Yoshiaki Uda

ICU presentation
14/4/2010
Background
Acute lung injury is characterized by
 Hypoxia
 Non-cardiogenic pulmonary oedema
 Low lung compliance
 Widespread capillary leakage

Defined as
 Bilateral chest infiltrates on CXR
 Pulmonary capillary wedge pressure < 18mmHg
 PaO2/FiO2 < 300
Cause of ALI
Direct Insult Indirect Insult
Common Uncommon Common Uncommon
Aspiration Inhalation injury Sepsis Acute pancreatitis
Pneumonia Pulmonary Severe trauma CABG surgery
contusion Shock TRALI
Fat emboli DIC
Near drowning Burn
Reperfusion Head injury

injury Drug overdose

Mechanism of ALI
Study Question

ALI worsens as intravascular hydrostatic

pressure rises and oncotic pressure falls.

Optimal fluid management in patients with acute

lung injury is unknown.

Diuresis or fluid restriction may improve lung

function but could jeopardize extrapulmonary
organ perfusion.
Study Design
Multi-centre, Prospective, Randomized, controlled clinical
trial
Inclusion criteria
Intubated and received positive-pressure ventilation
A ratio of PaO2/FiO2 < 300
Bilateral infiltrates on CXR consistent with pulmonary edema without evidence of left atrial
hypertension

Exclusion criteria
Presence of PAC at the diagnosis of ALI
Presence of ALI for > 48hr
Physician refusal
Presence of chronic condition that could independently influence survival, impair weaning, or
compromise compliance with the protocol (e.g. severe lung/neuromuscular disease)
Renal failure requiring RRT
Irreversible condition with high 6 month mortality (e.g. cancer)
Others (Age < 13, acute MI, morbid obesity, unable to obtain consent, BM Tx, lung Tx)
 Randomization
Study Design
Commencement of Ventilation as per
ARDS protocol (1hr post
randomization)

Conservative use of fluids Liberal Use of Fluid

(Aiming lower intravascular (Aiming higher
pressure) intravascular pressure)

4hr post
CVC PAC randomization
CVC PAC

Haemodynamic management + a specific fluid

strategy for 7 days or until unassisted ventilation.
Protocol Overview
Target range
Conservative Strategy – CVP<4mmHg or PAOP<8mmHg
Liberal Strategy – CVP of 10-14mmHg or PAOP of 14-18mmHg
Protocol design for Risk Minimization

During shock, diuretic administration was suspended until 12

hours after a fluid bolus or the reversal of shock
Prompt fluid administration was provided in the event of oligulia
or ineffective circulation
Diuretic therapy was avoided in patients with worsening renal
function and limited to a daily maximum
Protocol-mandated fluid administration in patients without shock
was limited to 3 boluses per day.
Fluid administration was withheld in patients without shock who
had severe hypoxaemia (FiO2<0.7) or a CI of at least 4.5L/min/m 2
of BSA
Endpoints

Primary
Mortality prior to hospital discharge to day 60

Secondary
Number of ventilator-free days at 7 and 28 days after enrolment
Number of ICU-free days at 7 and 28 days after enrolment
Number of organ failure-free days at day 7 and 28 days after enrolment
Reduction of the PaO2/FiO2 ratio on days 1-7 after catheter insertion
Improvement in Lung Injury Score on days 1-7 after catheter insertion
Others…
 20 North American Centers between
Jun 8, 2000 and Oct 3, 2005

Result - Enrolment
11,512 patients
screened

1,001 underwent
randomization

503 assigned to 498 assigned to

conservative fluid liberal fluid
management management

1 withdrew consent before study

treatment was received

503 analyzed 497 analyzed

Result – Baseline Characteristics
Protocol conduct
Conservative Strategy Liberal Strategy P-value
Mean time from ICU 43.8+/-2.5hr 41.3+/-1.6hr 0.42
admission to first
protocol intervention

Rate of Compliance 88% 91% 0.06

with instruction
Protocol instructions 4.1 5.1 <0.001
per day
Frusemide 41% 10% <0.001
administration (% of
instructions)
Fluid Bolus (% of 6% 15% <0.001
instructions)
Dobutamine use 6% 4%
>1 Blood transfusion 29% 39% <0.001
Fluid Management/Intravascular pressure over 7 days

Intravascular pressure over time: PAC

7 Days Cumulative Fluid Balance

Intravascular pressure over time: CVP

Respiratory value during fluid management
Main Outcome Variables
Cadiovascular failure SBP<90mmHg or the
need of vasopressor

Coagulation Plt count < 80,000per

abnormality cubic millimeter or less
Hepatic failure Serum bilirubin <
34micromol/L
Renal failure Serum Cr <
177micromol/L
 Study Message
 There was no significant difference between the conservative strategy and
the liberal strategy of fluid management in the primary outcome of 60-day
mortality.

 The conservative strategy improved lung function and shortened the

duration of mechanical ventilation and ICU without increasing
nonpulmonary-organ failures.
Study limitation

 Unable to blind the treatment

 Strict exclusion criteria

 Fluid strategy targeting only intravascular pressure measurements

 Very specific hemodynamic and ventilator protocols

 Timing of intervention not addressed

Thank You!