title: Early vancomycin, amikacin and gentamicin concentrations in pulmonary artery and pulmonary tissue are not affected by VA ECMO (venoarterial extracorporeal membrane oxygenation) in a pig model of prolonged cardiac arrest.
abstract: BACKGROUND
  ECMO (extracorporeal membrane oxygenation) is increasingly used in severe hemodynamic compromise and cardiac arrest (CA). Pulmonary infections are frequent in these patients. Venoarterial (VA) ECMO decreases pulmonary blood flow and antibiotic availability in lungs during VA ECMO treated CA is not known. We aimed to assess early vancomycin, amikacin and gentamicin concentrations in the pulmonary artery as well as tracheal aspirate and to determine penetration ratios of these antibiotics to lung tissue in a pig model of VA ECMO treated CA.
  
  
  METHODS
  Twelve female pigs, body weight 51.5 ± 3.5 kg, were subjected to prolonged CA managed by different modes of VA ECMO. Anesthetized animals underwent 15 min of ventricular fibrillation (VF) followed by continued VF with ECMO flow of 100 mL/kg/min. Immediately after institution of ECMO, a 30 min vancomycin infusion (10 mg/kg) was started and amikacin and gentamicin boluses (7.5 and 3 mg/kg, respectively) were administered. ECMO circuit, aortic, pulmonary arterial, and tracheal aspirate concentrations of antibiotics were measured at 30 and 60 min after administration; penetration ratios were calculated.
  
  
  RESULTS
  All 30 min antibiotic concentrations and 60 min concentration for gentamicin in the pulmonary artery were no different than the aorta. However, the 60 min pulmonary artery vancomycin and amikacin values were significantly higher than aortic, 19.8 (14.3-21.6) vs. 17.6 (14.2-19.0) mg/L, p = 0.009, and 15.6 mg/L (11.0-18.6) vs. 11.2 (10.4-17.2) mg/L, p = 0.036, respectively. One hour penetration ratios were 18.5% for vancomycin, 34.9% for gentamicin and 38.8% for amikacin.
  
  
  CONCLUSIONS
  In a pig model of VA ECMO treated prolonged CA, despite diminished pulmonary flow, VA ECMO does not decrease early vancomycin, gentamicin, and amikacin concentrations in pulmonary artery. Within 1 h post administration, antibiotics can be detected in tracheal aspirate in adequate concentrations.
authors.affiliation: 2nd Department of Medicine, Department of Cardiovascular Medicine, 1st Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic. Electronic address: jan.belohlavek@vfn.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Bělohlávek
authors.forename: Drahomíra
authors.initials: D
authors.lastname: Springer
authors.forename: Mikuláš
authors.initials: M
authors.lastname: Mlček
authors.forename: Michal
authors.initials: M
authors.lastname: Huptych
authors.forename: Tomáš
authors.initials: T
authors.lastname: Bouček
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hodková
authors.forename: Jaromír
authors.initials: J
authors.lastname: Fichtl
authors.forename: Vratislav
authors.initials: V
authors.lastname: Mrázek
authors.forename: Tomáš
authors.initials: T
authors.lastname: Zima
authors.forename: Aleš
authors.initials: A
authors.lastname: Linhart
authors.forename: Otomar
authors.initials: O
authors.lastname: Kittnar
mesh_terms: D000583:Amikacin / Q000493:pharmacokinetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D015199:Extracorporeal Membrane Oxygenation / Q000379:methods*; D005260:Female; D005839:Gentamicins / Q000493:pharmacokinetics; D006323:Heart Arrest / Q000628:therapy*; D008168:Lung / Q000378:metabolism*; D011651:Pulmonary Artery / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D014018:Tissue Distribution; D014640:Vancomycin / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D014640:Vancomycin; D000583:Amikacin
keywords: Antibiotic availability; Cardiac arrest; ECMO; Penetration ratio; Pulmonary tissue