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 Table of Contents  
Year : 2020  |  Volume : 9  |  Issue : 3  |  Page : 162-167

A literature review of selection of appropriate antiseptics when inserting intravenous catheters in premature infants: The challenge in neonatal intensive care unit

1 Department of Medical - Surgical, PhD Student in Nursing, School of Nursing and Midwifery, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Medical - Surgical, Nursing and Midwifery Faculty, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
3 Department of Psychology, Nursing Faculty, Meybod Nursing School, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
4 Department of Pediatric and Neonatal Intensive Care Nursing, Nursing and Midwifery Faculty, Nursing and Midwifery School, Shahid Beheshti University of Medical Sciences, Tehran, Iran
5 Depatment of Pediatrics, Nursing Faculty, Meybod Nursing School, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Date of Submission04-Jan-2020
Date of Decision27-Mar-2020
Date of Acceptance29-Mar-2020
Date of Web Publication07-Aug-2020

Correspondence Address:
Prof. Naiire Salmani
Nursing Faculty, Meybod Nursing School, Shahid Sadoughi University of Medical Sciences, Yazd
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcn.JCN_135_19

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Background: Reducing or preventing bloodstream infection caused by invasive intravenous catheterization, emphasizes the use of an effective topical antiseptics agent; however, because of the flaw in the evidence available regarding the choice of safe antiseptic to use on infants' skin under 2 months this issue remains controversial. The aim of this study was to investigate the types of antiseptics commonly used in neonatal intensive care units, consumption criteria and side effects of consumption and the effects of using antiseptics in premature infants. Methods: In this review, the total number of articles in PubMed, Scopus and ScienceDirect databases since 2010 were searched; titles and abstracts to identify relevant articles have been identified and 14 of the 48 searched articles were finally reviewed. Results: The review articles showed that different antiseptic-including chlorhexidine (CHG) 2% with alcohol base, pure CHG (in different density - 0.05%–2%), povidone-iodine 10%, isopropyl alcohol, 70% alcohol are used when inserting intravenous catheters in premature infants. Cutaneous side effect, systemic absorption and transient hyperthyroidism were reported as common side effects. Weight or age was criteria reported for antiseptic use. Various studies have been conducted to compare the effects of antiseptic with each other and different results have been reported.
Conclusion: There is a paucity of evidence-based consensus guidelines for the use of appropriate antiseptic for preparing the skin before placing the intravenous catheter in preterm babies. Further research and publications are required, which will help reduce the risk of line related hospital-acquired infections.

Keywords: Antiseptic, intravenous catheters, neonatal intensive care unit, premature infants

How to cite this article:
Bagheri I, Fallah B, Dadgari A, Farahani AS, Salmani N. A literature review of selection of appropriate antiseptics when inserting intravenous catheters in premature infants: The challenge in neonatal intensive care unit. J Clin Neonatol 2020;9:162-7

How to cite this URL:
Bagheri I, Fallah B, Dadgari A, Farahani AS, Salmani N. A literature review of selection of appropriate antiseptics when inserting intravenous catheters in premature infants: The challenge in neonatal intensive care unit. J Clin Neonatol [serial online] 2020 [cited 2021 Jan 19];9:162-7. Available from: https://www.jcnonweb.com/text.asp?2020/9/3/162/291641

  Introduction Top

Sepsis is one of the most common causes of infants' mortality in neonatal intensive care units,[1],[2],[3] which in addition to mortality can have other complications such as prolonged hospitalization, increased health care costs,[4] increased need for antibiotics and the possibility of developing resistant organisms.[5] 70% of neonatal sepsis is due to bloodstream infection caused by intravenous catheters,[6] which is one of the most dangerous and common nosocomial infections in infants under intensive care.[7] The main mechanism by which intravenous catheters are infected is bypassing bacteria through the skin where the catheter enters into the catheter's outer surface, which colonize it[8],[9] and then, they cause infection in the bloodstream.[8] The most common bacteria colonizing catheters in infants are coagulase-negative Staphylococci.[8],[9] Inappropriate skin disinfection before piercing the vein and catheter insertion is the main risk factor for catheter colonization with microorganisms and causes infection[9] and several factors, in parallel, make premature infants susceptible to this type of infection. Which includes the immature immune system with severely low immunoglobulin levels and low neutrophil storage[10] and delayed maturation of the skin. In a way that the colonization of the skin microorganisms of preterm infants is different from that of healthy infants.[11]

