Pentoxifylline fails to improve organ dysfunction and survival when used in the resuscitation of a porcine model of haemorrhage and abdominal sepsis.
Pentoxifylline is a phosphodiesterase inhibitor, known to suppress tumour necrosis factor-alpha production and improve cardiopulmonary parameters and survival in animal models of sepsis. Using a porcine model of abdominal trauma resulting from the combined insults of haemorrhage and infection, a randomised placebo-controlled trial was conducted of pentoxifylline (20 mg/kg bolus followed by 20 mg/kg infusion over 1 h) administered in addition to a colloid resuscitation regimen. Female Large White pigs (45-60 kg) were bled 40% of their blood volume and peritonitis was induced using E. coli (O18: K1: H7) in an autoclaved faecal suspension. Animals were resuscitated with either colloid alone (n=5) or colloid plus pentoxifylline (n=5). Pentoxifylline attenuated increases in mean arterial and pulmonary artery pressures and reduced both systemic and pulmonary vascular resistance. It worsened the lactic acidosis associated with 'septic shock' and failed to reduce serum TNF-alpha levels. Pentoxifylline, in the high doses used in this study, does not have a role as an adjunct to resuscitation in this clinically relevant model of trauma.
Parker
S J
SJ
Biomedical Sciences, DERA Porton Down, Salisbury, UK. medts@dera.gov.uk
Brown
D
D
Kenward
C E
CE
Watkins
P E
PE
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006470:Hemorrhage / Q000188:drug therapy* / Q000401:mortality; D007262:Infusions, Intravenous; D009102:Multiple Organ Failure / Q000517:prevention & control; D010431:Pentoxifylline / Q000008:administration & dosage*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D011897:Random Allocation; D012016:Reference Values; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D013552:Swine; D016896:Treatment Outcome
D010726:Phosphodiesterase Inhibitors; D010431:Pentoxifylline