Dissections INTERVENTIONAL

26 May 2009
Evidence-based Medicine for Surgeons

Less is more: improved outcomes in surgical patients with conservative fluid administration
and central venous catheter monitoring
Authors: Stewart RM, Park PK, , Hunt JP, et al
Journal: J American College of Surgeons 2009; 208: 725–737
Centre: University of Texas Health Science Center, San Antonio, TX, USA.
Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are common causes of
death and complications in surgical patients. Ideal fluid and hemodynamic management are
BACKGROUND controversial topics in the care of these patients. There are many strong opinions as to what
constitutes optimal fluid and catheter management, but there are very few strong clinical data
supporting either strategy in surgical and trauma patients.

RESEARCH QUESTION IN SUMMARY

Population Primary and secondary end point results

A posthoc, surgical subgroup LIB CON PAC CVC

analysis of 1,000 patients enrolled
in the FACTT (The ARDS Clinical Number 123 121 122 122
Trials Network Fluid and Catheter 60 day mortality # 18.70% 19.00% 20.50% 17.20%
Treatment Trial) with ARDS/ ALI.
Secondary end points (mean values at 28 days)
Indicator variable
Ventilator-free days * 13 15 13 16
A conservative (CON) versus a
Dialysis-free days # 22 24 23 23
liberal (LIB) strategy of fluid
management and the use of a ICU-free days # 12 14 12 14
pulmonary artery catheter (PAC)
or a central venous catheter
(CVC). LIB = liberal fluid management, CON = conservative fluid management
PAC = pulmonary artery catheter, CVC = central venous catheter
Outcome variable
* = statistically significant
Primary: death before discharge # = statistically nonsignificant
home during the first 60 days after
randomization. Secondary:
Authors' claim(s): “...A conservative fluid-administration strategy and
Ventilator-, ICU-, and dialysis-free
central venous catheter monitoring resulted in a major reduction in net fluid
days.
balance and led to more ventilator-free and ICU-free days in surgical
Comparison patients with ALI or ARDS. ...the mortality rate at 60 days after
randomization did not vary with fluid or catheter management.”
2x2 design as described above.

THE TISSUE REPORT

The authors are open enough to suggest "discounting any statistical analysis of unplanned posthoc analyses of randomized
clinical trials, so the catheter results should be interpreted with caution." For a subject as complex and challenging as post
surgical patients with ARDS/ ALI, this study is about as good as it is going to get. Whether the rigidity and meticulousness
with which the fluid protocols were followed in this controlled trial can ever be replicated in the messy, real world, remains
the lingering sore point. Validation of trial results in clinical practice often fails on this vital issue.

EBM-O-METER
Evidence level Overall rating Bias levels
Double blind RCT Sampling
Randomized controlled trial (RCT) Comparison
Trash Swiss Safe News-
Prospective cohort study - not randomized cheese worthy Measurement
Life's too Holds water
short for this Full of holes “Just do it”
Case controlled study
Interestingl | Novel l | Feasible l
Case series - retrospective  Ethical l | Resource saving l

The devil is in the details (more on the paper) ... 

© Dr Arjun Rajagopalan
 SAMPLING
Sample type Inclusion criteria Exclusion criteria Final score card
Simple random ARDS/ ALI in Pre-existing PAC ? LIB CON PAC CVP
surgical patients Duration of lung
Stratified random Target ? ? ? ?
(those admitted to a injury > 48 hrs 
Cluster surgical/ burn/ Comorbidities that Accessible 498 503 513 488
cardiac surgical could influence
Consecutive ICU; or with an survival, or Intended 123 121 122 122
Convenience APACHE III surgical compliance with the Drop outs 0 0 0 0
admission  protocol 
Judgmental Study 123 121 122 122

 = Reasonable | ? = Arguable |  = Questionable

Duration of the study: patients at 20 North American centers between June 8, 2000 and October 3, 2005
The original study had a statistical power of 90% to detect a reduction by 10% points in the primary end point
Definition of ARDS/ALI: Patients who were intubated and receiving positive-pressure ventilation, had a ratio of the
partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 300 (adjusted if the
altitude exceeded 1,000 m), and had bilateral infiltrates on chest radiography consistent with the presence of
pulmonary edema without evidence of left atrial hypertension.

Sampling bias: The study is a post hoc analysis of data collected in a randomized, controlled trial. Patients with
existing PA catheters - presumably a sicker sub group - were excluded.

COMPARISON
Randomized Case-control Non-random Historical None

Controls - details
Allocation details Patients were randomized using a 2X2 factorial design comparing a conservative (CON) versus
a liberal (LIB) strategy of fluid management and the use of a PAC or a central venous catheter
(CVC). Ventilation was according to the ARDS Network protocol. A standardized protocol was
used to guide the process of weaning patients from mechanical ventilation. The assigned
catheter insertion was performed within 4 hours after randomization. Fluid and hemodynamic
management was guided by an explicit and detailed protocol on the basis of 4 variables:
central venous pressure (CVP) or pulmonary artery occlusion pressure (PAOP); the presence
or absence of shock, oliguria and ineffective circulation.
Comparability There were no significant differences between the groups at the time of randomization.
Disparity -

Comparison bias: The 4 groups were well matched. Comorbidities were identically distributed.

MEASUREMENT
Measurement error
Device used Device error Observer error
Gold std.

Device suited to task

Training

Scoring

Blinding
Repetition

Protocols

Y ? N

1.Primary and secondary end points were ? N ? N N N N

extracted from the data base. No devices were
used.

Study personnel underwent mandatory training in the conduct of the protocol, including standardized methods to
measure vascular pressures.
Measurement bias: That inherent to post hoc analysis of data collected in a randomized, controlled trial.

© Dr Arjun Rajagopalan