To ebb or to flow ? Fluid management of the stable critically ill - - PowerPoint PPT Presentation

To ebb or to flow ? Fluid management of the stable critically ill patient

Canadian Society of Internal Medicine Annual Meeting 2019 Critical Care Extended Workshop Halifax, NS

• Dr. Marko Balan

CSI M Annual Meeting 2 0 1 9

Conflict Disclosures

Definition: A Conflict of Interest may occur in situations where the personal and professional interests of individuals may have actual, potential or apparent influence over their judgment and actions.

I have no conflicts to declare

Com pany/ Organization Details Advisory Board or equivalent Speakers bureau m em ber Paym ent from a com m ercial

• rganization. ( including gifts or
• ther consideration or ‘in kind’

com pensation) Grant( s) or an honorarium Patent for a product referred to

• r m arketed by a com m ercial
• rganization.

I nvestm ents in a pharm aceutical organization, m edical devices com pany or com m unications firm . Participating or participated in a clinical trial

The following presentation represents the views of the speaker at the time of the presentation. This information is meant for educational purposes, and should not replace other sources of information or your medical judgment. I intend to make therapeutic recommendations for medications that have not received regulatory approval.

Disclosure

Objectives

• 1. Review risks of fluid administration in critically ill patients.
• 2. Describe the concept of "active deresuscitation."
• 3. Examine commonly encountered issues with deresuscitation.
• 4. Discuss deresuscitation of the critically ill patient with renal

injury.

Defining the population

Rescue Optimization Stabilization De-escalation Time Fluid status

Vincent & De Backer, 2013; Hoste et al, 2014

Question 1

I n post-resuscitated critically ill patients which of the following has been associated with decreased 90-day mortality? A. Prone positioning in early severe ARDS B. I ntensive glucose control targeting 4.5-6.0mmol/ L C. Hydrocortisone in patients with septic shock D. Positive mean daily fluid balance in patients with AKI E. Pantoprazole in patients at risk for GI bleeding

Question 1

I n post-resuscitated critically ill patients which of the following has been associated with decreased 90-day mortality? A. Prone positioning in early severe ARDS ( PROSEVA 2 0 1 3 ) B. I ntensive glucose control targeting 4.5-6.0mmol/ L (NI CE SUGAR 2009) C. Hydrocortisone in patients with septic shock (ADRENAL 2018) D. Positive mean daily fluid balance in patients with AKI (FI NNAKI 2012) E. Pantoprazole in patients at risk for GI bleeding (SUP-I CU 2018)

Fluid… too much of a good thing?

• Venous congestion organ

edema/ dysfunction

• Impaired wound healing
• Skin and soft tissue infection,

pressure injuries

• Issues with venous access
• Patient discomfort, impaired

mobilization

https: / / study.com/ academy/ lesson/ fluid-volume-excess-symptoms-nursing- interventions.html

Fluid overload and clinical outcomes

Morbidity

• ↓ MV free days (Wiedermann et al, 2006;

Rosenberg et al, 2009)

• ↑ I CU LoS (Wiedermann et al, 2006; Rosenberg et

al, 2009; Stein et al, 2012; Bellomo et al, 2012)

• ↑ Hosp LoS (Bellomo et al, 2012)
• ↑ I ntra-abdo HTN (Malbrain et al, 2014)
• ↑ RRT (Wiedermann et al, 2006; Bellomo et al, 2012)

Mortality

• ↑ I CU m ortality (Stein et al, 2012; Vincent et al,

2006)

• ↑ Hosp m ortality (Murphy et al, 2009; Rosenberg

et al, 2009)

• ↑ 2 8 d m ortality (Sirvent et al, 2014)
• ↑ 6 0 d m ortality (Payen et al, 2008; Bouchard et

al, 2009)

• ↑ 9 0 d m ortality (Bellomo et al, 2012)

Silversides et al, 2017

• Meta-analysis, 49 studies (11 RCTs)
• Critically ill patients with ARDS, sepsis, SIRS, in the post-

resuscitation phase Conservative fluid management or deresuscitation Standard care or liberal fluid strategy vs.

