journal club- fluid balance and mortality in critically ill patients

7/30/2019 journal club- fluid balance and mortality in critically ill patients

1/39

Ubaidur RahamanSenior Resident, Critical CareMedicineS.G.P.G.I.M.S.


2/39

John H. Boyd, Jason forbes, Taka Aki Nakada, Keith R Walley, James A. Russell.

Fluid resuscitation in septic shock: A positive fluid balance and elevated

central venous pressures are associated with increased mortality.Crit Care Med 2011; 39(2)

Objective

To determine whether central venous pressure and fluid balance after resuscitation

for shock are associated with mortality


3/39

Intravenous fluids are important component of resuscitation in septic shock

EGDT and Survival Sepsis Guidelines have set a target for fluid administration

Background

How much?

When should I stop

Positive fluid balance

Prolong mechanical ventilation

Increased hospital stay

Increased mortality


4/39


5/39

Study design and methodology

Retrospective review of VAsopressin in Septic Shock Trial (VASST) study data,

Review of use of IV fluid during first 4 days

Outcome measures and endpointsFluid balance in the first 12 hours of resuscitation and during the next 4 days

Daily central venous pressure monitoring

VASST study was chosen for analysis

no mandatory fluid administration protocol,providing opportunity for studying prevalent practice of fluid administration

28 day mortality.

Two investigators of this study

James A. Russell and Keith R. Walley were also investigators in VASST study


6/39

Prospective, randomized, interventional, double blind trail

Conducted

between July 2001- April 2006

in 27 centers in Canada, Australia and United States

778 patients, > 16 years ageHaving septic shock and receiving minimum of 5 gm of NE/minute

Vasopressin in Septic Shock Trail (VASST)N Eng J Med 2008; 358:9:877-887

Vasopressin versus Norepinephrine Infusion in Patients with Septic ShockJames A. Russell, Keith R. Walley, Joel Singer, Anthony C. Gordon, Paul C. Hebert, James Cooper, Cheryl L. Holmes, Sangeeta Mehta, John T.

Granton, Michelle M. Storms, Deborah J. Cook, Jeffery J. Pressneill, Dieter Ayers, for the VASST investigators

Patients were divided into 2 groups

blinded Vasopressin

0.01-0.03U/min In addition to open label vasopressorsblinded NE

5-15g/min

Both groups were comparable in demographic and baseline characteristics including

Comorbidity, severity of illness, and sepsis treatment and ventilation supports

continued


7/39

Vasopressin in Septic Shock Trail (VASST)N Eng J Med 358:9:877-887

Vasopressin versus Norepinephrine Infusion in Patients with Septic ShockJames A. Russell, Keith R. Walley, Joel Singer, Anthony C. Gordon, Paul C. Hebert, James Cooper, Cheryl L. Holmes, Sangeeta Mehta, John T.

Granton, Michelle M. Storms, Deborah J. Cook, Jeffery J. Pressneill, Dieter Ayers, for the VASST investigators

End poing

Mortalilty rate 28 days after start of infusions

Conclusions

Low dose vasopressin did not reduce mortality rate as compared to NEamong patients with septic shock who were on NE

Subgroup analysisPatients with less severe septic shock ( receiving NE 5-14g/min),

mortality rate was lower in Vasopressin group than in NE group at 28 days.

( 26.5% vs. 35.7%, P=0.05)


8/39

Statistical analysis

After correction of age and severity of illness, patients were divided into:

a) 4 fluid balance quartiles.

b) 3 CVP groups- 12

Survival analysis performed using Cox Stratified survival analysis

and regression analysis with Breslow method of Ties.

Hazard ratio for death were calculated relative to

(a) quartile 4 fluid balance; (b) central venous pressure >12 mmHg group,

using Cox proportional hazards.

Difference in fluid between survivors and non survivors was

analyzed using Mann- Whitney rank sum test.


