Influence of venovenous extracorporeal membrane oxygenation on pharmacokinetics of vancomycin in lung transplant recipients

Abstract

What is known and objective The influence of venovenous extracorporeal membrane oxygenation (VV‐ECMO) on the population pharmacokinetics (PPK) of vancomycin in recipients after lung transplantation (LTx) is unknown. We investigated whether VV‐ECMO influences vancomycin PPK and determined optimal recommended dosage for patients after LTx. Methods We tested vancomycin serum concentration and calculated PPK parameters using NONMEM. To check for any potential influence of ECMO on vancomycin PK, we compared ECMO patients with a non‐ECMO patient control group, and patients before and after ECMO weaning as self‐control to analysed changes in vancomycin PK. Monte Carlo dosing simulation was conducted to explore vancomycin dosing regimens. Results Nineteen ECMO and 6 non‐ECMO lung transplant recipients were enrolled. Vancomycin serum concentrations did not significantly differ between patients with and without ECMO support. Comparison of separate vancomycin population pharmacokinetic models showed that ECMO patients had smaller peripheral compartment volume of distribution (V2) [Estimate (relative standard error, RSE, %) 19.7 (12) vs. 22 (17) L, P = .003] than non‐ECMO patients. For treatment of methicillin‐resistant Staphylococcus aureus (MRSA) infections with MIC ≤ 0.5 µg/mL, venous infusion of 400 mg vancomycin every 8 hours was recommended. For MRSA infection with MIC ≤ 1 µg/mL, the proposed dosage was 600 mg every 8 hours. What is new and conclusion Venovenous extracorporeal membrane oxygenation slightly alters vancomycin PK but does not significantly impact vancomycin serum concentration in patients after LTx. Dose adjustment is not necessary for VV‐ECMO support. Specific vancomycin dosing regimens with lower nephrotoxicity may benefit LTx recipients with VV‐ECMO.

Antibiotics and ECMO in the Adult Population—Persistent Challenges and Practical Guides

“…Analysis of retrospective data suggested no significant difference in drug concentration, Vd or clearance in ECMO vs. non-ECMO patients [104]. Vancomycin pharmacodynamics are largely unaffected by ECMO in several studies [103,105,106]. These results are not universal, as Park et al demonstrated decreased levels in ECMO patients despite similar elimination rates, as seen in prior studies [106,107].…”

“…Various properties of specific antibiotics directly influence ECMO effects on their pharmacodynamics. These include whether the antibiotic itself is lipophilic or hydrophilic, the tendency for protein binding, and the site of metabolic breakdown (Table 1) [82,102,103]. Furthermore, target MIC may vary by an agent or pathogen sensitivity.…”

“…Current recommendations are: loading dose of 25-30 mg/kg followed by 15-20 mg/kg q81-2h dosage, as guided by therapeutic monitoring [43]. Another proposed regimen specifically for methicillin-resistant staphylococcus aureus recommended 400 mg q8h for MIC ≤ 0.5 µg/mL, or 600 mg q8h if the MIC was ≤1 µg/mL [103].…”

“…Others trialed 0.5 g every 6 h in 10 ECMO vs. 18 non-ECMO patients, sampling after the fourth dose and finding an increased distribution volume yet decreased clearance, which also recommended increased dosing [112]. Overall, increased dosing may be required, up to 4 g/day in reported cases [43,103], with prolonged infusion of 1 g over 4 h q6h as a recommendable strategy [112].…”

Antimicrobial Exposure in Critically Ill Patients with Sepsis-Associated Multi-Organ Dysfunction Requiring Extracorporeal Organ Support: A Narrative Review

“…In vitro studies suggested large sequestration into the extracorporeal device of antimicrobials such as meropenem [ 77 ], cefazolin [ 76 ], teicoplanin [ 77 ], gentamicin [ 34 ], polymyxin B [ 77 ], vancomycin [ 78 ], micafungin [ 77 ], voriconazole [ 77 ], while this phenomenon was not reported for tigecycline [ 77 ], ciprofloxacin [ 79 ] and caspofungin [ 77 ]. In contrast, in vivo studies reported low bloodstream concentration during ECMO of teicoplanin [ 80 ] and voriconazole [ 81 ], while other antimicrobial concentrations were not significantly influenced by this device [ 20 , 82 , 83 , 84 , 85 , 86 , 87 ]. Recently, Shekar et al investigated antimicrobial exposure in 85 patients who received ECMO, 38 (44.7%) of whom were on RRT.…”