Download - THE 2nd AL JAHRA DAY

Using IV Fluids Wisely
Ali AlSahow
Indications for IV Fluids
1)
Maintenance fluids for patients who cannot eat >8hs (NPO / Ventilator / Acute GI illness)
2)
Replacement / Resuscitation in volume depletion
3)
Keep flow high in distal nephron / urinary tract to avert ischemia / toxicity / precipitation

Aminoglycosides / Ampho B / IV Acyclovir / Cisplatin / IV Contrast / TLS / Pigment nephropathy
4)
Correction of electrolytes / Acid – base disorders / Hypoglycemia
5)
Delivery of medications / Delivery of anesthetic / Delivery of radiocontrast agent
6)
To Keep Vein Open (TKVO)
Hoorn EJ. Intravenous Fluids: Balancing solutions. J Nephrol. 29/Nov/2016. Epub ahead of print
Ideal Resuscitation / Replacement IV Fluid
1.
Produces predictable & sustained increase in IV volume
2.
Has a chemical composition as close as possible to that of EC fluid
3.
Metabolized & completely excreted W/O accumulation in tissues
4.
Does not produce adverse metabolic or systemic effects
5.
Cost effective
JA Myburgh & MG Mythen. Resuscitation Fluids. N Engl J Med Sep/2013; 369:1243-1251
Available Resuscitation / Replacement IV Fluids
1.
Crystalloids
2.
Colloids = Plasma Expanders
3.
Blood & Blood Products
Crystalloids

Solutions with different electrolyte concentrations / pH / Osmolality
 Hypertonic
 Hypotonic
 Isotonic
 Balanced
vs Unbalanced
IC Space
67%
Cell Membrane
Interstitium
25% TBW
75%
Capillary Wall
25%
IV Space
8% TBW
Hypertonic Crystalloids:
1)

Contain higher concentrations of electrolytes than plasma – 3% NaCl

Small volume hypertonic fluid may provide More effective IV resuscitation than isotonic

With beneficial effects on CO & endothelial function

Not known if translates into better clinical outcome in Sepsis / ALI / Traumatic brain injury

Further investigation is warranted & it is considered experimental at this stage
F van Haren & K Zacharowski. What’s new in volume therapy in the ICU?. Best Practice & Research Clinical Anesthesiology. 2014 (28): 275-283
2)
Hypotonic Crystalloids:

Contain lower concentrations of electrolytes than plasma – 0.45% NaCl (½ NS)

Not for large volume fluid resuscitation
3)


Isotonic Crystalloids:
Contain same concentrations of electrolytes as plasma
Fluid remains in EC compartment distributed between interstitial & intravascular at 3:1
Unbalanced crystalloids:
A.

0.9% Normal Saline – NS is the dominant IV fluid used for both replacement & maintenance

Lacks buffer with a pH of 5.5 (Much more acidic than plasma) / 1.5 X normal Cl concentration
Balanced Crystalloids:
B.

Can be 1st line in major abdominal surgery / trauma / DKA since less AKI / Acidosis / Transfusion

Ringer’s Lactate & Ringer’s Acetate buffered to reduce Cl load / avoid acidosis / preserve RBF

Excessive infusion may cause metabolic alkalosis & D/T low osmolality may lower plasma osmolality



