Continuous renal replacement therapy-related strategies to avoid colistin toxicity: a clinically orientated review

Area of Science:

• Pharmacology
• Nephrology
• Infectious Diseases

Background:

• Polymyxins, including colistin, are crucial for treating multidrug-resistant Gram-negative infections.
• Colistin's use is limited by renal and neurological toxicity, necessitating careful dosing, especially in critically ill patients.
• Continuous renal replacement therapy (CRRT) is common in intensive care units for acute kidney injury or hemodynamic instability.

Purpose of the Study:

• To investigate the safety and efficacy of higher colistin doses in patients undergoing CRRT.
• To explore the pharmacokinetic interaction between colistin and CRRT.

Main Methods:

• Pharmacological data analysis and clinical experience review.
• Postulation of an optimized dosing regimen for colistin in CRRT patients.
• Emphasis on specific CRRT parameters like highly adsorptive membranes and citrate anticoagulation.

Main Results:

• Patients on CRRT can tolerate significantly higher colistin doses (high loading dose, up to 4.5 million IU t.i.d. maintenance).
• CRRT facilitates colistin clearance through filtration and membrane adsorption, preventing drug accumulation.
• Prolonged colistin treatment is feasible without increased toxicity in this population.

Conclusions:

• A 'CRRT rescue' therapy with optimized colistin dosing is proposed for severe infections.
• This approach requires specific CRRT configurations (highly adsorptive membranes, citrate anticoagulation) for maximal efficacy.
• Higher colistin doses can be safely administered to CRRT patients, expanding treatment options for resistant infections.