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1. Refractory Edema with CHF
Stepwise Approaches
Nephrology Perspectives
5th KUC Club – June 2014
Mohammed Abdel Gawad
Nephrology Specialist
Kidney & Urology Center (KUC)
Alexandria - EGY
drgawad@gmail.com

2. Download the review article about this
presentation from
www.kidneyadvances.com
to get more details and explanations
Volume 5, June, 2014

3. To get the presentation with full animations
please contact me on
drgawad@gmail.com

4. Generalized
edema
Heart
failure
Liver
cirrhosis
Nephrotic
syndrome
Renal
failure

5. Refractory Edema – Diuretic Resistance
Failure to decrease the extracellular fluid
volume despite liberal use of diuretics

6. Diuretics Action at a Glance

7. Mechanism of Development of
Refractory Edema
Prevents net fluid loss, even with
adequate therapeutic doses of diuretics
Ellison DH. Ann Intern Med. 1991;114(10):886

8. Mechanism of Development of
Refractory Edema
24-hour urine: A value above 100 mEq Na/day
indicates noncompliance with sodium restriction
Ellison DH. Ann Intern Med. 1991;114(10):886.

9. Mechanism of Development of
Refractory Edema
2010 Heart Failure Society of America (HFSA)
guidelines on acute decompensated HF (ADHF)
recommend a sodium intake of less than 2 g/day
Lindenfeld J, et al. J Card Fail. 2010;16(6):e1

10. Mechanism of Development of
Refractory Edema
Reduce the synthesis of prostaglandins
Ellison DH. Am J Kidney Dis. 1994;23(5):623
NSAIDs

11. Pre-Diuresis Precautions:
- Ensure dietary sodium restriction
- Stop NSAIDs
- Exclude aminoglycosides
Pre-Diuresis Lab: Serum Albumin, Urea/BUN,
Creatinine, Na, K, Ca, Mg, Uric acid , Hb, Ht%
Other lab Ix (as indicated)
Pre-diuresis Imaging: CXR, USS Abdomen &
Pelvis, ECHO.
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014

12. Pre-Diuresis Precautions:
- Ensure dietary sodium restriction
- Stop NSAIDs
- Exclude aminoglycosides
Pre-Diuresis Lab: Serum Albumin, Urea/BUN,
Creatinine, Na, K, Ca, Mg, Uric acid , Hb, Ht%
Other lab Ix (as indicated)
Pre-diuresis Imaging: CXR, USS Abdomen &
Pelvis, ECHO.
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Gallagher KL, Jones JK. Ann Intern Med. 1979;91(5):744

13. Pre-Diuresis Precautions:
- Ensure dietary sodium restriction
- Stop NSAIDs
- Exclude aminoglycosides
Pre-Diuresis Lab: Serum Albumin, Urea/BUN,
Creatinine, Na, K, Ca, Mg, Uric acid , Hb, Ht%
Other lab Ix (as indicated)
Pre-diuresis Imaging: CXR, USS Abdomen &
Pelvis, ECHO
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Gallagher KL, Jones JK. Ann Intern Med. 1979;91(5):744

14. Pre-Diuresis Precautions:
- Ensure dietary sodium restriction
- Stop NSAIDs
- Exclude aminoglycosides
Pre-Diuresis Lab: Serum Albumin, Urea/BUN,
Creatinine, Na, K, Ca, Mg, Uric acid , Hb, Ht%
Other lab Ix (as indicated)
Pre-diuresis Imaging: CXR, USS Abdomen &
Pelvis, ECHO
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Gallagher KL, Jones JK. Ann Intern Med. 1979;91(5):744

15. Mechanism of Development of
Refractory Edema
Decreased loop
diuretic secretion
Hypoalbuminemia

16. Glomerular
Filtration
Tubular
Reabsorption
Tubular
Secretion
Excretion
Mechanism of Development of
Refractory Edema
Normal
Nephron
M.Gawad. www.NephroTubeCNE.com
Opie LH, Kaplan NM, Pool-Wilson P, eds. Drugs for the Heart. 5th
edition. Diuretic therapy.
Decreased loop
diuretic secretion
Hypoalbuminemia

17. DA
Mechanism of Development of
Refractory Edema
Normal Loop
Diuretics
Secretion
M.Gawad. www.NephroTubeCNE.com
Opie LH, Kaplan NM, Pool-Wilson P, eds. Drugs for the Heart. 5th
edition. Diuretic therapy.
Decreased loop
diuretic secretion
Hypoalbuminemia

18. DA
Mechanism of Development of
Refractory Edema
Normal Loop
Diuretics
Secretion
M.Gawad. www.NephroTubeCNE.com
Opie LH, Kaplan NM, Pool-Wilson P, eds. Drugs for the Heart. 5th
edition. Diuretic therapy.
Decreased loop
diuretic secretion
Hypoalbuminemia