Silversides et al, 2017

Mortality RR 0.92 [ 0.82, 1.02]

Silversides et al, 2017

MV free days MD 1.82 [ 0.53, 3.10] I CU LoS MD -1.88 [ -3.64, -0.12]

Malbrain et al, 2014

• Meta-analysis, 47 studies, 11 RCTs
• 19 902 critically ill patients

Strategy attempting to

• btain negative fluid

balance or equilibrium at day 3 Comparator group not attempting to achieve negative fluid balance

• r equilibrium goal at

day 3 vs. Mortality: OR 0.42 [ 0.32, 0.55] I AH: MD -2.89 [ -3.95, -1.83]

Take home message

• Fluid overload is associated with poor outcomes in stable

critically ill patients

• Recom m endation: Strategies that limit excessive fluid

administration may be preferable over liberal fluid strategies.

Just an association?

• Dose effect
• Confounders
• Timing of fluid overload

Murphy et al, 2009

• Retrospective analysis of 212 pts with septic shock and ALI

Adequate initial fluid resuscitation

• IV bolus ≥20mL/kg
• CVP ≥8mm Hg
• within 6h after initiation of vasopressors

Conservative late fluid management

• Even to negative fluid balance
• n ≥2 consecutive days during first 7d
• after septic shock onset

Cumulative fluid balance

Murphy et al, 2009

nonsurvivors survivors

Mortality by group

I nitial resuscitation Adequate Adequate I nadequate I nadequate Post- resuscitation Conservative Liberal Conservative Liberal

Murphy et al, 2009

Shum et al, 2011

• Retrospective single centred cohort observational study
• 639 general ICU pts admitted for ≥3d

Shum et al, 2011

Tertile of APACHE I V ROD Rank Correlation Coefficient ( SMR and fluid gain d2 + 3 ) P value 0-13% 0.4 0.39 13-42% 0.9 0.07 > 42% 1 0 .0 4

Sakr et al 2017

• Observational international cohort study, 730 ICUs
• 1808 pts with sepsis
• septic shock 61% , ICU mortality 27.6% , hospital mortality 37.3%
• Stratified according to quartiles of cumulative fluid balance at

24h and 3d after ICU admission

Adjusted 28d mortality

Sakr et al, 2017 P = 0 .6 5 6 P = 0 .0 0 3

Just an association?

• Dose effect  the more fluid the worse the outcome
• Confounders  + FB independently associated with worse outcome
• Timing of fluid overload  days 2-3 appear to be a critical period
• This may be particularly important in the sickest pts

Take home message

• Recom m endation: Consider using ICU day 2-3 as an overall

fluid management reassessment point, much like antibiotic stewardship practices.

Question 2

• During a patient’s entire ICU admission which of the following is

responsible for the largest amount of fluid administered?

• A. Resuscitative fluids
• B. Enteral nutrition and oral fluids
• C. Maintenance fluids and medications
• D. Blood product transfusion

Question 2

• During a patient’s entire ICU admission which of the following is

responsible for the largest amount of fluid administered?

• A. Resuscitative fluids
• B. Enteral nutrition and oral fluids
• C. Maintenance fluids and m edications
• D. Blood product transfusion

Fluid Creep

• Unintentional, insidious and often unnoticed fluid
• Initially described in burn resuscitation literature (Pruitt 2000)

Regenmortel et al, 2018

Regenmortel et al, 2018

• 131 + / - 137mmol Na per day
• 130 + / - 111mmol Cl per day
• Not including sodium as part of fluids to dissolve medications
• Guideline recommendation is 1mmol/ kg/ d of Na and Cl each

(NICE, 2017)

