lectures ofthe egyptian society of nephrology and transplantation 2012

1. FLUID THERAPY IN ARF
Ayman El-Sebaie,
MRCP (UK)
Head of Nephrology Department, IMC

2. OVERVIEW
 Introduction.
 Definition.
 Diagnosis.
 Prevention.
 Management.

3. INTRODUCTION
 Incidence of ARF:
– Community: <1%
– Hospital 2-7%
– ICU 25%
Am J Kidney dis 2005;45:614-18

4. INTRODUCTION
 Death in ARF is common “50%“ but permanent
renal failure is uncommon “ 5%”
 The Madrid Acute Renal Failure Study Group
recorded a 70% mortality in ICU patients
compared to a 50% overall mortality.
Kidney Int 1998;66(supp):S16 – 24.

5. DEFINITION
 ARF is defined as an abrupt and sustained
reduction in renal function, occurring over hours
or days, sufficient to result in azotaemia.
 It may occur from a normal or abnormal baseline
level of function.

6. DEFINITION
 The first consensus definition of ARF has
been developed. It is called RIFLE, the initials
reflecting the terms Risk, Injury, Failure, Loss
and End Stage in relation to kidney function.
 This is classifying ARF into 3 severity
categories( Risk, Injury & Failure) and 2
clinical outcome categories ( Loss & ESRD)
Critical Care 2004, 8:R204-R212

8. GFR Criteria Urine Output Criteria
Risk S. Cr increased 1.5 times < 0.5ml/kg/h for 6h
Injury S. Cr increased 2.0 times <0.5ml/kg/h for 12 h
Failure S.Cr increased 3.0 times or <0.3ml/kg/h for 24h
Cr = 355 umol/L or anuria for 12h
Loss Persistent ARF , complete
loss of kidney
ESRD ESRD for longer than 3
months

10. CAUSES
The most common causes of ARF in ICU:
1-Sepsis
2-Post-operative(Cardiac & Vascular surgery)
3-Rhabdomyolysis
4-Liver diseases
5-Thrombotic microangiopathy.
5-Drug induced
Contrast Nephropathy
Osmotic nephropathy
Aminoglycosides, Ampheotricin ,etc

11. ARF: Risk factors for mortality
 Multi-organ failure
 Bacterial Sepsis
 Fungal sepsis
 Hypotension/vasopressors
 Ventilatory support
 Initiation of dialysis late in hospital course
 Oliguria/anuria: with oliguric ARF, mortality is >
50% compared to < 20% with non-oliguric ARF

12. Whatever the circumstances, the
‘‘
development of ARF in the ICU is
bad news.’’
Crit Care Clin 19 (2003) 233– 251

14. OVERVIEW
 Introduction.
 Definition.
 Diagnosis.
 Prevention.
 Management.

15. DIAGNOSIS
 Careful History :
– It should focus in 2 key areas:
 (1) Factors known to lower renal perfusion.
 (2) Known & potential nephrotoxins.
 Physical Examination:
– Skin
– Fundus
– CVS & Volume status
– Abdomen ( palpable bladder, renal tenderness.)
– Extremities
– Neuro-psychatric Abnormalities.

16. DIAGNOSIS
 Diagnostic tests :
(1) Rise in Ur & Cr are hallmarks of ARF
(2) Urine analysis.
(3) Urine Electrolytes.
(4) Urine output.
(5) Fluid challenge.
(6) Renal imaging:
(7) Renal Biopsy

18. OVERVIEW
 Introduction.
 Definition.
 Diagnosis.
 Prevention.
 Management.

20. In the ICU, the best time to
treat renal failure is before
it occurs.

21. Best cure is to prevent
 Have a high index of suspicion for
reversible factors - volume depletion,
decreasing cardiac function, sepsis, urinary
tract obstruction.
 Be sure patient is well-hydrated when
exposing patient to nephrotoxic drugs

22. Anticipate problems
 Avoid worsening the ARF:
– Adjust medicines for renal insufficiency
– Avoid nephrotoxins if possible
– Avoid intravascular volume depletion
(especially in third-spacing or edematous
patients)

23. PREVENTION
 Failed Agents studied for prevention of
ARF:
– DA1-agonist: Dopamine, Fenoldopam
– ANP analogues
– Adenosine antagonists : Theophyllin,
Pentoxifylline
– Calcium Antagonists: Nifedipine,Diltiazem
– Diuretics

24. PREVENTION
 Dopamine & ARF
– Although it augments renal blood flow and increases
urine volume and sodium excretion, this therapy does
not alter the course of ARF in critically ill humans
– dopamine can precipitate serious cardiovascular and
metabolic complications in critically ill patients.
– There is no longer a justification for using low-dose
dopamine in treating critically ill patients.
Critical care Review 2003

25. PREVENTION
 DIURETICS & ARF
– In patients with sustained oliguria despite high
doses of loop diuretics, this treatment should be
withdrawn.
– In responders, continuous infusions are
preferred because they are more effective and
associated with less toxicity than bolus
administrations.