19. A
Mechanism of Development of
Refractory Edema
Normal Loop
Diuretics
Secretion
M.Gawad. www.NephroTubeCNE.com
Opie LH, Kaplan NM, Pool-Wilson P, eds. Drugs for the Heart. 5th
edition. Diuretic therapy.
Decreased loop
diuretic secretion
Hypoalbuminemia
D

20. Mechanism of Development of
Refractory Edema
M.Gawad. www.NephroTubeCNE.com
Brater DC. N Engl J Med. 1998;339(6):387
Heart
CHF
(low COP)
Increased venous
pressure
A
A
A
A
Increasedvenous
pressure
Cardiac Cirrhosis
Decreased loop
diuretic secretion
Hypoalbuminemia
Mechanism of
hypoalbuminemia
in CHF

21. Mechanism of Development of
Refractory Edema
M.Gawad. www.NephroTubeCNE.com
Brater DC. N Engl J Med. 1998;339(6):387
Heart
CHF
(low COP)
Increased venous
pressure
A
D DA
Decreased loop
diuretic secretion
Hypoalbuminemia
Increasedvenous
pressure
Cardiac Cirrhosis

22. Mechanism of Development of
Refractory Edema
M.Gawad. www.NephroTubeCNE.com
Brater DC. N Engl J Med. 1998;339(6):387
Heart
CHF
(low COP)
Increased venous
pressure
A
DA
Decreased loop
diuretic secretion
Hypoalbuminemia
Increasedvenous
pressure
Cardiac Cirrhosis
D

23. Mechanism of Development of
Refractory Edema
M.Gawad. www.NephroTubeCNE.com
Brater DC. N Engl J Med. 1998;339(6):387
Heart
CHF
(low COP)
Increased venous
pressure
A DA
D
Increasedvenous
pressure
Decreased loop
diuretic secretion
Hypoalbuminemia
Increasedvenous
pressure
Cardiac Cirrhosis

24. Mechanism of Development of
Refractory Edema
M.Gawad. www.NephroTubeCNE.com
Brater DC. N Engl J Med. 1998;339(6):387
Heart
CHF
(low COP)
Increased venous
pressure
A D A
D
Decreased loop
diuretic secretion
Hypoalbuminemia
Increasedvenous
pressure
Cardiac Cirrhosis

25. When to give Loop Diuretic +
Albumin?
Loop diuretic + Albumin in hypoalbuminemic patients
(secondary to cirrhosis or nephrotic syndrome)
with mean plasma albumin 3.0 g/dL
No increase in the rate of furosemide excretion
Mutschler E et al. Kidney Int. 1999;55(2):629
Chalasani N et al. J Am Soc Nephrol. 2001;12(5):1010

26. When to give Loop Diuretic +
Albumin?
Pre-Diuresis Precautions,
Pre-Diuresis Lab and Pre-diuresis Imaging
Albumin infusion
in case of hypoalbuminemia (<2 g/dl)
Evidence supporting this is weak as
this has not been studied yet

27. To get the presentation with full animations
please contact me on
drgawad@gmail.com

28. Download the review article about this
presentation from
www.kidneyadvances.com
to get more details and explanations
Volume 5, June, 2014

29. Posture during Diuresis
Ring-Larsen H et al. Br Med J (Clin Res Ed). 1986;292(6532):1351
Cannot increase
cardiac output in
upright position
Renal perfusion
and urinary
diuretic delivery
will decrease
Renal Na &
H2O
reabsorption
increase

30. Posture during Diuresis
Supine position
associated with significantly higher mean
creatinine clearance and diuretic response
Ring-Larsen H et al. Br Med J (Clin Res Ed). 1986;292(6532):1351

31. IV Diuretic Therapy
Intermittent
IV Bolus
Continuous
IV Infusion

32. IV Diuretic Therapy
Intermittent
IV Bolus
Continuous
IV Infusion
Salvador DR et al. Cochrane Database Syst Rev. 2005; :CD003178
Felker GM et al. N Engl J Med. 2011;364(9):797
Rudy DW et al. Ann Intern Med. 1991;115(5):360
Efficacy ??
Safety ??

33. IV Diuretic Therapy
Salvador DR et al. Cochrane Database Syst Rev. 2005; :CD003178
Felker GM et al. N Engl J Med. 2011;364(9):797
Rudy DW et al. Ann Intern Med. 1991;115(5):360
Efficacy ??
Safety ??
Similar efficacy
Intermittent
IV Bolus
Continuous
IV Infusion

34. IV Diuretic Therapy
Efficacy ??
Safety ??
Salvador DR et al. Cochrane Database Syst Rev. 2005; :CD003178
Felker GM et al. N Engl J Med. 2011;364(9):797
Rudy DW et al. Ann Intern Med. 1991;115(5):360
Similar efficacy
Continuous IV is safer
(less ototoxicity)
Intermittent
IV Bolus
Continuous
IV Infusion

