Cleansing

Solutions in
ELBW
Article Review
Introduction
Skin functions:
Modulation of transepidermal water fluxes,
protection from dehydration and excessive water
influx, and maintenance of electrolyte homeostasis
Thermoregulation and minimisation of caloric losses
Antimicrobial defense
Protection from environmental toxins, trauma and
UV radiation
Tactile sensation
Introduction
Competent epidermal barrier necessary at birth to
maintain fluid homeostasis in extrauterine
environment
Barrier located in stratum corneum (outermost)
o mediated by lamellar bilayers of hydrophobic lipids (principally fatty
acids), cholesterol and ceramides
o located in extracellular spaces of multiple layers of tightly knit, anucleate
corneocytes, surrounded with protein and keratin-rich cornified cell
envelope
Premature infants skin
Epidermal permeability barrier forms during 3
rd
trimester;
developmentally immature in preterm infants:
Structural immaturity stratum corneum and epidermis thinner
Anchoring fibrils and anchoring filaments fewer and smaller
anchoring of epidermis and susceptibility to shear forces
Increased TEWL, heat loss, higher caloric demands, increased
potential for absorption of environmental toxins, and
compromised antimicrobial defense
Antibacterial acid mantle forms more slowly in ELBW
o Skin pH > 6.0 at birth, declines to 5.5 over 1
st
few weeks, then 5.0 over 1
st
month (4.95
in term infants within 1
st
week)
Formation of protective layer of vernix underdeveloped (starts
17-20W, well formed 36-38W)
Fat and zinc accumulate in 3
rd
trimester
o Low subcutaneous fat supply limits thermoregulation
o Zinc deficiency causes skin disruption, dermatitis
Premature infants skin
Barrier maturation in prems requires
2-4/52 (up to 8/52 in extreme prems)
Interfollicular cornification and
stratum corneum maturation
22-24W

Premature infants skin
Developmental immaturity and large surface area-to-body
mass ratio (10-15x greater in 25W compared to FT) causes
TEWL fluid losses up to 30% total BW in 24H (40-130
ml/kg/day)
This may be associated with:
Significant morbidity due to dehydration and
hypotension, increased risk off IVH and NEC
Electrolyte imbalance, esp hyperosmolar hypernatremia
(thus increased risk for IVH)
Thermal instability
Increased caloric demands as skin evaporative losses
may comprise up to 20% of total energy expenditure in <
30W
Rehydration of prems may exacerbate or induce PDA,
heart failure, pulmonary oedema, NEC
Safety and efficacy of
cleansing solutions
Infections leading cause of death in NICU,
especially in 1
st
2/52 of life as epidermal barrier
immature and functionally compromised
Premature infants suffer significant morbidity and
mortality, esp during 1
st
week of life (~2/3 NND)
Guidelines for the Prevention of Intravascular
Catheter-Related Infections (CDC, 2011)
o Numerous studies demonstrated less CRBSI using chlorhexidine skin prep
compared to povidone-iodine.
o No recommendation can be made for the safety or efficacy of
chlorhexidine in infants aged <2 months due to limited safety data
CDC Guidelines for the Prevention of
Intravascular Catheter-Related Infections
0.5% tincture of chlorhexidine vs 10% povidone
iodine no differences in CVC colonisation or CRBSI
Three-armed study (2% aqueous chlorhexidine
gluconate vs 10% povidone-iodine vs 70% alcohol):
2% aqueous chlorhexidine gluconate decreased
CRBSI compared with 10% povidone iodine or 70%
alcohol
Meta-analysis of 4,143 catheters: chlorhexidine
preparation reduced risk of catheter related
infection by 49% (95% CI .28 to .88) relative to
povidone iodine
RCT (n = 705) reported substantial decrease in
colonised catheters in neonates in chlorhexidine
impregnated sponge dressing group vs standard
dressings (15% vs 24%; RR = .6; 95% CI 5 0.5.9), but
no difference in CRBSI rates or BSI of unknown
source
Chlorhexidine impregnated sponge dressings
associated with localised contact dermatitis in
VLBW infants
o 15 (15%) of 98 VLBW developed localised contact dermatitis; four (1.5%) of
237 neonates >1,000 g developed this reaction (P < .0001)
o Infants <26 weeks GA with CVCs placed at age <8 days were at
increased risk for having localised contact dermatitis, whereas no infants
in the control group developed this local reaction