The maturation of the infants' skin depends on the age of pregnancy. In a way that premature infants lack an effective skin barrier. The stratum corneum, which is responsible for producing an effective epidermal barrier, has not grown well until 34–34 weeks of gestation. Hence, infants born under 34 weeks need about 4–5 weeks for skin maturation.[12],[13] Premature infants in the neonatal intensive care unit are exposed to a variety of invasive methods and effective skin disinfection before invasive procedures is an essential stage of care for these vulnerable patients[14] but there are no guidelines for choosing the right antiseptic for children younger than 2 months[15] and no antiseptics for infant use have been fully approved and introduced and this is due to concerns about the safety of antiseptics.[15],[16] Hence, we to carry out the present study with the aim of investigating the types of antiseptics commonly used in neonatal intensive care units, their consumption criteria, side effects, and the effects of antiseptics consumption in premature infants. Providing evidence for comparing antiseptics based on the mentioned dimensions for the neonatal care team and helping in deciding to choose the right antiseptic for intravenous catheter placement for premature infants are the other goals of this study.

  Methods Top

In this study, the total number of articles in PubMed, Scopus, science direct databases since 2010 were searched by the following keywords: preterm, premature, infant, neonate, antiseptic, disinfectant, peripheral venous catheter, central venous catheter, decontamination, central line insertion, peripheral line insertion, intravascular devices, neonatal intensive care unit, skincare. The inclusion criteria for the study include: articles being in the English language and articles being available in full text. Exclusion criteria include studies, in which antiseptics used in venous catheter placement, have not been considered and discussed, studies that did not focus solely on premature infants and in general, they have studied and reported term and premature infants together, studies in congress and conferences and reviewed studies.

  Results Top

Total number of articles searched from three databases based on the keywords was 48 articles. Thirteen articles were removed for duplication and 35 articles were studied for abstract review. Twenty-one articles met the exclusion criteria and were excluded, and 14 articles have been finally reviewed and their findings are presented in two sections.

Common antiseptics used in neonatal intensive care units


It has broad-spectrum bactericidal activity but is ineffective against mycoplasma and is nonsporicidal.

CHG is wide antimicrobial activity, and topical longevity makes it suitable for skin disinfection before invasive procedures.[17] In five studies, chlorhexidine (CHG) with different concentrations and combinations was used. In Canada, >85% of neonatal intensive care units use 2% CHG with 87% alcohol content and 2% pure CHG.[18] In the Norfolk and Norwich university hospitals of England, 38% of neonatal intensive care units use CHG 2% with a 70% alcohol content and 12% of neonatal intensive care units use CHG 0.5% with a 70% alcohol content.,[19] In the United States, it is reported that 61% of neonatal intensive care units use CHG with or without alcohol,[20] In New Zealand-Australia, 31.6% of neonatal intensive care units use pure CHG at different densities of 0.05%–2%,[21] In the United Kingdom, all neonatal intensive care units used pure CHG at a density of <1% or CHG 2% with an alcohol buffer.[22]

Complications following CHG administration with various concentrations and combinations have been reported. Systemic absorption is one of the reported complications. In Chapman et al.'s study, systemic uptake of CHG in preterm infants who had undergone peripherally inserted central catheter (PICC) was investigated. Results showed that 50% of infants had detectable serum CHG with a range of 16–206 ng/ml. Seven of the infants had the highest serum density of CHG in the 2nd to 3rd days after contact with CHG.[23]

Another reported complication was skin complications. In a US national survey conducted by Tamma et al. 25 of the 55 neonatal intensive care units (NICUs) (51%) CHG-related side effects were reported in infants weighing <1500 g at birth. All complications included skin reactions, including skin inflammation, superficial ulcers, and burns.[20] The findings were similar to findings released by the US National Survey of neonatal care units, that (53.3%) of respondents reported CHG-related skin complications. It was often described as tingling or burning of the skin.[24] Similarly, in the New Zealand-Australia survey, 29 nurses reported side effects after using the solution containing CHG; they have also reported 12 units of CHG-related skin complications such as skin inflammation, burns, and blisters.[21] In Canada, 68% of CHG users experienced skin burns, 61% experienced redness, skin irritation and fragility, and 13% experienced skin rashes.[18] In general, the skin complications of HCG use in premature infants were not surprising, and in most studies, these side effects have been reported; as in some studies the cause of these complications is alcohol in combination with CHG.[18],[19]