35. IV Diuretic Therapy
Salvador DR et al. Cochrane Database Syst Rev. 2005; :CD003178
Felker GM et al. N Engl J Med. 2011;364(9):797
Rudy DW et al. Ann Intern Med. 1991;115(5):360
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Intermittent
IV Bolus
Continuous
IV Infusion

36. SINGLE IV Effective Dose
(Loop Diuretics)
No natriuresis seen
until a threshold rate
of drug excretion in
urine is attained
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Rudy DW et al. Ann Intern Med. 1991;115(5):360.
D Craig Brater et al. Kidney Int 26: 183-189; doi:10.1038/ki.1984.153
Brater DC, et al. Livingstone, New York 1987. Vol 17

37. SINGLE IV Effective Dose
(Loop Diuretics)
Once a single effective dose has
been determined, administered
multiple times per day
Increased the dose to 60 or 80 mg,
rather than giving 40 mg twice a
day
Single effective dose is not reached
yet
No diuresis to 40 mg of furosemide
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Rudy DW et al. Ann Intern Med. 1991;115(5):360.
D Craig Brater et al. Kidney Int 26: 183-189; doi:10.1038/ki.1984.153
Brater DC, et al. Livingstone, New York 1987. Vol 17

38. SINGLE IV Effective Dose
(Loop Diuretics)
So simply, single effective
dose is the least dose
that will cause response
i.e. diuresis.
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Rudy DW et al. Ann Intern Med. 1991;115(5):360.
D Craig Brater et al. Kidney Int 26: 183-189; doi:10.1038/ki.1984.153
Brater DC, et al. Livingstone, New York 1987. Vol 17

39. MAXIMUN IV Effective Dose
(Loop Diuretics)
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Brater DC. N Engl J Med. 1998;339(6):387
Brater DC, et al. Churchill Livingstone, New York 1987. Vol 17.
2013 ACCF/AHA guideline for the management of heart failure: a report of the
Yancy CW, et al. J Am Coll Cardiol. 2013 Oct;62(16):e147-239.
Administering higher doses
will produce little or no
further diuresis,
a plateau is reached
The dose at which loop Na-
Cl transport is completely
inhibited

40. MAXIMUN IV Effective Dose
(Loop Diuretics)
Maximum IV Effective Dose
Normal eGFR
40 mg (over 5
minutes) to 80 mg
(over 20 minutes)
of furosemide,
1 to 2 mg
of bumetanide,
20 to 40 mg
of torsemide.
Moderate CKD
80 mg of furosemide
(over 20 minutes),
2 to 3 mg
of bumetanide,
20 to 50 mg
of torsemide.
Severe CKD
200 mg (over 40 to 50
minutes)
of furosemide,
8 to 10 mg
of bumetanide
50 to 100 mg
of torsemide.
ACC/AHA
recommendations:
160 to 200 mg (over
40 to 50 minutes) of
furosemide,
4 and 8 mg of
bumetanide
100 to 200 mg of
torsemide
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Brater DC. N Engl J Med. 1998;339(6):387
Brater DC, et al. Churchill Livingstone, New York 1987. Vol 17.
2013 ACCF/AHA guideline for the management of heart failure: a report of the
Yancy CW, et al. J Am Coll Cardiol. 2013 Oct;62(16):e147-239.

41. Intermittent IV Bolus
Pre-Diuresis Precautions,
Pre-Diuresis Lab and Pre-diuresis Imaging
Albumin infusion in case of hypoalbuminemia (<2 g/dl)
Initial intravenous bolus dose of furosemide is 20 to 40 mg (or equivalent)
Good
response
Continue the
same dose
with follow up
Little or no
response to intial
bolus dose
Double the dose every
2 hrs as needed up to
the maximum
recommended doses
Partial diuretic response to
once daily single effective or
maximum bolus dose
- Repeat loop diuretic dose
twice or even three times a day
- Add thiazide diuretic ??
Posture
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Almeshari K et al. J Am Soc Nephrol. 1993;3(12):1878
Rudy DW et al Ann Intern Med. 1991;115(5):360.
Brater DC, Voelker JR. In: Pharmacotherapy of Renal Disease and Hypertension, New York 1987. Vol 17.

42. Continuous IV Infusion
Salvador DR et al. Cochrane Database Syst Rev. 2005; :CD003178
Felker GM et al. N Engl J Med. 2011;364(9):797
Dormans TP et al. J Am Coll Cardiol. 1996;28(2):376
Rudy DW et al. Ann Intern Med. 1991;115(5):360
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Pre-Diuresis Precautions,
Pre-Diuresis Lab and Pre-diuresis
Imaging
Albumin infusion in case of
hypoalbuminemia (<2 g/dl)
IV loading bolus dose of
furosemide (or equivalent)
(Starting by single effective dose
up to maximum effective dose)
Continuous IV infusion
should not be tried in patients who
have not responded to repeated
bolus doses
(up to maximum effective dose )

