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Article: ‘Chlorhexidine solutions: risk of chemical burn injury to skin in premature infants ‘

We are writing to you to provide additional information regarding a recent review which was undertaken at a European level on the risk of chemical burns in neonates following the use of chlorhexidine solutions for skin antisepsis. Some information and recommendations for healthcare professionals were published in Drug Safety Update, November 2014.


However, we believe that those involved in the care of neonates would find it helpful to receive further information on the data that led to these recommendations, and we are writing to you as an organisation which includes such healthcare professionals in your membership. The additional information is set out below.

Background to the European Review

The review was triggered by MHRA as severe adverse events had been reported in preterm newborn infants who were treated with antiseptic solutions containing chlorhexidine prior to central venous catheterisation. The review looked at data from different sources, including Yellow Card data from the UK, published literature and cumulative reviews from companies with authorised medicinal chlorhexidine solutions.

Cases assessed

Overall 44 cases were identified in which neonates suffered chemical burns following the application of aqueous or alcohol based chlorhexidine solutions of different strengths. The majority of interventions were umbilical catheter insertions. Most cases occurred in extremely premature infants born at less than or equal to 26 weeks gestation or babies that weighed less than 1000g at birth; 29 cases occurred with alcohol-based chlorhexidine solutions (0.5% and 2%) and 11 cases with 2% aqueous solutions.

The severity of skin reactions ranged from erythema/severe redness to chemical burn/chemical injury, excoriation, skin breakdown. In 29 out of the 44 cases the term “burn” was used in the report and in some of these cases the burn was further characterised as large, severe, extensive, partial or full thickness. In 5 cases the chemical injury resolved but with severe sequelae, including scaring, discoloration and keloid formation.  The outcome was death in 5 cases. In 4 of them the authors considered that comorbidities of prematurity primarily led to this outcome, however, a possible contributory role of the chemical injuries cannot be excluded given the severity of the injuries.  In one of the fatal cases the patient was left lying on an incontinence mat soaked in this substance, causing an extensive chemical burn on the back of the neonate.

The review primarily focused on data regarding the use of chlorhexidine solutions; however, there were some literature data reporting on the use of chlorhexidine impregnated dressings in neonates and older children. Although the evidence is not extensive, these data highlighted a higher risk of cutaneous adverse events in neonates and older children with the use of chlorhexidine impregnated dressings, compared to the use of chlorhexidine solution only prior to the procedure.

Another area of concern in premature infants exposed to chlorhexidine is the potential for systemic absorption. Blood concentrations of chlorhexidine have been reported in preterm neonates following cutaneous exposure. Although it is evident that there is potential for systemic absorption of chlorhexidine following skin antisepsis in neonates, no systemic adverse reactions have been reported, including any short term neurological complications.

Data from studies examining the efficacy and safety of whole body or umbilical cord disinfection with chlorhexidine were also reviewed. Most of these studies derived from countries with high neonatal mortality rates, where different practices of disinfection (whole body or umbilical stump disinfection or intrapartum vaginal and neonatal wiping) have been tried to reduce the incidence of neonatal sepsis. Although these trials provide some reassurance for the use of chlorhexidine in term neonates, they do not provide significant safety information regarding the risks of chlorhexidine use in very and extremely preterm infants hospitalised in neonatal intensive care units (NICUs).

Clinical use

Finally it was recognised that although chlorhexidine is commonly used as an antiseptic prior to catheterisation in NICUs across EU, there are no clear guidelines, either European or international, with regard to skin antisepsis prior to invasive procedures in preterm neonates. There are limited data comparing different antiseptic agents, as well as different strengths and types of cutaneous chlorhexidine solutions in neonates.

Chlorhexidine is commonly used as an antiseptic prior to catheterisation in NICUs. However, a variety of different strengths and types of chlorhexidine solutions are recommended in different hospitals without clear justification of their use. As no efficacy data were reviewed, no robust recommendations could be provided on the most efficacious products and their safe use without a negative impact on local antisepsis and increased risk of neonatal catheter-related sepsis.