Ringer’s Acetate avoids the risk of lactate accumulation that can b seen with Ringer’s Lactate
May cause hyponatremia & may increase intracranial pressure transiently esp with disrupted BBB
Plasmalyte is the most physiologically balanced but expensive & awaiting more evidence to its value
 SaLt-ED – NCT02614040 – 10000 pts – 2017 & PLUS – NCT02721654 – 8800 pts – 2020
Negative Impact of 0.9% Normal Saline
Krajewski ML, Raghunathan K, Paluszkiewicz SM, Schermer CR, Shaw AD. Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation. Br J Surg. 2015;102(1):24–36
Shaw et al. Major Complications, Mortality, & Resource utilization After Open Abdominal surgery: 0.9% Saline compared to Plasma-Lyte. Ann Surg 2012;255:821-829
Chowdhury et al. A Randomized, Controlled, Double-Blind Crossover Study on the Effects of 2L Infusion of 0.9% Saline & Plasma-lyte 148 on RBF Velocity & Renal Cortical Tissue Perfusion in Healthy Volunteers.
Ann Surg2012;256:18-24
Yunos et al. Association Between a Cl-Liberal vs Cl-Restrictive IV Fluid Administration Strategy & Kidney Injury in Critically Ill Adults. JAMA 2012; 308:1566-1572
Rochwerg et al. Fluid Type & use of RRT in Sepsis: Systematic Review & Network Met-Analysis. FISSH Group. Intens Care Med. 2015;41(19):1561-1571
Raghunathan et al. Association between the Choice of IV Crystalloids & In-Hospital Mortality Among Critically Ill Adults with Sepsis. Crit Care Med. 2014;412(7):1585-1591
Shaw et al. Impact of IV Fluid Composition on Outcomes in Pts with SIRS. Crit Care. 2015;19:334Krajewski et al. Meta-Analysis of High- vs Low-Cl Content in perioperative & Critical Care Fluid Resuscitation. Br J Surg. 2015;102(1):24-36
Young et al. Effect of a Buffered Crystalloid Solution vs Saline on AKI Among Patients in ICU. SPLIT Trial. JAMA. 2015;314(16):1701-1710
1)
After infusion, crystalloids are rapidly distributed between IV space & interstitium
NS diffuses faster & in larger volume into the interstitium than balanced crystalloids
a)
Leaky endothelium in critical illness makes diffusion even faster predisposing to edema formation

Time to 1st micturition after boluses of crystalloids is shorter for balance crystalloids vs NS
b)

6h after infusion more NS retained than LR & most of retained fluid is in interstitium not IV space

Lower osmolality of balanced solutions reduces plasma osmolality reducing ADH release
2)
Hyperchloremia induces renal vasoconstriction / reduces renal perfusion & reduces GFR
3)
Hyperchloremic Normal Anion-Gap Metabolic Acidosis



4)
Expanding EC space with large volumes of Cl - rich & buffer - free fluid dilutes HCO3
Relationship between EC space volume expansion & reduction in HCO3 is not linear

Expanding EC space by 28% reduces serum HCO3 by only 10%

Acidosis maybe partially offset by IC HCO3 mobilization & H binding to albumin & Hemoglobin
Acidosis depresses myocardium / lowers SVR & response to inotropes / increases risk of arrhythmias
NS linked to plt dysfunction / coagulopathy / larger blood loss / higher need for blood products
2012 Cochrane review of difference between Cl-rich & Cl-restricted perioperative infusion
a)
I.
No difference in mortality / AKI / Bleeding
II.
Much higher need for plt transfusion in Cl-rich group & higher rates of acidosis

Observational studies & retrospective analyses in surgical pts & septic ICU pts
b)
I.
Higher rates of AKI / KRT / Postop infections / Need for blood products / CHF & AF / Acidosis
II.
May be higher mortality & hospital LOS in pts with high serum Cl level
Cochrane analysis of 6 Kidney Tx studies (NS vs Balanced) with 477 pts (70% LD)
c)
d)
Trials included highly heterogeneous in subjects / outcomes / used fluids (hypertonic / colloids)
I.
Higher rates of hyperchloremic metabolic acidosis & Probably higher rates of hyperkalemia
II.
No difference in Tx outcome between NS & Balanced crystalloids
Observational study in 158 liver Tx showed high NS usage plus high MELD score increase AKI

NaHCO3
(1.26% / 1.4% / 4.2% / 8.4%)
Indications:
NaHCO3 1.2% & 1.4% are for:
1) Hypovolemia with metabolic acidosis D/T fluid & HCO3 loss – Diarrhea / High-Output Ileostomy
2) Urine Alkalinization - Rhabdomyolysis
3) Drug intoxication – Salicylates / TCA
4) Prevention of AKI – Contrast – induced AKI – Not Superior to NS
A.
B.

