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Keywords:
Goals
Fluid therapy
Endpoint
Treatment outcome
Physiologic monitoring
a b s t r a c t
Purpose: To review the literature on goal directed uid therapy and evaluate the quality of evidence for each
combination of goal and monitoring method.
Materials and Methods: A search of major digital databases and hand search of references was conducted. All
studies assessing the clinical utility of a specic uid therapy goal or set of goals using any monitoring method
were included. Data was extracted using a pre-determined pro forma and papers were evaluated using GRADE
principles to assess evidence quality.
Results: Eighty-one papers met the inclusion criteria, investigating 31 goals and 22 methods for monitoring uid
therapy in 13052 patients. In total there were 118 different goal/method combinations. Goals with high evidence
quality were central venous lactate and stroke volume index. Goals with moderate quality evidence were sublingual
microcirculation ow, the oxygen extraction ratio, cardiac index, cardiac output, and SVC collapsibility index.
Conclusions: This review has highlighted the plethora of goals and methods for monitoring uid therapy. Strikingly,
there is scant high quality evidence, in particular for non-invasive G/M combinations in non-operative and nonintensive care settings. There is an urgent need to address this research gap, which will be helped by methodologies
to compare utility of G/M combinations.
2014 Elsevier Inc. All rights reserved.
1. Introduction
Almost 40 years ago, Shoemaker and colleagues published a
landmark study introducing the use of physiological goals to guide
uid therapy [1]. They demonstrated that mortality could be reduced
by titrating uid therapy to pre-determined cardiorespiratory variables. This was the birth of goal directed uid therapy (GDFT).
Since then many goals have been promoted to direct uid therapy,
both invasive and non-invasive [2]. Despite evidence demonstrating the
potential benet of GDFT in a number of disease states [3], there remains
no consensus about the most effective goals for uid therapy or the most
appropriate monitoring methods. As such, GDFT remains a well-accepted
concept that has not yet translated to an established standard of care.
Formal evaluation of the different goal/method (G/M) combinations for
GDFT has been hampered by the many different goals, the number of
methods to monitor uid therapy, the variation in study design, and the
lack of comparable controls. A new approach to evaluating G/M
Conicts of Interest and Sources of Funding: the authors have had no nancial
support in the preparation of this manuscript. The authors have no conicts of
interest to declare.
Corresponding author. Pancreas Research Group, Surgical Research Network,
Department of Surgery, School of Medicine, Faculty of Medical and Health Sciences,
University of Auckland, Private Bag 92019, Auckland 1023 (New Zealand). Tel.: +64
9 373 7599.
E-mail address: j.windsor@auckland.ac.nz (J.A. Windsor).
0883-9441/$ see front matter 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jcrc.2013.10.019
205
Table 1
Rating of evidence quality and usefulness
Factor
Descriptors
Study design
+1 Paper is an RCT
1 Paper is an observational study
0 Negligible limitations likely to cause biases in the
body of evidence
Study bias
1 Serious limitations likely to cause biases in the
body of evidence
2 Very serious limitations likely to cause biases in the
body of evidence
+1 Paper nds benet by targeting goal
Inconsistency
0 Paper nds no benet by targeting goal
1 Paper nds harm done by targeting goal
0 Negligible doubts about directness of measures used
in body of evidence
Indirectness
1 Serious doubts about directness of measures used
in body of evidence
2 Very serious doubts about directness of measures
used in body of evidence
0 No signicant result, or signicant results have
clinically signicant CI margins
Imprecision
1 Some key signicant results with questionably
clinically signicant CI margins
2 Signicant results with no clinically signicant
CI margins
0 No evidence of publication bias for body of evidence
(peer reviewed journal)
Publication bias
1 High probability of publication bias (non peer
reviewed journal)
2 Very high probability of bias (known previous non
publication of results)
Large effect
+2 Relative risk ratio N5 or b0.20
+1 Relative Risk Ratio 2-5 or 0.5-0.2
0 = Relative Risk Ratio 0.5-2 or not presented in
paper/not calculable
Bias causing conservatism +1 All possible biases are likely to cause conservative
estimation of effects
0 All possible biases are not likely to have this effect.
3. Results
3.1. Data overview
A total of 1118 articles published between 1984 and 2013 were
identied by the initial literature search. The inclusion and exclusion of
206
207
Table 2
Clinical studies and evidence quality by goal/method combination
Non invasive
Invasive
Non-ventilated
Goal
Monitoring method
Sublingual microcirculation ow
Mean arterial pressure
Urine output
Stroke volume
Maintenance of normal uid balance
Lactate clearance
Pulse oximeter-derived pleth variability index
Skeletal muscle O2 saturation
Lactate
Cerebral O2 saturation
Central venous pressure
Central venous lactate
Oxygen extraction ratio
Oxygen delivery index
Cardiac index
Mixed venous O2 saturation
Central venous O2 saturation
Moderate
Very low
Very low
Very low
Very low
Very low
Very low
Very low
Very low
Very low
Very low
High
Moderate
Low
Low
Low
Very low
2
2
2
1
4
1
3
1
2
1
1
1
1
4
3
1
10
Very low
Very low
Very low
Very low
Very low
Very low
High
Moderate
Moderate
Low
Low
Low
Low
Low
Very low
Very low
Very low
Very low
Very low
Very low
Very low
1
7
5
4
2
3
1
3
1
13
7
2
2
2
1
4
4
2
2
1
1
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[41]
[14,17,4246]
[36,4750]
[34,39,43,51]
[41,52]
[31,46,53]
[54]
[5456]
[57]
[19,5869]
[42,54,55,7073]
[74,75]
[76,77]
[30,78]
[79]
[73,8082]
[22,60,68,83]
[39,84]
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