title: Intra-tracheal delivery strategy of gentamicin with partial liquid ventilation.
abstract: Patients with pulmonary infection often present with ventilation and perfusion abnormalities, which can impair intravenous antibiotic therapy. Intra-tracheal (i.t.) administration has met with obstacles, such as inadequate delivery to affected lung regions and the disruption of gas exchange. We hypothesized that i.t. administration of a gentamicin (G)/perfluorochemical (PFC) suspension (G/PFC) would effectively deliver and distribute gentamicin to the lung, while maintaining gas exchange and non-toxic serum levels. In addition, we sought to compare serum G and lung levels and distribution of G when G/PFC is administered at the initiation of partial liquid ventilation (PLV) vs. during PLV. To test this hypothesis, 17 newborn lambs were ventilated by PLV with perflubron (LiquiVent) for 4 h using three different G (5 mg kg-1) administration techniques: i.t. slow-fill (SF) (n = 6; G/PFC over 15 min at start of PLV), i.t. top-fill (TF) (n = 6; G/PFC 10-65 min after start of PLV), intravenous (i.v.) (n = 5, aqueous injection at start of PLV). Serum levels of gentamicin were obtained 1, 15, 30 and 60 min after administration, and hourly there after for the remainder of the protocol (4 h). Arterial blood gas and pulmonary function measurements were obtained throughout the protocol. At the conclusion of the protocol, representative samples from each lung lobe, the brain and kidney were homogenized and assayed for gentamicin. All results are presented as the mean +/- SEM; P < 0.05. Over time, serum gentamicin levels were greatest (P < 0.05) in i.v. (11.0 +/- 2.3 micrograms ml-1), followed by TF (2.3 +/- 0.1 micrograms ml-1) and SF (0.8 +/- 0.1 microgram ml-1). The percentage of the administered dose remaining in the lungs after 4 h was greater (P < 0.05) following i.t. delivery (SF 23.8 +/- 4.3%, TF 13.7 +/- 2.5%) as compared to i.v. (3.7 +/- 0.5%). These findings suggest that for a given dose of G, both SF and TF delivery methods of G/PFC can enhance pulmonary, relative to systemic, antibiotic coverage.
authors.affiliation: Temple University School of Medicine, Department of Physiology, Philadelphia, PA 19140, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Cullen
authors.forename: C A
authors.initials: CA
authors.lastname: Cox
authors.forename: S J
authors.initials: SJ
authors.lastname: Hipp
authors.forename: M R
authors.initials: MR
authors.lastname: Wolfson
authors.forename: T H
authors.initials: TH
authors.lastname: Shaffer
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002245:Carbon Dioxide / Q000097:blood; D004334:Drug Administration Schedule; D005466:Fluorocarbons; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006842:Hydrocarbons, Brominated; D007442:Intubation, Intratracheal; D008168:Lung / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D012121:Respiration, Artificial / Q000379:methods*; D015656:Respiratory Mechanics / Q000187:drug effects; D012756:Sheep; D014018:Tissue Distribution
chemical_list: D005466:Fluorocarbons; D005839:Gentamicins; D006842:Hydrocarbons, Brominated; D002245:Carbon Dioxide; C003072:perflubron; D010100:Oxygen