This document discusses fluid resuscitation in acute kidney injury (AKI). It notes that AKI is common in critically ill patients, especially those with septic shock. While early goal-directed therapy was previously recommended, large trials found no benefit over usual care. The document discusses assessing volume status and differentiating fluid responders from non-responders using techniques like passive leg raising. It recommends crystalloids over colloids for initial fluid resuscitation in AKI. Normal saline may remain a reasonable first-line crystalloid but balanced solutions have not been shown to cause harm. Fluid overload can worsen outcomes and should be avoided.

1. Mohammed Mamdouh Abd Al-Bary
Resident of Internal Medicine (Nephrology)

2. In 1832, Robert Lewins described the effects of the
intravenous administration of an alkalinized salt solution
in treating patients during the cholera pandemic.
He observed that “the quantity of solution will depend on
the quantity of serum lost to place the patient in his
ordinary state”
Lewins’ observations are as relevant today as they were
nearly 200 years ago .

3. Rationale of Fluids in AKI
Resuscitation Fluids
Asses volume status
Fluid Overload
Where Do We Stand
Home Message

4. AKI And Rationale
Of Fluids

5.  AKI is a common complication affecting > 50 % of the patients admitted to
(ICU) as well as hospitalized patients (1)
 (AKI) is commonly associated with hemodynamic instability .
Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive care medicine. 2015;41(8):1411-1423.
Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators: Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005;294:813–818)
Increase
preload
SV COP Glomerular
pressure GFR
Maintenance of
urine output
promote diuresis dilute tubular toxins
 (BEST Kidney) study investigators : septic shock is the most common
factor contributing to AKI in intensive care units (ICUs), accounting for
47.5% of AKI patients (2)

6. In 2001, a single-center RCT on ‘early goal-directed therapy’
(EGDT) for the management of sepsis led to the widespread
adoption .
It was incorporated into the Surviving Sepsis Campaign (SSC)
guidelines in 2004 .
The 2012 SSC guidelines strongly recommended protocolized
resuscitation with quantitative end points .

8.  3 large multicenter RCT examining the effect of EGDT Vs usual care :
(ProCESS) Trial 2014
the Protocolized Care for Early Septic Shock
(ARISE) trial 2014
the Australasian Resuscitation in Sepsis Evaluation
(ProMISe) trial 2015
the Protocolised Management in Sepsis
NO significant differences in the incidence of AKI or use of RRT, irrespective of
the treatment approach used for severe sepsis

10.  Timely volume resuscitation and delivery of antibiotics have improved
dramatically since 2001: the mortality in the usual care group was just
over18% compared with 46.5% observed by Rivers and colleagues
 The average fluid administration during the first 72 hours in this single
center study was 13 L
 only 3 to 4 L of fluid intake was adequate in the first 72 hours
 In response, the 2016 Guidelines has removed EGDT resuscitation
targets

11. We recommend that in the resuscitation from sepsis-induced
hypo-perfusion, at least 30ml/kg of intravenous crystalloid fluid be
given within the first 3 hours. (Strong recommendation; low quality of evidence)
We recommend that following initial fluid resuscitation, additional
fluids be guided by frequent reassessment of hemodynamic status.
(Best Practice Statement)
We suggest that dynamic over static variables be used to predict
fluid responsiveness, where available. (Weak recommendation; low quality of
evidence)

12. How To Asses
Volume Status ?
Is it the volume status what matters ?

13.  Every patient with AKI should be assessed for volume status as a part of
hemodynamic optimization.
Available online 26 April 2017

15.  Basic physiology :
Since this slope of COP is unknown in a
given patient, an absolute value of any
“static” measure is not known.
 Measurement Errors :
CVP : a precise positioning of the pressure
transducer to the right atrium.
Must be measured at end-expiration .
Can Transmit high intrathoracic pressure .
 Volume Overload :
Can’t predict which patients will be
responsive .
CO = SV*HR
SV Depends on : preload , contractility and afterload
Frank starling law : increase in EDV >> Increase SV At a threshold further in
EDV >> decrease SV
Pitfalls:

17.  A “mini fluid challenge” has been described .
In an interesting study, the effects of only 100 mL of colloid on
stroke volume can predicted the response of cardiac output to
a 500 mL volume expansion.
Changes in stroke volume were estimated by Echo .
Fluid challenge :
 The “common” fluid challenge : 500-1000mL or 30mL/kg
Performing it several times a day leads to a significant fluid
overload.