Conclusions of the review

From the data reviewed the following conclusions were drawn:

  • Infants born at less than 32 weeks of gestational age and when chlorhexidine is applied within the first 2 weeks of life for skin disinfection prior to invasive procedures appear to be at greatest risk of skin toxicity. However, the frequency of chemical burns in neonates cannot be reliably determined as the extent of the exposure is unknown and overall reporting of adverse events in children is known to be low.


  • Although      the available data indicate a higher frequency of chemical burns with the      use of alcoholic solutions and with higher strength solutions, there are      limitations which do not allow drawing firm conclusions on which type of      products are safest for use in neonates, such as:


  1. the lack of exposure data (unknown denominator for different types of chlorhexidine products)
  2. the lack of data from companies with  certain strengths/types of chlorhexidine solutions, such as 0.5% and 2% aqueous chlorhexidine products.


It should be noted that efficacy data were not reviewed as part of this safety assessment so it was not possible to evaluate the antimicrobial profile of different chlorhexidine solutions or compare their benefit:risk profile. However, it is important to note that inadequate antiseptic regimes may lead to increased risk of neonatal sepsis and the safety concerns identified should be carefully evaluated against the risks of ineffective skin cleansing.


  • The effects of burn injuries in preterm neonates, who have many associated co-morbidities of prematurity, could be very serious, including prolonged hospitalisation, infection and potentially death.


  • Pooling around the umbilicus or under the infant has been identified as a significant risk factor for the occurrence of severe burns and deaths. It is necessary to change all wet or soaked materials, drapes and gowns before proceeding with catheter insertion and to avoid any prolonged contact skin exposure to chlorhexidine such as in skin folds. Dripping or pooling of the antiseptic on sheets, padding, positioning equipment, adhesive tape, and on or under the patient should be avoided.


  • Some authors and hospital guidelines advise using sterile water or saline to remove/wipe off the excess chlorhexidine solution as a measure to prevent adverse skin reactions. However, others advise against this practice as it is likely to shorten the duration of the antiseptic action of chlorhexidine. Therefore, a recommendation to rinse excess chlorhexidine solution has not been made as part of this review, until further evidence becomes available.


  • Many of the chlorhexidine containing products are available in multi-dose containers which are potentially associated with the use of excessive quantities in the NICU setting. Alternative dosage forms, such as single use products, should be used where such alternative options of the appropriate strength and type of chlorhexidine solution exist.

Further information on the European review can be found at: http://www.ema.europa.eu/docs/en_GB/document_library/PRAC_recommendation_on_signal/2014/09/WC500174026.pdf


Article: US mandatory in regional anaesthesia ?

Curr Opin Anaesthesiol. 2010 Jun;23(3):337-41. doi: 10.1097/ACO.0b013e328339276f.

Is ultrasound guidance mandatory when performing paediatric regional anaesthesia?

Lönnqvist PA.

Department of Paediatric Anaesthesia & Intensive Care, ALB/Karolinska University Hospital, Stockholm, Sweden. per-arne.lonnqvist@ki.se

Since Kapral in 1994 first described the use of real-time ultrasound-guided regional anaesthesia, this novel technique has gained widespread recognition in adult practice and has been shown to be associated with clinically relevant advantages. The aim of this manuscript is to review the currently published paediatric data associated with the use of ultrasound-guided regional anaesthesia.

Compared with alternative techniques ultrasound guidance is associated with an increased success rate, reduced onset time, moderately prolonged duration, reduced need for local anaesthetics and lower costs, and may also be considered to reduce the risk for complications.

Based on current data the use of ultrasound guidance is strongly recommended when performing peripheral nerve blocks in infants and children. Concerning ultrasound assistance in relation to paediatric neuroaxial blocks there is currently not enough supporting evidence to issue a general recommendation regarding its routine use.

Link to Pubmed


Article: Epidemiology and morbidity of regional anaesthesia

Paediatr Anaesth. 2010 Dec;20(12):1061-9. doi: 10.1111/j.1460-9592.2010.03448.x.

Epidemiology and morbidity of regional anesthesia in children: a follow-up one-year prospective survey of the French-Language Society of Paediatric Anaesthesiologists (ADARPEF).

Ecoffey C, Lacroix F, Giaufré E, Orliaguet G, Courrèges P; Association des Anesthésistes Réanimateurs Pédiatriques d’Expression Française (ADARPEF).

