scholarly journals Vancomycin Dosing in Pediatric Extracorporeal Membrane Oxygenation: Potential Impacts of New Technologies

2017 ◽  
Vol 22 (5) ◽  
pp. 358-363
Author(s):  
Kevin P. Lonabaugh ◽  
Kelly J. Lunsford ◽  
Gary Y. Fang ◽  
David A. Kaufman ◽  
Samuel D. Addison ◽  
...  
Keyword(s):  
Renal Function ◽  
Extracorporeal Membrane Oxygenation ◽  
Pediatric Patients ◽  
New Technologies ◽  
Total Daily Dose ◽  
Therapeutic Drug ◽  
Membrane Oxygenation ◽  
Drug Concentrations ◽  
Daily Dose ◽  
Serum Vancomycin

OBJECTIVES The objective of the current study was to evaluate the doses of vancomycin used to obtain therapeutic drug concentrations in pediatric patients on extracorporeal membrane oxygenation (ECMO), using new ECMO technologies. METHODS This was a single-center, retrospective study of patients treated with vancomycin while receiving ECMO using low-volume circuit technology. RESULTS A total of 28 patients were included in the analysis of the primary endpoint. Patients had a median age of 6 weeks (0–11 years) and a median weight of 3.45 kg (2.44–37.2 kg). Ultrafiltration was used in 89.3% of patients at initiation of ECMO regardless of baseline renal function, resulting in a median urine output of 2 mL/kg/hr at the time of the final vancomycin dose. Most patients started vancomycin at the same time as ECMO. The median total daily dose was 30 mg/kg/day. The median total daily dose in a subset of patients less than one year of age was 20 mg/kg/day. Nearly all patients had at least 1 therapeutic trough serum vancomycin concentration. A total of 16 patients completed their vancomycin course using an interval of every 12 hours or shorter. Half-life was calculated in a subset of 11 patients and the mean was found to be 12.3 ± 2.8 hours. CONCLUSIONS An initial dosing interval of every 12 hours to provide a total daily dose of 30 mg/kg/day is a possible option in pediatric patients on ECMO provided that renal function is normal at baseline. Monitoring of serum vancomycin concentrations for adjustment of dosing is required throughout therapy and is still warranted.

scholarly journals Population Pharmacokinetics and Pharmacodynamic Target Attainment of Vancomycin in Adults on Extracorporeal Membrane Oxygenation: A Prospective Cohort Study

2020 ◽  
Author(s):  
Younghee Jung ◽  
Dong-Hwan Lee ◽  
Hyoung Soo Kim
Keyword(s):  
Steady State ◽  
Extracorporeal Membrane Oxygenation ◽  
Population Pharmacokinetics ◽  
Total Daily Dose ◽  
Therapeutic Drug ◽  
Target Attainment ◽  
Mixed Effect ◽  
Point Distribution ◽  
Membrane Oxygenation ◽  
Population Pk

The aim of this study was to develop a population pharmacokinetics (PK) model for vancomycin and to evaluate its pharmacodynamic target attainment in adults on extracorporeal membrane oxygenation (ECMO). After a single 1,000 mg dose of vancomycin, samples were collected 9 times per patient prospectively. A population PK model was developed using a nonlinear mixed effect model. The probability of target attainment (PTA) of vancomycin was evaluated for various dosing strategies using Monte Carlo simulation. The ratio of the area under the vancomycin concentration-time curve at steady-state over 24 h to the minimum inhibitory concentration (AUC/MIC) was investigated by applying the vancomycin break point distribution of MICs for methicillin-resistant Staphylococcus aureus. A total of 22 adult patients with 194 concentration measurements were included. The population PK was best described by a three-compartment model with a proportional residual error model. Vancomycin clearance and steady state volume of distribution were 0.0542 L/h/kg (4.01 L/h) and 29.6 L (0.400 L/kg), respectively. If the treatment target was only AUC/MIC ≥400, a total daily dose of 3 to 4 g would be optimal (PTA ≥90%) for patients with normal renal function (estimated glomerular filtration rate [eGFR] = 60–120 mL/min/1.73 m2) when MIC was presumed to be 1 mg/L. However, AUC/MIC 400 to 600 was difficult to attain with any dosing strategy regardless of MIC and eGFR. Thus, it is hard to achieve efficacy and safety targets in patients on ECMO using the population dosing approach with Monte Carol simulations, and therapeutic drug monitoring should be implemented in these patients.