18. Only patients who show a significant increase in SV following a fluid
challenge are considered to benefit : fluid responders ( 50% of critically
ill patients )
In the non-responder , volume expansion will only exert adverse
effects, without any hemodynamic benefit.
We need to determine whether a patient will be fluid responsive or not
before Fluid administration ?
Observing if changes in cardiac preload will change of cardiac output or
stroke volume .

19. Passive Leg Raising (PLR) Test
 Increases preload and acts like a transient reversible
“self-Fluid challenge” - mimic increase 500-700 ml .
 In patients on MV : without any invasive device by the changes in
end-tidal CO2 .
 Intra-abdominal hypertension could be an obstacle

20. An increase of COP > 10% predicts the response to volume expansion .
A meta-analysis of all studies with the PLR test confirms its strong reliability .

21. Respiratory Variations of Stroke Volume and Pulse
Pressure?

22. v = max-min/ mean

23. Therefore, variations will be higher when a patient is a preload
dependent “fluid responder” .
Pulse Pressure and stroke volume variation :
Normally : 5-10 mm/Hg
Variation >10 (13) = Fluid responsive
The farther from 13 the higher is its diagnostic power

24. • Spontaneous ventilation
• Low tidal volume < 8 ml / kg
• Arrhythmia
• Open chest or low compliance
Not valid in :

25. The end-expiratory occlusion (EEO) test :
15 sec increase VR and COP in fluid responders.
Reliable in arrhythmia or ARDS (low tidal volume) .
Oesophageal Doppler :
Measures blood flow velocity in the descending aorta .
The respiratory variation of IVC and SVC:
Exacerbated by hypovolemia
Reliable in arrhythmia and Spont breathing
None-invasive (Echocardiography)
Affected by : operator dependent – increase PEEP .

26. Acute Circulatory Failure
Obvious Hypovolemia ?
Start Volume Expansion Asses Preload Dependency
Spontaneous ventilation
Low tidal volume < 8 ml / kg
Arrhythmia
Open chest or low compliance
EEO - PLR test
Mini Fluid Challenge PPV / SSV
EEO - PLR test
Mini Fluid Challenge
the very initial phase of septic shock
hypovolemic shock
diarrhea, vomiting, or DKA

29. Resuscitation Fluids

30.  Colloids : mostly remain in the intravascular space due to high molecular weight
.
 Crystalloids : Distribute across compartments according to tonicity of the
solution
The fraction of fluid remaining in the intravascular space decreases with
decrease the tonicity.
Has been associated with interstitial edema.

33. Crystalloid versus HES
(CHEST) Trial 2012 : The Scandinavian Starch for Severe
Sepsis/Septic Shock Trial (6S) 2012 :7000 ICU patients
Significant increase in the rate of RRT
and AKI with HES.
No significant increase in mortality .
800 patients with severe sepsis
Significant increase in mortality with HES

35. (ALBIOS) trial 2014
Albumin Italian Outcome Sepsis :
20% albumin to crystalloid in
resuscitation of 1818 septic patient :
no survival benefit through day 90
(SAFE) study 2004
Saline versus Albumin Fluid Evaluation :
4% albumin versus normal saline in 6,997
critically ill patients, :
no difference in all-cause mortality at 28
days
no significant difference in hemodynamic
resuscitation end points with volume
albumin 1 : 1.4 saline
association of albumin with higher mortality
in patients with traumatic brain injury

38. 30,994 patients undergoing major abdominal surgery
Effect on Morbidity
No effect on mortality

39. Decreased renal artery flow
and cortical perfusion

40. lower incidence of AKI lower incidence of RRT
1500 patients in the two groups

41. 21 studies involving 6253 patients
Higher risk of AKI

42. No overall significant increase in mortality

44. Is it the END For Normal Saline ?

45. No difference in the RRT incidenceNo difference of AKI incidence
No difference in Mortality

46. Until the results of PLUS are known, NS could remain the 1st choice for
crystalloid fluid .
saline costs $0.86 per litre while Plasma-Lyte costs $1.62
Stick with what is tested or change to more expensive fluids only on a very strong basis
No fluid is ideal, Balanced Solutions are not balanced in fact .
Crit Care Med. 2016 Aug;44(8):1538-40.
8,800 participant double-blind RCT with a primary end point of day 90 mortality

48. KDIGO guidelines suggests that isotonic crystalloids, rather than
colloids be used as initial management for the expansion of
intravascular volume in patients at risk for AKI or with AKI in the absence
of hemorrhagic shock .
 We recommend use of crystalloid over colloid for initial fluid resuscitatio
as initial treatment for AKI .
2017

49.  We recommend crystalloids as the fluid of choice for resuscitation in
patients with sepsis and septic shock (Strong recommendation, moderate
quality of evidence).
 We suggest using albumin in addition to crystalloids when patients require
substantial amounts of crystalloids (weak recommendation, low quality of
evidence).

