Sepsis and Oxidative Stress in the Newborn: From Pathogenesis to Novel Therapeutic Targets

Table 2

Main evidence from clinical studies on melatonin and pentoxifylline treatment in neonatal sepsis.

Enrolled population	Interventional procedure	Outcomes	Ref.
Melatonin
30 newborns: 10 sepsis/10 sepsis and melatonin treatment/10 controls	Melatonin, 20 mg/kg orally within 12 hours of sepsis diagnosis (2 doses, 10 mg/kg each, separated by 1-hour interval)	Reduced MDA + 4-HDA at 1 and 4 hours after treatment in septic treated versus septic untreated infants; Reduced WBC count, ANC, CRP 24 hours after treatment in septic treated versus septic untreated infants	[63]
40 newborns: 20 sepsis/20 sepsis and melatonin treatment	Melatonin, 20 mg/kg orally, single dose	Reduced CRP and better clinical improvement at 24 and 72 hours after treatment in treated versus untreated infants	[99]
50 newborns: 25 sepsis/25 sepsis and melatonin treatment	Melatonin, 20 mg/kg orally, single dose	Reduced sepsis score at 24 and 48 hours after treatment in treated versus untreated infants	[100]
Pentoxifylline
120 newborns: 60 LOS/60 LOS and pentoxifylline treatment	Pentoxifylline, 5 mg/kg/h IV for 6 hours for 6 days	Reduced TNF-alpha, vasopressor need, duration of respiratory support, duration of antibiotics, hospital stay, incidence of DIC, and thrombocytopenia in treated versus untreated infants; No differences in mortality	[105]
Meta-analysis of 6 randomized or quasi-randomized trials; 416 newborns	Pentoxifylline, continuous IV infusion, different dosing regimens	Reduced all-cause mortality, reduced hospital stay in septic treated versus untreated septic infants; Reduced mortality in the subgroup of preterm newborns, proven sepsis, and Gram-negative sepsis in septic treated versus untreated septic infants	[106]

MAD: malondialdehyde; 4-HDA: 4-hydroxylalkenals; WBC: white blood cell; ANC: absolute neutrophil count; CRP: C-reactive protein; DIC: disseminated intravascular coagulopathy; LOS: late-onset sepsis.