NaHCO3 8.4%
1)
Life - threatening hyperkalemia with acidosis
2)
Good choice for severe hyponatremia
3)
Poor choice for volume resuscitation
Avoid / use with caution:
A.
B.
C.
Respiratory acidosis
Hypokalemic Acidosis
Do not mix with Ca – containing solutions as they may precipitate
Frost Paul. Intravenous fluid therapy in adult inpatients BMJ 2015; 350 :g7620
Colloids
IC Space
67% TBW
Cell Membrane
Interstitium
25% TBW
Capillary Wall
IV Space
8% TBW
100%
Proteins & large molecules
Suspended within crystalloid solutions
Stay in IV space for longer D/T limited
movement across capillary wall
Create oncotic pressure gradient across
vessel wall pulling water into IV space
Vascular Fluid
Homeostasis
A.

The classic Starling principle of 1896
Opposing oncotic & hydrostatic pressures balance fluid transport to / from interstitium across vessel wall
Starling EH:
On the absorption of fluids from
connective tissue spaces
J Physiol 1896; 19:312-326
The Revised Starling principle
Endothelial Surface Layer = Endothelial Glycocalyx Layer
Web of membrane bound, negatively charged glycoproteins &
proteoglycans cover endothelial luminal surface

1)
 Hydrostatic pressure–mediated fluid leak thus preventing edema
2)
ESL Semipermeable to anionic macromolecules such as albumin

Albumin leaks at 5% per hour & returns via lymphatics
3)
Mediates sheer stress from blood flow through endothelial cell
4)
Prevents leucocyte-endothelium & plt-endothelial adhesions

No evidence interstitial fluids is reabsorbed into venules through
oncotic pressure gradient but returns via lymphatics

ESL is compromised in ischemia / sepsis / surgery / inflammation /
DM / hypervolemia / oxidized lipids
 Fluid leakes into the interstitium
Ding et al. IV fluids & AKI. Blood Purification 2017;43:163-172. Raghunathan et al. Choice of fluid in acute
illness: What should be given?. An International Consensus. Br Jour of Anesthesia 2014; 113 (5):772-83
JA Myburgh & MG Mythen. Resuscitation Fluids. N Engl J Med Sep/2013; 369:1243-1251
B.

In theory: Faster IV volume expansion / Longer retention in IV space / Less infused volume. However
a)
To create significant oncotic pressure gradient must have  Colloid MW /  Concentration /  t½
b)
Degree of volume expansion with colloids is modestly greater than crystalloids (1.3 : 1)
c)
IV space expansion by crystalloids in hypovolemia is greater than that achieved in health

d)
e)
In acute volume loss or redistribution, low hydrostatic pressure prolongs filling effect of crystalloids
Compromised ESL increases capillary permeability allowing colloid leakage into interstitium

So colloid retention in IV space may not be greater than crystalloid

Colloids leakage into interstitium reduces oncotic pressure gradient facilitating fluid extravasation

Continuous movement of water from IC to EC spaces can cause cellular dehydration
Colloids are expensive & have a short shelf life
1- Hydroxyethyl Starch (HES)
1)
Not better in short-term hemodynamic resuscitation endpoints except CVP
2)
Higher Mortality / AKI & KRT rates esp with higher MW & higher molecular substitution
3)
Higher substitution may make HES accumulate in skin / spleen / liver / kidneys

EMA – PRAC / ESICM / Surviving Sepsis Campaign / FDA recommends avoiding HES
Perner et al. Hydroxyethyl Starch 130/0.42 versus Ringer’s Acetate in Severe Sepsis – The 6S Trial. NEJM Jul/2012; 367:124-134
Myburgh et al. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care. The Chest Trial. NEJM Nov/2012; 367:1901-1911
Brunkhorsts et al. Intensive Insulin Therapy & 10% Pentastarch (HES 200/0.5) Resuscitation in Severe Sepsis. The VISEP Trial. NEJM Jan/2008; 358: 125-139
2- Gelatin
1)
Large molecules tend to gel / solidify during storage