Therefore, it seems that the density of CHG would be a determining factor involved in skin lesions. As the target in high-density CHG solutions is to increase bacterial cleansing power[25] but increased CHG density can be associated with skin burns; as one case of skin burns in premature infants was reported by Neri et al. following the consumption of alcohol-based CHG of 0.5% and recommended that the density of CHG used in premature infants be <1%, especially in the 1st week after birth.[26] Focusing on various studies, skin burns have been reported as a common complication of CHG use in different densities and compounds, and skin burns in premature infants can lead to hypothermia, dehydration, sepsis, and renal failure.[27] Therefore, most neonatal specialists consider the loss of skin cohesion to be an important limiting factor for stopping the use of CHG antiseptics.[20] In a study in Canada, 5% of povidone-iodine users and 27% of alcohol users in neonatal intensive care units reported the occurrence of burns and skin fragility in infants.[18] Neurotoxicity complications have been considered. Johnson, et al. in a survey of neonatal intensive care staff about CHG complications and their concerns about CHG use, stated that no neurotoxicity effects were reported but it was mentioned as a matter of concern in open questions.[24]

Also in the study by Tamma et al. which NICU personnel was surveyed regarding the complications of CHG use no neurotoxicity was reported[20] but it has been presented as an important complication that may arise from the use of antiseptics including CHG. However, due to the lack of vigorous studies investigating the effects of antiseptic uptake on neurons, the questions in this area remains unanswered.[28]

In limited studies, the criteria for using CHG in preterm infants have been studied. A Study in Canada concerning the use of CHG has reported that 75% of neonatal intensive care units do not have any age restrictions. About 18% of them meet the age limit for infants under 25 weeks and 13% of them use CHG antiseptics for infants over 30 weeks.[18] In a study in the United States, Tamma et al. reported that 42% of units tested for premature infants <28 weeks did not use CHG antiseptics, 40% used weight criteria and they are forbidden to use CHG antiseptics for weighing <1000 g.[20]


Iodine compounds are used in two iodophor forms: povidone-iodine and poloxamer-iodine. Iodines are rapidly bactericidal, fungicidal, tuberculocidal, virucidal, and sporicidal.[17] It has been used as a disinfectant in some studies. In Canada, 35% of neonatal intensive care units use povidone-iodine[18] and in New Zealand-Australia, 5.3% use povidone-iodine.[21] Complications following povidone-iodine administration have been reported. In a study directed by Kieran et al., evaluation of thyroid-stimulating hormone (TSH) levels after using povidone-iodine 10% for catheter insertion in central vein showed that in 5% of premature infants TSH had increased and were treated with levothyroxine.[29] Furthermore 17 neonatal intensive care units (59% of the total sample) in the Shah and Tracy study declared experiencing hypothyroidism in premature infants following the topical use of povidone-iodine.[30] In fact, premature infants exposed to povidone-iodine are more vulnerable than term infants. In the way that topical exposure to iodine in premature infants can lead to abnormal thyroid function, especially in infants younger than 32 weeks. This is due to the lack of maturity of the Wolf-Chaykov effect, which appears at the age of 36–40 weeks of the fetus.[31]


Alcohols possess broad-spectrum antimicrobial activity against most bacteria, fungi, and viruses but are not sporicidal.[17] In New Zealand-Australia, 5.3% of neonatal intensive care units use 70% alcohol[21] and in Canada, 22% of neonatal intensive care units use isopropyl alcohol.[18]

The effects of using antiseptics and comparing them with each other

In the study of Janssen et al., antiseptic CHG 0.2% with acetate and 0.5% CHG with alcohol were used before central venous catheterization in infants <26 weeks, and the effects of these two types of disinfectants in terms of skin complications the incidence of blood infection was also cheeked out. The results showed that the extent of skin burn in the group receiving 0.2% CHG antiseptic was lower than the group receiving 0.5% CHG antiseptic. There was no significant difference in the incidence of blood infection between the two groups. Moreover, acetate-based 0.2% CHG antiseptic was suggested as a suitable antiseptic for preterm infants younger than 26 weeks.[32]

In a study by Rundjan et al., the effects of three skin disinfectants, including alcohol 70%, povidone-iodine 10%, and acetidine was examined on the count of infants skin bacterial in neonatal intensive care units undergoing peripheral vein catheterization. Results showed no statistically significant differences in the bacterial count of the three groups. However, clinically, bacterial counts in the samples in the betadine group (97.54% decrease in bacterial count) and the acetidine group (97.52% decrease in bacterial count) were lower than in the alcohol group (there was 89.07% decrease in bacterial count). Moreover, the study concludes that although acetidine has reduced bacterial counts well; however, it is not different from betadine and alcohol.[33]

