and Fatemeh Ghane Sharbaf2
(1)
Department of Pediatrics Section of Nephrology, Rush University Medical Center, Chicago, IL, USA
(2)
Department of Pediatrics Section of Nephrology, Mashhad University of Medical Sciences, Mashhad, Iran
Drug Removal During CRRT: Basic Principles
Appropriate drug dosing in the acute kidney injury (AKI) patient treated with continuous renal replacement therapies (CRRT) is an important consideration to optimize therapeutic outcomes and to minimize drug toxicity [1–3]. Underdiagnosed and untreated AKI may lead to chronic kidney disease and end-stage renal disease [4]. When adjusting drug doses for the AKI patient, drug doses should be adjusted based on the renal and CRRT clearance of the drug, the degree of renal impairment, and the potential nephrotoxicity of the prescribed drug. The sum of renal creatinine clearance and CVVH ultrafiltration provides a starting point for subsequent antibiotic dosing. Medication dosing for children with AKI needs to be individualized based on pharmacokinetics and pharmacodynamics principles of the prescribed drugs whenever possible [5–11]. Both the volume of distribution and half-life of several drugs are markedly increased in the presence of AKI, and thus larger loading doses may need to be administered to achieve the target serum concentration. It is also necessary to know the degree of protein binding and the half-life of the concerned drug. Because of the presence of a positive fluid balance in the early stages of AKI, the dosing regimen for many drugs, especially antimicrobial agents, should be initiated at normal dosage regimens. When available, therapeutic drug monitoring should be used, especially for drugs with low therapeutic index. Guidelines whether or not dose adjustment is required for children with AKI is provided in Table 5.1.
Table 5.1
Pediatric drug dosage adjustments during continuous veno-venous hemofiltration (CVVH)a
Drug category | Protein binding (%) | SC | V d L/kg | t 1/2 h | Normal dose (GFR 100) | Dose in CVVH <1–2 L/h GFR < 15–30 |
|---|---|---|---|---|---|---|
Analgesic | ||||||
Acetaminophen | 20–50 | 0.93 | 0.2–0.4 | 2–3 | 5 mg/kg iv q8h | No change |
Acetylsalicylic | >99 | 50 | 0.25 | 0.8 | 10 mg/kg q4–6h | No change |
Codeine | 7 | NA | 3–6 | 3 | 0.5–1 mg/kg q6h | 75 % dose reduction |
Ibuprofen | 90–99 | NA | 0.14 | 1.8 | 5–10 mg/kg q6h | No change |
Ketorolac | >99 | NA | 0.1–0.3 | 5 | 0.25–1 mg/kg q6h | No change |
Fentanyl | 80–85 | 0.29 | 2.4 | 2.6 | 1–5 mcg/kg q6h | 75 % dose reduction |
Meperidine | 60–85 | NA | 2.4 | 11 | 0.5–2 mg/kg infusion | 75 % dose reduction |
Methadone | 60–90 | NA | 4.5 | 8–49 | 0.5 mg/kg q6h | 0.5 mg/kg q24h |