Smaller molecules with lower oncotic pressure & shorter IV persistence are used
2)
IV persistence is shorter than that of albumin or HES & t½ = 2.5 h
3)
Gelatin may be associated with AKI in observational data
4)
IV colloids cause 4% of all perioperative anaphylactic reactions & most of it are D/T gelatin
Bayer et al. Perioperative Fluid Therapy with Tetrastarch & Gelatin in Cardiac Surgery – A Prospective Sequential Analysis. Crit Care Med 2013, 41 (11): 2532-2542
Bayer et al. Renal Effects of Synthetic Colloids & Crystalloids in Pts with Severe Sepsis: A Prospective Sequential Comparison. Crit Care Med 2011; 39 (6): 1335-1342
Bayer et al. Effects of fluid resuscitation with synthetic colloids (6% HES 130/0.4 or 4% Gelatin) or crystalloids alone on shock reversal, fluid balance & outcomes in severe sepsis. Cri Care Med;
Sep/2012:2543-2551
Harper et al. Suspected Anaphylactic Reactions Associated with Anesthesia. Anesthesia Feb/2009; 64(2): 199-211
3- Dextran

May improve blood flow by reduced viscosity & anticoagulation (plt inhibition / profibrinolysis)

No specific indication apart from acute volume expansion

Small dextran filtered by kidneys & large dextran slowly metabolized over a few weeks

High concentration of smaller dextran molecules may cause osmotic diuresis
4- Albumin
A.
Albumin is not superior to crystalloids in terms of mortality or organ dysfunction (1,4,5)
 Surviving sepsis suggest restricting albumin to pts who have received large volume of crystalloids
 Hyperoncotic albumin may be better in terms of mortality & AKI (12)
Weak evidence suggesting a potential mortality benefit in pts with sepsis
B.
(1,2,3,4,5)
Beneficial role for albumin in CLD / Cirrhosis (6,7)
I. Albumin in combination with vasoconstrictors helps manage HRS & improves survival in HRS type 1
 Lack of GFR improvement post volume expansion with albumin & diuretic D/C aid in HRS diagnosis
ii. Albumin infusion in ESLD reduces mortality & prevents AKI in SBP compared to antibiotics alone
iii. Improves outcome as adjunct to large volume paracentesis (>5L) for diuretic-resistant ascites
C.
D.