A sensible look at insensible losses

• “4-2-1” rule (Holliday & Segar, 1957)
• Pts on enteral/ parenteral nutrition: 10ml/ kg/ d (Cox, Acta

Anaesthesiol Scand, 1987)

• Ventilated: ↓ ~ 30-40%
• Febrile: ↑ 13-25% per degree above 37°C

Take home message

• Majority of fluids administered to critically ill patients is

“unintentional” yet significant in volume

• Recom m endation:
• Avoid routine use of maintenance fluid
• Consider IV  PO medications
• double concentrate IV infusions (heparin, norepinephrine)
• HIGH threshold for fluid bolus administration in stable critically

ill patients

Fluid removal

• Spontaneous by patient
• Pharmacologically managed
• Mechanical fluid removal

Active deresuscitation

• Context-specific
• Goal directed
• Safety checkpoints
• Frequent reassessments

Silversides et al, 2018

• Retrospective cohort study in UK and Canada
• 400 critically ill adults receiving invasive MV for ≥24h
• ~ 5L cumulative fluid balance over 7d (higher in non-survivors)
• 52.3% of all pts had deresuscitative measures, typically

initiated on days 2 or 3

• Practices varied significantly by site

Silversides et al, 2018

• Fluid balance on day 3 was an independent risk factor for 30d

mortality, OR 1.26/ L

• Greater fluid balance on day 3 associated with greater organ

dysfunction, longer ICU LoS, and duration of MV

• Negative fluid balance achieved with deresuscitative measures was

associated with lower mortality

• Pts with positive fluid balance on day 3, deresuscitative measures

were not associated with increased 30d mortality

Wiedermann et al, 2006

• Multicenter prospective RCT of pts with ALI (P: F < 300)
• ARDSnet lung protective ventilation protocol
• Randomized to conservative vs liberal fluid strategy

CVP PAOP Conservative < 4 < 8 Liberal 10-14 14-18

Wiedermann et al, 2006

Clinical variable Definition Shock MAP < 60mm Hg Need for vasopressor Oliguria u/ o < 0.5mL/ kg/ h Effective Circulation CI < 2.5L/ min/ m 2 Cold, mottled skin cap refill time > 2s I nterventions:

• KVO IV
• Fluid bolus
• Furosemide
• Vasopressors
• Dobutamine

Wiedermann et al, 2006

Outcom e Conservative Liberal P value Mortality at 60d (% ) 25.5 28.4 0.30 Ventilator-free days (d 1-28) 14.6± 0.5 12.1± 0.5 < 0 .0 0 1 ICU-free days (d 1-7) 0.9± 0.1 0.6± 0.1 < 0 .0 0 1 ICU-free days (d 1-28) 13.4± 0.4 11.2± 0.4 < 0 .0 0 1

Wiedermann et al, 2006

• Conservative fluid strategy led to better outcomes
• Frequent reassessments
• Cumulative fluid balance difference of 7L over 7d
• Safety endpoints
• Higher rates of met alkalosis and electrolyte imbalances in

conservative group

• No difference vasopressor or RRT use

Take home message

• A few studies have shown that active deresuscitation appears to

be safe and associated with improved clinical outcomes

Question 3

• A 53 year old male admitted to your I CU with severe pancreatitis is POD4 from decompressive

laparotomy due to abdominal compartment syndrome, and POD2 from last vacuum dressing

• change. The surgeon is planning to take him back to the OR for possible abdominal closure
• today. The patient was agitated at this morning’s SAT and the propofol infusion was

subsequently increased to 3mg/ kg/ hr (50mcg/ kg/ min) after which he was started on norepinephrine 0.05mcg/ kg/ min (3.5mcg/ min). ScvO2 is 70% and lactate is normal. How would you manage this patient’s fluid status? 1. Give small fluid bolus due to ScvO2 value 2. Check response to passive leg raise and give fluid bolus only if test suggests fluid responsiveness 3. Minimize fluid intake, too early to start diuresis due to norepinephrine 4. Minimize fluid intake and give furosemide bolus

