Avoiding Chlorhexidine Burns in Preterm Infants The authors report no con flict of interest or relevant financial relationships Correspondence Mariano Paternoster, PhD, Department of Advanced Biomedic[.]
CONTEMPORARY PERSPECTIVES Avoiding Chlorhexidine Burns in Preterm Infants Mariano Paternoster, Massimo Niola, and Vincenzo Graziano Correspondence Mariano Paternoster, PhD, Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Via Pansini 5, Edificio 20, 1 piano, Naples 80131, Italy mariano.paternoster@unina.it ABSTRACT Chlorhexidine is a skin antiseptic agent frequently used for off-label indications in NICUs Changes to the safety labeling of chlorhexidine products for use in preterm infants were recently made because of the risk of severe chemical burns We provide tips for a safer use of chlorhexidine to prevent injury in newborns and to help health care professionals protect themselves against burn injury claims JOGNN, 46, 267–271; 2017 http://dx.doi.org/10.1016/j.jogn.2016.10.007 Accepted October 2016 Keywords chemical burns chlorhexidine malpractice claims preterm infants Mariano Paternoster, PhD, is an assistant professor in the Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy Massimo Niola, PhD, is an associate professor in the Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy Vincenzo Graziano, PhD, is an assistant professor in the Department of Advanced Biomedical Sciences, School of Medicine, University of Naples Federico II, Naples, Italy The authors report no conflict of interest or relevant financial relationships http://jognn.org C hlorhexidine is a local antiseptic that has an important role in the prevention of catheterassociated bloodstream infections (Marschall et al., 2014) Its application to a newborn’s umbilical cord reduces all-cause neonatal mortality (Imdad et al., 2013) However, as of today, there are insufficient safety data to recommend the use of chlorhexidine in infants less than months of age (Chapman, Aucott, & Milstone, 2011; O’Grady et al., 2011) Accordingly, less effective alternative agents, such as povidone–iodine or alcohol, are used instead (Garland et al., 2001) Over the years, several researchers reported severe chemical burns associated with the use of alcohol-based or water-based chlorhexidine solutions for skin antisepsis before invasive procedures in neonates (Andersen, Hart, Vemgal, & Harrison, 2005; Espuny et al., 2010; Kutsch, & Ottinger, 2014; Lashkari, Chow, & Godambe, 2012; Mannan, Chow, Lissauer, & Godambe, 2007; Reynolds, 2005; Sivathasan, Sivathasan, & Vijayarajan, 2010; Upadhyayula, Kambalapalli, & Harrison, 2007) Such events raise serious concerns, especially when considering that chemical burns in infants who weigh less than 1,500 g can be life threatening (Tamma, Aucott, & Milstone, 2010) Despite being contraindicated in this age group, chlorhexidine is frequently used for off-label indications in NICUs for infants younger than months of age (Bryant, Zerr, Huskins, & Milstone, 2010; Tamma et al., 2010) without causing major adverse effects if used safely (Curry, Honeycutt, Goins, & Gilliam, 2009; Taylor et al., 2011) Off-label means the use of a medication in a different manner from that specified in the drug regulatory agency–approved packaging label or insert (Stafford, 2008) Off-label use arises through many pathways but in NICUs usually entails the use of drugs for the unapproved subpopulations of the tiniest newborns In recent years, major American and European health associations and agencies, although recognizing the effectiveness of chlorhexidine for the prevention of infection in premature newborns, have provided a number of reports on its potential risks and safe use For example, in 2011, the American Pediatric Surgical Association Outcomes and Clinical Trials Committee reported that the use of alcohol-based chlorhexidine as a cutaneous antiseptic decreased the risk of catheter colonization and/or catheterrelated bloodstream infections compared with 10% povidone–iodine (Huang et al., 2011) However, recommendations were made to use it with care in neonates and premature infants because it could increase the risk of skin irritation for systemic absorption (Huang et al., 2011) In May 2012, the U.S Food and Drug Administration Center for Drug Evaluation and Research ª 2017 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses Published by Elsevier Inc This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) 267 CONTEMPORARY PERSPECTIVES Changes to the safety labeling of chlorhexidine products were recently made in the United States and Europe because of the risk of chemical burns in preterm infants followed suit and approved changes to the safety labeling of chlorhexidine-based topical antiseptic products The new label reiterated once again instructions to use the antiseptic with care in premature newborns or infants younger than months of age because of an increased risk of irritation or chemical burns (U.S Food and Drug Administration, 2012) Likewise, in June 2014, the UK Medicines and Healthcare Products Regulatory Agency urged British physicians to use chlorhexidine solution with maximum care after severe adverse effects occurred in 28 infants born at less than 32 weeks gestation who were treated with the solution within the first few days of life (Siddique, 2014) In particular, in the Drug Safety Update, issued by the same agency, health care providers were urged to administer the chemical