Morphine | 20–35 | 0.65 | 3.3 | 2.5 | 0.05–0.2 mg/kg iv q2–4h | 75 % dose reduction |
Antibiotics | ||||||
Aciclovir | 9–33 | 0.85 | 0.7 | 2–3 | 10 mg/kg iv q8h | Normal dose iv q24h |
Amikacinb | <20 | 0.95 | 0.2–0.7 | 1.6-2.5 | 20 mg/kg (max 1.5 g) iv q24h | 10 mg/kg iv q24h |
Amoxicillin | 15–20 | 0.85 | 1.3 | 5–20 | 5–15 mg/kg iv q8h | No change |
Amphotericin liposomal | 90 | NA | 0.1–0.4 | 6–10 | 3–5 mg/kg iv q24h | No change |
Ampicillin | 17–20 | 0.8 | 0.32 | 1–1.8 | 50 mg/kg iv q8h | No change |
Azithromycin | 10–50 | NA | NA | 6–8 | 5 mg/kg q12 | No change |
Aztreonam | 50–60 | NA | 0.25 | 2 | 80–120 mg/kg q8h | No change |
Benzylpenicillin | 60 | NA | 0.3–0.4 | 0.5–1.2 | 25–50 mg/kg iv in q8h | No change |
Cefaclor | 20–50 | NA | 0.24–0.35 | 1 | 10–20 mg/kg iv q12h | No change |
Cefazolin | 70–86 | NA | 0.13–0.22 | 2 | 50–100 mg/kg iv q8h | 505 dose reduction |
Cefotaxime | 40 | NA | 0.3 | 1.5 | 50 mg/kg iv q8–12h | No change |
Ceftazidime | <10 | NA | 0.2–0.4 | 1 | 25 mg/kg iv q8h | No change |
Ceftriaxone | 85–95 | 0.66 | 0.35 | 8 | 80 mg/kg (max 2 g) iv q24h | No change |
Cefuroxime | 33 | 0.66 | 0.19 | 1.5 | 25–50 mg/kg iv q8h | 25–50 mg/kg iv q12–24 h |
Cidofovir | <10 | NA | 0.3 | 15–25 | 5 mg/kg iv q 1–2 weeks | 2 mg/kg iv q1-2 weeks |
Ciprofloxacin | 20–40 | 0.7 | 2–3 | 4–5 | 10 mg/kg (max 400 mg) iv q12h | 25 % reduction q 12 h |
Clindamycin | >90 | 0.4 | 0.6–1.2 | 2–3 | 5–10 mg/kg (max 1.2 g) iv q6h | No change |
Co-amoxiclav (amoxicillin + clavulanic acid) | 17–30 | NA | 0.2–0.4 | 0.9 | 30 mg/kg (max 1.2 g) iv q8h | 50 % dose reduction |
Co-trimoxazole (trimethoprim + sulfamethoxazole) | 50–66 | NA | 0.3–2.2 | 5.5–17 | 40–60 mg/kg ivq12h | 50 % dose reduction |
Erythromycin | 70–95 | 0.3 | 0.6–1.2 | 2 | 12.5–25 mg/kg iv q6h | No change |
Flucloxacillin | 95 | NA | 0.13 | 2–3 | 25–100 mg/kg iv q8h | No change |
Fluconazole | 12 | NA | 0.6–1.2 | 15–20 | 6–12 mg/kg iv q72h | No change |
Ganciclovir | 1–2 | 0.84 | 0.4–0.8 | 3–28 | 5 mg/kg iv q12h | 50 % dose reduction |
Gentamicinb | 1–30 | 0.95 | 0.2–0.5 | 1–3 | 7 mg/kg iv q24h | 4 mg/kg iv q24h |
Imipenem | 13–21 | 1 | 0.5 | 1–1.3 | 15 mg/kg (max 500 mg) iv q6h | 25 % dose reduction |
Isoniazid | 10–15 | NA | NA | 2.8 | 10–15 mg/kg q12–24h | No change |
Ketoconazole | 85–99 | NA | 2–4 | 8 | 3–6 mg/kg q24h | No change |
Levofloxacin | 25–38 | 0.8 | NA | NA | 5–10 mg/kg q24h | No change |
Meropenem | 2 | NA | 0.4 | 1.5–2.3 | 10–20 mg/kg iv q8h | No change |
Metronidazole | <20 | 0.8 | 1.1 | 6–12 | 7.5 mg/kg (max 500 mg) iv q8h | No change |
Nafcillin | 90 | 0.2 | 0.35 | 1 | 15–50 mg/kg iv q4–6h | No change |
Flaxacillin | 20–30 | NA | NA | NA | 15 mg/kg iv q12h | No change |
Piperacillin | 20–30 | NA | 0.2 | 0.7 | 200 mg/kg q4h | 200 mg/kg q8h |
