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MANNITOL
DR GEETANJALI S VERMA
DEPT OF ANESTHESIA
GEETANJALI S VERMA
• Osmotic diuretic
– Freely filterable at glomerulus
– Ltd reabsorption fm renal tubules
– Resist metabolism
– Pharmacologically inert
• 6 carbon sugar
GEETANJALI S VERMA
• Doesn’t undergo metabolism
• Not absorbed from GIT
• Doesn’t enter cells
• Clearance from plasma by glomerular
filtration
GEETANJALI S VERMA
MOA
Completely filtered at glomeruli
↓
Increases osmolarity of renal tubular fluid
Prevents re absorption of water
↓
Na+ dilution in retained water
Less re absorption of Na+
↓
Urinary excretion of Na+, Cl-, HCO3-
(urinary pH not altered)
GEETANJALI S VERMA
GEETANJALI S VERMA
Increases plasma osmolarity
↓
Draws fluid fm intra to extra cellular spaces
↓
Acute expansion of intravascular fluid volume
↓
Decreases brain bulk, increases renal blood flow
to medulla
GEETANJALI S VERMA
Oxygen radical scavenger
↓
Prevents cellular swelling
Reduces renal tubular obstruction
GEETANJALI S VERMA
USES
1. Prophylaxis against acute renal failure
2. D/d of acute oliguria
3. T/t of increased ICP
4. To decreased IOP
GEETANJALI S VERMA
West J Med. 1979 October; 131(4): 277–284
• Allen R. Nissenson, MD, Raymond E. Weston, MD, and Charles R. Kleeman, MD
• Author information ► Copyright and License information ►
Abstract
• Mannitol may be useful clinically both as a diuretic and as an obligate extracellular
solute. As a diuretic it can be used to treat patients with intractable
edema states, to increase urine flow and flush out debris from the
renal tubules in patients with acute tubular necrosis, and to increase
toxin excretion in patients with barbiturate, salicylate or bromide
intoxication. As an obligate extracellular solute it may be useful to
ameliorate symptoms of the dialysis disequilibrium syndrome, to
decrease cerebral edema following trauma or cerebrovascular
accident, and to prevent cell swelling related to renal ischemia
following cross-clamping of the aorta. Largely unexplored uses for
mannitol include its use as an osmotic agent in place of dextrose in peritoneal
dialysis solutions, its use to maintain urine output in patients newly begun on
hemodialysis, and its use to limit infarct size following acute myocardial infarction.
GEETANJALI S VERMA
• Acute renal failure prophy
– After cardiovasc surg, transplantn, extensive
trauma, surg in jaundiced pt, nephrotoxic condn
– Van Valenberg et al , 1984 : ARF less in pts
receiving mannitol prior to revascularisation of
transplanted kidney
GEETANJALI S VERMA
• Diagnosis of acute oliguria
– 0.25g/kg IV
– Urine output increased = intravasc fluid vol
depletion
– No increase = glomerular/ renal tubular fn
compromised
GEETANJALI S VERMA
• t/t of increased ICP
– 0.25-1 g/kg
– Increases plasma osm – withdraws fluid fm brain
tissues
– Vasodil of vasc smooth muscle
– Decreases rate of formn of CSF
– Effective within 10-15mins of adm, lasts for 2hrs
– No rebound increase
GEETANJALI S VERMA
Bratton – J Neurotrauma - 2007
GEETANJALI S VERMA
Francony – Crit Care Med - 2008
GEETANJALI S VERMA
Mannitol
… but
No oxygenation improvement compared to HS
Oddo – JNNP - 2009Sakowitz – J Trauma - 2007
Mannitol
PtiO2
PitO2:
- normal = 35 mm Hg
- Ischemic threshold < 10-15 mm Hg GEETANJALI S VERMA
NATO study
To prove non-inferiority of HS vs mannitol on brain metabolism
Sample size : 30 patients
15 mannitol (1 g/kg), 15 HS 7.5% (2 mL/kg)
Same osmotic load
Main objective : effects on lactate/pyruvate ratio (redox
potential)
Secondary objectives : effects on ICP, PtiO2, cerebral glucose
GEETANJALI S VERMA
Conclusion
ICP
reduction
Improved
oxygenation
Effects on
neuroinflammatory
response
Haemodynamic
benefit
Limited
volume
Mannitol Yes No Limited No No
HS Yes Yes Yes Yes Yes
GEETANJALI S VERMA
• Reduction of IOP
– Increases plasma osm, withdraws fluid fm
intraocular space
GEETANJALI S VERMA
C/I
• Well established anuria due to severe renal disease.
• Severe pulmonary congestion or frank pulmonary edema.
• Active intracranial bleeding except during craniotomy.
• Severe dehydration.
• Progressive renal damage or dysfunction after institution of
mannitol therapy, including increasing oliguria and
azotemia.
• Progressive heart failure or pulmonary congestion after
institution of mannitol therapy.
• Do not administer to patients with a known hypersensitivity
to mannitol.
