2020B12 Outline the effects of intravenously administering 500mL of 20% mannitol.
Outline the potential problems associated with its use.

 

List:

·         Introduction: mannitol

·         Cerebral

·         Circulatory

·         Renal

 

Intro:

Summary

·   Large (182g/mol) and polar hence does not cross cell membranes including blood-brain barrier

·   Substance derived from mannose, a monosaccharide

·   Uses: emergency reduction in ICP, osmotic diuresis

Numbers

·   20% mannitol -> 200mg/mL –> 1100mOsmol/L (cf. plasma 290mOsmol/L)

·   20% 500mL = 550mosmoles

Fluid shifts

·   Volume expansion phase (VE): ↑500mL plasma volume, ↑plasma osmolality -> contraction of ICF

·   Volume contraction phase (VC): osmotic diuresis, ↓plasma volume

 

Renal:

VE

Direct:

·   Mannitol freely filtered, not reabsorbed, not secreted

·   ↑Tonicity of glomerular filtrate -> impairment of proximal tubular reabsorption (most important effect)

·   ↑Renal plasma flow rate, washout of medullary interstitium

·   ↑Urine flow rate (osmotic drag)

Compensation:

·   ↑ Na+/K+ exchange in distal nephron due to high flow rate

VC

Direct:

·   ↓GFR if mAP <70 (failed autoregulation)

Compensation:

·   ↑ Na+/K+ exchange in distal nephron: due to aldosterone

 

Circulatory:

VE

Direct:

·   ↑Preload -> risk of APO

Compensation:

·   ANP: ↑RA stretch -> ↑release -> diuresis, natriuresis

VC

Direct:

·   ↓Preload -> ↓CO, ↓mAP, ↓organ perfusion -> lactic acidosis if severe

·   Vascular irritation

Compensation:

·   RAAS: ↓mAP -> ↑renin/angiotensin 2/aldosterone -> ↑Na+ and H2O reabsorption, vasoconstriction

·   ADH: ↓blood volume (if 10%) -> ↑release -> ↑H2O reabsorption

·   SNS: ↓blood vol -> ↑release -> vasoconstriction, ↑CO

 

Cerebral:

VE

·   Osmotic dehydration

·   Hence ↓brain volume, ↓ICP

VC

·   Production of idiogenic osmoles (glycine, glutamine, taurine, inositol etc.)

·   Hence risk of rebound cerebral oedema

 

 

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