Rifampicin | 80 | 0.2 | 0.66 | 1–3.8 | 10 mg/kg (max 500 mg) iv q12h | No change |
Streptomycin | 34 | NA | NA | 5–8 | 20–40 mg/kg iv q24h | 7.5 mg/kg q24h |
Ticarcillin | 45–65 | NA | 0.22 | 1.1 | 80 mg/kg (max 3.2 g) q8h | No change |
Tobramycin | 44–50 | 1.6 | 1.6 | 11 | 60 mg/kg iv q12h | 50 % dose reduction |
Vancomycinb | 55 | NA | 0.4–0.7 | 5.6 | 15 mg/kg iv q8h | 10 mg/kg iv q12h |
Anticoagulants | ||||||
Heparinc | 95 | <0.1 | 1 | 2 | 10–25 U/kg/h | No change |
Warfarin | >90 | 0.02 | 0.05 | 50 | 0.5–8 mg q24h | No change |
Anticonvulsants | ||||||
Carbamazepine | 75–90 | 74 | 0.25 | 1.3 | 5–10 mg/kg q12h | 75 % dose reduction |
Phenobarbital | 30–50 | 0.6 | 0.8 | 80 | 3–7 mg/kg q24h | 10 mg/kg q 6-8 h |
Phenytoin | 80–90 | 0.1 | 0.6 | 20 | 3–7 mg/kg q8h | No change |
Valproic acid | 80–93 | 0.1 | 0.2–1 | 9–16 | 10–30 mg/kg q12h | No change |
Antihistamines | ||||||
Cimetidine | 19 | 0.8 | 1 | 2 | 4–8 mg/kg q12h | 50 % dose reduction |
Diphenhydramine | 78 | NA | 3–6 | 5–11 | 1 mg/kg q4–6h | No change |
Famotidine | 15–20 | NA | 1–1.5 | 2–4 | 0.5 mg/kg q12h | No change |
Terbutaline | 25 | NA | 1.6 | 5.7 | 0.1–0.4 mg/kg/min iv infusion | No change |
Antihypertensive agents | ||||||
Amlodipine | 93 | NA | 21 | 40 | 0.05–0.17 mg/kg q24h | No change |
Captopril | 30 | NA | 1.5 | 1.5 | 0.1–0.5 mg/kg q6–8h | 75 % dose reduction |
Clonidine | 20–40 | 0.7 | 2.1 | 8 | 2.5–5 mcg/kg q12h | No change |
Enalapril | <50 | 0.5 | 1.7 | 11 | 0.1 mg/kg q12h | 75 % dose reduction |
Hydralazine | 85–90 | 0.15 mg/Kg q8h | ||||
Isradipine | 95 | 0.13 | 1.5 | 1 | 0.05–0.2 mg/kg q8h | No change |
Labetalol | 50 | 0.4–3 mg/h iv infusion | No change | |||
Lisinopril | 25 | NA | NA | 5–6 | 0.1 mg/kg q12–24h | 0.50 % dose reduction |
Nifedipine | 95 % | 0.08 | 1.2 | 2.8 | 0.25–0.5 mg/kg q6–8h | No change |
Prazosin | 95 | 0.03 | 0.6 | 2.9 | 0.2–1 mg/kg q12h | No change |
Propranolol | 60–90 | 0.07 | 4.3 | 3.5 | 0.1–1 mg/kg q6h | No change |
Cardiovascular agents | ||||||
Amiodarone | 96 | 0.03 | 61 | N/A | 5–10 mg/kg q24h | No change |
Atenolol | <5 | 1 | 0.43 | 6 | 1–2 mg/kg q24h | No change |
Atropine | 14–22 | 0.5 | 2.9 | 2–4 | 0.5–1 mg q5–30min | No change |
Digoxin | 20–55 | 0.8 | 6.5 | 40 | 250 mcg q24h | 62.5 mcg q24h |
Dobutamine | NA | NA | 0.2 | 2 | 2–20 mcg/kg/min iv infusion | No change |
Dopamine | NA | NA | NA | 5.5 | 2–20 mcg/kg/min iv infusion | No change |
Epinephrine | N/A | NA | <0.1 | <0.1 | 0.01–1 mcg/kg/min iv infusion | No change |
Milrinone | 70 | NA | 0.38 | 2.3 | 0.25–0.75 mcg/kg/min iv infusion | 0.33 mcg/kg/min iv infusion |
Procainamide | 15–20 < div class='tao-gold-member'>
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