DOES LONG-TERM CONTINUOUS ADMINISTRATION OF PENTOXIFYLLINE AFFECT PLATELET-FUNCTION IN THE CRITICALLY ILL PATIENT

Objective: The methylxanthine derivative pentoxifylline (PTX) is one o f those promising substances which are under current investigation to modify or limit inflammatory response. Antiaggregation activity has al so been described that may contribute to the beneficial effects of thi s substance. Long-term effects on platelet function have not been eluc idated yet. Design: Prospective, randomized study. Setting: Clinical i nvestigation on a surgical intensive care unit of a university hospita l. Patients: 26 trauma patients and 26 patients suffering from sepsis secondary to major operations were consecutively studied. Intervention s: The patients prospectively received either 1.5 mg/kg per h pentoxif ylline continuously for 5 days (after a loading dose of 600 mg) (traum a-PTX, n = 13; sepsis-PTX, n = 13) or saline solution as placebo (trau ma-control; n = 13; sepsis-control, n = 13). Measurements: On the day of admission (trauma patients) or day of the diagnosis of sepsis and a t 12:00 p.m. during the next 5 days, platelet aggregation induced by a denosine diphosphate (ADP 2.0 mu mol/l), collagen (4 mu l/ml), and epi nephrine (25 mu mol/l) tvas determined by a turbidimetric method from arterial blood samples. Standard coagulation screen was also monitored . Main results: In untreated trauma and sepsis patients, maximum plate let aggregation induced by all three agonists decreased during the fir st few days after inclusion in the study [trauma: ADP -17.1 +/- 8.0 re l% (% change from baseline); sepsis: ADP -26.1 +/- 5.6 rel%]. In due c ourse, maximum platelet aggregation recovered, reaching the baseline v alue or even exceeding it (trauma patients). In the PTX-treated patien ts, platelet aggregation was significantly less impaired (sepsis group : ADP -4.4 +/- 3.3 rel%) or even increased beyond baseline values in t he first few days of the study (trauma group: ADP 16.1 +/- 8.0 rel%). Fibrinogen plasma levels were lower in the non-treated control groups (p < 0.05) than in the PTX groups. Conclusions: Continuous infusion of PTX for 5 days did not impair platelet function in critically ill pat ients. In both trauma and sepsis patients, the usual deterioration in platelet function was even attenuated, which may be due to the effects of PTX on cytokine release (e.g., reduction in tumor necrosis factor and interleukin-l), improvement in microcirculation, or additional fib rinolytic effects.