HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Material All Versions of this Article: 293/4/H2487    most recent 00589.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Minneci, P. C. Articles by Solomon, S. B. Search for Related Content PubMed PubMed Citation Articles by Minneci, P. C. Articles by Solomon, S. B.

A canine model of septic shock: balancing animal welfare and scientific relevance

¹Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland; ²North Carolina State University Raleigh, North Carolina; ³Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland; and ⁴Department of Surgery, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Submitted 18 May 2007 ; accepted in final form 10 July 2007

A shock canine pneumonia model that permitted relief of discomfort with the use of objective criteria was developed and validated. After intrabronchial Staphylococcus aureus challenge, mechanical ventilation, antibiotics, fluids, vasopressors, sedatives, and analgesics were titrated based on algorithms for 96 h. Increasing S. aureus (1 to 8 x 10⁹ colony-forming units/kg) produced decreasing survival rates (P = 0.04). From 4 to 96 h, changes in arterial-alveolar oxygen gradients, mean pulmonary artery pressure, IL-1, serum sodium levels, mechanical ventilation, and vasopressor support were ordered based on survival time [acute nonsurvivors (24 h until death, n = 8) subacute nonsurvivors (>24 to 96 h until death, n = 8) survivors (96 h until death, n = 22) (all P < 0.05)]. In the first 12 h, increases in lactate and renal abnormalities were greatest in acute nonsurvivors (all P < 0.05). Compared with survivors, subacute nonsurvivors had greater rises in cytokines and liver enzymes and greater falls in platelets, white cell counts, pH, and urine output from 24 to 96 h (all P < 0.05). Importantly, these changes were not attributable to dosages of sedation, which decreased in nonsurvivors [survivors vs. nonsurvivors: 5.0 ± 1.0 vs. 3.8 ± 0.7 ml·h^–1·(fentanyl/midazolam/ medetomidine)^–1; P = 0.02]. In this model, the pain control regimen did not mask changes in metabolic function and lung injury or the need for more hemodynamic and pulmonary support related to increasing severity of sepsis. The integration into this model of both specific and supportive titrated therapies routinely used in septic patients may provide a more realistic setting to evaluate therapies for sepsis.

sepsis; dog; Staphylococcus aureus