Question 3

• A 53 year old male admitted to your I CU with severe pancreatitis is POD4 from decompressive

laparotomy due to abdominal compartment syndrome, and POD2 from last vacuum dressing

• change. The surgeon is planning to take him back to the OR for possible abdominal closure
• today. The patient was agitated at this morning’s SAT and the propofol infusion was

subsequently increased to 3mg/ kg/ hr (50mcg/ kg/ min) after which he was started on norepinephrine 0.05mcg/ kg/ min (3.5mcg/ min). ScvO2 is 70% and lactate is normal. How would you manage this patient’s fluid status? 1. Give small fluid bolus due to ScvO2 value 2. Check response to passive leg raise and give fluid bolus only if test suggests fluid responsiveness 3. Minimize fluid intake, too early to start diuresis due to norepinephrine 4 . Minim ize fluid intake and give furosem ide bolus

Indications and Timing

• ADQI consensus (Goldstein et al, 2014):
• if fluid contributes or is likely to contribute to pt morbidity
• delayed weaning from MV
• disrupted wound healing
• impaired organ recovery
• suboptimal rehabilitation
• Other considerations:
• lactate clearance, vasoactive support, central venous oxygenation
• Stable/ low dose vasopressors not a contraindication

Commonly encountered issues with deresuscitation

• Furosemide administration
• Hypernatremia
• Metabolic alkalosis
• Hypoalbuminemia

Question 4

• The patient returns from the OR, and the surgeon was unable to close the
• abdomen. As such you decide to continue diuresis. Choose the correct

statement? 1. Furosemide bolus daily as there is no benefit to infusion 2. Furosemide bolus as it is less likely to cause tinnitus compared to infusion 3. Furosemide bolus followed by infusion because it has been shown to lead to greater diuresis 4. Furosemide infusion without bolus to avoid hypotension

Question 4

• The patient returns from the OR, and the surgeon was unable to close the
• abdomen. As such you decide to continue diuresis. Choose the correct

statement? 1. Furosemide bolus daily as there is no benefit to infusion 2. Furosemide bolus as it is less likely to cause tinnitus compared to infusion 3 . Furosem ide bolus follow ed by infusion because it has been show n to lead to greater diuresis 4. Furosemide infusion without bolus to avoid hypotension

Salvador et al, 2005

• 8 RCTs, 254 pts with class III or IV heart failure
• Continuous infusion resulted in:
• ↑ diuresis (weighted mean difference 271mL/ hr)
• ↓ tinnitus, hearing loss (RR 0.06)
• ↓ hospital LoS by 3.1d (* single study)
• ↓ all cause in mortality (* * two studies)
• No difference in electrolyte disturbances
• Limitations: heterogeneity, small sample sizes

Ng et al, 2018

• Systematic review and Meta-analysis
• Critically ill adult pts with fluid overload
• 9 studies (RCTs, observational studies, case-control studies)

Mortality

Hospital LoS

Urine output in first 24h

* No significant changes in creatinine or eGFR

Hypernatremia

• Independently associated with increased mortality (Hoorn et al,

2008; Linder et al, 2007)

• Thirst  agitation/ delirium

Bihari et al, 2016

• Prospectively randomized 40 pts with fluid overload (as per

attending or > 10% admission body weight)

• Exclusions: regular or recent diuretic use, baseline Cr > 180umol/ L,

CPC-C cirrhosis, RRT Furosemide 1mg/ kg IV max 60mg vs. Furosemide 1mg/ kg IV max 60mg Indapamide 5mg PO

Bihari et al, 2016

Furosem ide Furosem ide + I ndapam ide P value Fluid administered (mL/ d) 1915 1509 0.53 Urine output (mL/ d) 2478 2826 0.79 Fluid balance (mL/ d)