E.
F.
Albumin with lasix better than lasix alone in hypoalbuminemic pts with ALI / ARDS
Improve diuresis / Weight / O2 Sat / HR While maintaining BP - MAP & GFR
(8)
Albumin (& Colloids) may increase ICP in traumatic brain Injury increasing mortality
 Colloids are hypo-osmolar compared to plasma increasing the risk of brain edema
(9, 10, 11)
Treating albumin per se does not improve outcome esp if baseline >20 or Achieved level <30(1, 4)
1- Caironi et al. Albumin Replacement in pts with Severe Sepsis or Septic Shock. ALBIOS Study. NEJM Apr/2012; 370 (15): 1412-1421 – No Mortality
Benefit but maybe better 90 d survival is septic shock with albumin
2- Finfer et al. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Subgroup Analysis of SAFE Study.
Intensive Care Med. 2011 Jan;37(1):86-96. May benefit pts with sepsis
3- Delaney et al. The role of albumin as a resuscitation fluid for patients with sepsis: a systematic review and meta-analysis. Crit Care Med. 2011
Feb;39(2):386-91. Meta-analysis showing benefit for pts with sepsis
4- Finfer et al. A Comparison of 4% Albumin & Saline for Fluid Resuscitation in the ICU The SAFE Study. NEJM 2004; 350: 2247-2256 – No Outcome
Difference
5- Charpentier et al. Efficacy & tolerance of hyperoncotic albumin administration in septic shock pts: EARSS study [abstract]. Intensive Care Med. 2011,
37 (Suppl 2): S115-0438. No difference in mortality rates
6- Sort et al. Effect of Intravenous Albumin on Renal Impairment and Mortality in Patients with Cirrhosis and Spontaneous Bacterial Peritonitis. N Engl J
Med 1999; 341:403-409August 5, 1999. Albumin in cirrhosis with SBP
7- Slerno et al. Albumin treatment regimen for type 1 hepatorenal syndrome: a dose–response meta-analysis. BMC Gastroenterology201515:167. Metaanalysis showing mortality benefit for albumin in HRS type 1
8- Martin et al. Albumin & Furosemide Therapy in Hypoproteinemic Patients with Acute Lung Injury. Crit Care Med2002;30:2175-2182
9- Myburgh et al. Saline or Albumin for Fluid Resuscitation in Patients with Traumatic Brain Injury. Post hoc Analysis of the SAFE Study. N Engl J Med
Aug/2007; 357:874-88 – Dangerous in traumatic brain injury
10- Cooper et al. Albumin resuscitation for traumatic brain injury: is intracranial hypertension the cause of increased mortality?. The SAFE Study. J
Neurotrauma. 2013 Apr 1;30(7):512-8. Albumin increase ICP in TBI
11- Van Aken et al. Fluid resuscitation in patients with traumatic brain injury: what is a SAFE approach?. Current Opinion in Anesthesiology: Oct/2012; 25
(5): 563–565.
12- Wiedermann, Dunzendorfer, Gaioni, et al. Hyperoncotic Colloids & AKI: A Meta Analysis of Randomized Trials. Crit Care 2010; 14:R191
Appropriate indications for albumin use
A.
Inappropriate indications for albumin use
Appropriate for which there is widespread consensus
1)
Chronic / Acute hypoalbuminemia > 25g/L
 W/O edema & / or hypotension
1)
Paracentesis – 5g/l ascetic fluid removed after removal of 5l
2)
Therapeutic plasmapheresis
3)
Spontaneous bacterial peritonitis with antibiotics
2)
Malnutrition
Occasionally appropriate when criteria are fulfilled
3)
Wound Healing
1)
Liver cirrhosis with refractory ascites if albumin < 20g/l
4)
Non-Hemorrhagic shock
2)
When non-protein colloids are contraindicated:
I. Pregnancy / breast feeding
II. Acute liver failure
III. Advanced CKD
IV. Hypersensitivity
5)
Ascites responsive to diuretics
6)
Burns in the 1st 24 hrs
7)
Protein losing entropathies &
malabsorption
3)
Hemorrhagic shock if no response to large crystalloid volume
8)
Acute / Chronic Pancreatitis
4)
Hepatorenal syndrome
9)
Hemodialysis
5)
Nephrotic syndrome when albumin < 20 + effective volume
depletion & pulmonary edema
10)
Cerebral ischemia
6)
Burns > 30% BSA after the 1st 24 hrs
11)
Ovarian hyperstimulation syndrome
B.
Liumbruno et al. Recommendations for use of albumin & immunoglobulins. Italian Society of Transfusion Medicine & Immunohaematology (SIMTI) Working Party. Blood Transfus 2009; 7: 216-34
Fluid Overload in the Critically Ill Patient
Relationship between volume status & complications is U - Shaped
Complications seen at both extremities
ADQI Definition of Fluid overload: An increase in body weight of over 10%
Excess Fluid = Total input – total output / initial body weight
Jörres, Hasper & Oppert. Fluid overload in AKI. Oxford Textbook of Clinical Nephrology
Pathophysiology of Fluid Overload

1)
Causes of Fluid Overload
Excessive Fluid Intake:
a)
b)
2)
3)