GEETANJALI S VERMA
A/E
• Cardiac failure pts – pulm edema
• Hypovolemia
• Electrolyte imbalance
• Plasma hyperosmolarity
GEETANJALI S VERMA
AVAILABILITY
Conc % g/100ml mOsm/L pH
5 5 274 6.3
10 10 549 6.3
15 15 823 6.3
20 20 1098 6.3
25 25 1372 5.9
GEETANJALI S VERMA

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Mannitol

  • 1. MANNITOL DR GEETANJALI S VERMA DEPT OF ANESTHESIA GEETANJALI S VERMA
  • 2. • Osmotic diuretic – Freely filterable at glomerulus – Ltd reabsorption fm renal tubules – Resist metabolism – Pharmacologically inert • 6 carbon sugar GEETANJALI S VERMA
  • 3. • Doesn’t undergo metabolism • Not absorbed from GIT • Doesn’t enter cells • Clearance from plasma by glomerular filtration GEETANJALI S VERMA
  • 4. MOA Completely filtered at glomeruli ↓ Increases osmolarity of renal tubular fluid Prevents re absorption of water ↓ Na+ dilution in retained water Less re absorption of Na+ ↓ Urinary excretion of Na+, Cl-, HCO3- (urinary pH not altered) GEETANJALI S VERMA
  • 6. Increases plasma osmolarity ↓ Draws fluid fm intra to extra cellular spaces ↓ Acute expansion of intravascular fluid volume ↓ Decreases brain bulk, increases renal blood flow to medulla GEETANJALI S VERMA
  • 7. Oxygen radical scavenger ↓ Prevents cellular swelling Reduces renal tubular obstruction GEETANJALI S VERMA
  • 8. USES 1. Prophylaxis against acute renal failure 2. D/d of acute oliguria 3. T/t of increased ICP 4. To decreased IOP GEETANJALI S VERMA
  • 9. West J Med. 1979 October; 131(4): 277–284 • Allen R. Nissenson, MD, Raymond E. Weston, MD, and Charles R. Kleeman, MD • Author information ► Copyright and License information ► Abstract • Mannitol may be useful clinically both as a diuretic and as an obligate extracellular solute. As a diuretic it can be used to treat patients with intractable edema states, to increase urine flow and flush out debris from the renal tubules in patients with acute tubular necrosis, and to increase toxin excretion in patients with barbiturate, salicylate or bromide intoxication. As an obligate extracellular solute it may be useful to ameliorate symptoms of the dialysis disequilibrium syndrome, to decrease cerebral edema following trauma or cerebrovascular accident, and to prevent cell swelling related to renal ischemia following cross-clamping of the aorta. Largely unexplored uses for mannitol include its use as an osmotic agent in place of dextrose in peritoneal dialysis solutions, its use to maintain urine output in patients newly begun on hemodialysis, and its use to limit infarct size following acute myocardial infarction. GEETANJALI S VERMA
  • 10. • Acute renal failure prophy – After cardiovasc surg, transplantn, extensive trauma, surg in jaundiced pt, nephrotoxic condn – Van Valenberg et al , 1984 : ARF less in pts receiving mannitol prior to revascularisation of transplanted kidney GEETANJALI S VERMA
  • 11. • Diagnosis of acute oliguria – 0.25g/kg IV – Urine output increased = intravasc fluid vol depletion – No increase = glomerular/ renal tubular fn compromised GEETANJALI S VERMA
  • 12. • t/t of increased ICP – 0.25-1 g/kg – Increases plasma osm – withdraws fluid fm brain tissues – Vasodil of vasc smooth muscle – Decreases rate of formn of CSF – Effective within 10-15mins of adm, lasts for 2hrs – No rebound increase GEETANJALI S VERMA
  • 13. Bratton – J Neurotrauma - 2007 GEETANJALI S VERMA
  • 14. Francony – Crit Care Med - 2008 GEETANJALI S VERMA
  • 15. Mannitol … but No oxygenation improvement compared to HS Oddo – JNNP - 2009Sakowitz – J Trauma - 2007 Mannitol PtiO2 PitO2: - normal = 35 mm Hg - Ischemic threshold < 10-15 mm Hg GEETANJALI S VERMA
  • 16. NATO study To prove non-inferiority of HS vs mannitol on brain metabolism Sample size : 30 patients 15 mannitol (1 g/kg), 15 HS 7.5% (2 mL/kg) Same osmotic load Main objective : effects on lactate/pyruvate ratio (redox potential) Secondary objectives : effects on ICP, PtiO2, cerebral glucose GEETANJALI S VERMA
  • 18. • Reduction of IOP – Increases plasma osm, withdraws fluid fm intraocular space GEETANJALI S VERMA
  • 19. C/I • Well established anuria due to severe renal disease. • Severe pulmonary congestion or frank pulmonary edema. • Active intracranial bleeding except during craniotomy. • Severe dehydration. • Progressive renal damage or dysfunction after institution of mannitol therapy, including increasing oliguria and azotemia. • Progressive heart failure or pulmonary congestion after institution of mannitol therapy. • Do not administer to patients with a known hypersensitivity to mannitol. GEETANJALI S VERMA
  • 20. A/E • Cardiac failure pts – pulm edema • Hypovolemia • Electrolyte imbalance • Plasma hyperosmolarity GEETANJALI S VERMA
  • 21. AVAILABILITY Conc % g/100ml mOsm/L pH 5 5 274 6.3 10 10 549 6.3 15 15 823 6.3 20 20 1098 6.3 25 25 1372 5.9 GEETANJALI S VERMA