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

Phases

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

·  Volume contraction (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)

·  Does not protect against renal failure

Compensation:

·  ↑ Na+/K+ exchange in distal nephron -> ↑Na+, ↓K+ (due to high flow rate)

VC

Direct:

·  ↓GFR if mAP <70

Compensation:

·  ↑ Na+/K+ exchange in distal nephron -> ↑Na+, ↓K+ (due to aldosterone)

 

Circulatory:

VE

Direct:

·  ↑Preload -> risk of APO

·  ↓Viscosity -> ↑regional microcirculatory flow (incl. CNS)

·  Thrombophlebitis (hence require CVC)

Compensation:

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

VC

Direct:

·  ↓Preload -> ↓CO, ↓mAP, ↓cerebral perfusion

·  ↑Viscosity -> ↓regional microcirculatory flow

·  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 -> ↓CNS volume -↓ICP

·  Only occurs if BBB intact

·  Peak effect 30-45mins, duration 6 hours

VC

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

·  Hence risk of rebound cerebral oedema

 

 

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