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

Abstract

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 10(9) 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 (< or =24 h until death, n = 8) > or = subacute nonsurvivors (>24 to 96 h until death, n = 8) > or = survivors (> or =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 x h(-1) x (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.

Washing older blood units before transfusion reduces plasma iron and improves outcomes in experimental canine pneumonia

“…All animals were provided conventional intensive care unit support, including prophylaxis for gastrointestinal ulcer (famotidine 1 mg/kg iv, every 12 hours) and deep venous thrombosis (heparin 3000 IU, sq, every 8 hours) as well as procedures to prevent pressure ulcers (regular position change). Mechanical ventilation, fluid support, and vasopressor therapy were also used and titrated using physiological and laboratory end points using previously described algorithms 1,25 (see the supplemental Methods). Animals alive at 96 hours were considered survivors and were killed while still sedated (Beuthanol; 75 mg/kg IV).…”

“…1 Briefly, anesthetized animals day 0 were instrumented (external jugular vein catheter, femoral artery catheter, and urinary catheter) followed with placement of a balloon-tipped pulmonary arterial thermodilution catheter and a tracheostomy performed as described. 1,25 Following these procedures, animals were weaned off inhalation anesthesia, and continuous sedation (fentanyl, midazolam, and medetomidine) and mechanical ventilation via a tracheostomy tube were initiated. At time 0 hours (T0), S aureus isolates were prepared and administered via bronchoscope into the right lower lobe of the lung.…”

“…At time 0 hours (T0), S aureus isolates were prepared and administered via bronchoscope into the right lower lobe of the lung. 25 The dose of S aureus (1.5 3 10 9 CFU/kg suspended in 1 mL of PBS), based on previous studies, produced 100% lethality with unwashed older stored canine blood and 30% mortality with fresher blood. The bacterial dose was determined spectrophotometrically and confirmed turbidometrically as previously described.…”

Mortality increases after massive exchange transfusion with older stored blood in canines with experimental pneumonia

“…18 After these procedures, animals were weaned off anesthesia; continuous sedation (fentanyl, midazolam, and medetomidine), and mechanical ventilation via the tracheostomy tube were initiated (see supplemental Methods); and a balloon-tipped pulmonary arterial thermodilution catheter was placed via the introducer. At time 0 (T0), animals underwent bronchoscopy and inoculation of the right lower lobe with S aureus (see supplemental Methods).…”

“…Conventional intensive care unit support used during the ventilation of critically ill large animals was administered as previously described. 18 Animals alive at 96 hours were considered survivors and then euthanized while still sedated (Beuthanol; 75 mg/kg IV). …”