43. IV loading dose of furosemide (or
equivalent)
Normal or near normal renal function
(eGFR >75 mL/min)
Continuous Furosemide infusion, 5 mg/h (or
equivalent)
Impaired renal function
(eGFR <30 mL/min)
Continuous Furosemide infusion, 20 mg/h(or
equivalent)
Follow Up UOP after 2 hrs:
Minimal required UOP: 0.5-1 ml/kg/h, which can be increased according clinical
situation
Inadequate or NO UOP
a second bolus is given
followed by a higher infusion rate of 30 mg/h
± Thiazide Initial dose
Follow Up UOP after 2 hrs
If inadequate or No UOP: a second bolus is given
followed by a higher infusion rate of 40 mg/h up to
4 mg/min (but the risk of ototoxicity and other side
effects is high )
± Thiazide maximum dose
Follow Up UOP after 2 hrs
No UOP
UF
Adequate
UOP
Assess UOP every 2 hrs
Increase or decrease
infusion rate
according to
monitoring
parameters
Convert to oral
therapy
Continuous IV
Infusion
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Hunt SA et al. Circulation. 2009;119(14):e391
Brown CB et al. Clin Nephrol. 1981;15(2):90
Brater DC. N Engl J Med. 1998;339(6):387
Gallagher KL, Jones JK. Ann Intern Med. 1979;91(5):744.
Posture

44. IV loading dose of furosemide (or
equivalent)
Normal or near normal renal function
(eGFR >75 mL/min)
Continuous Furosemide infusion, 5 mg/h (or
equivalent)
Impaired renal function
(eGFR <30 mL/min)
Continuous Furosemide infusion, 20 mg/h(or
equivalent)
Follow Up UOP after 2 hrs:
Minimal required UOP: 0.5-1 ml/kg/h, which can be increased according clinical
situation
Inadequate or NO UOP
a second bolus is given
followed by a higher infusion rate of 10 mg/h
± Thiazide Initial dose
Follow Up UOP after 2 hrs
If inadequate or No UOP: a second bolus is given
followed by a higher infusion rate of 20 mg/h up to
4 mg/min (but the risk of ototoxicity and other side
effects is high )
± Thiazide maximum dose
Follow Up UOP after 2 hrs
No UOP
UF
Adequate
UOP
Assess UOP every 2 hrs
Increase or decrease
infusion rate
according to
monitoring
parameters
Convert to oral
therapy
Continuous IV
Infusion
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Hunt SA et al. Circulation. 2009;119(14):e391
Brown CB et al. Clin Nephrol. 1981;15(2):90
Brater DC. N Engl J Med. 1998;339(6):387
Gallagher KL, Jones JK. Ann Intern Med. 1979;91(5):744.
Posture

45. Equivalent doses of other loop
diuretics to furosemide dose
Furosemide
IV
Torsemide
IV / PO
Bumetanide
IV / PO
20 mg 10 mg 1 mg
40 mg 20 mg 2 mg

46. If IV Furosemide is Ineffective
If the patient is resistant to IV
furosemide, it is not likely to
respond to an equivalent
intravenous dose of any other loop
diuretic
Can I Switch to Equivalent IV Dose of
Bumetanide or Torsemide?
Brater DC. N Engl J Med. 1998;339(6):387

47. When to Add Thiazide Diuretic?
Na
Loop Diuretics
block Na-K-Cl
Co transporter
Na
Na
Na
Na-Cl
Co transporter
M.Gawad. www.NephroTubeCNE.com
Almeshari K et al. J Am Soc Nephrol. 1993;3(12):1878
Abdallah JG et al. J Am Soc Nephrol. 2001;12(7):1335
Knauf H, Mutschler E. Cardiology. 1994;84(suppl 2):18-26.

48. When to Add Thiazide Diuretic?
Na
Loop Diuretics
block Na-K-Cl
Co transporter
Na
Na
NaNa-Cl
Co transporter
M.Gawad. www.NephroTubeCNE.com
Almeshari K et al. J Am Soc Nephrol. 1993;3(12):1878
Abdallah JG et al. J Am Soc Nephrol. 2001;12(7):1335
Knauf H, Mutschler E. Cardiology. 1994;84(suppl 2):18-26.

49. When to Add Thiazide Diuretic?
Loop Diuretics
block Na-K-Cl
Co transporter
Na-Cl
Co transporter
With Chronic use of Loop Diuretics
Flow-dependent hypertrophy
M.Gawad. www.NephroTubeCNE.com
Almeshari K et al. J Am Soc Nephrol. 1993;3(12):1878
Abdallah JG et al. J Am Soc Nephrol. 2001;12(7):1335
Knauf H, Mutschler E. Cardiology. 1994;84(suppl 2):18-26.