Service d’Anesthésie Réanimation Chirurgicale 2, Hôpital Pontchaillou, Université de Rennes 1, Rennes, France. claude.ecoffey@chu-rennes.fr

The French-Language Society of Paediatric Anaesthesiologists (ADARPEF) designed a 1-year prospective, multicenter and anonymous study to update both epidemiology and morbidity of regional anesthesia in children.

From November 2005 to October 2006, data from participating hospitals were recorded using an identification form, a data recording form, and a complication form. Information collected included the characteristics of the hospitals, the number and type of regional anesthetics (RA), the age of the involved children as well as the incidence, and type of complications.

Data collected in 47 institutions included 104,612 pure general anesthesias (GAs), 29,870 GAs associated with regional blocks, and 1262 pure regional blocks. Central blocks accounted for 34% of all RA. Peripheral blocks (66%) were upper or lower limb blocks (29% of peripheral blocks), trunk blocks, and face blocks (71%). In children aged ≤3 years, the percentage of central blocks was similar to the peripheral ones (45% vs 55), while in older children, peripheral blocks were more than four times used than central ones. Complications (41 involving 40 patients) were rare and usually minor. They did not result in any sequelae. The study revealed an overall rate of complication of 0.12%; CI 95% [0.09-0.17], significantly six times higher for central than for peripheral blocks.

As a result of the low rate of complications, RA techniques have a good safety profile and can be used to provide postoperative analgesia. In addition, the results should encourage anesthesiologists to continue to use peripheral instead of central (including caudal) blocks as often as possible when appropriate.

Link to Pubmed


Article: the use and incidence of complications of pediatric regional anesthesia

Anesth Analg. 2012 Dec; 115(6): 1353-64. doi: 10.1213 / ANE.0b013e31825d9f4b. Epub 2012 Jun 13.

Pediatric Regional Anesthesia Network (PRAN): a multi-institutional study of the use and incidence of complications of pediatric regional anesthesia.

Polaner DM, Taenzer AH, Walker BJ, Bosenberg A, Krane EJ, Suresh S, Wolf C, Martin LD.

Departments of Anesthesiology and Pediatrics, Children’s Hospital Colorado, 13123 East 16th Ave., B090, Aurora, CO 80045, USA. david.polaner@ucdenver.edu

Regional anesthesia is increasingly used in pediatric patients to provide postoperative analgesia and to supplement intraoperative anesthesia. The Pediatric Regional Anesthesia Network was formed to obtain highly audited data on practice patterns and complications and to facilitate collaborative research in regional anesthetic techniques in infants and children.

We constructed a centralized database to collect detailed prospective data on all regional anesthetics performed by anesthesiologists at the participating centers. Data were uploaded via a secure Internet connection to a central server. Data were rigorously audited for accuracy and errors were corrected. All anesthetic records were scrutinized to ensure that every block that was performed was captured in the database. Intraoperative and postoperative complications were tracked until their resolution. Blocks were categorized by type and as single-injection or catheter (continuous) blocks.

A total of 14,917 regional blocks, performed on 13,725 patients, were accrued from April 1, 2007 through March 31, 2010. There were no deaths or complications with sequelae lasting >3 months (95% CI 0-2:10,000). Single-injection blocks had fewer adverse events than continuous blocks, although the most frequent events (33% of all events) in the latter group were catheter-related problems. Ninety-five percent of blocks were placed while patients were under general anesthesia. Single-injection caudal blocks were the most frequently performed (40%), but peripheral nerve blocks were also frequently used (35%), possibly driven by the widespread use of ultrasound (83% of upper extremity and 69% of lower extremity blocks).

Regional anesthesia in children as commonly performed in the United States has a very low rate of complications, comparable to that seen in the large multicenter European studies. Ultrasound may be increasing the use of peripheral nerve blocks. Multicenter collaborative networks such as the Pediatric Regional Anesthesia Network can facilitate the collection of detailed prospective data for research and quality improvement.

Comment in
Pediatric regional anesthesia: drawing inferences on safety from prospective registries and case reports. [Anesth Analg. 2012]

Link to Pubmed