Early: Aggressive Blood products & fluid administration to improve CO & hemodynamic targets
I.
Hemodynamic targets of resuscitation (BP / CVP) poor predictors of CO & tissue perfusion
II.
Acute illness / Chronic disease / Medications unpredictably alter CV system response to IV fluids
III.
EGDT trials showed no mortality difference but high vasopressors & ICU admissions in active arm
Late: Continuous IV infusion despite positive balance & Obligate daily fluids in excess of losses
Poor Urine Output
Pre-existing advanced CKD / Severe CHF / 3rd Spacing
Fluid buildup in interstitium causes progressive organ dysfunction & poorer outcomes
I.
Impairs O2 & metabolite diffusion
II.
Obstruction of capillary blood flow & lymphatic drainage
III.
Disturbed cell to cell interaction
Impact of Fluid Overload on Organ Function
O'Connor & Prowle. Fluid Overload. Crit Care Clin Oct/2015;31(4):803 – 821.
Claure-Del Granado & Mehta. verload in ICU: Evaluation & Management. BMC Nephrology 2016,17:109

Cerebral Edema:
Impaired cognition / Delirium

Myocardial Edema:
Conduction Disturbances / Impaired Contractility / Diastolic Dysfunction

Pulmonary Edema:
Impaired Gas Exchange / Reduced Lung Compliance / Increased Work of Breathing / More failure

Raised Renal Venous Pressure / Congestion + Renal Interstitial Edema + Intraabdominal HTN:
Reduced RBF & GFR  AKI with further Salt & Water Retention  Worsening congestion & Edema

Hepatic Congestion:
Impaired Synthetic Function / Cholestasis

Gut Edema:
Malabsorption / Ileus

Tissue Edema:
Poor Lymph Drainage / Poor Wound Healing / Wound Infection / Pressure Ulcer / Muscle Weakness
1)
2)
3)
4)
5)
6)
7)
Impact of Fluid Overload on Outcomes
(1)
- Marker of disease severity vs contributor
1)
Positive fluid balance a strong predictor of death
2)
AKI pts with fluid overload had higher 30 & 90d mortality than AKI pts W/O fluid overload
(2)

AKI pts who had KRT & survived had less excess fluid at KRT initiation & cessation than non-survivors

Renal recovery lower in pts with fluid overload
Retrospective analysis of VASST showed mean fluid balance +4.2L at 12h & +11L at d 4
3)

(7)
The greater the fluid balance the worse the outcome esp in pts with CVP > 12 mmHg
FACTT study: Better lung function / Shorter ICU stay / No surge in KRT with restrictive policy
4)
(8,9)

At day 7: Neutral fluid balance in conservative arm & + 7 L fluid gain in liberal arm

Greater fluid overload at time of KRT initiation associated with less renal recovery & higher mortality

For each 1% increase in % fluid overload above 10% at KRT initiation, risk of death increases by 3%

Post hoc analysis showed improved survival with negative fluid balance achieved with diuretics
Principles of Fluid Infusion to avoid complications
(13,14,15,16,17)
1)
Avoid IV route if possible & provide needs via oral / enteral route
2)
Indicate reasons for IV fluid therapy taking into consideration toxicity & cost as we do with drugs:

3)

Follow the resuscitation / replacement 4 phases: Rescue / Optimization / Stabilization / De-escalation

Consider delivering routine maintenance IV fluids during daytime to promote sleep
Indicate Type / Rate / Volume / Duration of IV fluid therapy

4)
5)
Consider various types of fluids composition / physiochemical features / cost & chose most appropriate
Calculate all other sources of fluids when prescribing IV fluids - Oral & Enteral intake / Medications

Minimize all non-essential fluid therapy in the de-escalation phase / Minimize fluid volume of IV meds

Use solutions with high calories per volume for enteral nutrition
Monitor Volume Status / Weight / In & Out Charts / Lab Values / Access Site to avoid fluid overload


