Antiarrhythmics

Amiodarone

• Contraindicated in second‑ or third-degree heart block (without pacemaker), symptomatic bradycardia (without pacemaker) or sick sinus syndrome (without pacemaker).
• Check that QT interval is <500 milliseconds before use as amiodarone may increase risk of arrhythmia by prolonging the QT interval. Avoid use if risk factors for prolonged QT interval cannot be corrected

Adenosine

Atropine

Digoxin

Loading in Renal Impairment

• Loading dose $=V_D\times$ target concentration, so clearance doesn’t affect it (see Clinical Significance)
  • But $V_D$ falls in renal impairment, as uraemia reduces tissue binding (from about 7 L/kg to about 4–5 L/kg), so the load still needs reducing
• Jusko–Koup estimate, using lean body weight (digoxin doesn’t distribute into fat):

$$V_D(\text{L})\approx 3.8\times \text{weight (kg)}+3.1\times \text{CrCl (mL/min)}$$

• e.g. 70 kg lean, IV, target 0.8 µg/L (≈1 nmol/L):

CrCl (mL/min)	$V_D$	Loading dose
100	≈580 L	≈460 mcg
30	≈360 L	≈290 mcg
Anuric	≈270 L	≈215 mcg

• Rule of thumb: reduce the load by about 30–50% in severe CKD or ESRD
  • A higher target (e.g. 1.2 µg/L for rate control) scales the dose up proportionally
  • For an oral load, divide by bioavailability (about 0.7 for tablets)

Digoxin loading dose

Works through IBW, CrCl (Cockcroft–Gault), $V_D$ (Jusko–Koup) and the load at each target, with a button to copy the working into a note. Interactive on the website.

In Practice

• Give the load in divided doses, e.g. half, then a quarter at 6 h and a quarter at 12 h if needed
  • Before each step, reassess HR, ECG, K⁺ and a level (≥6 h after the dose)
  • In renal impairment it’s often reasonable to give a single 250 mcg IV dose and reassess, rather than committing to a full load
• Reduce the maintenance dose much more than the load: clearance is about 70% renal, and $t_{1/2}$ goes from about 36 h to about 3.5–5 days in anuria
  • Without a load, steady state takes about 1 week with normal renal function and 2–3 weeks in ESRD, which is why a cautious load is still worth giving and why an overshoot lasts a long time
• Toxicity lasts longer in renal failure
  • Not meaningfully removed by dialysis because of its large $V_D$
  • After digoxin Fab, the Fab–digoxin complex is cleared slowly and free digoxin can rebound days later, so monitor for longer
• Amiodarone raises digoxin levels by about 70–100%, so halve the digoxin dose. This adds to the renal adjustment, and many ICU patients have both