion of the paper that an approach using
continuous measurement of CI may be promising in tailoring plasma expansion
in cirrhotic patients is not supported by the data.
9. The main findings of the study are the significant correlations found for GEDVI
and CI/SVI and the correlation of the changes of GEDVI and CI, SVI respectively,
following a volume challenge. Where these correlations significant for CVP? If
not it would prove the superiority of volumetric markers of preload, hence results
of the ROC curve is meaningless for this and above reasons quoted in point 1.
Minor essential revisions
There are many instances where wrong terms are used. The paper needs quite
considerable editing before potential publication.
Statistical review
I don’t think the statistics need to be seen by a statistician the data appears
sound.
I declare that I have no competing interests.
Reviewer's report
Title:Circulatory effects of albumin infusion and assessment of fluid
responsiveness of cardiac index by transpulmonary thermodilution in patients
with advanced cirrhosis of the liver and impaired renal function. A prospective
interventional study.
Version: 1Date:11 March 2008
Reviewer: Georg Auzinger
Reviewer's report:
This is in essence an interesting study into the haemodynamic effects of volume
loading with hyperoncotic albumin in patients with advanced cirrhosis at risk of
renal failure. The authors attempted to assess fluid responsiveness with the aid
of the transpulmonary thermodilution technique.
The study can’t be accepted in its present form and major compulsory revisions
are suggested.
1. The title of the study is misleading as only static variables of pre- and afterload
were studied. The conclusion that the studied parameters are poor predictors of
volume responsiveness is understandable, the wrong parameters were studied.
To assess fluid responsiveness dynamic indices are required. The authors
comment in their discussion that this was not possible given that none of the
patients underwent positive pressure ventilation; however fluid responsiveness
can be assessed in spontaneously breathing patients with the use of passive leg
raising manouvers as previously shown by Teboul as well as Lamia et al., or by
assessing respiratory variations in CVP see Magder et al. In essence the authors
are in fact reporting on markers of preload rather than predictors of preload
dependency or fluid responsiveness.
2. The fact that it is difficult to augment central blood volume in cirrhotics does
not invalidate the value of intra thoracic blood volume as a marker of preload as
suggested in the background section on page 4.
3. Did the authors measure intraabdominal pressures (IAP) in this cohort of
patients? The incidence of IAH is significant in patients with decompensated
cirrhosis and ascites. If this data is available it should be reported as it may have
influenced CVP readings. Presence of IAH makes CVP a poor marker of preload.
IAP readings should be correlated with CVP and GEDV to assess its influence on
the measured parameters.
4. What was the indication for fluid loading? Fluid responsiveness does not mean
that the patients needs volume. Less than 50% of “volume challenges” resulted
in an >10% increase in CI. The patients were as per inclusion criteria free of
sepsis, not receiving vasopressors or inotropic agents and not actively bleeding.
The sole presence of renal dysfunction in the absence of hypovolemia or
hypotension does not necessarily justify volume loading. Was there any
suggestion of imbalance between oxygen delivery and consumption? Is data on
central venous saturation or arterial lactate available?
5. Were any of the patients receiving terlipressin during the study period? If yes
the comment that none of the patients received vasopressor medication is
factually incorrect.
6. The authors stipulate in the discussion that SVRI as an indicator of afterload
was the best predictor of fluid responsiveness. Generally speaking afterload is
not thought to influence the immediate hemodynamic response to a volume
challenge. The authors quote an interesting study by Kumar et al in support of
their findings, alluding to preload independent mechanisms of fluid
responsiveness (change in contractility and afterload). I would contest this notion
for various reasons: In the cited study only healthy volunteers were studied. The
incidence of occult cardiac dysfunction in cirrhosis is substantial, including both
systolic and diastolic dysfunction which will result in different response to volume
loading. There was no significant increase of preload (EDV) seen with fluid
loading in Kumar’s study, which contrasts the findings of the present study. Use
of SVRI as an indicator of afterload is too simplistic without knowledge of cardiac
chamber diameter and wall thickness all of which determine myocardial wall
tension or afterload (Laplace’s law). Finally there is a potential flaw with the use
of SVRI as a marker of fluid responsiveness due to mathematical coupling in the
calculation of SVRI and its dependence on CI.
7. Why did the authors wait for an hour prior to performing repeat haemodynamic
measurements? This practice contrasts usual practice of testing for volume
responsiveness with rapid infusion of volume and assessment of the immediate
haemodynamic response. Was there a concern of some of the patients being
volume overloaded?
8. The last sentence in the conclusion of the paper that an approach using
continuous measurement of CI may be promising in tailoring plasma expansion
in cirrhotic patients is not supported by the data.
9. The main findings of the study are the significant correlations found for GEDVI
and CI/SVI and the correlation of the changes of GEDVI and CI, SVI respectively,
following a volume challenge. Where these correlations significant for CVP? If
not it would prove the superiority of volumetric markers of preload, hence results
of the ROC curve is meaningless for this and above reasons quoted in point 1.