CDC Guidelines for the Prevention of
Intravascular Catheter-Related Infections
Absorption and tolerability of aqueous
chlorhexidine gluconate used for skin antisepsis
prior to catheter insertion in preterm neonates
CHG absorption into blood of preterm infants after topical
exposure
20 infants, <32W GA, >48HOL but < 14DOL
2% aqueous CHG impregnated cloth before PICC insertion
Blood samples 1-2H and 6-12H after CHG exposure from
extremity not exposed to CHG
10/20 infants had detectable CHG concentration, highest
concentration 48-72H after exposure
No correlation of serum concentration to GA, BW or CGA
No increase in AST/ALT after exposure, no increase in
creatinine (except 1 infant with sepsis)
No CRBSI
No CHG-related skin toxicity
Absorption and tolerability of aqueous
chlorhexidine gluconate used for skin antisepsis
prior to catheter insertion in preterm neonates
No data on clinical relevance of trace CHG
absorption
No safety data on tolerable blood CHG
concentration and what level there may be
adverse consequences
Several studies in term infants and adults showing
safety and tolerance after CHG exposure, no
reports of adverse consequences; but preterm
infants have developing neurologic systems and
immature drug clearance this possible higher risk of
adverse outcome
Does skin cleansing with chlorhexidine affect skin
condition, temperature and colonization in
hospitalized preterm low birth weight infants? A RCT
Chlorhexidine is shown to reduce skin flora and incidence
of sepsis, although predominantly term neonates
Study on LBW prem 28-36W; 0.25% free
chlorhexidine (= 0.44% chlorhexidine digluconate)
Skin condition at 24H, D3, D7; skin temperature at 30 min,
1H, 6H; colonisation rate of axilla and groin at 24H and
72H after intervention chlorhexidine vs NS vs no
cleansing
62% risk reduction in skin colonisation at 24H compared
to no cleansing (RR: 0.38; 95% CI: 0.15, 0.98), but no
significant reduction when compared to NS cleansing
(RR: 0.42; 95% CI: 0.16, 1.10); no significant difference at
72H (?small sample size)
No significant difference in skin condition
Safety and Impact of Chlorhexidine
Antisepsis Interventions for Improving
Neonatal Health in Developing Countries
Contact dermatitis was reported in 5% of ELBW infants after
long-term (> 7 days) placement of chlorhexidine-impregnated
dressings for CVC may have been caused by occlusive
dressing instead of chlorhexidine
No infants receiving skin prep with 0.5% chlorhexidine
developed dermatitis, nor those receiving full-body wiping,
bathing, or umbilical cord cleansing with chlorhexidine
32 consecutive daily bathing of hospitalised newborns (n = 34;
29 preterm) with 4.0% chlorhexidine (Hibiscrub)
o 10/23 heel prick samples positive for chlorhexidine samples probably
contaminated from residual chlorhexidine on skin
o 5/24 venous blood samples had detectable chlorhexidine all < 36W GA thus
increased epidermal permeability due to immature skin development
Potential for absorption appears to be reduced when
chlorhexidine is applied in aqueous or other nonethanol-
based formulations
No indication that low levels of chlorhexidine detected in the
blood samples resulted in any harmful effects clinically
Safety of chlorhexidine gluconate used
for skin antisepsis in the preterm infant
Chlorhexidine: phenol derivatives, chlorinated
cationic biguanide; bacteriocidal, increasing cell
membrane permeability with more rapid onset of
action; effective against Gram-positive and Gram-
negative bacteria
Leaves a residue on the skin
Binds more strongly to protein in outermost layer of
skin, withstanding removal by alcohol and
immediately decreasing organisms on sskin after
one application
Garland et al reported severe contact dermatitis with
CHG-impregnated dressing over catheter sites
15 (15%) of 98 infants <1000 g and 4 (1.5%) of 237 infants
>1000 g developed related contact dermatitis under
dressing most occurred in neonates < 28W and < 1/52
olf
?secondary to CHG or external pressure from occlusive
adhesive dressing restricting capillary perfusion to skin
causing local skin breakdown
No contact dermatitis reported in infants receiving full-
body CHG skin cleansing when occlusive dressings were
not necessary, even for severe prem/VLBW
Alcohol alone can cause skin burns in preterm infants,
therefore impact of CHG as trigger of skin breakdown in
alcohol-based CHG preparations is unknown
Safety of chlorhexidine gluconate used
for skin antisepsis in the preterm infant
Literature review of 11 studies demonstrated
adverse effects in 4 studies, ranging from self-limited
rash to severe skin irritation (4/36 < 1000g and <48H
of age)
From three studies reporting CHG absorption in
preterm infants, there were no reports of severe
adverse reactions in the patients, including no
neurological complications or skin toxicity.

