Meropenem Dosing for Sepsis in Patients on CVVHD at 1000 mL/hr
For a septic patient on CVVHD running at 1000 mL/hr, administer meropenem 1000 mg intravenously every 8 hours as a 30-minute bolus infusion, or alternatively 500 mg every 6 hours if treating organisms with MIC 2-4 mg/L. 1
Initial Dosing Strategy
Administer a full loading dose of 1000 mg immediately, regardless of renal function, as loading doses are determined by volume of distribution (not renal clearance) and are essential to rapidly achieve therapeutic levels in critically ill septic patients with expanded extracellular volume from fluid resuscitation 2, 3.
The standard maintenance regimen of 1000 mg every 8 hours achieves adequate plasma concentrations above the MIC for most susceptible pathogens (MIC ≤2 mg/L) during CVVHD 1, 4, 5.
Pharmacokinetic Considerations Specific to CVVHD
At CVVHD flow rates around 1000 mL/hr (approximately 24 L/day), meropenem clearance is primarily influenced by residual diuresis rather than CRRT intensity 1.
In oligoanuric patients (minimal residual urine output), total body clearance averages 3.68 L/hr, with CVVHD contributing approximately 1.2-1.6 L/hr of drug removal 1, 6.
Patients with preserved diuresis (>500 mL/24hr) have significantly higher meropenem clearance and may require dose adjustments 1.
The elimination half-life during CVVHD ranges from 2.5-4.8 hours, substantially shorter than the 13.7 hours seen in anuric patients not receiving renal replacement therapy 1, 7, 5.
Optimizing Pharmacodynamic Targets
For beta-lactam antibiotics like meropenem, the critical pharmacodynamic parameter is time above MIC (T>MIC), with optimal outcomes in severe sepsis requiring 100% T>MIC 3.
Dosing Based on Target Organism MIC:
For susceptible organisms (MIC ≤2 mg/L):
For organisms at resistance breakpoint (MIC 2-4 mg/L):
Alternative high-dose regimen: 1500 mg every 12 hours or 750 mg every 8 hours both achieve therapeutic targets during CVVHD 6.
Extended Infusion Strategy
Consider administering meropenem as a 3-4 hour extended infusion rather than 30-minute bolus to optimize T>MIC, particularly in patients with preserved diuresis or when treating less susceptible organisms 1, 3.
Extended infusions improve pharmacodynamic target attainment and have demonstrated improved clinical outcomes in critically ill septic patients, with a recent meta-analysis showing independent protective effect of continuous beta-lactam therapy 3.
Monitoring Residual Diuresis
Measure 24-hour urine output daily as this is the single most important clinical parameter affecting meropenem clearance during CVVHD 1.
Patients with residual diuresis >500 mL/24hr have approximately 22% higher meropenem clearance per 100 mL of additional urine output 1.
This simple bedside parameter allows dose titration without expensive therapeutic drug monitoring 1.
Critical Pitfalls to Avoid
Never reduce or omit the loading dose due to renal dysfunction—this is a common error that delays achievement of therapeutic concentrations 2.
Do not underdose based on older recommendations suggesting 500 mg every 12 hours, as these regimens fail to achieve 100% T>MIC targets necessary for optimal outcomes in severe sepsis 1, 7.
Avoid assuming CRRT intensity alone determines dosing requirements—residual renal function is equally or more important than dialysis flow rate 1.
Do not delay antibiotic administration to adjust for renal function; give the full dose immediately as each hour of delay increases mortality in sepsis 2, 3.
Special Considerations for Septic Shock
In septic shock with hemodynamic instability, CVVHD is preferred over intermittent hemodialysis as it facilitates fluid balance management during aggressive resuscitation 3, 8.
Meropenem is removed by CVVHD (13-53% depending on modality), but removal is predictable and less variable than with intermittent hemodialysis 7.
The excellent tolerability profile of meropenem allows for higher dosing without significant toxicity concerns, making it preferable to risk underdosing in critically ill septic patients 7.