50. When to Add Thiazide Diuretic?
Loop Diuretics
block Na-K-Cl
Co transporter
Na-Cl
Co transporter
With Chronic use of Loop Diuretics
Flow-dependent hypertrophy
M.Gawad. www.NephroTubeCNE.com
Almeshari K et al. J Am Soc Nephrol. 1993;3(12):1878
Abdallah JG et al. J Am Soc Nephrol. 2001;12(7):1335
Knauf H, Mutschler E. Cardiology. 1994;84(suppl 2):18-26.
Na
Na
Na
Na

51. When to Add Thiazide Diuretic?
Loop Diuretics
block Na-K-Cl
Co transporter
Na-Cl
Co transporter
With Chronic use of Loop Diuretics
Flow-dependent hypertrophy
M.Gawad. www.NephroTubeCNE.com
Almeshari K et al. J Am Soc Nephrol. 1993;3(12):1878
Abdallah JG et al. J Am Soc Nephrol. 2001;12(7):1335
Knauf H, Mutschler E. Cardiology. 1994;84(suppl 2):18-26.
Na
Na
Na
Na
Diuretic braking
phenomenon

52. When to Add Thiazide Diuretic?
Loop Diuretics
block Na-K-Cl
Co transporter
Na-Cl
Co transporter
With Chronic use of Loop Diuretics
Flow-dependent hypertrophy
Sequential nephron blockade - Thiazides
M.Gawad. www.NephroTubeCNE.com
Almeshari K et al. J Am Soc Nephrol. 1993;3(12):1878
Abdallah JG et al. J Am Soc Nephrol. 2001;12(7):1335
Knauf H, Mutschler E. Cardiology. 1994;84(suppl 2):18-26.
Na
Na
Na
Na
Diuretic braking
phenomenon

53. To get the presentation with full animations
please contact me on
drgawad@gmail.com

54. Download the review article about this
presentation from
www.kidneyadvances.com
to get more details and explanations
Volume 5, June, 2014

55. When to Add Thiazide Diuretic?
Start or add Thiazides if
Patient with known
long term use of loop
diuretics
Partial diuretic response to
bolus or continuous IV
infusion diuretic therapy

56. Intermittent IV Bolus
Pre-Diuresis Precautions,
Pre-Diuresis Lab and Pre-diuresis Imaging
Albumin infusion in case of hypoalbuminemia (<2 g/dl)
Initial intravenous bolus dose of furosemide is 20 to 40 mg (or equivalent)
Good
response
Continue the
same dose
with follow up
Little or no
response to intial
bolus dose
Double the dose every
2 hrs as needed up to
the maximum
recommended doses
Partial diuretic response to
once daily single effective or
maximum bolus dose
- Repeat loop diuretic dose
twice or even three times a day
- Add thiazide diuretic ??
Posture
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Almeshari K et al. J Am Soc Nephrol. 1993;3(12):1878
Rudy DW et al Ann Intern Med. 1991;115(5):360.
Brater DC, Voelker JR. In: Pharmacotherapy of Renal Disease and Hypertension, New York 1987. Vol 17.
When to start
with Thiazide?
if the patient
was chronically
on oral
diuretics since
long time

57. IV loading dose of furosemide (or
equivalent)
Normal or near normal renal function
(eGFR >75 mL/min)
Continuous Furosemide infusion, 5 mg/h (or
equivalent)
Impaired renal function
(eGFR <30 mL/min)
Continuous Furosemide infusion, 20 mg/h(or
equivalent)
Follow Up UOP after 2 hrs:
Minimal required UOP: 0.5-1 ml/kg/h, which can be increased according clinical
situation
Inadequate or NO UOP
a second bolus is given
followed by a higher infusion rate of 30 mg/h
± Thiazide Initial dose
Follow Up UOP after 2 hrs
If inadequate or No UOP: a second bolus is given
followed by a higher infusion rate of 40 mg/h up to
4 mg/min (but the risk of ototoxicity and other side
effects is high )
± Thiazide maximum dose
Follow Up UOP after 2 hrs
No UOP
UF
Adequate
UOP
Assess UOP every 2 hrs
Increase or decrease
infusion rate
according to
monitoring
parameters
Convert to oral
therapy
Continuous IV
Infusion
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Hunt SA et al. Circulation. 2009;119(14):e391
Brown CB et al. Clin Nephrol. 1981;15(2):90
Brater DC. N Engl J Med. 1998;339(6):387
Gallagher KL, Jones JK. Ann Intern Med. 1979;91(5):744.
When to start
with Thiazide?
if the patient
was chronically
on oral
diuretics since
long time
Posture