26. PREVENTION
 DIURETICS & ARF
– Mehta showed that diuretic use in ICU patients
with ARF was associated with greater in-
hospital mortality and non recovery of renal
function.
– high-dose loop diuretics should be used
cautiously in critically ill patients with ARF.
JAMA 288:2547-2553, 2002

27. PREVENTION
 Aggressive hydration, minimizing
nephrotoxins, and maintenance of "adequate"
mean arterial pressure remain the main non -
pharmacologic strategies to prevent ARF in the
ICU.
 Recentdata suggest that N-acetylcysteine may
reduce the incidence of ARF secondary to
radio-contrast agents.
Crit Care Clin. 2005 Apr;21(2):281-9.

28. OVERVIEW
 Introduction.
 Definition.
 Diagnosis.
 Prevention.
 Management.

29. MANAGEMENT
In the ICU, the best time to
treat renal failure is before
it occurs.

30. MANAGEMENT
 Management Priorities in ARF:
– Search for and correct prerenal & postrenal
– Review medications and stop nephrotoxic drugs
– Optimize cardiac output & renal blood flow
– Restore & or increase urine flow.
– Monitor fluid intake & output, measure body
weight daily
– Provide early nutritional support
– Search and aggressively treat infections
– Initiate dialysis before uremic complications

31. MANAGEMENT
 (1) Volume Homeostasis.
 (2) Electrolyte Homeostasis.
 (3) Acid-Base Homeostasis.
 (4) Uremia.
 (5) Nutritional.
 (6) Dialysis.

32. Potential Errors in Fluid Management in
the Patient with or at Risk of ARF
 Insufficient fluid administration:
 In the oliguric patient one may be afraid
of inducing lung edema with excessive
fluid administration, so that fluid
restriction is often adopted, but while
limiting edema formation, this can
maintain kidney hypoperfusion and
worsen renal function.

33.  Excessive use of diuretics:
 It may be an attractive option to maintain
urine output with diuretics.
 Actually, from a conceptual point of view,
diuretics could decrease the oxygen demand of
the renal tubules by inhibiting the Na+-K+-Cl–
pump.
 The major risk with use of diuretics is inducing
hypovolemia if diuretics are given in the
absence of hypervolemia.

34.  Excess fluid administration:
 All too often, fluid is given to oliguric patients
without sufficient monitoring or without careful
attention to which variables are being monitored,
with the focus being only on urine output.
 CVP monitoring in some patients is mandatory.

35.  meta-analysis of studies also suggested an
increased risk of temporary deafness and tinnitus
with use of high doses of furosemide ,an effect
that is often under-recognized . Ho KM, Sheridan
DJ (2007).
 The key indication for diuretics in patients with
acute renal failure is hypervolemia, and rather than
being used routinely in all patients, diuretics
should be restricted to those with fluid overload.

36. Tips about Types of fluids to be
used in ARF
 Among the colloids, the use of human albumin has
been decreasing following several studies and
meta-analyses that failed to demonstrate its
superiority over other colloids in addition to its
high costs .Vincent JL, Sakr Y, Sprung CL, et al (2006)
 Several synthetic colloid solutions exist, but none
is ideal. Gelatin solutions have a relatively low
molecular weight (MW) and as such have a
limited effect on volume expansion with limited
oncotic effects and relatively short (2–3 h)
intravascular persistence

37.  Their superiority over crystalloids in terms
of volume expansion is, therefore,
restricted. Moreover, gelatin solutions can
induce anaphylactic reactions, although they
are usually transient and of limited severity,
and they may compromise clot formation -
although to a lesser degree than some of the
other colloids (Niemi TT, Kuitunen AH (2005)

38.  Dextrans are mixtures of glucose polymers
synthesized by the bacteria Leuconostoc
mesenteroides. Dextran 70 (MW 70,000 Da) has
been the most widely used dextran for fluid therapy.
 Although they are efficient volume expanders,
dextran solutions are associated with a substantial
risk of anaphylactic reaction, even when hapten
prophylaxis is given, and also have antihemostatic
effects.

