Ceftriaxone Clearance Estimates in Pediatric Patients on Extracorporeal Membrane Oxygenation Therapy

First Author(s)

• 

  Francisco Cervantes Contreras

  University of Cincinnati College of Medicine
  Cincinnati, Ohio

  Disclosure information not submitted.

  Slides and Audio

Co-Author(s)

• TM

  Tomoyuki Mizuno, PhD

  Assistant Professor
  Cincinnati Children's Hospital Medical Center, United States

  Disclosure information not submitted.
• MD

  Min Dong, PhD

  Assistant Professor
  Cincinnati Children's Hospital Medical Center, United States

  Disclosure information not submitted.
• PT

  Peter Tang, PhD

  Associate Professor
  Cincinnati Children's Hospital Medical Center, United States

  Disclosure information not submitted.
• TA

  Trent Arbough, BS

  Medical Student
  University of Cincinnati College of Medicine, United States

  Disclosure information not submitted.
• AV

  Alexander Vinks, PharmD, PhD, FCP

  Professor, Division Director
  Cincinnati Children's Hospital Medical Center, United States

  Disclosure information not submitted.
• JK

  Jennifer Kaplan, MD, MS, FCCM

  Professor, Attending Physician
  Cincinnati Children's Hospital Medical Center, United States

  Disclosure information not submitted.
• ST

  Sonya Tang Girdwood, MD, PhD

  Assistant Professor
  Cincinnati Children's Hospital Medical Center, United States

  Disclosure information not submitted.

Title: Ceftriaxone Clearance Estimates in Pediatric Patients on Extracorporeal Membrane Oxygenation Therapy

Case Report Body:

Introduction:
Beta-lactams are used in critically ill patients. Case reports in adults suggest Extracorporeal Membrane Oxygenation (ECMO) does not significantly affect ceftriaxone (CRO) pharmacokinetics (PK) or pharmacodynamics (PD). No studies describe ECMO effects on CRO in children. We provide case reports of CRO PK/ PD of 2 children on ECMO, using free CRO concentrations obtained by opportunistic sampling, a validated CRO population PK model in critically ill children (not on ECMO) developed by our group, and Bayesian estimation in MWPharm++. We estimated clearance (CL) and evaluated PD target attainment [concentrations above 4x the CLSI breakpoint for S. pneumococcus (4mg/L)].

Description:
Patient 1 is an 11yo 25kg male with fever and cough. Chest x-ray revealed airway foreign body. He was placed on veno-venous ECMO due to respiratory failure and given 52 mg/kg CRO q12h. He received 2 CRO doses then transitioned to piperacillin-tazobactam. He developed cardiac arrest on Day 1 requiring 3 minutes of CPR. After a total ECMO course of 42h, he received 52 mg/kg q12h CRO dosing. Allometrically-scaled CRO CL on ECMO was 10L/h/70kg (1.2 relative standard error, RSE) and off ECMO was 8.9L/h/70kg (1.7 RSE) with 12% difference between CL’s. Both CRO CL were elevated compared to our model-predicted CL of 5.4L/h/70kg. Measured CRO concentrations (range: 5.2-17.3 mg/L) were >4xCLSI breakpoint for 100% of dosing intervals. Patient 2 is a 2yo 13kg male admitted after nonfatal submersion and hypothermia (temp 27°C). He was in pulseless electrical activity (PEA) when EMS arrived and developed ventricular fibrillation. He underwent 90m of CPR with PEA on ED arrival. He was cannulated for veno-arterial ECMO to facilitate rewarming. He received 50 mg/kg CRO q12h for 7d on ECMO. ECMO CL was 9.2L/h/70kg (1.4 RSE), higher than our model-predicted CL of 3.2L/h/70kg. No concentrations were obtained off ECMO. CRO concentrations (range: 8.6-37.9 mg/L) were >4xCLSI breakpoint for 100% of all dosing intervals.

Discussion:
Due to increased CL in both patients while on and off ECMO, we observed concentrations lower than what the population model predicted. However, concentrations remained above the PD target, supporting that q12h dosing is sufficient to maintain concentrations >4xCLSI breakpoint in pediatric critically ill patients on ECMO.