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Ubaidur Rahaman Senior Resident, Critical Care Medicine S.G.P.G.I.M.S. Lucknow, India
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
Background
Intravenous fluids are important component of resuscitation in septic shock EGDT and Survival Sepsis Guidelines have set a target for fluid administration
METHODS
James A. Russell and Keith R. Walley were also investigators in VASST study
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 age Having septic shock and receiving minimum of 5 gm of NE/minute
Patients were divided into 2 groups blinded Vasopressin 0.01-0.03U/min blinded 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
Conclusions Low dose vasopressin did not reduce mortality rate as compared to NE
among patients with septic shock who were on NE
Subgroup analysis
Patients 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)
Statistical analysis
After correction of age and severity of illness, patients were divided into: a) 4 fluid balance quartiles. b) 3 CVP groups- <8, 8-12, >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.
RESULT
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
Fluid intake, urine output, and net fluid balance (ml) at 12 hours and day 4
Quartile 1 Intake At 12 hours Quartile 2 4520 (3700-5450) 1590 (960-2560) 2880 (2510-3300) 18,500 (15,700-22,500) 11,000 (8210-14,500) 8120 (6210-9090) Quartile 3 6110 (5330-7360) 1180 (600-2070) 4900 (4290-5530) 22,800 (19,700-26,700) 9960 (6940-12,900) 13,000 (11,800-14,700) Quartile 4
2900
(2050-3900)
10,100
(8430-12,100)
3 1/2 11 2 1/2 13
Output
2200
(1100-3920)
1260
(600-2400)
Balance
710
(-132-1480)
8150
(7110-10,100)
Intake At Day 4
16,100
(12,800-19,700)
30,600
(26,200-36,000)
Output
14,600
(11,500-20,100)
8350
(5100-12,300)
Balance
1560
(-723-3210)
20,500
(17,700-24,500)
At 12 hours
At day 4
Fluid balance Group Quartile 1 12 hours Quartile 2 Quartile 3 Quartile 1 Day 4 Quartile 2 Quartile 3
Adjusted Hazard ratio vs quartile 4 0.569 (0.405-0.799) 0.581 ( 0.414-0.816) 0.762 (0.562-1.033) 0.466 (0.299-0.724) 0.512 (0.339-0.775) 0.739 (0.503-1.087)
CVP
NE
at 12 hours
CVP
NE
at Day 4
At 12 hours
At Day 4
Hazard ratio
CVP Group
Adjusted Hazard ratio vs CVP > 12 mmHg 0.606 ( 0.363-0.913) 0.762 ( 0.562-0.943) 0.903 ( 0.484-1.686) 0.764 ( 0.542-1.078)
CVP < 8 mmHg 12 Hours CVP 8-12 mmHg CVP < 8 mmHg Day 4 CVP 8-12 mmHg
A CVP <8 mmHg at 12 hours is associated with improved survival, whereas it does not correlate on subsequent days.
Net fluid balance ( ml) CVP Group All patients CVP < 8 mmHg CVP 8-12 mmHg CVP >12 mmHg Survivors 3444 (1861-5984) 3015 (1296-4987) (12962727 (1227-5491) 3975 (2387-6614) Non survivors 4429 (2537-6560) 2281 (802-5711) (8023112 (1559-4809) 5237 (3140-7773) p <0.001 NS NS < 0.001
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).
A more positive fluid balance early in resuscitation and cumulatively over 4 days is associated with an increased mortality. But there is a point at which too little fluid is indeed harmful. CVP becomes unreliable marker of fluid responsiveness as well as fluid balance after 12 hours. Optimal survival occurred with a positive fluid balance of approximately 3 L at 12 hours.
CVP achieved at 12 hours <8 mmHg-9% of patients 8-12 mmHg- 28% of patients >12 mmHg- 62% of patients
CVP not indicator of volume status Ongoing Changes in ventricular compliance Ongoing changes in lung and thoracic compliance and resultant changes in mechanical ventilatory support
Intake
16,100- 30,600
13,443 vs 13,358
EGDT vs standard arm
Study strength
number of patients- 778 Statistical analysis
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 whether positive fluid balance is marker of SOI or administration of excessive fluid causes mortality.
REVIEW OF LITERATURE
Negative Fluid Balance Predicts Survival in Patients With Septic Shock* A Retrospective Pilot Study
Fadi 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 of treatment survived 5 of 25 patient who failed to achieve a negative fluid balance of > 500 mL by day 3 of treatment survived
Non survivors had higher mean APACHE II score and higher first day SOFA scores were more likely to require vasopressors and mechanical ventilation that negative fluid balance achieved in any of the first 3 days of septic shock portends a good prognosis
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
conservative strategy group during first 28 days had Improved oxygenation index and lung injury score Higher ventilator free days Lesser ICU stay Without increasing incidence or prevalence of shock during the study or use of dialysis during first 60 days
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
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
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
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