Quantification and Dosing of Renal Replacement Therapy in Acute Kidney Injury: A Reappraisal

Clark, William R.; Leblanc, Martine; Ricci, Zaccaria; Ronco, Claudio

doi:10.1159/000475457

Cited by 27 publications

(16 citation statements)

References 68 publications

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“…and CL NCA is the NCA derived total apparent drug clearance. 7,[19][20][21][22] The following equations were used to calculate the predicted total clearance for each patient:…”

Section: Continuous Renal Replacement Therapy Proceduresmentioning

confidence: 99%

Optimizing ceftaroline dosing in critically ill patients undergoing continuous renal replacement therapy

et al. 2021

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Background and Objectives: Currently, no dosing information exists for ceftaroline fosamil in patients undergoing continuous renal replacement therapy (CRRT). The objectives of this study are to characterize the pharmacokinetics of ceftaroline in critically ill patients undergoing CRRT modalities and to derive individualized dosing recommendations. Methods: This pharmacokinetic study aimed to enroll critically ill patients receiving ceftaroline fosamil and any CRRT modality from adult intensive care units. Selection of the specific CRRT modality and dosing regimen was based on clinical discretion. Pre-filter, post-filter, and ultrafiltrate samples were obtained before the administration of the fourth dose, after the completion of the infusion, and up to five additional time points post-infusion. Plasma concentrations were measured using a validated ultra-high performance liquid chromatography assay. Individual pharmacokinetic parameters were calculated using non-compartmental analysis. Results: Four patients were enrolled to investigate the need for dosing adjustments. The average sieving coefficient for ceftaroline was 0.81 ± 0.1, indicating high filter efficiency. The average volume of distribution was 41.8 L (0.48 L/kg) and is within the previously reported range in patients with normal renal function. Non-renal clearance accounted for more than 50% of the total clearance observed in patients. The observed pharmacokinetic profiles suggest that the pharmacodynamic target for 2log 10 CFU reduction from baseline (%fT >1 mg/L of 50%) was met for each patient. Due to the impact of CRRT and non-renal clearance, dosing recommendations were derived for different ranges of effluent flow rates and adjusted body weights. For a patient with an adjusted body weight of 70 kg and receiving CRRT at an effluent flow rate of 3 L/h, a ceftaroline fosamil dosing regimen of 400 mg every 12 h is proposed. Conclusion: Ceftaroline is cleared extensively in critically ill patients receiving CRRT and may impact pharmacodynamic target achievement. Dose adjustments should be based on the intensity of the CRRT regimen, patient weight, and the clinical status of the patient.

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“…and CL NCA is the NCA derived total apparent drug clearance. 7,[19][20][21][22] The following equations were used to calculate the predicted total clearance for each patient:…”

Section: Continuous Renal Replacement Therapy Proceduresmentioning

confidence: 99%

Optimizing ceftaroline dosing in critically ill patients undergoing continuous renal replacement therapy

et al. 2021

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“…4), 27 and percentage of total drug clearance contributed by CVVH (Eq. 5) 28 at each sampling time point:…”

Section: Patient Data Collectionmentioning

confidence: 99%

“…4), 27 and percentage of total drug clearance contributed by CVVH (Eq. 5) 28 15 The following equations were used to calculate the new dose for each patient 29 : Renal Disease formula), or blood urea nitrogen was further evaluated. 30 Current literature reports that total LEV clearance is ~ 0.96 mL/minute/kg.…”

Section: Pk Analysismentioning

confidence: 99%

A Practice‐Based, Clinical Pharmacokinetic Study to Inform Levetiracetam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration (PADRE‐01)