This 644 g baby sustained extensive burns after cleansing with chlorhexidine 0.5% with 70% methanol during
umbilical catheterisation. He became hypothermic (32.6C), hypernatraemic, then developed systemic fungal
sepsis with extensive skin breakdown. After 2/52, skin healed without apparent cosmetic damage,
but he died from renal failure 25/7 later.
Aquaeous chlorhexidine gluconate 2% used to before umbilical catheter insertion soon after birth in a DCDA 25
weeker. 2H later, skin in RIF, right flank, periumbilical area, perineum and groin turned erythematous. After 6H,
the skin became pale. Epithelium was lost in affected areas diagnosed mixed-depth, partial-thickness burns.
These injuries completely healed with conservative management over 4 weeks with no residual scarring.
Use with Caution
Complications of severe burns:
Hypothermia, excessive water loss, sepsis, and renal
failure.
Pain and stress can adversely affect neuronal
maturation in the brain, and skin scarring and
depigmentation
If CHG is going to be used frequently in preterm
infants, it is important to identify which component,
the CHG or the ethanol, causes skin irritation in this
population and to develop formulations of CHG
products that can be more safely administered to
these infants.

Use with Caution
Wiping off excess chlorhexidine with normal saline
may help reduce skin irritation, but there are reports
of skin burns even after cleansing skin with NS
Dry immediately and avoid prolonged contact,
avoid pooling of cleanser under infant
Higher risks of skin irritation in 1
st
48HOL
Alcohol based skin cleansers associated with higher
risk of skin irritation reported to cause extensive
burns in prems, where skin vulnerability
accentuated by hypoxia and hypothermia
Additional measures for
skin care
Avoid alkali bathing soap (pH up to 9) alter skins pH,
takes up to 1H for term skin to regain acidic property,
takes even longer for prems (inteferes with acid mantle)
proliferation of bacterial growth and increases
permeability of skin surface
Barrier products e.g. emollients (white soft paraffin) adds
lipid layer to surface of the skin, and/or provides lipids
which can penetrate stratum corneum, simulating
effects of naturally occurring lipids protect skin from
irritants and microorganisms and prevent increased TEWL
through damaged areas
Humidified environment 85-90% in 1
st
week, gradually
reducing by 40% over 2-3/52 prevents excessive TEWL

References
OGrady NP, Alexander M, Dellinger EP, Gerberding JL, Heard SO, Maki DG et al.
Guidelines for the prevention of intravascular catheter-related infections, 2011. The
Hospital Infection Control Practices Advisory Committee, Center for Disese Control
and Prevention.
Mullany LC, Darmstadt GL, Tielsch JM. Safety and impact of chlorhexidine antisepsis
interventions for improving neonatal health in developing countries. Pediatr Infect
Dis J 2006; 25(8): 665675.
Chapman AK, Aucott SW, Milstone AM. Safety of chlorhexidine gluconate used for
skin antisepsis in the preterm infant. J Perinatol 2012; 32(1): 49.
Reynolds PR, Banerjee S, Meek JH. Alcohol burns in extremely low birthweight
infants: still occurring. Arch Dis Child Fetal Neonatal Ed 2005; 90(1): F10.
Sankar MJ, Paul, VK, Kapil A, Kalaivani M, Agarwal R, Darmstadt GL, Deorari AK.
Does skin cleansing with chlorhexidine affect skin condition, temperature and
colonization in hospitalized preterm low birth weight infants?: a randomized clinical
trial. J Perinatol 2009; 29: 795-801.
Chapman AK, Aucott SW, Gilmore MM, Advani S, Clarke W, Milstone AM.
Absorption and tolerability of aqueous chlorhexidine gluconate used for skin
antisepsis prior to catheter insertion in preterm neonates. J Perinatol 2013; 33: 768-
771.
Upadhyayula S, Kambalapalli M, Harrison CJ. Safety of anti-infective agents for skin
preparation in premature infants. Arch Dis Child 2007;92:6467.
Lashkari HP, Chow P, Godambe S. Aqueous 2% chlorhexidine-induced chemical
burns in an extremely premature infant. Arch Dis Child Fetal Neonatal Ed 2011.
Lund C, Kuller J, Lane A, Lott JW, Raines DA. Neonatal Skin Care: The Scientific Basis
for Practice. Neonatal Network 1999; 18 (4): 15-26.