Div: Describe calculations of loading dose & maintenance dose for IV infusion. What factors may affect these values in critically ill?


Dose Rate
  • Maintenance dose (mg/hr) = DESIRED SS [ ] (mg/L) x CLEARANCE (L/hr)
  • Loading dose (mg) = DESIRED SS [ ] (mg/L) x VD (L)

Steady State Concentration

  • SS = administered rate equals rate of elimination
Steady State Concentration

Maintenance Dose Continuous Infusion

  • Maintenance dose (mg/hr) = desired SS [ ] x Clearance
    • SS occurs when dose rate = clearance rate
    • Takes 3 – 5 half lives

Maintenance Dose Regular Dosing

  • Achieves SS in steps
  • But again, in 5 half lives

This is ok if drug is going to have some long T effect, but for pain/AF you need immediate drug action & ∴ a LOADING DOSE

Loading Dose

  • LD rapidly achieves SS sooner

LD = DESIRED SS [  ] x Vd

In an infusion SS & therapeutic effect achieved quicker

→ Same effect, but takes longer without load

NB: giving drug PO → all loading/maintenance dose need to be divided by OBA unless OBA is 100%

Effect of Critical Illness on Ld/Maintenance Dose



Effect CI

↑VD (fluid overload)

↓VD (hypovolaemia)

Impact LD/Maintenance


↑Maintenance dose/dose rate



Effect CI

↓renal clearance

↑renal clearance

↓hepatic clearance

↑hepatic clearance

Impact LD/Maintenance

↓maint dose/dose rate

Loading dose no change

↑maint dose/dose rate

No change LD

↓maint dose/dose rate

↓LD PO because less 1st pass

No change LD IV

↑maint dose/dose rate

IV load no change

PO load ↑ because ↑1st pass



Effect CI

↓PPB/competition for PPB

↓gut absorption

Impact LD/Maintenance

↑free drug


Give IV unreliable

Drug Examples

  • Theophylline – 300mg tabs = 37.5mg/hr = infusion rate
  • Phenobarbitone – huge VD → ↑LD for this VD would be lethal
  • Morphine – poor OBA → not given orally
  • Gentamicin – rapid renal clearance
    • ↓renal function =
      • No ∆ LD
      • ↓dose/interval of maintenance dose