Kalaria

Armahizer

McCarthy

et al. 2020

Clinical Translational Sci

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Limited data exist on the effect of continuous renal replacement therapy (CRRT) methods on anti‐epileptic drug pharmacokinetics (PK). This prospective practice‐based PK study aims to assess the impact of continuous venovenous hemofiltration (CVVH), a modality of CRRT, on levetiracetam PK in critically ill patients and to derive individualized dosing recommendations. Eleven patients receiving oral or intravenous levetiracetam and CVVH in various intensive care units at a large academic medical center were enrolled to investigate the need for dosing adjustments. Prefilter, postfilter, and ultrafiltrate samples were obtained before dosing, after the completion of the infusion or 1‐hour postoral dose, and up to 6 additional time points postinfusion or postoral administration. Patient‐specific blood and ultrafiltrate flow rates and laboratory values were also collected at the time of sampling. The average sieving coefficient (SC) for levetiracetam was 0.89 ± 0.1, indicating high filter efficiency. Six of the 11 patients experienced concentrations outside the reported therapeutic range (12–46 mg/L). The average volume of distribution was 0.73 L/kg. CVVH clearance contributes a major fraction of the total levetiracetam clearance (36–73%) in neurocritically ill patients. The average bias and precision of the estimated vs. observed total clearance value was ~ 10.6% and 21.5%. Major dose determinants were identified to be SC and effluent flow rate. Patients with higher ultrafiltrate rates will have increased drug clearance and, therefore, will require higher doses in order to match exposures seen in patients with normal renal function.

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“…Previous studies have discussed the derivation for various CRRT based metrics using principles of fluid dynamics. [21][22][23][24] The sieving coefficient (Equation 1), 21 effluent flow rate (Equation 2), 22 CVVH clearance (Equation 3), 22,23 filtration fraction (Equation 4) 24 and percentage of total drug clearance contributed by CVVH (Equation 5) 25 at each sampling time point were estimated using the following equations:…”

Section: Pharmacokinetic Analysismentioning

confidence: 99%

A prospective, real‐world, clinical pharmacokinetic study to inform lacosamide dosing in critically ill patients undergoing continuous venovenous haemofiltration (PADRE‐02)

Kalaria

Armahizer

McCarthy

et al. 2021

Brit J Clinical Pharma

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Aims: Although the use of continuous renal replacement therapy (CRRT) has increased, limited dosing information exists on the effect of CRRT on antiepileptic drug pharmacokinetics. The objectives of this practice-based study are to evaluate the pharmacokinetics of lacosamide and recommend individualized dosing recommendations in critically ill patients receiving continuous venovenous haemofiltration (CVVH).Methods: Seven patients receiving lacosamide and CVVH in a neurocritical care unit were enrolled. Pre-filter, post-filter and ultrafiltrate samples were obtained at baseline, right after the completion of the infusion, and up to six additional sampling time points post-administration. Patient-specific flow rates and clinical measures were also collected simultaneously at the time of sampling. Plasma concentrations were measured using a validated high-performance liquid chromatography with ultraviolet radiation detection (HPLC-UV) bioanalytical method. Non-compartmental analysis was utilized to characterize the pharmacokinetics of lacosamide. Results:The observed mean sieving coefficient for lacosamide was 0.80 ± 0.10, suggesting high removal of lacosamide. Concentrations measured in six out of seven patients were observed to be outside the therapeutic range (5-12 mg/L). The estimated average volume of distribution was found to be similar to healthy patients (0.58 L/kg). The mean bias and precision of the estimated total clearance was À2.53% and 14.9%, respectively. Simulations of various doses suggest that effluent flow rate-based dosing regimens could be used to individualize lacosamide therapeutics.Conclusions: CVVH clearance contributed a major fraction of the total lacosamide clearance in neurocritically ill patients. Given that drug clearance increases with higher effluent flow rates, lacosamide dosing regimens should be increased to match exposures observed in patients with normal renal function.

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Quantification and Dosing of Renal Replacement Therapy in Acute Kidney Injury: A Reappraisal

Cited by 27 publications

References 68 publications

Optimizing ceftaroline dosing in critically ill patients undergoing continuous renal replacement therapy

Optimizing ceftaroline dosing in critically ill patients undergoing continuous renal replacement therapy

A Practice‐Based, Clinical Pharmacokinetic Study to Inform Levetiracetam Dosing in Critically Ill Patients Undergoing Continuous Venovenous Hemofiltration (PADRE‐01)

A prospective, real‐world, clinical pharmacokinetic study to inform lacosamide dosing in critically ill patients undergoing continuous venovenous haemofiltration (PADRE‐02)

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