with extreme caution, and the following safety measures were recommended: (a) to apply only the minimum amount of chlorhexidine solution required without allowing it to accumulate, (b) to remove any excess solution and any soaked materials, drapes, or gowns from the skin, and (c) to monitor patients frequently to detect and manage cutaneous adverse effects at an early stage (UK Medicines and Healthcare Products Regulatory Agency, 2014b) Later that year, European health officials revisited the safety issue Indeed, in September 2014, the European Medicines Agency Pharmacovigilance Risk Assessment Committee approved changes to the safety labeling of chlorhexidine products for use in infants and issued the following statements: “Use with care in newborn babies, especially those born prematurely,” “Use with care in neonates, especially those born before 32 weeks of gestation and within the first weeks of life,” and “May cause chemical skin burns” (pp 5–6) The European Medicines Agency Pharmacovigilance Risk Assessment Committee also recommended that all relevant hospital physicians, nursing staff, and pharmacists responsible for neonatal/pediatric intensive care units be officially informed about the increased risks of skin-related adverse events In short, the agency reported that the risk of severe chemical injuries after exposure to alcohol-based or water-based chlorhexidine solutions was higher in preterm infants, especially those born before 32 weeks gestation and within the first weeks of life Therefore, it 268 Avoiding Chlorhexidine Burns cautioned providers to administer the minimum amount of chlorhexidine solution required to avoid accumulation in skin folds or underneath an infant’s body Furthermore, the agency recommended the removal of any soaked materials, drapes, or gowns from the skin Finally, it pointed out the importance of closely monitoring patients to detect and manage cutaneous adverse effects at an early stage In November 2014, a new edition of the Drug Safety Update was issued by the UK Medicines and Healthcare Products Regulatory Agency (2014a) with further instructions on how to manage the potentially excessive quantities of chlorhexidine in multidose containers Successively, Beresford (2015) published in the Journal of Neonatal Nursing the data of the European review In this article, he reported all the data pored over by the European review, including yellow card data on chlorhexidine adverse reactions, published literature, and cumulative reviews from companies with authorized medicinal chlorhexidine solutions Overall, 44 cases of chemical burns after the application of chlorhexidine solutions were identified Most occurred in extremely premature infants born at 26 or fewer weeks gestation or in infants who weighed less than 1,000 g at birth Twenty-nine cases occurred after exposure to alcohol-based chlorhexidine solutions (0.5% and 2% chlorhexidine gluconate in 70% alcohol), whereas 11 cases occurred after exposure to 2% aqueous solutions In five cases, the chemical injury resolved but with severe sequelae, including scaring, discoloration, and keloid formation Death was reported in five cases Four of these deaths were judged to be attributable to comorbidities associated with preterm birth However, severe chemical injuries were also considered as a possible contributory cause, as suggested by the severe skin burns found on the back of one of these infants In summary, the author identified the common use of chlorhexidine in NICUs for off-label indications while highlighting that different hospitals were recommending the use of a variety of different strengths and types of solutions despite not having clear guidelines or data on their safety Nursing Implications The health cautionary reports issued by health care agencies will undoubtedly promote a growing awareness of the risks of chlorhexidinerelated burns Although current data are scarce, JOGNN, 46, 267–271; 2017 http://dx.doi.org/10.1016/j.jogn.2016.10.007 http://jognn.org Paternoster, M., Niola, M., and Graziano, V CONTEMPORARY PERSPECTIVES it is clear that chlorhexidine antiseptic treatment in neonates is justifiable only if its potential benefits can outweigh the risks This is particularly true in reference to the health care provider’s duty to avoid pain and suffering in infants From a medicolegal perspective, we believe that awareness of these adverse reactions will, in the long run, produce not only an increase in malpractice lawsuits against health care providers but also a harshening of medical liability charges compared with in the past It is not by chance that the authors’ institution recently experienced three criminal lawsuits for alleged medical negligence against the health care professionals of NICUs for chlorhexidine-related burns, because the chemical injuries resulted in scarring Until now the authors have had experience with lawsuits for burns from unsafe infant warming methods but not from chlorhexidine products To act in the best interest of preterm infants and to reduce the cases of chlorhexidine-related burns, we suggest a number of considerations First, the use of this chemical substance must be approved by the parents or caregivers In theory, physicians are allowed to use chemical substances off-label or adjust the recommended doses, so long as tolerability and effectiveness are evidence-based and the expected benefits are proportional to the potential risks In such