Reviewer's report
Title:Plasma disappearance rate of Indocyanine green is a prognostic indicator
in acute liver failure
Version: 1Date:24 August 2009
Reviewer: Daniel Inderbitzin
Reviewer's report:
Congratulations to the authors for a well written manuscript describing the value
of ICG-Plasma-Disappearance-Rate (ICG-PDR) in the setting of acute liver
failure.
ICG-PDR was determined daily in 25 patients with acute liver failure and values
below 6.3%/min on study day 1 were found to correlate with a fatal course of the
liver disease. An ICG-PDR value at any timepoint below 5.3%/min predicted
death or the need for urgent liver transplantation.
Major remarks:
Our own early experiences with ICG-PDR coincide with the results presented in
the paper (Inderbitzin et al JoGS 2005; 9; 1155-1162, Fig 2). All surgical patients
with values greater than 5.0%/min survived, while the others required liver
transplantation or deceased.
However, in a second step we expanded ICG measurements on patients after
extended liver resections with limited hepatic reserve and expected to be able to
predict survival early on in the clinical course. Unfortunately, conflicting results
were obtained, and we observed a considerable rate of ICG-measurement
failures (due to unstable signal quality) in hemodynamically unsteady patients
(i.e. around 10-20%, data not published).
To determine the precision of ICG-PDR we therefore decided to measure
ICG-PDR in completely anhepatic patients (n=24) during liver transplantation
(Bruegger et al JoGS 2008; 12; 67-72). Unfortunately, ICG-PDR values were
clearly different from zero (average: 1.55%/min) and even extreme values of
ICG-PDR (i.e. 5.4 and 7.8%/min) were seen in completely anhepatic patients
(Table1).
This precision problem is reflected in the overlap of your raw-data in Figure 1
(survivors vs non-survivors). You face the general problem that on one side
cohort prediction is quite good, but does on the other side not help in
decision-making in the individual case (i.e. you found an ICG-PDR of 0.0%/min
on day 4 in a survivor, and on the other hand an ICG-PDR of 10.0%/min in a
non-survivor).
From my point of view the mentioned published findings merit discussion in the
manuscript and words of caution about the precision and the (physiologically
completely unclear) extrahepatic ICG elimination or decay have to be included in
the discussion section.
Minor remarks:
Were 100% of ICG-measurements technically possible? If not please report the
failure rate in the results section.
Statistics: Why did you choose to use Mann-Whitney U? Non-normal distribution
of data?
Thank you for the opportunity to review your paper. It was a privilege and a
pleasure.
PD Dr. med. Daniel Inderbitzin
Senior Staff Member
Department of Visceral Surgery and Medicine
University Hospital Bern
CH 3010 Bern
daniel.Inderbitzin@insel.ch
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
Daniel Inderbitzin
Reviewer's report
Title:Plasma disappearance rate of Indocyanine green is a prognostic indicator
in acute liver failure
Version: 1Date:24 August 2009
Reviewer: Daniel Inderbitzin
Reviewer's report:
Congratulations to the authors for a well written manuscript describing the value
of ICG-Plasma-Disappearance-Rate (ICG-PDR) in the setting of acute liver
failure.
ICG-PDR was determined daily in 25 patients with acute liver failure and values
below 6.3%/min on study day 1 were found to correlate with a fatal course of the
liver disease. An ICG-PDR value at any timepoint below 5.3%/min predicted
death or the need for urgent liver transplantation.
Major remarks:
Our own early experiences with ICG-PDR coincide with the results presented in
the paper (Inderbitzin et al JoGS 2005; 9; 1155-1162, Fig 2). All surgical patients
with values greater than 5.0%/min survived, while the others required liver
transplantation or deceased.
However, in a second step we expanded ICG measurements on patients after
extended liver resections with limited hepatic reserve and expected to be able to
predict survival early on in the clinical course. Unfortunately, conflicting results
were obtained, and we observed a considerable rate of ICG-measurement
failures (due to unstable signal quality) in hemodynamically unsteady patients
(i.e. around 10-20%, data not published).