6)
Resuscitation / Replacement of ongoing losses / Maintenance / Forced diuresis / KVO
Management of fluid overload is difficult:
Difficult to assess volume state in critically ill & Difficult to remove excess fluid leaked to interstitium
Stop IV fluids as soon as it is possible
1- Vincent et al. Sepsis in European ICUs: Results of the SOAP Study. Crit Care Med Feb/2006; 34 (2): 344-353.
Multicenter, Observational Cohort in 3147 ICU pts – 37% Sepsis & 36% AKI
2- Bouchard et al. Fluid Accumulation, Survival & Recovery of Kidney Function in Critically Ill Pts with AKI. PICARD Study. Kid Intern Aug/2009; 76 (4): 422-427.
Prospective, Multicenter , Observational Study of 618 pts
3- Boyd et al. Fluid Resuscitation in Septic Shock: Positive Fluid Balance & Elevated CVP Associated with Increased Mortality. Crit Care Med 2011;39:259-265
4- Peake et al . al. Goal-Directed Resuscitation for Patients with Early Septic Shock. ARISE Investigators. N Engl J Med 2014; 371: 1496-1506
5- Angus et a. Protocol-Based Care for Early Septic Shock. N Engl J Med 2014; 371: 386
6- Mouncey et al. Trial of Early, Goal-Directed Resuscitation for Septic Shock. N Engl J Med 2015; 372:1301-1311
7- Wiedemann et al. Comparison of Two Fluid – Management Strategies in Acute Lung Injury (FACCT Trial). NEJM Jun/2016; 354:2564-2575
8- Grams et al. Fluid Balance, Diuretic Use & Mortality in Acute Kidney Injury. Clin J Am Soc Nephrol May/2011; 6 (5): 966 – 973
9- Grissom et al. Fluid Management with a Simplified Conservative Protocol for ARDSA. Crit Care Med 2015; 43: 288-295
10- Bellom, Cass, Cole, Finfer, . An observational Study: Fluid balance & Patient Outcome in the RENAL Trial. Crit Care Med. 2014; 40 (6): 1753 – 1660
11- Southerland, Zappitelli, Alexander, et al. Fluid overload & Mortality in Children receiving CRRT: The Prospective Pediatric CRRT Registry. Am J Kidney
Dis.2010;55(2):316-325
12- Rosner et al. Indications & Management of Mechanical Fluid Removal in Critical Illness – 12th ADQ Consensus Conference (2013). British Journal of
Anesthesia Sep/2014; 113 (S): 764 – 71
13- O'Connor & Prowle. Fluid Overload. Crit Care Clin Oct/2015; 31 (4): 803 – 821
14- Piccoli et al. Relationship between CVP & BIVA in Critically Ill Pts. Crit Care Med. 2008; 28(1): 132-137
15- Claure-Del Granado & Mehta. verload in the ICU: Evaluation & Management. BMC Nephrology 2016, 17: 109
16- IV fluid therapy in adults in hospital | 1-Recommendations | Guidance & guidelines | NICE. https://www.nice.org.uk/guidance/cg174/chapter/1-recommendations.
17- JA Myburgh & MG Mythen. Resuscitation Fluids. N Engl J Med Sep/2013; 369:1243-1251
Pharmacological Management of Fluid Overload

Distinguish between total quantity of fluid overload & fluid to be removed safely per 24h


(1)
Removal method depends on renal function / UO / Fluid Overload Severity / Metabolic Complications
 No difference between 2 in terms of AKI incidence or in pts with AKI in AKI progression / Outcome (3)
If fluid overload is causing morbidity & KRT is not yet indicated then use diuretics:
(1,2)

Delayed weaning / Suboptimal rehabilitation / Impaired wound healing while hemodynamically stable

Start with a diuretic challenge: IV Frosemide 1-1.5 mg/kg

Infusion may achieve better diuresis & less Ototoxicity at less dose +/- less worsening AKI /  K

Maximum infusion dose is 40 mg/h but consider stopping after 12-14hrs if no response

UO of 3ml/kg/h rarely causes IV volume depletion in grossly edematous pt (4)

Manage causes of diuretic resistance & Consider adding albumin

Add thiazide to prevent distal structural adaptations to prolonged furosemide use & reduce resistance

Monitor for K (K supplement +/- K sparing diuretics) / Mg / metabolic alkalosis esp if on thiazide too

