Aqueous chlorhexidine 1% versus 2% for neonatal skin antisepsis: a randomised non-inferiority trial

Abstract

ObjectiveTo evaluate whether 1% aqueous chlorhexidine gluconate (CHG) when compared with 2% aqueous chlorhexidine gluconate is non-inferior for neonatal skin antisepsis.DesignParallel, blinded, non-inferiority randomised trial.SettingLevel III, academic, neonatal intensive care unit.PatientsInfants born at 260/7 to 426/7 weeks of gestation from June 2019 to December 2019.InterventionsParticipants were randomised to skin antisepsis by either 1% aqueous CHG or 2% aqueous CHG.Main outcome measuresThe primary outcome was the proportion of negative skin swab cultures after skin antisepsis. Secondary outcomes were local skin reactions at 0, 6, 12 and 24 hours and plasma chlorhexidine levels in a subset of the study population.ResultsA total of 308 neonates with a median gestation age of 34 (31–37) weeks and mean birth weight of 2029 g were randomised on 685 occasions (1% CHG: n=341; 2% CHG: n=344). 93.0% of the post-antisepsis skin swabs were sterile in 1% CHG group compared with 95.6% of the swabs in the 2% CHG group (risk difference −2.7%, 95% CI −6.2% to +0.8%). The lower bound of 95% CI crossed the pre-specified absolute non-inferiority limit of 5%. Neonates developed mild dermatitis on 16 (2.3%) occasions. There was no significant difference in median plasma CHG levels in the two groups, 19.6 (12.5–36.4) and 12.6 (8.7–26.6) ng/mL, respectively.ConclusionsApplication of 1% aqueous CHG was not shown to be non-inferior to 2% chlorhexidine aqueous for skin antisepsis in neonates. There were no severe skin-related adverse events in either of the two groups.Trial registration numberCTRI/2019/06/019822; (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=33453&EncHid=&userName=CTRI/2019/06/019822)

SHEA Neonatal Intensive Care Unit (NICU) White Paper Series: Practical approaches for the prevention of central-line–associated bloodstream infections

“…Mild dermatitis was identified in 2.3% of infants in each group, with the worst being transient slightly pink discoloration of the skin without edema. Percutaneous absorption of chlorhexidine occurred in all 59 sampled infants but did not differ by the concentration of the aqueous preparation with the median CHG concentration at 24 hours being 19.6 ng/ml and 12.6 ng/ml in the 1% and 2% aqueous CHG group, respectively (14). Therefore, use of the lower CHG concentration does not offer any substantial safety advantage.…”

“…As an alternative to alcohol-based CHG solutions that may potentiate skin irritation and cutaneous CHG absorption, some NICUs use 1% or 2% aqueous CHG for skin antisepsis. In a randomized, blinded, non-100 inferiority trial of 308 infants who were 26 to 42 weeks' gestation, the use of 1% aqueous CHG for skin antisepsis was comparable to a 2% aqueous CHG solution when assessed by the proportion of negative skin swab cultures after skin antisepsis (14).…”

“…While more detailed than the recommendations provided in this document, it could serve as a useful model for NICUs seeking to implement the use of CHG. Infants (≥8 weeks of age) may benefit from a higher CHG concentration (i.e., 2%) (14) (see Figure 1). For CVC insertion, some centers use 2% aqueous rather than alcohol-based CHG in extremely preterm infants (<28 weeks' gestation), but recommend that, once dried, CHG should be rinsed off the skin with sterile water to prevent burns.…”

“…1). 14 For CVC insertion, some centers use 2% aqueous rather than alcohol-based CHG in extremely preterm infants (<28 weeks gestation), but recommend that, once dried, CHG should be rinsed off the skin with sterile water to prevent burns. However, Garland et al 15 showed that the application of 2% CHG in 70% isopropyl alcohol for skin antisepsis before CVC placement and with each weekly dressing change in infants weighing ≥1500 grams and ≥7 days of age was not associated with dermatitis although cutaneous absorption of CHG occurred in 15% of infants.…”

Antiseptic drugs and disinfectants with experience of the second year of COVID-19 pandemic-related side effects

“…Immunologic : In a clinical trial of aqueous chlorhexidine (1% vs 2%) used for neonatal skin antisepsis in a parallel, blinded, non-inferiority randomized design ( n = 308), the risk of contact dermatitis was similar in the two groups, 2.3%. There was also no significant difference in plasma chlorhexidine levels in the two groups ( Sharma et al, 2021 ) [C]. In a narrative report on 15 years of experience with hand sanitizer solution in 159 healthcare workers followed through that period, allergic contact dermatitis to chlorhexidine was determined as “rare” (no quantitative data provided) ( Quenan & Piletta, 2021 ) [C].…”