Minor essential revisions
There are many instances where wrong terms are used. The paper needs quite
considerable editing before potential publication.
Statistical review
I don’t think the statistics need to be seen by a statistician the data appears
sound.
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Circulatory effects of albumin infusion and assessment of fluid
responsiveness of cardiac index by transpulmonary thermodilution in patients
with advanced cirrhosis of the liver and impaired renal function. A prospective
interventional study.
Version: 1Date:11 March 2008
Reviewer: Georg Auzinger
Reviewer's report:
This is in essence an interesting study into the haemodynamic effects of volume
loading with hyperoncotic albumin in patients with advanced cirrhosis at risk of
renal failure. The authors attempted to assess fluid responsiveness with the aid
of the transpulmonary thermodilution technique.
The study can’t be accepted in its present form and major compulsory revisions
are suggested.
1. The title of the study is misleading as only static variables of pre- and afterload
were studied. The conclusion that the studied parameters are poor predictors of
volume responsiveness is understandable, the wrong parameters were studied.
To assess fluid responsiveness dynamic indices are required. The authors
comment in their discussion that this was not possible given that none of the
patients underwent positive pressure ventilation; however fluid responsiveness
can be assessed in spontaneously breathing patients with the use of passive leg
raising manouvers as previously shown by Teboul as well as Lamia et al., or by
assessing respiratory variations in CVP see Magder et al. In essence the authors
are in fact reporting on markers of preload rather than predictors of preload
dependency or fluid responsiveness.
2. The fact that it is difficult to augment central blood volume in cirrhotics does
not invalidate the value of intra thoracic blood volume as a marker of preload as
suggested in the background section on page 4.
3. Did the authors measure intraabdominal pressures (IAP) in this cohort of
patients? The incidence of IAH is significant in patients with decompensated
cirrhosis and ascites. If this data is available it should be reported as it may have
influenced CVP readings. Presence of IAH makes CVP a poor marker of preload.
IAP readings should be correlated with CVP and GEDV to assess its influence on
the measured parameters.
4. What was the indication for fluid loading? Fluid responsiveness does not mean
that the patients needs volume. Less than 50% of “volume challenges” resulted
in an >10% increase in CI. The patients were as per inclusion criteria free of
sepsis, not receiving vasopressors or inotropic agents and not actively bleeding.
The sole presence of renal dysfunction in the absence of hypovolemia or
hypotension does not necessarily justify volume loading. Was there any
suggestion of imbalance between oxygen delivery and consumption? Is data on
central venous saturation or arterial lactate available?
5. Were any of the patients receiving terlipressin during the study period? If yes
the comment that none of the patients received vasopressor medication is
factually incorrect.
6. The authors stipulate in the discussion that SVRI as an indicator of afterload
was the best predictor of fluid responsiveness. Generally speaking afterload is
not thought to influence the immediate hemodynamic response to a volume
challenge. The authors quote an interesting study by Kumar et al in support of
their findings, alluding to preload independent mechanisms of fluid
responsiveness (change in contractility and afterload). I would contest this notion
for various reasons: In the cited study only healthy volunteers were studied. The
incidence of occult cardiac dysfunction in cirrhosis is substantial, including both
systolic and diastolic dysfunction which will result in different response to volume
loading. There was no significant increase of preload (EDV) seen with fluid
loading in Kumar’s study, which contrasts the findings of the present study. Use
of SVRI as an indicator of afterload is too simplistic without knowledge of cardiac
chamber diameter and wall thickness all of which determine myocardial wall
tension or afterload (Laplace’s law). Finally there is a potential flaw with the use
of SVRI as a marker of fluid responsiveness due to mathematical coupling in the
calculation of SVRI and its dependence on CI.
7. Why did the authors wait for an hour prior to performing repeat haemodynamic
measurements? This practice contrasts usual practice of testing for volume
responsiveness with rapid infusion of volume and assessment of the immediate
haemodynamic response. Was there a concern of some of the patients being
volume overloaded?
8. The last sentence in the conclusion of the paper that an approach using
continuous measurement of CI may be promising in tailoring plasma expansion
in cirrhotic patients is not supported by the data.
9. The main findings of the study are the significant correlations found for GEDVI
and CI/SVI and the correlation of the changes of GEDVI and CI, SVI respectively,
following a volume challenge. Where these correlations significant for CVP? If
not it would prove the superiority of volumetric markers of preload, hence results
of the ROC curve is meaningless for this and above reasons quoted in point 1.
Minor essential revisions
There are many instances where wrong terms are used. The paper needs quite
considerable editing before potential publication.
Statistical review
I don’t think the statistics need to be seen by a statistician the data appears
sound.
I declare that I have no competing interests.
assistant