9/39


10/39

Daily fluid intake, urine output and

fluid balance at 12 hours and days1-4

Cumulative daily fluid intake, urine output

and fluid balance at 12 hours and days1-4


11/39

Fluid intake, urine output, and net fluid balance (ml)

at 12 hours and day 4

Quartile 1 Quartile 2 Quartile 3 Quartile 4

At 12

hours

Intake 2900(2050-3900)

4520

(3700-5450)

6110

(5330-7360)10,100

(8430-12,100)

Output 2200(1100-3920)

1590

(960-2560)

1180

(600-2070)1260

(600-2400)

Balance 2880 4900

3

1/2

(-132-1480) (2510-3300) (4290-5530) (7110-10,100)

At

Day 4

Intake 16,100(12,800-19,700)

18,500

(15,700-22,500)

22,800

(19,700-26,700)30,600

(26,200-36,000)

Output 14,600(11,500-20,100)

11,000(8210-14,500)

9960(6940-12,900) 8350(5100-12,300)

Balance 1560(-723-3210)

8120

(6210-9090)

13,000

(11,800-14,700)20,500

(17,700-24,500)

11

2

1/2

13


12/39

Cox survival curves forFluid balance quartiles

adjusted for age, APACHE II score and dose of NE

At 12 hours At day 4


13/39

Hazard ratio fordeath according to fluid balance quartiles

Fluid balance Group Adjusted Hazard ratio vs quartile 4

12 hours

Quartile 1 0.569 (0.405-0.799)

Quartile 2 0.581 ( 0.414-0.816)

uar e . (0.562-1.033)

Day 4

Quartile 1 0.466 (0.299-0.724)

Quartile 2 0.512 (0.339-0.775)

Quartile 3 0.739 (0.503-1.087)

Hazard ratio are shown with 95% CI


14/39


Predicts mortality at 12 hours as well as at day 4


15/39

Linear regression analysis for

correlation of fluid balance with CVP and dose of NE

CVP NE

at 12 hours


16/39

Linear regression analysis for

correlation of fluid balance with CVP and dose of NE

CVP NE

at Day 4


17/39


Correlates modestly with CVP and dose of NE at 12 hours

but not at day 4.


18/39

Cox survival curves for CVPadjusted for age, APACHE II score and dose of NE

At 12 hours At Day 4


19/39

Hazard ratio fordeath according to CVP group

CVP Group Adjusted Hazard ratio vs

CVP > 12 mmHg

12 Hours

CVP < 8 mmHg 0.606 ( 0.363-0.913)

CVP 8-12 mmHg 0.762 ( 0.562-0.943)

Day 4

CVP < 8 mmHg 0.903 ( 0.484-1.686)

CVP 8-12 mmHg 0.764 ( 0.542-1.078)

Hazard ratio are shown with 95% CI


20/39

A CVP


21/39

12 hours fluid balance:

Survivors vs non survivors within CVP groups

CVP Group

Net fluid balance ( ml)

pSurvivors Non survivors

All patients 3444 (1861-5984) 4429 (2537-6560) 12 mmHg 3975 (2387-6614) 5237 (3140-7773) < 0.001


22/39

Though at 12 hours less positive fluid balance was associated with lower mortality

overall

But in CVP < 8mmHg: reverse was true

(survivors tended towards a more positive fluid balance).


23/39

AUTHORS

DISCUSSIONAnd

CONCLUSIONS


24/39

A more positive fluid balance early in resuscitation and cumulatively over 4 days

is associated with an increased mortality.

.

CVP becomes unreliable marker of fluid responsiveness as well as

fluid balance after 12 hours.

Optimal survival occurred with a positive fluid balance ofapproximately 3 L at 12 hours.


25/39

CVP achieved at 12 hours

12 mmHg- 62% of patients

SSG appeared in 2004 ( VASST study started enrollment in 2001)

Previous guidelines defined limit of fluid resuscitation as pulmonary edema.

Belief that patient might be having reduced ventricular compliance,

needing higher CVP (>12).

Why EGDT target CVP was overshot


26/39

CVP not indicator of volume status

On oin Chan es in ventricular com liance

Ongoing changes in lung and thoracic compliance and resultant changes

in mechanical ventilatory support


27/39

Mechanism of positive fluid balance leading to increased mortality

Increased EVLW- ALI and increased WOB- prolonged mechanical ventilation.

Delayed renal recovery and renal associated mortality.


28/39

Positive fluid balance and mortality- when compared to EGDT study

VASST study EGDT study

12/6h

Intake 2900-10,100 5000 vs 3500EGDT vs standard arm

Day 4 Intake 16,100- 30,600 13,443 vs 13,358EGDT vs standard arm


29/39

My

DISCUSSION

CONCLUSIONS


30/39

Study strength number of patients- 778

Statistical analysis

Study limitations, weakness, potentials for bias

Retrospective nature

Type of fluid, crystalloid or colloid not documented.

