Loading Dose Administration in Critically Ill Patients

Antimicrobials Requiring Loading Doses

• The American Thoracic Society recommends that loading doses should be administered for critically ill patients requiring rapid achievement of therapeutic drug concentrations, particularly for antimicrobials with low volumes of distribution, such as polymyxins, beta-lactams, and vancomycin, regardless of renal function or severity of illness 1, 2, 3
• The Infectious Diseases Society of America suggests that colistin requires a loading dose of 6-9 million IU in all patients, including those with renal dysfunction, because plasma concentrations remain suboptimal for 2-3 days before reaching steady state without a loading dose 1, 4
• The Society of Critical Care Medicine recommends that polymyxin B requires a loading dose of 2-2.5 mg/kg to achieve optimal plasma levels on the first day 1, 4
• The American College of Chest Physicians advises that all critically ill patients should receive a loading dose when starting beta-lactam therapy, independent of whether continuous or intermittent administration is planned 2, 3
• The European Society of Clinical Microbiology and Infectious Diseases suggests that the loading dose should equal the standard intermittent dose (e.g., 4g piperacillin if planning 12g/24h continuous infusion) 2, 3
• Meta-analysis data shows mortality reduction only occurs when loading doses precede continuous infusions (RR 0.63 vs 0.56 without loading dose), as recommended by the Society of Critical Care Medicine 2, 3
• The American Heart Association recommends that for seriously ill patients with suspected MRSA infection, administer a loading dose of 25-30 mg/kg (actual body weight) of vancomycin 5
• The Infectious Diseases Society of America suggests that loading doses enable rapid achievement of therapeutic concentrations in critically ill patients with expanded extracellular volume from fluid resuscitation 5, 6

Cardiovascular Medications

• The American College of Cardiology recommends that esmolol requires a loading dose of 500 mcg/kg (0.5 mg/kg) over 1 minute before starting maintenance infusion to rapidly control heart rate in tachyarrhythmias 8
• The European Society of Cardiology suggests that amiodarone requires 150 mg over 10 minutes as a loading dose for stable narrow-complex tachycardias or pre-excited atrial arrhythmias 8
• The American Heart Association advises that digoxin requires 8-12 mcg/kg total loading dose, with half administered initially over 5 minutes 8

Key Principles for Loading Dose Administration

• The Society of Critical Care Medicine recommends that loading doses are essential for drugs with low volumes of distribution in critically ill patients because these patients have expanded extracellular volumes from fluid resuscitation 2, 3, 5, 6
• The American College of Clinical Pharmacy suggests that loading doses are not affected by renal dysfunction and should be administered at full doses even in patients with acute kidney injury or chronic kidney disease 1, 4, 6, 7
• The European Society of Clinical Microbiology and Infectious Diseases advises that only maintenance doses require adjustment for renal function 1, 4

Common Pitfalls to Avoid

• The Infectious Diseases Society of America recommends that never use fixed 1-gram doses for vancomycin loading as this results in underdosing in most patients, especially those weighing >70 kg 5
• The Society of Critical Care Medicine suggests that do not skip loading doses when initiating continuous infusions of beta-lactams, as this delays achievement of therapeutic concentrations and may contribute to treatment failure 2, 3
• The American College of Clinical Pharmacy advises that avoid giving loading doses to patients already on maintenance therapy unless levels are documented to be subtherapeutic 6