• 691
• 770

0.38 Sodium balance (mmol/ d)

• 20
• 110

0 .0 2 Urinary Cr Cl (mL/ min/ 1.73m 2) 118 211 0 .0 1 Serum sodium 139  141 140  140 0 .0 4 6 Edema score (0-16) 8.5  7.3 8.1  4.8 0 .0 4

Metabolic alkalosis

• When severe, pH > 7.55
• Mental status changes, seizures
• Arrhythmias
• Hypoventilation
• Management:

1. Correct hypokalemia (> 4.5) and hypomagnesemia 2. If fluid overloaded, or if contributing to hypoventilation in pts with compensated resp acidosis  acetazolam ide 5 0 0 -1 0 0 0 m g I V BI D 3. If nearly euvolemic  consider limiting diuresis

Hypoalbuminemia

• Response to furosemide is blunted in hypoalbuminemia (Inoue et al, 1987)
• Studies in non-critically ill patients have generally shown increased in

diuresis but limited data on clinical outcomes (Elwell et al, 2003)

• RCT of 190 pts with ARDS and serum albumin < 60g/ L (Martin et al, 2005)
• Given furosemide + placebo or furosemide + albumin (furosemide by infusion)
• Albumin treated group had greater increases in P: F ratio and net fluid loss
• Non-albumin treated pts had more fluid boluses for hypotension and fewer shock-

free days

Take home message

• Furosemide infusion leads to increased diuresis but clinical outcomes not consistent
• I nfusion should only be given after bolus
• I nfusion may be safer than bolus regimen
• Hypernatremia should be avoided/ managed, consider thiazide/ thiazide-like diuretic
• Metabolic alkalosis should be addressed when severe, consider acetazolamide
• Consider albumin in severely hypoalbuminemic pts (< 20g/ L) to augment furosemide

diuresis

• Should be given before furosemide
• Use concentrated preparation (20-25% )
• Avoid in pts with TBI , stroke

Deresuscitation in the critically ill patient with AKI

Peeters et al, 2015

Deresuscitation in the critically ill patient with AKI

• Critically ill patients with AKI: fluid overload is associated with

increased mortality (Bouchard et al, 2009; Teixeira et al, 2013; Grams et

al, 2011; Payen et al, 2008)

• Diuretic use showed mixed results:
• Improved survival (Teixeira et al, 2013; Grams et al, 2011)
• Increased risk of death or nonrecovery of renal function

(Mehta et al, 2002)

Furosemide stress test (Chawla et al, 2013)

• Predicts progression to AKIN stage III in resuscitated critically ill pts with

early AKI

• May aid in earlier identification of pts who may require mechanical fluid

removal

Furosemide stress test (Chawla et al, 2013)

• < 200mL over 2h  sens 87% , spec 84% for progression to stage III

AKI

• Prospectively validated with sens 74% , spec 90% (Rewa et al, 2019)
• Predicted need for RRT in follow-up study (Koyner et al, 2015)

Furosem ide naïve 1 m g/ kg Furosem ide-exposed ( w ithin last 7 d) 1 .5 m g/ kg

Mechanical fluid removal

• Established fluid overload
• Failed diuretic therapy
• Life-threatening fluid overload and severe renal dysfunction
• High risk of developing fluid overload
• Fluid overload and refractory electrolyte disorders
• Fluid overload and uremic symptoms

Rosner et al, 2014

Take home messages

• Deresuscitation therapy in critically ill patients with AKI has led to

mixed results.