58. IV loading dose of furosemide (or
equivalent)
Normal or near normal renal function
(eGFR >75 mL/min)
Continuous Furosemide infusion, 5 mg/h (or
equivalent)
Impaired renal function
(eGFR <30 mL/min)
Continuous Furosemide infusion, 20 mg/h(or
equivalent)
Follow Up UOP after 2 hrs:
Minimal required UOP: 0.5-1 ml/kg/h, which can be increased according clinical
situation
Inadequate or NO UOP
a second bolus is given
followed by a higher infusion rate of 10 mg/h
± Thiazide Initial dose
Follow Up UOP after 2 hrs
If inadequate or No UOP: a second bolus is given
followed by a higher infusion rate of 20 mg/h up to
4 mg/min (but the risk of ototoxicity and other side
effects is high )
± Thiazide maximum dose
Follow Up UOP after 2 hrs
No UOP
UF
Adequate
UOP
Assess UOP every 2 hrs
Increase or decrease
infusion rate
according to
monitoring
parameters
Convert to oral
therapy
Continuous IV
Infusion
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Hunt SA et al. Circulation. 2009;119(14):e391
Brown CB et al. Clin Nephrol. 1981;15(2):90
Brater DC. N Engl J Med. 1998;339(6):387
Gallagher KL, Jones JK. Ann Intern Med. 1979;91(5):744.
When to start
with Thiazide?
if the patient
was chronically
on oral
diuretics since
long time
Posture

59. How to Administer Thiazide Diuretic?
Timing of combination therapy depends
upon the route
Pitt B, Zannad F, Remme WJ, et al. N Engl J Med. 1999;341:709-716
Oral thiazide
IV Loop Diuretics
Same route
Same time
by 2-5 hours,
since the
peak effect
of the
thiazide is 4-
6 hours after
ingestion

60. When to Add Spironolactone?
When to Add
Spironolactone?
New York Heart
Association classes
III and IV
(circulating aldosterone
concentrations are
increased )
Low or low-normal
serum potassium
with loop diuretic
therapy
Before the addition
of a thiazide
diuretic
Fliser D et al. Kidney Int. 1994;46(2):482.
Pitt B et al. N Engl J Med. 1999;341:709-716.

61. Intermittent IV Bolus
Pre-Diuresis Precautions,
Pre-Diuresis Lab and Pre-diuresis Imaging
Albumin infusion in case of hypoalbuminemia
(<2 g/dl)
Initial intravenous bolus dose of furosemide is 20 to 40 mg (or equivalent)
Good
response
Continue the
same dose
with follow up
Little or no
response to
initial bolus dose
Double the dose every
2 hrs as needed up to
the maximum
recommended doses
Partial diuretic response to
once daily single effective or
maximum bolus dose
- Repeat loop diuretic dose
twice or even three times a day
- Add thiazide diuretic ??
Posture
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Almeshari K et al. J Am Soc Nephrol. 1993;3(12):1878
Rudy DW et al Ann Intern Med. 1991;115(5):360.
Brater DC, Voelker JR. In: Pharmacotherapy of Renal Disease and Hypertension, New York 1987. Vol 17.
When to start
with Thiazide?
if the patient
was chronically
on oral
diuretics since
long time
When to add
Spironolactone?
1- CHF (NYHA Class III and IV)
2- If hypokalemia is present
at first or with follow up.
3- Before the addition of a
thiazide diuretic

62. IV loading dose of furosemide (or
equivalent)
Normal or near normal renal function
(eGFR >75 mL/min)
Continuous Furosemide infusion, 5 mg/h (or
equivalent)
Impaired renal function
(eGFR <30 mL/min)
Continuous Furosemide infusion, 20 mg/h(or
equivalent)
Follow Up UOP after 2 hrs:
Minimal required UOP: 0.5-1 ml/kg/h, which can be increased according clinical
situation
Inadequate or NO UOP
a second bolus is given
followed by a higher infusion rate of 30 mg/h
± Thiazide Initial dose
Follow Up UOP after 2 hrs
If inadequate or No UOP: a second bolus is given
followed by a higher infusion rate of 40 mg/h up to
4 mg/min (but the risk of ototoxicity and other side
effects is high )
± Thiazide maximum dose
Follow Up UOP after 2 hrs
No UOP
UF
Adequate
UOP
Assess UOP every 2 hrs
Increase or decrease
infusion rate
according to
monitoring
parameters
Convert to oral
therapy
Continuous IV
Infusion
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Hunt SA et al. Circulation. 2009;119(14):e391
Brown CB et al. Clin Nephrol. 1981;15(2):90
Brater DC. N Engl J Med. 1998;339(6):387
Gallagher KL, Jones JK. Ann Intern Med. 1979;91(5):744.
When to start
with Thiazide?
if the patient
was chronically
on oral
diuretics since
long time
When to add
Spironolactone?
1- CHF (NYHA Class III and IV)
2- If hypokalemia is present
at first or with follow up.
3- Before the addition of a
thiazide diuretic
Posture

