2. Fluid Management in AKI
By
KamalOkashaMD
Prof ofMedicineandHeadofNephrology
TantaUniversity,Egypt
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
3. Agenda
• AKI: Definition & Causes
• AKI: Classification
• AKI: Epidimiology
• AKI: Prognosis
• AKI: Treatment principles
• Role of loop diuretics
• Fluid balance
• Selection of Resuscitation Fluid
• Fluid overload in AKI and its mechanism
• Conclusion
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
4. Agenda
• AKI: Definition & Causes
• AKI: Classification
• AKI: Epidimiology
• AKI: Prognosis
• AKI: Treatment principles
• Role of loop diuretics
• Fluid balance
• Selection of Resuscitation Fluid
• Fluid overload in AKI and its mechanism
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
5. AKI- Definition and causes
• Acute kidney injury (AKI) is defined as an abrupt or rapid decline in
renal filtration function. This condition is usually marked by a rise in
serum creatinine concentration or by azotemia (a rise in BUN
concentration).
• AKI may be classified into 3 general categories, as follows:
• Prerenal: in response to severe volume depletion and hypotension,
with structurally intact nephrons.
• Intrinsic: in response to cytotoxic, ischemic, or inflammatory insults
to the kidney, with structural and functional damage
• Postrenal: due to obstruction to the passage of urine.
Schrier RW, et al.: J Clin Invest. 2004. 114(1):5-14.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
6. AKI – Urine output
• Approximately 50-60% of all causes of AKI are nonoliguric.
• Oliguria is defined as a daily urine volume of less than 400 mL
and has a worse prognosis.
• Anuria is defined as a urine output of less than 100 mL/day
and, if abrupt in onset, suggests bilateral obstruction or
catastrophic injury to both kidneys.
Schrier RW, et al.: J Clin Invest. 2004. 114(1):5-14.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
7. AKI- cardiovascular complications
• Cardiovascular complications e.g. heart failure have been
observed in as many as 35% of patients with AKI.
• Fluid overload secondary to oliguric AKI is a particular risk for
elderly patients with limited cardiac reserve.
Ronco C, et al.: Cardiorenal syndrome. J Am Coll Cardiol. 2008. 52(19):1527-39.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
9. Agenda
• AKI: Definition & Causes
• AKI: Classification
• AKI: Epidimiology
• AKI: Prognosis
• AKI: Treatment principles
• Role of loop diuretics
• Fluid balance
• Selection of Resuscitation Fluid
• Fluid overload in AKI and its mechanism
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
10. Management of AKI in Critical Cases, Kamal Okasha 29/7/2017
Definition and staging
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
11. Agenda
• AKI: Definition & Causes
• AKI: Classification
• AKI: Epidimiology
• AKI: Prognosis
• AKI: Treatment principles
• Role of loop diuretics
• Fluid balance
• Selection of Resuscitation Fluid
• Fluid overload in AKI and its mechanism
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
12. AKI - Epidimiology
• The estimated incidence rate of AKI during hospitalization in
USA is 2-5%.
• AKI develops within 30 days postoperatively in approximately
1% of general surgery cases and arises in up to 67% of
intensive care unit (ICU) patients.
• In kidney transplants, 21% developed AKI within the first 6
months after transplantation.
Kheterpal S, et al.: Anesthesiology. 2009 Mar. 110(3):505-15.
Goldberg R & Dennen P.: Adv Chronic Kidney Dis. 2008. 15(3):297-307.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
13. Agenda
• AKI: Definition & Causes
• AKI: Classification
• AKI: Epidimiology
• AKI: Prognosis
• AKI: Treatment principles
• Role of loop diuretics
• Fluid balance
• Selection of Resuscitation Fluid
• Fluid overload in AKI and its mechanism
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
14. AKI - Prognosis
• The prognosis for patients with AKI is strongly relate to:
• Cause of renal failure.
• Presence or absence of preexisting kidney disease,
• The duration of renal dysfunction prior to therapeutic
intervention.
• AKI correlated inversely with eGFR and was associated with a
higher mortality rate and a higher incidence of subsequent
ESRD at each level of baseline eGFR.
