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Clindamycin clearance during CytoSorb hemoadsoption case report and pharmacokinetic study
Poli EC1, Simoni C2, André P3, Buclin T3, Longchamp D2, Perez MH2, Ferry T2, Schneider AG1. 1 Adult Intensive Care Unit, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland 2 Paediatric Intensive Care Unit, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland 3 Laboratory of Clinical Pharmacology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
04/30/2019
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Summary
CoW 18/2019 – This report describes the case of a previously healthy 14-year-old male patient (body weight 75 kg), with a 2-day history of flu-like symptoms and a combination of altered mentation, fever, hypotension and hypoglycemia, who was admitted to the hospital via the Emergency Services.
Case presentation
In the face of probable septic shock, he received fluids and vasoconstrictors as well as empiric antibiotic therapy (ceftriaxone)
The patient was intubated and protective ventilation initiated
Despite these early measures, he remained hypoxic and hypotensive on hospital admission, with severe metabolic and respiratory acidosis on blood gas analysis
His condition continued to deteriorate despite ongoing fluid resuscitation and corticotherapy, with increased vasoconstrictor requirements, his hypoxia worsened and persistent lactic acidosis (plasma lactate 8 mmol/l) developed
Pulseless activity cardiac arrest occurred, after 5 mins of cardio-pulmonary resuscitation return of spontaneous circulation
A peripheral veno-arterial (VA) ECMO was inserted, and the patient was admitted to the pediatric intensive care unit (PICU)
Chest X-ray revealed bilateral infiltrates with an almost complete white left lung and blood tests were consistent with a massive hyperinflammatory syndrome (procalcitonin 742 µg/l, CRP 49 mg/l)
Tracheal aspirates revealed Influenza B virus and PVL positive, methicillin-resistant S. aureus (PVL-MRSA)
Anti-infective therapy was switched to intravenous zanamivir, amoxicillin-clavulanate, vancomycin and clindamycin
Over the following day, arterial cannulation was responsible for right leg ischemia requiring emergency thromboendarterectomy
Peripheral ECMO was converted to central ECMO
Despite adequate anti-infective therapy, the patient’s condition failed to improve with persistent lactic acidosis and high dose vasoconstrictor requirements over the following 3 days
On the evening of day 3 post admission, the decision was made to insert a CytoSorb adsorber directly into the ECMO circuit
Treatment
4 treatments with CytoSorb were run for a total therapy duration of 81 hours
Cytosorb was used in combination with VA ECMO
Measurements
Hemodynamics and catecholamine requirements
Monitoring of clindamycin drug levels during CytoSorb therapy (plus development of a pharmacokinetic model)
Results
Initiation of CytoSorb together with ECMO therapy was associated with a rapid and sustained decrease in noradrenalin, vasopressin and dopamine requirements already within 12 hours of treatment and all vasoactive substances could be tapered off during the 4 treatment sessions
CytoSorb did not seem to show any significant effects on the clindamycin plasma concentrations
Patient Follow-Up
Continuous veno-venous hemofiltration was applied from day 6 to 10
Despite the initial improvements, VA-ECMO could not be weaned until day 31, when it was transitioned to VV-ECMO (complete left lung necrosis and persistent air-leak)
Tracheotomy was performed on day 36 and VV-ECMO weaned on day 39
Unfortunately, due to right leg ischemia, transtibial amputation of the right inferior limb was necessary on day 43
Finally, a left-sided pneumonectomy was performed on day 86
The patient was discharged from ICU on day 114 and eventually from hospital on day 156 without any neurological sequelae
Conclusion
In this patient with refractory septic shock secondary to PVL-MRSA infection, the combination of Cytosorb incorporated into a running VA ECMO circuit was associated with a decrease in catecholamine requirements and a spectacular clinical recovery
With the applied pharmacokinetic model incorporating variable plasma clearance based on serial plasma concentration measurements which were performed before, during and after Cytosorb use, the authors could show that the use of Cytosorb did not seem to result in significant clindamycin removal so therefore its use with CytoSorb appears to not require an adaptation of dosage
CytoSorb usage was safe and feasible without technical problems
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