Natriuretics (Nesiritide) have no additional benefit over loop diuretics alone in HF (6)

Aquaretics (Tolvaptan) may improve symptoms / weight / Na but not HF morbidity or mortality (7)
Mechanical Fluid Removal

Indications: (8)
1.
Diuretics failure / Diuretics unlikely to work / High ototoxicity risk / Presence of side effects (Cr / K)
2.
Fluid overload with severe metabolic complications
3.
High risk of developing fluid overload in pts with poor kidney function / acute lung injury
Massive blood products / Parenteral nutrition / High volume drug therapy


Prescription: (8)


Choice of modality (Intermittent vs Continuous) depends on pts hemodynamic stability
Do not use diuretics to aid stopping KRT but give in intermittent KRT to maintain fluid removal process

Total UF goals depends on total amount of fluid accumulated & requires proper assessment

Removal rate depending on fluid inputs & losses / expected speed of vascular refilling / pt’s tolerance

UF can be isolated / sequential / concomitant to diffusive process

No clear criteria for stopping mechanical fluid removal

UO of > 0.5 ml/d W/O diuretics or > 2 L/d with diuretics may be considered
1- Martin et al. Continuous Infusion of Loop Diuretics in the Critically Ill: A Review of the Literature. Crit Care Med. 1994;22(8):1323-1329
2- Salvador et al. Continuous infusion versus bolus injection of loop diuretics in congestive heart failure. Cochrane Database Syst Rev 2004: CD003178
Shah et al. Effect of Admission Oral Diuretic Dose on Response to Continuous vs Bolus IV Diuretics in Acute HF. Am Heart J. 2012; 164 (6):862-86834- Bellopmo et al. Diuretic Therapy in Fluid overloaded & HF pt. Contrib Nephrol. 2010;164:153-163
5- Ng et al. Comparison of bumetanide- & metolazone-based diuretic regimens to furosemide in acute HF. J Cardiovasc Pharmacol Ther 2013; 18: 345–53
6- Gottlieb SS et al. Effects of nesiritide & predictors of UO in ADHF: results from ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide & Decompensated HF). J Am Coll Cardiol 2013; 62: 1177–83
7- Konstam, Gheorghiade, Burnett Jr, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: EVEREST Outcome Trial. JAMA 2007;297:1319–31
8- Rosner et al. Indications & Management of Mechanical Fluid Removal in Critical Illness. Brit Jour Anesthesia. Sep/2014; 113(5): 764-771
Conclusions
1.
2.
IV Fluids are IV Drugs so c onsider Type / Volume / Rate / Indications / Contraindications / AE / Cost
Resuscitation is a component of a complex physiological process
I.
II.
III.
3.
Identify the fluid that is most likely to be lost & replace it with equivalent volume
 No clearly superior fluid in a heterogeneous population of critically ill pts in terms of mortality
Consider serum Na / Osmolality / Acid-base Status when selecting a resuscitation fluid
Fluid needs change over time in critically ill pt so monitor cumulative fluid balance & changes in weight
 Excessive IV fluid infusion leads to interstitial edema which is associated with adverse outcome
Different categories of pts require different specific considerations
Isotonic balanced solutions should be considered as initial resuscitation fluid for most acutely ill pts
 Is it time to reconsider NS as the default fluid of choice?
II. Consider saline as initial resuscitation fluid for hypovolemia with metabolic alkalosis
III. Use isotonic crystalloids (Balanced / Unbalanced) & avoid colloids for pts with traumatic brain injury
IV. Consider albumin use during the early phase of resuscitation for pts with severe sepsis / septic shock
V. Avoid HES / Gelatin / Dextran for acute resuscitation esp in pts with severe sepsis or AKI / Risk of AKI
VI. Safety of hypertonic saline has not been well established
I.
4.
5.
Avoid fluid overload by following principles of IV fluid administration & early use off inotropes
Choice between pharmacological & mechanical fluid removal requires careful pt assessment