To determine the precision of ICG-PDR we therefore decided to measure
ICG-PDR in completely anhepatic patients (n=24) during liver transplantation
(Bruegger et al JoGS 2008; 12; 67-72). Unfortunately, ICG-PDR values were
clearly different from zero (average: 1.55%/min) and even extreme values of
ICG-PDR (i.e. 5.4 and 7.8%/min) were seen in completely anhepatic patients
(Table1).
This precision problem is reflected in the overlap of your raw-data in Figure 1
(survivors vs non-survivors). You face the general problem that on one side
cohort prediction is quite good, but does on the other side not help in
decision-making in the individual case (i.e. you found an ICG-PDR of 0.0%/min
on day 4 in a survivor, and on the other hand an ICG-PDR of 10.0%/min in a
non-survivor).
From my point of view the mentioned published findings merit discussion in the
manuscript and words of caution about the precision and the (physiologically
completely unclear) extrahepatic ICG elimination or decay have to be included in
the discussion section.
Minor remarks:
Were 100% of ICG-measurements technically possible? If not please report the
failure rate in the results section.
Statistics: Why did you choose to use Mann-Whitney U? Non-normal distribution
of data?
Thank you for the opportunity to review your paper. It was a privilege and a
pleasure.
PD Dr. med. Daniel Inderbitzin
Senior Staff Member
Department of Visceral Surgery and Medicine
University Hospital Bern
CH 3010 Bern
daniel.Inderbitzin@insel.ch
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
Daniel Inderbitzin
Please review this paper.
user
Reviewer's report
Title:Plasma disappearance rate of Indocyanine green is a prognostic indicator
in acute liver failure
Version: 1Date:24 August 2009
Reviewer: Daniel Inderbitzin
Reviewer's report:
Congratulations to the authors for a well written manuscript describing the value
of ICG-Plasma-Disappearance-Rate (ICG-PDR) in the setting of acute liver
failure.
ICG-PDR was determined daily in 25 patients with acute liver failure and values
below 6.3%/min on study day 1 were found to correlate with a fatal course of the
liver disease. An ICG-PDR value at any timepoint below 5.3%/min predicted
death or the need for urgent liver transplantation.
Major remarks:
Our own early experiences with ICG-PDR coincide with the results presented in
the paper (Inderbitzin et al JoGS 2005; 9; 1155-1162, Fig 2). All surgical patients
with values greater than 5.0%/min survived, while the others required liver
transplantation or deceased.
However, in a second step we expanded ICG measurements on patients after
extended liver resections with limited hepatic reserve and expected to be able to
predict survival early on in the clinical course. Unfortunately, conflicting results
were obtained, and we observed a considerable rate of ICG-measurement
failures (due to unstable signal quality) in hemodynamically unsteady patients
(i.e. around 10-20%, data not published).
To determine the precision of ICG-PDR we therefore decided to measure
ICG-PDR in completely anhepatic patients (n=24) during liver transplantation
(Bruegger et al JoGS 2008; 12; 67-72). Unfortunately, ICG-PDR values were
clearly different from zero (average: 1.55%/min) and even extreme values of
ICG-PDR (i.e. 5.4 and 7.8%/min) were seen in completely anhepatic patients
(Table1).
This precision problem is reflected in the overlap of your raw-data in Figure 1
(survivors vs non-survivors). You face the general problem that on one side
cohort prediction is quite good, but does on the other side not help in
decision-making in the individual case (i.e. you found an ICG-PDR of 0.0%/min
on day 4 in a survivor, and on the other hand an ICG-PDR of 10.0%/min in a
non-survivor).
From my point of view the mentioned published findings merit discussion in the
manuscript and words of caution about the precision and the (physiologically
completely unclear) extrahepatic ICG elimination or decay have to be included in
the discussion section.
Minor remarks:
Were 100% of ICG-measurements technically possible? If not please report the
failure rate in the results section.
Statistics: Why did you choose to use Mann-Whitney U? Non-normal distribution
of data?
Thank you for the opportunity to review your paper. It was a privilege and a
pleasure.
PD Dr. med. Daniel Inderbitzin
Senior Staff Member
Department of Visceral Surgery and Medicine
University Hospital Bern
CH 3010 Bern
daniel.Inderbitzin@insel.ch
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Acceptable
Statistical review: Yes, but I do not feel adequately qualified to assess the
statistics.
Declaration of competing interests:
'I declare that I have no competing interests'
Daniel Inderbitzin
assistant