Pannu N, et al.: Am J Kidney Dis. 2011 Aug. 58(2):206-13.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
15. AKI - Prognosis
• The in-hospital mortality rate for AKI is 40-50%.
• The mortality rate for ICU patients with AKI is higher (>50% in
most studies), particularly when AKI is severe enough to
require dialysis treatment.
• ICU patients with sepsis-associated AKI have significantly
higher mortality rates than do non-septic AKI patients.
Uchino S, et al.: JAMA. 2005 Aug 17. 294(7):813-8.
Bagshaw SM, et al.: Clin J Am Soc Nephrol. 2007 May. 2(3):431-9.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
16. Agenda
• AKI: Definition & Causes
• AKI: Classification
• AKI: Epidimiology
• AKI: Prognosis
• AKI: Treatment principles
• Role of loop diuretics
• Fluid balance
• Selection of Resuscitation Fluid
• Fluid overload in AKI and its mechanism
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
17. Agenda
• AKI: Definition & Causes
• AKI: Classification
• AKI: Epidimiology
• AKI: Prognosis
• AKI: Treatment principles
• Role of loop diuretics
• Fluid balance
• Selection of Resuscitation Fluid
• Fluid overload in AKI and its mechanism
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
18. AKI- Treatment principles
• There is no specific pharmacologic therapy proven to
treat AKI secondary to hypoperfusion and/or sepsis.
• The therapeutic or preventive intervention that has an
established beneficial effect in the management of AKI is
the IV administration of isotonic sodium chloride
solution.
• It should be given in quantities sufficient to keep the
patient euvolemic or even hypervolemic.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
19. AKI- Treatment principles
• Sepsis has been reported to account for approximately 50% of
patients with AKI in ICUs.
• Fluid administration is frequently necessary to stabilize the
patient with severe sepsis or septic shock.
• Maintenance of volume homeostasis and correction of biochemical
abnormalities remain important treatment goals.
Shigehiko U, et al.: JAMA 2005. 294: 813–818.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
20. Agenda
• AKI: Definition & Causes
• AKI: Classification
• AKI: Epidimiology
• AKI: Prognosis
• AKI: Treatment principles
• Role of loop diuretics
• Fluid balance
• Selection of Resuscitation Fluid
• Fluid overload in AKI and its mechanism
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
21. AKI- Role of loop diurtics
• Furosemide can be used to correct volume overload when
patients are still responsive; this often requires high
intravenous (IV) doses.
• The response to furosemide can be taken as a good
prognostic sign.
Chorin E, et al.: Int J Cardiol. 2016 Oct 11. 226:42-47.
Briguori C.: Cardioangiol. 2012. 60 (3):291-7.
Briguori C, et al.: Circulation. 2011. 124 (11):1260-9.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
22. AKI- Role of loop diurtics
• Frequently, IV doses of loop diuretics are needed in AKI to
maintain urine output.
• IV infusions are often helpful in intensive care settings, in which
larger doses are necessary.
• This method promotes a sustained natriuresis with reduced
ototoxicity compared with conventional intermittent bolus
dosing.
Chorin E, et al.: Int J Cardiol. 2016 Oct 11. 226:42-47.
Briguori C.: Cardioangiol. 2012. 60 (3):291-7.
Briguori C, et al.: Circulation. 2011. 124 (11):1260-9.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
23. Agenda
• AKI: Definition & Causes
• AKI: Classification
• AKI: Epidimiology
• AKI: Prognosis
• AKI: Treatment principles
• Role of loop diuretics
• Fluid balance
• Selection of Resuscitation Fluid
• Fluid overload in AKI and its mechanism
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
24. AKI: Treatmentprinciples : Fluid balance
• In the patient with septic shock, early intervention with fluid
resuscitation within the first 6 hours in the emergency
department (ED) has been described as Early Goal-Directed
Therapy (EGDT).
• The study included patients with systemic inflammatory
response syndrome.
Rivers E, et al.: N Engl J Med., 2001. 345: 1368–1377.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
25. EGDT
• The predefined physiologic goals of EGDT within 6 hours of
diagnosis are:
• Mean arterial pressure ≥ 65 mmHg
• Central venous pressure between 8 and 12 mmHg.
