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

5. 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 Prophylaxis against acute renal failure D/d of acute oliguria T/t of increased ICP 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 a meliorate 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 - 2009 Sakowitz – 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

17. 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

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