Clarke et al. initiated a clinical trial to evaluate the safety and efficacy of gluconate CHG 2% dissolved in water in comparison to gluconate CHG 2% dissolved in isopropyl alcohol 70% for skin disinfection before central skin vein catheterization in premature infants. In this study, in both groups, neonatal skin condition was checked before catheterization, 10–30 min after catheterization, daily until catheter removal, and up to 48 h after catheter removal. When the catheter needs to be removed, after removing the covers on the catheter, first using a swap, a sample of the skin is removed, next disinfection is done with the considered solution and then, the second sample is removed by swab from the skin. In the next step, the catheter is removed through the sterile method by trained individuals and the tip of the catheter and the proximal part of the catheter near the catheter insertion into the skin are cut through sterile scissors, placed in sterile containers and sent to the laboratory to check the colony status of the microorganism. Peripheral blood culture is also sent to check for the presence of the organism in the blood and its compliance with the microorganism in the catheter. This study is currently ongoing.[34]

Kieran et al. conducted a study to compare the effect of povidone-iodine 10% and CHG 2% based on 70% alcohol on premature infants undergoing central venous catheter placement. In this study three outcomes were examined, including skin reactions, thyroid function status, and incidence of circulatory infection after catheterization. The results showed that 2% of infants disinfected with 2% CHG based on 70% alcohol and 1% of infants disinfected with povidone-iodine had a skin reaction and no significant difference was observed between the two groups. About 8.8% of neonates disinfected with 2% CHG based on 70% alcohol and 7.7% of neonates disinfected with povidone-iodine developed a circulatory infection due to catheterization. TSH level was increased in 12 infants disinfected with povidone-iodine, 8 of them required treatment with thyroxine. While TSH hormones were increased in none of the infants disinfected with 2% CHG based on 70% alcohol.[29]

Chapman et al. conducted a study to examine the uptake and tolerance of CHG gluconate dissolved in water used to disinfect skin before PICC catheterization in preterm infants. The selected skin location for catheterization was cleaned with a cloth containing 500 mg CHG before insertion of PICC. The nurse examined the skin that was exposed to CHG daily through the PICC transparent dressing and recorded erythema or any complication. Furthermore, blood samples were collected, before CHG exposure 1–2 h, 6–12 h, 48 h, and 72 h after CHG exposure. Laboratory examination revealed that the density of CHG in premature infants was 1.6–206 ng/ml. Seven neonates had the highest serum density of CHG on days 2–3 after exposure. Furthermore, in this study, there was no evidence of increased transaminases (aspartate transaminase and alanine transaminase) after CHG exposure. Moreover, there was no evidence of skin toxicity associated with CHG in any infants. There was only one neonate with a small area of mild erythema associated with PICC biological dressing.[23]

Tayebi Myaneh et al. conducted a study to compare the effect of CHG 2% and povidone-iodine 10% on bacterial colonization rate in preterm infants who underwent peripheral vein catheterization procedures. In preterm infants CHG group 2%, the selected area of the skin for catheterization was sprayed with 1%–2% CHG 2%, 30 s time was given, then the considered area was cleaned with sterile cotton and catheterization was performed. In the infants of the povidone-iodine 10% group, the selected area for catheterization was cleaned with povidone-iodine 10% cotton. And it was given time to dry, then the remaining povidone-iodine was cleaned by cotton impregnated with70% alcohol, and then catheterization was done. 48 h later, the catheter was removed, and the tip of the catheter was cut to 1 cm and placed in a sterile tube containing half a cc of normal saline and sent to the laboratory for cultivation. Laboratory results showed that 7 of 106 neonates had positive culture, which 5 of them belonged to the povidone-iodine group (4 cases had negative coagulase Staphylococcus and one case had warm-positive bacteria) and two cases belonged to CHG2% group (two cases had negative coagulase staphylococcus. Moreover although there was a higher number of positive cultures in the povidone-iodine group, there was no statistically significant difference.[35]

  Conclusion Top

Premature infants are particularly vulnerable in the first 2–3 weeks after birth as the epidermis layer, which normally prevents chemicals entering the body, is immature and materials with low molecular weight, soluble in water and soluble in fat can all be absorbed through the skin and may cause unexpected systemic effects.[28] Review of the present papers showed that there are no clear guidelines focusing on disinfecting the skin before invasive procedures in preterm infants, especially very low birthweight or extremely low birthweight infants younger than 32 weeks to achieve sterile venous insertion in the neonatal intensive care unit. Hence, it seems defining an appropriate guideline on how to determine the appropriate antiseptic to use for premature infants is one of the priorities of the neonatal intensive care unit that should be the focus of neonatal specialists and neonatal intensive care nurses. In this regard, reviewing the results of various studies on the side effects of antiseptics and comparing their effects could be a helpful step to support evidence-based care and improve the quality of care provided to premature infants. Also doing clinical trial studies to check the effects of different antiseptics on preterm infants along with checking their systemic uptake and their effects on the developing nervous system are among the topics that need to be researched, and few studies have addressed them so far.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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