Sedation with alfentanil versus fentanyl in patients receiving extracorporeal membrane oxygenation: outcomes from a single-centre retrospective study

Perfusion ◽  
2019 ◽  
Vol 35 (2) ◽  
pp. 104-109
Author(s):  
Mike Barker ◽  
Alison A Dixon ◽  
Luigi Camporota ◽  
Nick A Barrett ◽  
Ruth Y Y Wan
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Patient Outcomes ◽  
Total Daily Dose ◽  
Patient Demographics ◽  
Membrane Oxygenation ◽  
Published Evidence ◽  
Daily Dose ◽  
Before And After ◽  
Analgesic Agents ◽  
Score Apache

Introduction: In November 2016, our institution switched from alfentanil to fentanyl for analgesia and sedation in adult patients receiving extracorporeal membrane oxygenation. There is no published evidence comparing the use of alfentanil with fentanyl for sedation in extracorporeal membrane oxygenation patients. We conducted a retrospective observational study to explore any significant differences in patient outcomes or in the prescribing of adjunct sedatives before and after the switch. Methods: Patients were retrospectively identified from a prospectively recorded database of all patients who received extracorporeal membrane oxygenation at our institution between January 2016 and October 2017. Patients included those sedated with alfentanil or fentanyl. The total daily doses of intravenous opioids (alfentanil or fentanyl) were calculated for each patient, and the prescribing of adjunctive sedative or analgesic agents was recorded. Patient demographics, extracorporeal membrane oxygenation modality, clinical outcomes including mortality and length of intensive care and hospital stay were recorded. Results: A total of 174 patients were identified, 69 on alfentanil and 95 on fentanyl. There was no difference found between groups for mode of extracorporeal membrane oxygenation, age, Acute Physiology and Chronic Health Evaluation 2 score (APACHE II) and Charlson score, except for body mass index (p = 0.002). No differences in patient outcomes was observed between groups, although patients in the alfentanil group received a significantly higher median total daily dose of adjuvant sedatives (quetiapine (p = 0.016) and midazolam (p = 0.009)). Conclusions: No differences in patient outcomes were found between extracorporeal membrane oxygenation patients sedated with alfentanil compared with fentanyl. There was a statistically significant reduction in some adjunctive sedatives in patients managed with a fentanyl-based regimen. Prospective studies are required to confirm these results.

scholarly journals Effects of ex vivo Extracorporeal Membrane Oxygenation Circuits on Sequestration of Antimicrobial Agents

2021 ◽  
Vol 8 ◽  
Author(s):  
Yuan Zhang ◽  
Hongbin Hu ◽  
Qing Zhang ◽  
Qing Ou ◽  
Huayou Zhou ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Antimicrobial Agents ◽  
Ex Vivo ◽  
Polymyxin B ◽  
Therapeutic Drug ◽  
Control Groups ◽  
Drug Degradation ◽  
Membrane Oxygenation ◽  
Drug Concentrations

