High volume haemodiafiltration in treatment of severe sepsis – impact on pharmacokinetics of antibiotics and inflammatory response
Date
2015-09-30
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Abstract
Sepsis – organismi ülepiiriline reaktsioon infektsioonile - ja selle kõige raskemad vormid, raske sepsis ja septiline šokk, on oluline tervishoiuprobleem. Sepsise ravi võtmeküsimusteks on õige antibakteriaalne ravi, kiire infektsioonikolde kontroll ja ülepiirilise põletikureaktsiooni pidurdamine. Põletikureaktsiooni pidurdamiseks on kasutatud mediaatorite kehavälist eemaldamist teatud tüüpi neeruasendusravi - suuremahulise hemodiafiltratsiooni (HVHDF) abil. Kuigi potentsiaalselt efektiivne põletikureaktsiooni ravis, võib HVHDF organismist eemaldada liigselt antibiootikume, muutes ebaefektiivseks infektsiooni ravi. Käesoleva töö eesmärgiks oli kirjeldada kahe antibiootikumi, doripeneemi ja piperatsilliin/tasobaktaami käitumist HVHDF-i ajal, et leida vajalikud annused, ning kirjeldada selle meetodi toimet patsiendi vereringele ja põletikumediaatorite kontsentratsioonile vereseerumis. Selleks koguti raskes sepsises ja septilises šokis ägeda neerupuudulikkusega patsientidelt 12 vereproovi ühe annuse doripeneemi ja piperatsilliin/tasobaktaami manustamise järgselt ja määrati nende ravimite kontsentratsioonid. Enne ja pärast 10-tunnist HVHDF-i registreeriti patsientide vereringe näitajad ja määrati põletikumediaatorite kontsentratsioonid vereseerumis. Leidsime suured patsientidevahelised erinevused ravimikontsentratsioonides ühesuguse annuse manustamise järgselt. Nii doripeneemi kui piperatsilliin/tasobaktaami keskmine eemaldumine organismist HVHDF-i ajal oli umbes kaks korda aeglasem kui tervetel vabatahtlikel. Raskes sepsises ja septilises šokis ägeda neerupuudulikkusega patsientide raviks HVHDF-i ajal sobivad normaalse neerufunktsiooniga patsientidele soovitatud annused. Suurte patsientidevaheliste erinevuste tõttu on täpsemaks annustamiseks vajalik ravimi kontsentratsioonide jälgimine ravi ajal. Patsientide vereringe paranes HVHDF-i ajal, vereringe paranemine ei olnud tingitud põletikumediaatorite kontsentratsiooni vähenemisest.
Sepsis – a systemic, deleterious host response to infection – and its most complicated forms, severe sepsis and septic shock remain a major healthcare problem. The key issues in the treatment of sepsis are adequate antibacterial therapy, rapid source control and handling of the systemic inflammatory reaction. Nonselective extracorporeal removal of mediators by a specific method of renal replacement therapy - high volume haemodiafiltration (HVHDF) has been used to control systemic inflammation. While potentially effective in inhibiting the systemic reaction, HVHDF may lead to excessive removal of antibiotics and ineffective antibacterial treatment. We aimed to describe the pharmacokinetics of two antibiotics – doripenem and piperacillin/tazobactam during HVHDF in order to define optimal dosing for this method. We also aimed to describe the impact of HVHDF on the patients’ circulation and inflammatory mediator profile. After a single dose of doripenem and piperacillin/tazobactam 12 blood samples were collected from severe sepsis and septic shock patients with renal failure. Before and after a 10 hour HVHDF session the patients’ haemodynamic variables and serum inflammatory mediator concentrations were measured. We found high interpatient variability in the serum concentrations of both antibiotics after administering the same dose to everyone. The mean clearance of both antibiotics from the body was about twice slower than in healthy volunteers. Doses recommended by the manufacturer for patients with normal renal function could be used during HVHDF to treat severe sepsis and septic shock in patients with renal failure. Due to high interpatient variability monitoring the concentrations of both antibiotics during treatment would allow more precise dosing. While the patients’ circulation improved during HVHDF, the improvement was not caused by decrease of inflammatory mediator concentrations.
Sepsis – a systemic, deleterious host response to infection – and its most complicated forms, severe sepsis and septic shock remain a major healthcare problem. The key issues in the treatment of sepsis are adequate antibacterial therapy, rapid source control and handling of the systemic inflammatory reaction. Nonselective extracorporeal removal of mediators by a specific method of renal replacement therapy - high volume haemodiafiltration (HVHDF) has been used to control systemic inflammation. While potentially effective in inhibiting the systemic reaction, HVHDF may lead to excessive removal of antibiotics and ineffective antibacterial treatment. We aimed to describe the pharmacokinetics of two antibiotics – doripenem and piperacillin/tazobactam during HVHDF in order to define optimal dosing for this method. We also aimed to describe the impact of HVHDF on the patients’ circulation and inflammatory mediator profile. After a single dose of doripenem and piperacillin/tazobactam 12 blood samples were collected from severe sepsis and septic shock patients with renal failure. Before and after a 10 hour HVHDF session the patients’ haemodynamic variables and serum inflammatory mediator concentrations were measured. We found high interpatient variability in the serum concentrations of both antibiotics after administering the same dose to everyone. The mean clearance of both antibiotics from the body was about twice slower than in healthy volunteers. Doses recommended by the manufacturer for patients with normal renal function could be used during HVHDF to treat severe sepsis and septic shock in patients with renal failure. Due to high interpatient variability monitoring the concentrations of both antibiotics during treatment would allow more precise dosing. While the patients’ circulation improved during HVHDF, the improvement was not caused by decrease of inflammatory mediator concentrations.
Description
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Keywords
sepsis, hemodialüüs, põletik, antibiootikumid, farmakokineetika, septicemia, hemodialysis, inflammation, antibiotics, pharmacokinetics