• Recom m endation:
• Consider if pt responsive and strong indications
• Avoid in diuresis-nonresponsive pts
• Consider using furosemide stress test to identify patients at high

risk for progression to severe AKI and possible need for RRT

Conclusion

• Fluid management is an important component of the care of critically

ill patients and should be actively managed throughout their illness

• More evidence is accumulating showing harms of excessive fluid

administration

• Deresuscitation should be actively pursued in diuretic-responsive

patients

• Consider pearls for issues related with aggressive deresuscitation

References (1)

• Bihari S, Holt AW, Prakesh S, et al. Addition of indapamide to frusemide increases natriuresis and creatinine clearance but not diuresis, in fluid overloaded ICU patients. Journal of Critical Care 2016; 33: 200-6.
• Bouchard J, Soroko SB, Chertow GM, et al. Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury. Kidney International 2009; 76: 422-7.
• Carter L, Fluid Volume Excess: Symptoms & Nursing Interventions. Retrieved from: https: / / study.com/ academy/ lesson/ fluid-volume-excess-symptoms-nursing-interventions.html
• Chawla LS, Davison DL, Brasha-Mitchell E, et al. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care 2013; 17: R207.
• Cox P. Insensible water loss and its assessment in adult patients: a review. Acta Anaesthesiol Scand 1987; 31: 771-6.
• Elwell RJ, Spencer AP, Eisele G. Combined furosemide and human albumin treatment for diuretic-resistance edema. Ann Pharmacother 2003; 37: 695-700.
• Geurin C, Reignier J, Richard JC, et al. Prone positioning in severe acute respiratory distress syndrome. NEJM 2013; 368(23): 2159-68.
• Goldstein S, Bagshaw S, Cecconi M, et al. Pharmacological management of fluid overload. BJA 2014; 113(5): 756-63.
• Grams ME, Estrella MM, Coresh J, et al. Fluid balance, diuretic use, and mortality in acute kidney injury. Clin J Am Soc Nephrol 2011; 6: 966-73.
• Holliday MA, Segar WE. The maintenance need for water in parenteral fluid therapy. Pediatrics 1957; 19(5): 823-32.
• Hoste EA, Maitland K, Brudney CS, et al. Four phases of intravenous fluid therapy: a conceptual model. BJA 2014; 113(5): 740-7.
• Inoue M, Okajima K, Itoh K, et al. Mechanism of furosemide resistance in analbuminemic rats and hypoalbuminemic patients. Kidney International 1987; 32: 198-201.
• Koyner JK, Davison DL, Brasha-Mitchell E, et al. Furosemide stress test and biomarkers for the prediction of AKI severity. J Am Soc Nephrol 2015; 26: 2023-31.
• Krag M, Marker S, Perner A, et al. Pantoprazole in patients at risk for gastrointestinal bleeding in the ICU. NEJM 2018; 379(23): 2199-2208.
• Malbrain MLNG, Cordemans C, Van Regenmortel N. Fluid overload is not only of cosmetic concern (Part II): Results from a meta-analysis and practical approach. ICU Management 2012; 12: 34−37.
• Malbrain MLNG, Marik PE, Cordemans C, et al. Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice. Anaesthesiology Intensive Therapy 2014; 46(5): 361-80.

References (2)

• Martin GS, Moss M, Wheeler AP, et al. A randomized, controlled trial of furosemide with or without albumin in hypoproteinemic patients with acute lung injury. Crit Care Med 2005; 33: 1681-7.
• Mehta RL, Pascual MT, Soroko S, et al. Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA 2002; 288(20): 2547-53.
• Murphy CV, Schramm GE, Doherty JA, et al. The importance of fluid management in acute lung injury secondary to septic shock. CHEST 2009; 136: 102-9.
• Ng KT, Velayit A, Khoo DKY, et al. Continuous infusion versus intermittent bolus injection of furosemide in critically ill patients: a systematic review and meta-analysis. J Cardiothoracic and Vascular Anesthesia 2018; 32: 2303-10.
• NICE guidelines. Intravenous fluid therapy in adults in hospital. 2013; available at: nice.org.uk/ guidance/ cg174
• NICE SUGAR Investigators. Intensive versus conventional glucose control in critically ill patients. NEJM 2009; 360(13): 1283-97.
• Payen D, de Pont AC, Sakr Y, et al. Sepsis Occurrence in Acutely Ill Patients (SOAP) Investigators: A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care 12: R74, 2008.
• Peeters Y, Lebeer M, Wise R, Malbrain ML. An overview on fluid resuscitation and resuscitation endpoints in burns: past, present and future. Part 2—avoiding complications by using the right endpoints with a new personalized protocolized approach.