Objectives: Our ex vivo study was designed to determine the sequestration of teicoplanin, tigecycline, micafungin, meropenem, polymyxin B, caspofungin, cefoperazone sulbactam, and voriconazole in extracorporeal membrane oxygenation (ECMO) circuits.Methods: Simulated closed-loop ECMO circuits were prepared using 2 types of blood-primed ECMO. After the circulation was stabilized, the study drugs were injected into the circuit. Blood samples were collected at 2, 5, 15, 30 min, 1, 3, 6, 12, and 24 h after injection. Drug concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry. Control groups were stored at 4°C after 3, 6, 12, and 24 h immersing in a water bath at 37°C to observe spontaneous drug degradation.Results: Twenty-six samples were analyzed. The average drug recoveries from the ECMO circuits and control groups at 24 h relative to baseline were 67 and 89% for teicoplanin, 100 and 145% for tigecycline, 67 and 99% for micafungin, 45 and 75% for meropenem, 62 and 60% for polymyxin B, 83 and 85% for caspofungin, 79 and 98% for cefoperazone, 75 and 87% for sulbactam, and 60 and 101% for voriconazole, respectively. Simple linear regression showed no significant correlation between lipophilicity (r2 = 0.008, P = 0.225) or the protein binding rate (r2 = 0.168, P = 0.479) of drugs and the extent of drug loss in the ECMO circuits.Conclusions: In the two ECMO circuits, meropenem and voriconazole were significantly lost, cefoperazone was slightly lost, while tigecycline and caspofungin were not lost. Drugs with high lipophilicity were lost more in the Maquet circuit than in the Sorin circuit. This study needs more in vivo studies with larger samples for further confirmation, and it suggests that therapeutic drug concentration monitoring should be strongly considered during ECMO.

scholarly journals Therapeutic Drug Monitoring of Vancomycin in Pediatric Patients With Extracorporeal Membrane Oxygenation Support

2018 ◽  
Vol 23 (4) ◽  
pp. 305-310 ◽  
Author(s):  
Brenda L. Zylbersztajn ◽  
Giannina Izquierdo ◽  
Roxana C. Santana ◽  
Christian Fajardo ◽  
Juan P. Torres ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Extracorporeal Membrane Oxygenation ◽  
Therapeutic Range ◽  
Drug Monitoring ◽  
Pediatric Patients ◽  
Kidney Injury ◽  
Therapeutic Drug ◽  
Optimal Dosage ◽  
Membrane Oxygenation ◽  
Adjusted Dose

OBJECTIVES Determine pharmacokinetic (PK) parameters and optimal dosage of vancomycin for children on extracorporeal membrane oxygenation (ECMO). METHODS Retrospective PK study of vancomycin in pediatric patients on ECMO who received IV vancomycin 40 to 60 mg/kg/day every 6 hours. Patients were analyzed according to the presence of acute kidney injury (AKI) and requirement of renal replacement therapy (RRT). RESULTS Data from 40 children, with a median age of 2.7 years of age (1 month to 14 years) were evaluated. Thirty-two patients (80%) received vancomycin. Vancomycin therapeutic drug monitoring was performed in 29 patients. The subgroup without AKI or RRT were 15. With initial doses, vancomycin trough levels were within therapeutic range in 53% of patients. After dose change, 93% of patients achieved therapeutic levels. The adjusted dose was 40 (34–60) mg/kg/day every 6 hours. Estimated PK parameters were clearance (CL) 1.67 (1–1.67) mL/kg/min; volume of distribution (Vd) 0.73 (0.7–0.9) L/kg; and half-life (t½) 6.2 (4.9–8.06) hours. In the AKI subgroup, 11 patients, the initial median dose was 40 (30–45) mg/kg/day every 8 (6–12) hours. Trough concentrations of vancomycin were within therapeutic range in 27% of patients. After dose modifications, 63% of patients achieved target trough concentration. The final adjusted dose was 20 mg/kg/day (15–30) every 12 (12–24) hours. Estimated PK parameters were Vd 1.16 (0.68–1.6) L/kg; CL 0.83 (0.38–1) mL/kg/min; and a t½ of 23.6 (16.2–31) hours. CONCLUSIONS In patients without AKI or RRT, Vd of vancomycin was similar and CL was lower compared to pediatric critically ill patients without ECMO. Treatment could be started at 40 mg/kg/day every 6 hours. In patients with AKI, the use of lower doses should be used.

scholarly journals A Large Retrospective Assessment of Voriconazole Exposure in Patients Treated with Extracorporeal Membrane Oxygenation

2021 ◽  
Vol 9 (7) ◽  
pp. 1543
Author(s):  
Ruth Van Daele ◽  
Britt Bekkers ◽  
Mattias Lindfors ◽  
Lars Mikael Broman ◽  
Alexander Schauwvlieghe ◽  
...  
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Invasive Pulmonary Aspergillosis ◽  
Membrane Oxygenation ◽  
Retrospective Assessment ◽  
Large Patient ◽  
Drug Concentrations ◽  
Daily Dose ◽  
Large Patient Population ◽  
The Impact ◽  
Significant Covariates

