Effect of the immunomodulating agent, pentoxifylline, in the treatment of sepsis in prematurely delivered infants: A placebo-controlled, double-blindtrial
R. Lauterbach et al., Effect of the immunomodulating agent, pentoxifylline, in the treatment of sepsis in prematurely delivered infants: A placebo-controlled, double-blindtrial, CRIT CARE M, 27(4), 1999, pp. 807-814
Objective: To evaluate the influence of the methylxanthine derivative, pent
oxifylline, on plasma levels of tumor necrosis factor (TNF)-alpha interleuk
in (IL)-1, and IL-6 in prematurely delivered infants with generalized bacte
rial infections and to assess the effect of this immunomodulating drug on t
he clinical outcome in newborns with sepsis,
Design: A prospective, randomized, double-blind trial.
Setting: The neonatal intensive therapy units in university teaching hospit
als.
Patients: One hundred patients with sepsis admitted during a 1.5 yr period,
Interventions: Patients were randomly assigned to receive pentoxifylline (p
entoxifylline group) in a dose of 5 mg/kg/hr for 6 hrs on 6 successive days
or an identically presented placebo (placebo group).
Measurements and Main Results: Only infants with sepsis confirmed by positi
ve blood culture were recruited into the study, There were no significant d
ifferences at randomization between the pentoxifylline and placebo groups w
ith regard to the birth weight, gestational age, gender, Apgar score, hypot
ension, neutropenia, thrombocytopenia, metabolic acidosis, plasma levels of
cytokines, and occurrence of shock, Plasma levels of TNF, IL-l, and IL 6 w
ere evaluated before and after the drug or placebo administration on the fi
rst, third, and sixth days of therapy. Cytokines were determined by immunoe
nzymetric test EASIA (TNF) and Endogen Interleukin Elisa (IL-1, IL-6), The
frequency of Gramnegative sepsis was similar in both groups (37.5% and 36.8
%), Pentoxifylline significantly diminished plasma TNF levels (p =.009) but
had no effect on plasma IL-l levels. Mean plasma IL-6 levels, which were m
easured in the pentoxifylline group on the 6th day of the study, were signi
ficantly lower compared with respective data obtained in the placebo group.
Only 1 of 40 infants with sepsis in the pentoxifylline group died, whereas
6 of 38 infants in the placebo group did not survive (p =.046), An increas
ed incidence of disordered peripheral circulation and metabolic acidosis (p
=.048), anuria or oliguria (p =.03), disseminated intravascular coagulatio
n (p =.043), and the occurrence of clinical symptoms of necrotizing enteroc
olitis (p =.025) was observed in the course of sepsis in infants in the pla
cebo group.
Conclusion: Pentoxifylline significantly affects the synthesis of TNF and I
L 6 as well as reduces the mortality rate in premature infants with sepsis,
The dosage and schedule of drug administration in this study attenuated th
e severity of the clinical course of sepsis in this group of patients.