63. IV loading dose of furosemide (or
equivalent)
Normal or near normal renal function
(eGFR >75 mL/min)
Continuous Furosemide infusion, 5 mg/h (or
equivalent)
Impaired renal function
(eGFR <30 mL/min)
Continuous Furosemide infusion, 20 mg/h(or
equivalent)
Follow Up UOP after 2 hrs:
Minimal required UOP: 0.5-1 ml/kg/h, which can be increased according clinical
situation
Inadequate or NO UOP
a second bolus is given
followed by a higher infusion rate of 10 mg/h
± Thiazide Initial dose
Follow Up UOP after 2 hrs
If inadequate or No UOP: a second bolus is given
followed by a higher infusion rate of 20 mg/h up to
4 mg/min (but the risk of ototoxicity and other side
effects is high )
± Thiazide maximum dose
Follow Up UOP after 2 hrs
No UOP
UF
Adequate
UOP
Assess UOP every 2 hrs
Increase or decrease
infusion rate
according to
monitoring
parameters
Convert to oral
therapy
Continuous IV
Infusion
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Hunt SA et al. Circulation. 2009;119(14):e391
Brown CB et al. Clin Nephrol. 1981;15(2):90
Brater DC. N Engl J Med. 1998;339(6):387
Gallagher KL, Jones JK. Ann Intern Med. 1979;91(5):744.
When to start
with Thiazide?
if the patient
was chronically
on oral
diuretics since
long time
When to add
Spironolactone?
1- CHF (NYHA Class III and IV)
2- If hypokalemia is present
at first or with follow up.
3- Before the addition of a
thiazide diuretic
Posture

64. IV High-Dose Furosemide and
Hypertonic Saline Solutions
Pre-Diuresis Precautions,
Pre-Diuresis Lab and Pre-diuresis Imaging
Albumin infusion in case of hypoalbuminemia (<2 g/dl)
or
Hypertonic Saline

65. IV High-Dose Furosemide and
Hypertonic Saline Solutions
Excessive diuresis
Hypovolemia and reduced
cardiac output
Diminish GFR
Nieminen MS, Bohm M, Cowie MR, et al. Eur Heart J. 2005;26:384-416.

66. IV High-Dose Furosemide and
Hypertonic Saline Solutions
Excessive diuresis
Hypovolemia and reduced
cardiac output
Diminish GFR
Nieminen MS, Bohm M, Cowie MR, et al. Eur Heart J. 2005;26:384-416.
Maintaining an adequate
intravascular volume will
maintain good renal
perfusion

67. IV High-Dose Furosemide and
Hypertonic Saline Solutions
Nieminen MS et al. Eur Heart J. 2005;26:384-416.
Paterna S et al. Adv Ther. 1999;16:219-28.
Paterna S et al. Eur J Heart Fail. 2000;2:305-13.
Licata Get al. Am Heart J. 2003;145:459-66
High dose IV furosemide
+
Small volume HSS (150 mL of 1.4%-4.6% NaCl) twice a day
Improves
clinical
signs and
symptoms
Improves
severity of
illness
(NYHA
class)
Improves
urine
output and
sodium
excretion
Serum
creatinine
level
decreased
Reduce
mortality and
hospital
readmission
rates

68. Monitoring
Lab:  Na, K (daily)
 Urea/BUN, Creatinine (daily)
 Hb, Ht% (daily)
 ABG
 Ca, Mg
 Uric Acid
 Serum Albumin
 Other lab Ix (as indicated)
Radiology
(as needed):
 CXR
 USS Abdomen & Pelvis
 ECHO

69. Monitoring
Clinical: Weight measurement: should be performed at the same
time each day, usually in the morning, prior to eating and
after voiding
Signs of hypovolemia (not less than 4 times/day):
o Weakness
o Hypotension
o orthostatic hypotension
o cool extremities
o + elevated serum creatinine
o + rapidly elevated Ht%
Signs of ototoxicity (not less than 4 times/day):
o decreased hearing
o Tinnitus
o deafness: transient (most lasting 30 minutes
to 24 hours) or permanent deafness

70. Switching from IV to Oral Loop
Diuretics
When to start? It depends on the clinical decision of the treating
physician.
Decreased intestinal perfusion
Reduced intestinal motility
Intestinal mucosal edema
Krämer BK, Schweda F, Riegger GA. Am J Med. 1999;106(1):90
Reduce the diuretic
absorption

71. Switching from IV to Oral Loop
Diuretics
Dosage • The oral dose of Furosemide is approximately twice the
intravenous dose.
• The oral dose of Torsemide & Bumetanide is the same as the
intravenous dose.
= =
Furosemide Torsemide & Bumetanide
Hunt SA et al. Circulation. 2009;119(14):e391
Wargo KA, Banta WM. Ann Pharmacother. 2009;43(11):1836

72. Take Home Messages

73. Pre-Diuresis Precautions:
- Ensure dietary sodium restriction
- Stop NSAIDs
- Exclude aminoglycosides
Pre-Diuresis Lab: Serum Albumin, Urea/BUN,
Creatinine, Na, K, Ca, Mg, Uric acid , Hb, Ht%
Other lab Ix (as indicated)
Pre-diuresis Imaging: CXR, USS Abdomen &
Pelvis, ECHO.
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014

74. Pre-Diuresis Precautions,
Pre-Diuresis Lab and Pre-diuresis Imaging
Albumin infusion in case of hypoalbuminemia (<2 g/dl)
or
Hypertonic Saline
Posture