50. HES : Don’t USE ( HARM) .
Dextran and Gelatin : NOT Studied .
Albumin : No Beneficial Effect .
Normal Saline: still the standard ?!
Balanced Crystalloids : No harmful effect . May
decrease Risk of AKI

51. FLUID OVERLOAD

52. Total body water approximately 60% of
body weight.
Two thirds TBW is intracellular fluid while
the remaining third is in the extracellular
fluid.
The water the extracellular fluid: 75% in the
interstitium, 20% in the plasma and 5%
acting as transcellular fluid.

56.  Hypotension, pain and tissue injury > + sympathetic system > +
RAS , ADH > trigger sodium and water retention.
Hypoalbuminemia > Increased vascular permeability in sepsis >
capillary ‘leakiness’ > distributive shock
Vascular endothelium is disrupted : dysfunction of glycocalyx >
increase in capillary leak, and interstitial edema > fluid overload >
More dysfunction “vicious cycle”
The relationship between fluid input and natriuresis is weak >
Fluid overload .
Why Intersitial Edema occurs during acute illness ?
“The 3rd Space : Where has all the fluid gone?”

57. ,
The Nature Of IV Fluids :
 Crystalloids : don’t remain in vascular space for long .
After 90 min : The intravascular volume effect of Ringer's lactate
is below 20% in normal condition , decreases to 5% in critical illness
eg: sepsis .
 Colloids : increased capillary permeability > extravasation into
extracellular space > increasing interstitial oncotic pressure >
worsen edema .
accumulation of low-molecular-weight fractions in renal tubules
and osmotic nephrosis .

58. Fluid Overload is extremely HARMFUL !
1 in 5 patients suffers harm
through injudicious fluid use.
Fluid overload (FO) = the total
input - total output / initial BW
Adverse outcomes occur when
reaching more than 10%
Chart fluid input and output
more accurate than measuring
BW changes with a scale
Estimation of fluid status changes in critically ill patients: fluid balance chart or
electronic bed weight?
Padhi S, Bullock I, Li L, Stroud M, National Institute for H, Care Excellence
Guideline Development G. Intravenous fluid therapy for adults in hospital:
summary of NICE guidance. Bmj. 2013;347:f7073

59. Proven by many studies :

60. The belief that infusions of large volumes of intravenous fluids can
improve organ perfusion and prevent or treat AKI is not supported by
data and does not reflect the complex nature of AKI
In FACCT Trial positive fluid balance carried a ‘dose effect’ association
with the risk of death, with 1.6-fold higher risk per liter/day of fluid
accumulated

61. CVP may be used to guide fluid balance ≤12 hrs into septic shock but
becomes an unreliable marker of fluid balance thereafter.
CVP > 8 mmHg may decrease renal blood flow and associated with an
increased risk of AKI and mortality .

63.  Diuretics should be used to treat FO ; however, they should not be
continued if there is no an adequate response
 Unresponsive patients should be considered for early initiation of RRT .
 From a renal standpoint: unless there is clinically evident dehydration,
there is no No clear evidence that aggressive hydration can change
renal outcome, except in contrast-induced AKI.

64. Available online 26 April 2017
A combination of all parameters (both static and dynamic) should
be performed .
The amount of fluid to be given should be individualized .
Vasopressors should be considered as soon as possible if volume
repletion has not achieved the hemodynamic goal.
We recommend a target of MAP of 65 to 85 mm Hg

65. We do not recommend diuretics for prevention and/or treatment of
AKI but may be used in the setting of fluid overload .
We recommend a furosemide stress test (FST) after adequate fluid
repletion under monitored conditions .
Volume depletion is a major risk factor for AKI and Volume overload
can worse renal function .

66. Aggressive Fluid
Replacement
Aggressive prevention
of Fluid Overload
Static Measures
Is the patient
hypovolemic ?
Dynamic Measures
Will the patient be
Fluid responsive ?
Normal Saline Balanced Crystalloids
Protocolized
Approach
Individualized Approach

67. It is a Question of Balance One Size Doesn’t Fit All
Personalized
Both Hypervolemia and hypovolemia are Bad