• Improvement of blood lactate levels
• Central venous oxygen saturation > 70%.
• Urine output ≥ 0.5 ml/kg/h.
Rivers E, et al.: N Engl J Med., 2001. 345: 1368–1377.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
26. • The EGDT group received more fluid, blood transfusions, and
inotropic use with dobutamine.
• The physiologic parameters were improved in the EGDT group
during the first 6 hours and over the next 3 days.
• In-hospital mortality was less in the EGDT group.
Rivers E, et al.: N Engl J Med., 2001. 345: 1368–1377.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
27. • This study examined liberal versus conservative fluid
management in intubated ICU patients.
• Greater cumulative fluid accumulation over an average of 6
days (10.2 L vs 3.7 L in the liberal vs conservative group,
respectively) was present..
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
28. Cumulative fluid balance over the first 7 days by fluid-management group (median
values and interquartile range).
Grams ME, et al.: Clin J Am Soc Nephrol. 2011. 6(5):966-973.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
29. Fluid balance and mortality
• The conclusion of this study: Patients
who can be stabilized with less
volume resuscitation fare better.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
30. Agenda
• AKI: Definition & Causes
• AKI: Classification
• AKI: Epidimiology
• AKI: Prognosis
• AKI: Treatment principles
• Role of loop diuretics
• Fluid balance
•Selection of Resuscitation Fluid
• Fluid overload in AKI and its mechanism
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
31. Fluid Management in ICU, Kamal Okasha 27/2/2018
1. Acute resuscitation
Goal is restoration of effective intravascular volume, organ perfusion
and tissue oxygenation.
Fluid accumulation and a positive fluid balance.
2. Maintenance
Goal is maintenance of the intravascular volume.
Prevent unnecessary fluid loading and mitigate fluid accumulation.
3. Fluid removal
Goal is ‘active de-escalation’ with fluid removal.
Secondary organ injury may result from failure to remove unnecessary volume.
Hoste EA, Maitland K, Brudney CS, Mehta R, Vincent JL, Yates D, Kellum JA, Mythen MG, Shaw AD: Three
phases of intravenous fluid therapy: a conceptual model. Br J Anaesth 2014; 113: 740–747.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
32. Fluid Management in ICU, Kamal Okasha 27/2/2018
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
33. Fluid Management in ICU, Kamal Okasha 27/2/2018
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
34. Fluid Management in ICU, Kamal Okasha 27/2/2018
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
36. Fluids - Crystalloids and Colloids
Fluid Management in ICU, Kamal Okasha 27/2/2018
Myburgh JA, Mythen MG: Resuscitation fluids. N Engl J Med 2013; 369: 1243–1251.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
37. Fluids - Crystalloids and Colloids
Fluid Management in ICU, Kamal Okasha 27/2/2018
Myburgh JA, Mythen MG: Resuscitation fluids. N Engl J Med 2013; 369: 1243–1251.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
38. Fluids - Crystalloids and Colloids
Fluid Management in ICU, Kamal Okasha 27/2/2018
• Cross sectional study of 391 ICUs in 25 countries to describe the types of fluids
administered during fluid resuscitation.
• Data collected in 2007 and published in 2010.
• Findings in a 24 hour period:
• 37.1% of patients received resuscitation fluid.
• Main indicators for administering crystalloid or colloid were impaired perfusion
(45%) or to correct abnormal vital signs (35%).
• Overall
• Colloid given to more patients than crystalloids (23 vs 15%) and Colloid given in
more episodes than crystalloid (48 vs 33%).
• The choice of fluid was most strongly related to location of the prescriber.
Finfer S, Liu B, Taylor C, Bellomo R, Billot L, Cook D, Du B, McArthur C, Myburgh J; SAFE TRIPS Investigators:
Resuscitation fluid use in critically ill adults: an international cross sectional study in 391 intensive care units. Crit
Care 2010; 14:R185.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
39. Fluids - Crystalloids and Colloids
Fluid Management in ICU, Kamal Okasha 27/2/2018
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
40. Selection of Resuscitation Fluid
• The Saline versus Albumin Fluid Evaluation (SAFE) randomized,
double-blind trial in medical and surgical ICUs in Australia and
New Zealand compared resuscitation in 7000 critically ill
patients with normal saline versus 4% human albumin
The SAFE Study Investigators: N Engl J Med, 2004. 350: 2247–2256.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
41. Selection of Resuscitation Fluid
• The study demonstrated that albumin was safe, but there was no
difference in 28-day survival between saline and albumin
administration
• There were also no differences in number of days spent in the ICU or
hospital, and the days on mechanical ventilation were also
comparable.
