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Abstract
Neonatal sepsis is frequently associated with pathological activation of the coagulation system, leading to microcirculation derangement and multiple organ dysfunction syndrome (MODS). The key role in the pathogenesis of sepsis has been attributed to pro-inflammatory cytokines. Proinflammatory cytokines trigger the development of disseminated intravascular coagulation (DIC) via the tissue factor-dependent pathway of coagulation. The methylxanthine derivative pentoxifylline (PTX) is one of the promising substances which are under current investigation to modify or limit inflammatory response. PTX has been found to interrupt early gene activation for tumour necrosis factor, interleukin-1, interleukin-6 and tissue factor production and to improve survival from sepsis.
The current work was designed to evaluate the potential prophylactic effects of PTX against sepsis-induced microcirculation derangements in Egyptian neonates. This was accomplished by assessing coagulation related parameters, DIC incidence and serum lactic acid levels. Incidence of MODS and Length of hospital stay of the survivors were also reported.
Thirty seven neonates with sepsis were divided into 2 groups, 17 neonates in the PTX group and 20 in the placebo groups. Patients were randomly assigned to receive PTX (PTX group) in a dose of 5mg/kg/hr for 6 hours for 6 successive days or the same volume of normal saline as placebo (placebo group).
The following were measurements performed in each group before and after treatment: a) coagulation related parameters: PT, APTT, fibrinogen and D-dimer; b) lactate; c) CRP; d) CBC; e) hemodynamic measurements: arterial blood pressure, heart rate, capillary refill, and urinary output.
The current study showed a statistically significant difference between the two groups in CRP levels post PTX treatment, a slight decrease in the incidence of DIC was observed in the test group; which in association with the remarkable increase in clinical bleeding frequency and disordered capillary perfusion in the placebo group indicate an improvement in microcirculation by PTX. A steady decline in lactate levels occurred in the test group compared to an increase in the lactate values of the placebo neonates. In addition, incidence of MODS was lower significantly in the PTX treated infants. This was clearly reflected on the hospital stay duration of the survivors. In conclusion: PTX use in septic neonates decreased the microcirculatory derangement as evidenced by a lower incidence of DIC and bleeding. PTX shortened the length of hospital stay and significantly affected the incidence of MODS. Mortality rate was not affected by PTX use.