Does long-term continuous administration of pentoxifylline affect platelet function in the critically ill patient?

OBJECTIVE

The methylxanthine derivative pentoxifylline (PTX) is one of those promising substances which are under current investigation to modify or limit inflammatory response. Anti-aggregation activity has also been described that may contribute to the beneficial effects of this substance. Long-term effects on platelet function have not been elucidated yet.

DESIGN

Prospective, randomized study.

SETTING

Clinical investigation on a surgical intensive care unit of a university hospital.

PATIENTS

26 trauma patients and 26 patients suffering from sepsis secondary to major operations were consecutively studied.

INTERVENTIONS

The patients prospectively received either 1.5 mg/kg per h pentoxifylline continuously for 5 days (after a loading dose of 600 mg) (trauma-PTX, n = 13; sepsis-PTX, n = 13) or saline solution as placebo (trauma-control; n = 13; sepsis-control, n = 13).

MEASUREMENTS

On the day of admission (trauma patients) or day of the diagnosis of sepsis and at 12:00 p.m. during the next 5 days, platelet aggregation induced by adenosine diphosphate (ADP 2.0 mumol/l), collagen (4 microliters/ml), and epinephrine (25 mumol/l) was determined by a turbidimetric method from arterial blood samples. Standard coagulation screen was also monitored.

MAIN RESULTS

In untreated trauma and sepsis patients, maximum platelet aggregation induced by all three agonists decreased during the first few days after inclusion in the study [trauma: ADP - 17.1 +/- 8.0 rel% (% change from baseline); sepsis: ADP -26.1 +/- 5.6 rel%]. In due course, maximum platelet aggregation recovered, reaching the baseline value or even exceeding it (trauma patients). In the PTX-treated patients, platelet aggregation was significantly less impaired (sepsis group: ADP -4.4 +/- 3.3 rel%) or even increased beyond baseline values in the 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 patients. 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-1), improvement in microcirculation, or additional fibrinolytic effects.