Antiseptic efficacy and plasma chlorhexidine levels following two different methods of application of 1% aqueous chlorhexidine gluconate for skin disinfection in preterm newborns: a randomized controlled trial

Many neonatal units have started using Chlorhexidine gluconate for neonatal skin antisepsis. However, there is in-vitro evidence of inhibition of neurite growth. The current study aimed to compare two methods of its local application, for the extent of systemic absorption and antiseptic efficacy. Parallel group, blinded, randomised trial, at a Level III, neonatal intensive care unit. Between December 2020 to July 2022, neonates from 28 to 34 weeks gestation, were randomized to local skin antisepsis by either- (a) 1% aqueous chlorhexidine (CHG aq) followed by cleansing off the residual agent with sterile water swab (Cleansing group) or (b)1% CHG aq followed by air drying (No cleansing group). The outcome measures were the proportion of post antisepsis skin swabs with no/insignificant growth, and the plasma chlorhexidine levels. Of the total of 457 enrollments (Cleansing: n = 230; No Cleansing: n = 227), 216 (93.91%) in "Cleansing" vs. 221 (97.36%) in "No cleansing" (risk difference -3.45%, 95% CI -7.2 to 0.28%; p = 0.072) had no/insignificant growth post-antisepsis. The lower bound of the confidence interval crossed the pre-specified non-inferiority limit of 5%. The median (IQR) plasma chlorhexidine levels were not significantly different between the two groups (7.9 (5.6, 17.9)) ng/mL in Cleansing vs. 6.5 (4.6, 17.7) in No cleansing groups (p = 0.437). Cleansing with sterile water after application of chlorhexidine in preterm neonates was not shown to be non-inferior compared to no cleansing, for skin antisepsis efficacy. Systemic absorption occurred to a similar extent despite cleansing off the residual agent. CTRI/2020/10/028719.