Anaesthesiol Intensive Ther. 2015; 47: 15–26.

• Pruitt BA. Protection from excessive resuscitation: “pushing the pendulum back.” J Trauma 2000; 49: 567–8.
• Regenmortel NV, Vebrugghe W, Roelant E, et al. Maintenance fluid therapy and fluid creep impoase more significant fluid, sodium, and shloride burdens than resuscitation fluids in criticall ill patients: a retrospective study in a tertiary mixed ICU population.

Intensive Care Med 2018; 44: 409-17.

• RENAL Replacment Therapy Study Investigators. An observational study fluid balance and patient outcomes in the randomized evaluation of normal vs. augmented level of replacement therapy trial. Crit Care Med 2012; 40(6): 1753-1760.
• Rewa OG, Bagshaw SM, Wang X, et al. The furosemide stress test for prediction of worsening acute kidney injury in critically ill patients: a multicenter, pros[ ective, observational study. J Crit Care 2019, 52: 109-14.
• Rosenberg AL, Dechert RE, Park PK, et al. Association of cumulative fluid balance on outcome in acute lung injury: a retrospective review of the ARDSnet tidal volume study cohort. J Int Care Med 2000; 24(1): 35-46.
• Rosner MH, Osterman M, Mururgan R, et al. indications and management of mechanical fluid removal in critical illness. BJA 2014; 113(5): 764-71.

References (3)

• Sakr Y, Birri PNR, Kotfis K, et al. Higher fluid balance increases the risk of death from sepsis: results from a large international audit. Crit Care Med 2017; 45(3): 386-94.
• Salvador DRK, Ramos GGC, Punzalan FER. Continuous infusion versus bolus injection of loop diuretics in congestive heart failure. Cochrane Database of Systematic Reviews 2004, 1, Art. No.: CD003178
• Shum HP, Lee FMH, Chan KC, et al. I nteraction between fluid balance and disease severity on patient outcome in the critically ill. J Crit Care 2011; 26: 613-9.
• Silversides JA, Fitzgerald E, Manickavasagam US, et al. Deresuscitation of patients with iatrogenic fluid overload is associated with reduced mortality in critical illness. Crit Care Med 2018; 46(10): 1600-7.
• Silversides JA, Major E, Ferguson AJ, et al. Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic

review and meta analysis. I ntensive Care Med 2017; 43: 155-70.

• Sirvent JM, Ferri C, Baró A, et al. Fluid balance in sepsis and septic shock as a determining factor of mortality. AJEM 2015; 33: 186-9.
• Stein A, de Souza LV, Belettini CR, et al. Fluid overload and changes in serum creatinine after cardiac surgery: predictors of mortality and longer intensive care stay. A prospective cohort study. Crit Care 2012; 16: R99.
• Teixeira C, Garzotto F, Piccinni P, et al. Fluid balance and urine volume are independent predictors of mortality in acute kidney injury. Crit Care 2013; 17: R14.
• Vaara et al. Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prosective FI NNAKI study. Crit Care 2012; 16(5): R197.
• Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. NEJM 2018; 378(9): 797-808.
• Vincent JL, & De Backer D. Circulatory shock. NEJM 2013; 369(18): 1726-34.
• Vincent JL, Sakr Y, Sprung CL, et al. Sepsis in European intensive care units: Results of the SOAP study. Crit Care Med 2006: 34(2): 344-53.
• Wiedermann HP, et al, National Heart, Lung, and Blood I nstitute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Comparison of two fluid-management strategies in acute lung injury. NEJM 2006;

354: 2564-75.

Thank you

• Questions?

marko.balan@dal.ca Please complete CSIM presentation evaluation.