39.  A recent study reported that therapy of septic patients
with a particular HES 10% solution (200/0.5) was
associated with higher rates of acute renal failure and
renal replacement therapy than was Ringer’s lactate
solution Brunkhorst FM, Engel C, Bloos F, et al (2008)
 Newer forms of HES may have fewer adverse effects
on renal function, but until more data are available, they
should be used with caution in patients with, or at risk
of, acute renal failure.

40.  Dextran solutions may also precipitate renal failure
by accumulation of the molecule in the renal tubules
and/or hyperviscosity.
 The development of hydroxyethyl starches (HESs)
was met with some excitement in the hope that these
fluids would prove effective without adverse effects.

42. MANAGEMENT
 Patients with stable isolated ARF and no
evidence of volume overload or gross
electrolyte and acid-base disturbance can
often be managed conservatively without
RRT.
 Recent studies suggest that unnecessary
dialysis itself may delay recovery of renal
function. Kidney Int 1998;54:1817– 31.

43. MANAGEMENT
 Indications of Dialysis in ARF:
– Uremic symptoms.
– Uremic pericarditis.
– Volume overload.
– Hyperkalaemia.
– Metabolic acidosis.
– Other electrolyte abnormalities.

44. MANAGEMENT
 Common wisdom is to start RRT in patients
with ARF before azotemic solutes cause
clinical symptoms.
 RRT needs of the ICU ARF patient vary
from patient to patient and cannot be
considered a single problem solved by a
single RRT prescription.

45. Continuous VS. Intermittent
Therapy in ARF
Despite the widespread use of CRRT in critically ill
patients with ARF, there are few data supporting its
benefits over conventional (IHD)
Despite greater volume control, CVVHD did not lead
to improvement in survival, preservation of urine
output, or renal recovery compared with IHD in
patients with ARF
Augustine et al. Am J Kidney Dis. 2004; 44: 6

46. Reasons for Using CRRT
Mehta and Letter: Am J Nephrol 1999; 19:377-382

47. Advantages of using CRRT
Suitable for hemodynamically unstable patients
Precise volume control
Effective control of uremia, ↑ PO4 & ↑ K+

48. Advantages of using CRRT
Rapid control of metabolic acidosis
Improved nutritional support (full protein diet)
May be an adjuvant therapy in sepsis

49. Disadvantages of using CRRT
Expense – probably the same as IHD
Anticoagulation – to prevent extracorporeal
circuit from clotting
Heparin: Initially 25 IU/Kg, maintenance is by
10 IU/Kg/h, to achieve PTT 45-65 sec.

51. TAKE HOME MESSAGES
 Acute renal failure is common and is associated with
poor outcomes in ICU patients.
 Adequate intravascular volumes and renal perfusion
must be maintained to limit the development of acute
renal failure. However, excess volume replacement
carries its own risks.
 We have inadequate tools to assess and monitor fluid
balance and responsiveness, especially in patients with
capillary leak syndromes, and, currently, carefully
conducted, repeated fluid challenges represent the best
way of determining ongoing fluid needs.

52. TAKE HOME MESSAGES
 ›› Adequate fluid balance and good renal
perfusion must be targeted in critically ill patients
to reduce the risks of developing acute renal
failure.
 ›› Fluid resuscitation and management are
complicated in acute renal failure, and these
patients must be carefully and closely monitored.
 .

53. TAKE HOME MESSAGES
 ›› No intravenous fluid is perfect, and fluid choices
should be based on individual patient’s requirements.
 Both hypervolemia and hypovolemia can be
detrimental.
 Diuretic use in patients with acute renal failure should
be restricted to patients with hypervolemia.
 In many patients, it may be wiser to use smaller
amounts of several different types of fluid than a large
amount of any single solution

54. TAKE HOME MESSAGES
 While crystalloids represent a good initial choice
of fluid, for large or continuing losses, colloid
solutions must also be used.
 No fluid is ideal, and fluid selection should be
individualized depending on specific patient needs
and known adverse effects of the different fluid
types; in many patients, it may be wiser to infuse
smaller amounts of several different types of
solution so that the benefits of each type can be
maximized while limiting the risks.

55. Thank You For Your
Attention

56. Questions?