75. Efficacy ??
Safety ??
Salvador DR et al. Cochrane Database Syst Rev. 2005; :CD003178
Felker GM et al. N Engl J Med. 2011;364(9):797
Rudy DW et al. Ann Intern Med. 1991;115(5):360
Similar efficacy
Continuous IV is safer
(less ototoxicity)
Intermittent
IV Bolus
Continuous
IV Infusion

76. Intermittent IV Bolus
Pre-Diuresis Precautions,
Pre-Diuresis Lab and Pre-diuresis Imaging
Albumin infusion in case of hypoalbuminemia (<2 g/dl)
Initial intravenous bolus dose of furosemide is 20 to 40 mg (or equivalent)
Good
response
Continue the
same dose
with follow up
Little or no
response to intial
bolus dose
Double the dose every
2 hrs as needed up to
the maximum
recommended doses
Partial diuretic response to
once daily single effective or
maximum bolus dose
- Repeat loop diuretic dose
twice or even three times a day
- Add thiazide diuretic ??
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Almeshari K et al. J Am Soc Nephrol. 1993;3(12):1878
Rudy DW et al Ann Intern Med. 1991;115(5):360.
Brater DC, Voelker JR. In: Pharmacotherapy of Renal Disease and Hypertension, New York 1987. Vol 17.

77. IV loading dose of furosemide (or
equivalent)
Normal or near normal renal function
(eGFR >75 mL/min)
Continuous Furosemide infusion, 5 mg/h (or
equivalent)
Impaired renal function
(eGFR <30 mL/min)
Continuous Furosemide infusion, 20 mg/h(or
equivalent)
Follow Up UOP after 2 hrs:
Minimal required UOP: 0.5-1 ml/kg/h, which can be increased according clinical
situation
Inadequate or NO UOP
a second bolus is given
followed by a higher infusion rate of 30 mg/h
± Thiazide Initial dose
Follow Up UOP after 2 hrs
If inadequate or No UOP: a second bolus is given
followed by a higher infusion rate of 40 mg/h up to
4 mg/min (but the risk of ototoxicity and other side
effects is high )
± Thiazide maximum dose
Follow Up UOP after 2 hrs
No UOP
UF
Adequate
UOP
Assess UOP every 2 hrs
Increase or decrease
infusion rate
according to
monitoring
parameters
Convert to oral
therapy
Continuous IV
Infusion
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Hunt SA et al. Circulation. 2009;119(14):e391
Brown CB et al. Clin Nephrol. 1981;15(2):90
Brater DC. N Engl J Med. 1998;339(6):387
Gallagher KL, Jones JK. Ann Intern Med. 1979;91(5):744.

78. IV loading dose of furosemide (or
equivalent)
Normal or near normal renal function
(eGFR >75 mL/min)
Continuous Furosemide infusion, 5 mg/h (or
equivalent)
Impaired renal function
(eGFR <30 mL/min)
Continuous Furosemide infusion, 20 mg/h(or
equivalent)
Follow Up UOP after 2 hrs:
Minimal required UOP: 0.5-1 ml/kg/h, which can be increased according clinical
situation
Inadequate or NO UOP
a second bolus is given
followed by a higher infusion rate of 10 mg/h
± Thiazide Initial dose
Follow Up UOP after 2 hrs
If inadequate or No UOP: a second bolus is given
followed by a higher infusion rate of 20 mg/h up to
4 mg/min (but the risk of ototoxicity and other side
effects is high )
± Thiazide maximum dose
Follow Up UOP after 2 hrs
No UOP
UF
Adequate
UOP
Assess UOP every 2 hrs
Increase or decrease
infusion rate
according to
monitoring
parameters
Convert to oral
therapy
Continuous IV
Infusion
M.Gawad. Kidney Advances Journal. Volume 5, June, 2014
Hunt SA et al. Circulation. 2009;119(14):e391
Brown CB et al. Clin Nephrol. 1981;15(2):90
Brater DC. N Engl J Med. 1998;339(6):387
Gallagher KL, Jones JK. Ann Intern Med. 1979;91(5):744.

79. If the patient is resistant to IV
furosemide, it is not likely to respond to
an equivalent intravenous dose of any
other loop diuretic
Brater DC. N Engl J Med. 1998;339(6):387

80. Start or add Thiazides if
Patient with known
long term use of loop
diuretics
Partial diuretic response to
bolus or continuous IV
infusion diuretic therapy

81. When to Add
Spironolactone?
New York Heart
Association classes
III and IV
(circulating
aldosterone
concentrations are
increased )
Low or low-normal
serum potassium
with loop diuretic
therapy
Before the addition
of a thiazide
diuretic
Fliser D et al. Kidney Int. 1994;46(2):482.
Pitt B et al. N Engl J Med. 1999;341:709-716.

82. Monitoring
Lab, Radiology & Clinically

83. Mohammed Abdel Gawad
Thank You