2014B14 Outline the effects of intravenously administering 500mL of 20% mannitol.
Outline the potential problems associated with its use.

 

List:

·         Introduction: mannitol

·         Fluid compartment effects

·         Organ system effects

 

Intro: mannitol:

Summary

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

·   Substance derived from mannose, a monosaccharide

·   Causes plasma volume expansion (VE) then contraction (VC) i.e. significant fluid shifts

·   Uses: emergency reduction in ICP, osmotic diuresis

Numbers

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

·   20% 500mL = 550mosmoles

 

Fluid compartments:

VE

·   ECF expands >500mL

o  Initial ↑↑plasma volume

o  Then ¾ interstitial, ¼ plasma after equilibration

·   ICF contracts

VC

·   Due to osmotic diuresis

·   ECF contracts

·   ICF contracts

 

Electrolytes:

VE

·   Osmolality: ↑↑

·   Electrolyte concentrations ↓ due to dilution by osmosis

VC

·   Osmolality: ↑

·   Aldosterone -> ↑synthesis and activity Na+K+ATPase -> ↑activity ENaC and ROMK -> ↑ECF [Na+], ↓[K+]

·   If ↑Na+ rapid -> risk central pontine myelinolysis

·   If ↑K+ severe -> arrhythmia

·   If severe: tissue ↓perfusion -> lactic acidosis – doesn’t belong here

 

Endocrine:

VE

Aim to ↓plasma volume:

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

VC

Aim to ↑plasma volume:

·   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

 

Renal:

VE

·   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)

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

VC

·   ↓GFR if mAP <70 (failed autoregulation)

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

 

CVS:

VE

·   ↑Preload -> risk of APO

VC

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

·   Vascular irritation

 

CNS:

VE

·   Osmotic dehydration: water moves from ICF to ECF

·   ↓brain volume, ↓ICP

VC

·   Production of idiogenic osmoles causes offset +/- rebound cerebral oedema

·   (glycine, glutamine, taurine, inositol etc.)

 

 

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