Unable to decide whether fluid balance and CVP are simply

markers of Severity of illness or independently affect outcome


31/39

Applicability and impact on intensive care physicians

good applicability and impact

But

Each patient is unique in dysfunction of cardiovascular, lung and renal physiology

and even in same patient this derangement is dynamic with time

so confusion will prevail- to give or not to give, how much to give, when not to give

Additional thoughts or comments

Fluid is not always an answer to optimize hemodynamics and perfusion,

as PEEP is not to improve oxygenation

Students conclusions and recommendations

A prospective randomized trail of conservative vs liberal fluid strategy in

septic shock is required to prove that whetherpositive fluid balance is

marker of SOI or administration of excessive fluid causes mortality.


32/39


33/39

CHEST 2000; 117:17491754

Negative Fluid Balance Predicts Survival in Patients With Septic Shock*

A Retrospective Pilot StudyFadi Alsous, Mohammad Khamiees, Angela DeGirolamo, Yaw Amoateng-Adjepong, Constantine A.

Manthous

Retrospective study

36 patients, age16-85 years with septic shock

Patient undergone dialysis prior to admission not included

All 11 patients who achieved a negative balance of > 500 mL on 1 of the first 3 days

5 of 25 patient who failed to achieve a negative fluid balance of > 500 mL by day 3

of treatment survived

that negative fluid balance achieved in any of the first 3 days of septic shock portends

a good prognosis

Non survivors had higher mean APACHE II score and higher first day SOFA scores

were more likely to require vasopressors and mechanical ventilation


34/39

N Engl J Med 2006;354:2564-75

Comparison of Two Fluid- Management Strategies in Acute Lung InjuryThe National Heart, Lung and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network

Randomized controlled prospective trail

1000 patients with ALI

Explicit protocol for fluid management was applied for 7 days

Both groups were comparable in baseline characteristics including comorbidity,

severity of illness and hemodynamics

Mean cumulative fluid balance during first 7 days

Conservative group: -137491 ml

Liberal strategy group: 6992502 ml

continue


35/39

conservative strategy group during first 28 days had

Improved oxygenation index and lung injury score

Higher ventilator free days

Lesser ICU stay

N Engl J Med 2006;354:2564-75

Comparison of Two Fluid- Management Strategies in Acute Lung InjuryThe National Heart, Lung and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network

Without increasing incidence or prevalence of

shock during the study

or

use of dialysis during first 60 days

No significant difference in 60 day mortality


36/39

Crit Care Med. 2006 Feb;34(2):344-53.

Sepsis in European intensive care units: results of the SOAP study.Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D;

Sepsis Occurrence in Acutely Ill Patients Investigators.

Prospective multicenter observational study

All new adult admissions to a participating intensive care unit between May 1 and 15, 2002

3,147 adult patients, median age- 64 yrs

positive fluid balance was among the strongest prognostic factors for death


37/39

Kidney Int 2009;76:422-427

Fluid accumulation, survival and recovery of kidney function in critically ill

patients with acute kidney injury.Bouchard J, soroko SB, Chertow GM, Jonathan H, T. Alp I, Ravindra L. Mehta,

Program to Improve Care in Acute Renal Disease ( PICARD study Group)

Prospective multicenter observational study

618 adult critically ill patients with AKI

Fluid overload- increase in body weight 10% of baseline

Fluid overloaded patients had

significantly higher APACHE III score, SOFA score,

Mechanical ventilation and vasopressor requirements

Mortality at 30 days and hospital discharge was significantly higher in patients with fluid overload

continue


38/39

Kidney Int 2009;76:422-427

Fluid accumulation, survival and recovery of kidney function in critically ill

patients with acute kidney injury.Bouchard J, soroko SB, Chertow GM, Jonathan H, T. Alp I, Ravindra L. Mehta,Program to Improve Care in Acute Renal Disease ( PICARD study Group)

In survivors percentage fluid accumulation was lower

at AKI diagnosis ( statistically non significant)

at dialysis initiation and cessation in patients requiring RRT

Patients who did not require RRT

Incremental increase in mortality, with proportional increase in days with fluid overload, after AKI diagnosis

In dialyzed patients, mortality increased, in relation to proportion of dialysis days with fluid overload

Patients with fluid overload at dialysis initiation, who ended dialysis without fluid overload, had better survival

Patients with fluid overload at peak creatinine level, were less likely to recover kidney function


39/39

So first interpret it, then assimilate it and finallyimplement it

7KDQN

journal club- fluid balance and mortality in critically ill patients

Documents