• Because isotonic saline is less expensive than albumin, the
consensus has emerged that isotonic crystalloid solutions should be
the preferred resuscitation fluid in critically ill patients.
The SAFE Study Investigators: N Engl J Med, 2004. 350: 2247–2256.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
44. • In cirrhotic patients who develop spontaneous bacterial
peritonitis, a randomized study compared antibiotic
alone (cefatoxine) versus the same antibiotic plus
albumin (1.5 g/kg immediately on diagnosis, then 1 g/kg
on day 3).
• The addition of albumin therapy
decreased renal failure and improved
survival.
Sort P, et al.: N Engl J Med, 1999. 341: 403–409.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
45. HES
• Hydroxyethyl starch (HES) is a less expensive colloid alternative for
albumin.
• However, HES has negative effects on coagulation
and causes an “osmotic nephrosis” that can lead
to renal impairment
Dickenmann M, et al.: Am J Kidney Dis, 2008. 51: 491–503.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
47. • The fact that saline increases chloride levels more than
balanced crystalloids is likely the prime factor.
• There has been a hypothesis that balanced crystalloids are
more aligned with human blood, and there were theories
about why that might be better for use in humans.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
48. • In the Isotonic Solutions and Major Adverse Renal Events
Trial (SMART), 15,802 adults treated in five ICUs at a
single academic center were assessed.
• The primary outcome of the trial was:
• major adverse kidney events within 30 days, defined as death,
new renal replacement therapy, or persistent renal dysfunction (a
doubling of creatinine from baseline)
• in the 30 days after administration and before hospital discharge.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
49. • Patients who received balanced crystalloids were more likely
to meet the primary outcome than those who received saline.
• There were fewer in-hospital deaths in the crystalloid group
than in the saline group
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
50. Agenda
• AKI: Definition & Causes
• AKI: Classification
• AKI: Epidimiology
• AKI: Prognosis
• AKI: Treatment principles
• Role of loop diuretics
• Fluid balance
• Selection of Resuscitation Fluid
• Fluid overload in AKI and its mechanism
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
51. Fluid Overload in AKI
• Although early fluid resuscitation is frequently necessary in
patients with severe sepsis or septic shock, several
observational studies have demonstrated a correlation
between fluid overload and mortality in critically ill adults and
children with AKI.
Brandstrup B, et al.: Ann Surg, 2003. 238: 641–648.
Foland JA, et al.: Crit Care Med, 2004. 32: 1771–1776.
Van Biesen W, et al.: J Nephrol, 2005. 18: 54–60.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
52. • A prospective, multicenter observational study of 618 critically
ill patients examined the effect of fluid overload
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
53. Cumulative probability of survival by fluid overload status.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
54. Mortality rate by final fluid accumulation relative to baseline weight and
stratified by dialysis status
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
55. Mortality rate by categorical percentage of dialysis days with fluid overload
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
56. Conclusion
• The clinical and physiological studies cited above demonstrate
that the ideal fluid strategy in AKI has not been developed.
• Early protocol-designed fluid resuscitation may prevent the
occurrence of AKI, particularly in patients with severe sepsis
and septic shock.
• The preferred evidence-based resuscitation fluid is a
crystalloid solution.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha
57. Conclusion
• Persistent fluid overload in AKI patients may lead to hypoxia,
mechanical ventilation, ARDS, and increased mortality.
• Judicious fluid removal, may improve survival in AKI patients
secondary to improved pulmonary, cardiac, and renal
function.
• The effects of conservative versus liberal fluid administration
on mortality in patients with AKI… studies.
• Balanced crystalloids are more aligned with human blood and
might be better for use in humans.
August,13,2018
MIHCriticalcarenephrology,prof
KOkasha