Archimedes

Safety of anti‐infective agents for skin preparation in premature infants

Report by

S Upadhyayula, Rotherham General Hospital, Rotherham, UK; doctorshankar2000@hotmail.com

M Kambalapalli, C J Harrison, Rotherham General Hospital, Rotherham, UK

A baby sustained extensive skin burns after the use of a skin preparation (alcoholic chlorhexidine). Following this event the hospital started using an aqueous preparation of chlorhexidine 0.05%. Was this the right choice and what is the evidence for the use of this or any other skin preparation in preterm infants?

Structured clinical question

In preterm infants of <28 weeks' gestation [patient] what is the choice of skin preparation prior to invasive procedures on the unit [intervention] in terms of safety or least complications and prevention of infection [outcome]?

Search strategy and outcome

Primary source: Medline (1956–2005), MeSH terms were used. An advance search was carried out and close matches from mapping were chosen and another search was carried out using explode and major subheadings. Secondary sources: Cochrane and EMBASE.

Search terms: Premature and anti‐infective agents and invasive procedures and safety and complications.

Search outcome: Only four hits matched all our search criteria. We further searched for trials that looked at the safety and efficacy of different antimicrobials with out restricting the age group. We found two hits that specifically answered our question.^{1 2} See table 2.

Table 2 Details of articles found.

Citation	Study group	Study type	Outcome	Key results	Comments
Watkins	Case reports of 2 patients	Case report	None specified	Chemical burns from skin	Extremely low birth weight
and	who sustained skin burns			preparation	infants have high skin
Keogh	following the use of				permeability
(1992)3	alcoholic skin preparation				Major burns are possible
					after brief exposure to solution
					Care is needed in the
					selection of such solutions
Reynolds	Case reports of 2 patients	Images in	None specified	Morbidity from skin	Great care must be taken to
et al	who sustained extensive	neonatal		burns	avoid pooling of the
(2005)4	abdominal burns following	medicine			cleanser under the infant
	the use of 0.5% chlorhexidine				Saline must be used for
	in 70% methanol				cleaning the immature skin
Buhrer	24 preterm babies had	Prospective	Transient erythematous	One infant had culture	The solution does not
et al	2% phenoxyethanol and	trial	skin reaction was	proven sepsis	cause skin damage in the
(2002)5	0.1% octenidine as		noted in the 23 week	Urinary concentration of	extreme preterm infant
	antiseptic for skin		babies	2‐phenoxyethanol was 12‐	Although absorbed by the
	preparation			fold versus the original	skin it is extensively
				compound in boys	metabolised
Garland	826 infants were exposed	Prospective	Chlorhexidine based	Incidence of catheter	The overall rate of catheter
et al	to 10% povidone iodine	non‐randomised	preparations are better	colonisation with	related bacteraemia was
(1995)6	and 0.5% chlorhexidine	trial	than iodine based	chlorhexidine was 4.7%	low at 0.25%
	sequentially over a		preparations for	(20/418, p = 0.01)	Chlorhexidine based
	6 month period		decreasing catheter	Incidence with povidone	preparation are better than
			colonisation	iodine was 9.3% (38/408)	iodine based ones
Hibbard	106 subjects were treated	Randomised	Chlorhexidine	Chlorhexidine gluconate	All three antiseptics
et al	with one or two of	parallel	gluconate in isopropyl	plus isopropyl alcohol	significantly reduced
(2002)1	three antiseptics	group open	alcohol has better	provided significantly	abdominal and inguinal
	(chlorhexidine gluconate	labelled	persistent antimicrobial	more persistent	microbial counts from
	plus isopropyl alcohol,	clinical trial	activity than isopropyl	antimicrobial activity on	baseline at 10 min,
	70% isopropyl alcohol,		alcohol or aqueous	abdominal sites than	6 h and 24 h
	2% chlorhexidine)		chlorhexidine alone	isopropyl alcohol	Chlorhexidine plus alcohol
				(p = 0.03) or chlorhexidine	provided more persistent
				gluconate (p = 0.028) at 24 h	antimicrobial activity

Commentary

Care of the preterm infant in neonatal units is challenging and involves a lot of support. Placement of central lines is an important aid in delivering this care and it is a common practice to use an alcohol based skin preparation (0.5% chlorhexidine in 70% methanol) prior to this procedure. However, this preparation has the potential to cause skin burns.⁷

Burns in this population of infants may be associated with increased mortality and morbidity. There is also the possible impact of burns (pain and stress) on neuronal migration and hence long‐term outlook.⁴

Evidence for the use of an appropriate agent in this population of infants in sparse; this is understandable because of the ethical issues related to carrying out research in these patients. A considerable proportion of the evidence that we found was in the form of case reports.³

A clinical study comparing skin antisepsis and the safety of different skin preparations¹ in adults showed that aqueous chlorhexidine, chlorhexidine in isopropyl alcohol or isopropyl alcohol alone had good immediate antimicrobial activity but that chlorhexidine in alcohol had more persistent activity; all had an excellent safety profile. Unfortunately, we cannot apply adult data to our population as has been highlighted by cases such as ours.

Clinical bottom line

• Extremely preterm infants are at risk of burns from the use of alcoholic skin preparations, but no comparative data are available to suggest the best preparation for this group of patients. (Grade C)

• Making sure there is no pooling seems to be the most effective method of avoiding problems related to skin burns in infants. (Grade C)

• Alcohol based preparations have good antibacterial activity in adults and have an excellent safety profile. (Grade C)

A review article examined analyses comparing the activity and safety of current antiseptics.² Six randomised, controlled, single blind, parallel group clinical trials were assessed to determine the best preoperative skin preparation. The agents examined included chlorhexidine with isopropyl alcohol (chlorhexidine gluconate with 70% isopropyl alcohol, or another combination of the two) 2% chlorhexidine alone, 4% chlorhexidine alone, 70% isopropyl alcohol alone and 10% povidone iodine alone. An antiseptic containing a combination of two antiseptics with different mechanisms of action consistently and significantly demonstrated better antimicrobial activity than a single antiseptic alone. It was also demonstrated that chlorhexidine or povidone iodine alone did not in some studies qualify as a suitable antiseptic agent. Again, all of these trials were on adults and no side effects were noted.

One paper looked at an alternative agent, octenidine, and reported it to be safe.⁵ However, this study examined a small population of infants (24) and on further enquiry we found that the preparation contained arachis oil and hence is not a viable alternative in the UK.

The EPIC project updating the national evidence based guidelines for preventing health care‐associated infections in NHS hospitals in England reported that both alcoholic and aqueous preparations of chlorhexidine provide concentrations of chlorhexidine that are higher than the minimal inhibitory concentration for most nosocomial bacteria and yeasts. Both 0.5% and 1% alcoholic solutions and 0.5% and 2% aqueous solutions were examined.⁸ However, there is no mention of its safety in preterm infants.

We also contacted the manufacturer (Seton Health Care Group, Oldham, Uk) seeking more information but did not learn anything new. It was evident to us from our search that the currently used agents have the potential to cause considerable harm to infants. However, no safer alternative is supported by evidence and this reinforces the need to examine this issue more closely. Research must be carried out to find a safe and effective agent if we are to not make things more difficult for an already challenged population.