BENEFICIAL CARDIOPULMONARY EFFECTS OF PENTOXIFYLLINE IN EXPERIMENTAL SEPSIS ARE LOST ONCE SEPTIC SHOCK IS ESTABLISHED

Objective: To determine the effects of pretreatment and posttreatment with pentoxifylline in a porcine model of gram-negative sepsis. Design : Nonrandomized controlled trial. Study Subjects: Young Yorkshire swin e. Interventions: Six groups of ventilated swine were studied for 5 ho urs. Group 1 swine (control, n=8) received saline solution only. Group 2 swine (sepsis, n=8) received a 1-hour infusion of Pseudomonas aerug inosa. Groups 3, 4, and 5 swine received the P aeruginosa infusion and a 20 mg/kg bolus followed by a 6 mg/kg per hour infusion of pentoxify lline. Group 3 swine (n=6) received pentoxifylline prior to the onset of sepsis; group 4 swine (n=6) received pentoxifylline at 1 hour and g roup 5 swine (n=4) at 2 hours after the onset of the P aeruginosa infu sion. Group 6 swine (control pentoxifylline, n=3) received pentoxifyll ine only. Outcome Measures: Hemodynamic variables, neutrophil counts a nd CD18 expression, tumor necrosis factor activity, and arterial blood gases were measured hourly. Bronchoalveolar lavage was performed at 0 and 5 hours to measure neutrophil and protein content. Results: All v ariables remained unchanged in the control and control pentoxifylline groups. Both pretreatment and posttreatment with pentoxifylline signif icantly attenuated lung injury and improved arterial PaO2. The cardiac index was significantly improved by administration of pentoxifylline in groups 3 and LC. Administration of pentoxifylline to group 5 animal s in established septic shock caused uncontrolled, fatal systemic hypo tension in two of the four animals. Plasma tumor necrosis factor activ ity, blood polymorphonuclear leukocyte counts, and CD18 expression wer e unaffected by the administration of pentoxifylline. Conclusions: Pen toxifylline protects against pulmonary and systemic hemodynamic derang ements in fulminant sepsis and protects against pulmonary dysfunction. Pentoxifylline has a ''therapeutic window'' when given in established sepsis; if administration is delayed until overt septic shock occurs, it may then have deleterious effects.