Background: Voriconazole is one of the first-line therapies for invasive pulmonary aspergillosis. Drug concentrations might be significantly influenced by the use of extracorporeal membrane oxygenation (ECMO). We aimed to assess the effect of ECMO on voriconazole exposure in a large patient population. Methods: Critically ill patients from eight centers in four countries treated with voriconazole during ECMO support were included in this retrospective study. Voriconazole concentrations were collected in a period on ECMO and before/after ECMO treatment. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure and to assess the impact of possible saturation of the circuit’s binding sites over time. Results: Sixty-nine patients and 337 samples (190 during and 147 before/after ECMO) were analyzed. Subtherapeutic concentrations (<2 mg/L) were observed in 56% of the samples during ECMO and 39% without ECMO (p = 0.80). The median trough concentration, for a similar daily dose, was 2.4 (1.2–4.7) mg/L under ECMO and 2.5 (1.4–3.9) mg/L without ECMO (p = 0.58). Extensive inter-and intrasubject variability were observed. Neither ECMO nor squared day of ECMO (saturation) were retained as significant covariates on voriconazole exposure. Conclusions: No significant ECMO-effect was observed on voriconazole exposure. A large proportion of patients had voriconazole subtherapeutic concentrations.

Long‐term renal function after venoarterial extracorporeal membrane oxygenation

2021 ◽  
Vol 36 (3) ◽  
pp. 815-820
Author(s):  
Brian Ayers ◽  
Milica Bjelic ◽  
Neil Kumar ◽  
Katherine Wood ◽  
Bryan Barrus ◽  
...  
Keyword(s):  
Renal Function ◽  
Extracorporeal Membrane Oxygenation ◽  
Membrane Oxygenation ◽  
Venoarterial Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation outcomes in children with hemophagocytic lymphohistiocytosis

Perfusion ◽  
2016 ◽  
Vol 32 (2) ◽  
pp. 151-156 ◽  
Author(s):  
Katherine Cashen ◽  
Roland L Chu ◽  
Justin Klein ◽  
Peter T Rycus ◽  
John M Costello
Keyword(s):  
Risk Factors ◽  
Extracorporeal Membrane Oxygenation ◽  
Cardiac Failure ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Pediatric Patients ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Hemorrhagic Complication ◽  
Membrane Oxygenation ◽  
Va Ecmo

Introduction: Pediatric patients with hemophagocytic lymphohistiocytosis (HLH) may develop refractory respiratory or cardiac failure that warrants consideration for extracorporeal membrane oxygenation (ECMO) support. The purposes of this study were to describe the use and outcomes of ECMO in pediatric HLH patients, to identify risk factors for hospital mortality and to compare their ECMO use and outcomes to the ECMO population as a whole. Methods: Pediatric patients (⩽ 18 years) with a diagnosis of HLH in the Extracorporeal Life Support Organization (ELSO) Registry were included. Results: Between 1983 and 2014, data for 30 children with HLH were available in the ELSO registry and all were included in this study. All cases occurred in the last decade. Of the 30 HLH patients, 24 (80%) had a respiratory indication for ECMO and six (20%) had a cardiac indication (of which 4 were E-CPR and 2 cardiac failure). Of the 24 respiratory ECMO patients, 63% were placed on VA ECMO. Compared with all pediatric patients in the ELSO registry during the study period (n=17,007), HLH patients had worse hospital survival (non-HLH 59% vs HLH 30%, p=0.001). In pediatric HLH patients, no pre-ECMO risk factors for mortality were identified. The development of a hemorrhagic complication on ECMO was associated with decreased mortality (p=0.01). Comparing HLH patients with respiratory failure to patients with other immune compromised conditions, the overall survival rate is similar (HLH 38% vs. non-HLH immune compromised 31%, p=0.64). Conclusions: HLH is an uncommon indication for ECMO and these patients have increased mortality compared to the overall pediatric ECMO population. These data should be factored into decision-making when considering ECMO for pediatric HLH patients.

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