cases, however, it is necessary to clarify the choice of an off-label drug prescription, to obtain written informed consent to the treatment, and to evaluate the long-term effects Health care professionals should consider providing more information to parents or caregivers than they normally would with a labeled drug and engage them more closely in the decision Indeed, because chlorhexidine is commonly used in NICUs for off-label indications, we cannot emphasize enough the importance of obtaining an educated informed consent before its use It is the duty of health care providers to inform parents or caregivers about the high effectiveness of chlorhexidine in the prevention of infections and about the existence of other but less effective options, like povidone-iodine or alcohol It is equally important to underscore the potential risk to the infant of skin burns after chlorhexidine treatment, as well as the infant’s greater risks of infection if consent is refused There is a paucity of evidence to guide an informed choice about the most suitable JOGNN 2017; Vol 46, Issue Awareness of the risk of chlorhexidine chemical burns may prevent pain and suffering in infants antiseptic to use before invasive procedures in the NICU (Ponnusamy, Venkatesh, & Clarke, 2014) Health care professionals should rely on their own and their colleagues’ expertise as well as on sufficiently documented information collected in their NICU with regard to the efficacy, safety, and dosage of the skin antisepsis preparation usually used The decision to use chlorhexidine may be positively influenced by the NICU’s baseline rate of neonatal chemical burns In a NICU with a low rate of chlorhexidine preparation use or with a lack of awareness of drug use data, the benefit from use of other but less effective skin antiseptics may be quite high, and vice versa This information should be provided to parents or caregivers to obtain a well-informed consent The individual infant’s unique clinical status should be considered to assess the risk/ benefit ratio of the drug Another crucial aspect is to compile and keep the infant’s medical chart painstakingly updated on the use of chlorhexidine In particular, it will be indispensable to regularly document the infant’s skin condition after each cleansing and chemical application This documentation provides evidence that health care professionals diligently followed the prevention protocol reported in the health care agency guidelines to detect skin reactions at an early stage Omission of such documentation makes health care providers very vulnerable to malpractice claims, should an infant injury occur For example, in Italy, Law n 189 (2012) stated that (a) the health care professional who, in his/her medical practice, adheres to guidelines and best practices accredited by the scientific community cannot be held criminally liable for slight negligence and (b) compliance with the guidelines must be taken into account by a judge when quantifying the damages, hence reducing the amount paid to the patient Besides the importance of keeping medical charts, the NICU team can play an important role in helping to build the evidence base for chlorhexidine skin antisepsis in infants by routinely collecting, reporting and publishing their experiences In the case of chemical burns, the hospital should take immediate action to offer the best available treatment and, if necessary, promptly consult with other specialists, including burn and plastic surgeons 269 CONTEMPORARY PERSPECTIVES Avoiding Chlorhexidine Burns systematic review Journal of Pediatric Surgery, 46(10), 2000– Safe use of chlorhexidine protects infants and helps health care professionals avoid burn injury claims 2011 http://dx.doi.org/10.1016/j.jpedsurg.2011.06.017 Imdad, A., Mullany, L C., Baqui, A H., Arifeen, S E., Tielsch, J M., Khatry, S K., … Bhutta, Z A (2013) The effect of umbilical cord cleansing with chlorhexidine on omphalitis and neonatal In conclusion, having an adequate knowledge of the overall nature of chlorhexidine and its use as an off-label antiseptic, strictly adhering to relevant health care agencies’ guidelines, obtaining a wellinformed consent from parents or caregivers, and keeping an updated medical record will not only benefit the health of preterm infants but also help providers to avoid potential malpractice claims Because of a lack of evidence to direct chlorhexidine use in the NICU’s subpopulations of neonates, well-designed neonatal multicenter randomized controlled trials are needed to assess the risk/ benefit ratio of chlorhexidine for skin antisepsis for neonates below a certain age and/or birth weight mortality in community settings in developing countries: A metaanalysis BMC Public Health, 13(Suppl 3) http://dx.doi.org/ 10.1186/1471-2458-13-s3-s15 Kutsch, J., & Ottinger, D (2014) Neonatal skin and chlorhexidine: A burning experience Journal of Neonatal Nursing, 33(1), 19–23 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for the prevention central catheter team on neonatal catheter-related bloodstream of central venous catheter infections: An American Pediatric infection Advances in Neonatal Care, 11(2), 122–128 http://dx Surgical Association outcomes and clinical trials committee doi.org/10.1097/anc.0b013e318210d059 JOGNN, 46, 267–271; 2017 http://dx.doi.org/10.1016/j.jogn.2016.10.007 http://jognn.org Paternoster, M., Niola, M., and Graziano, V CONTEMPORARY PERSPECTIVES UK Medicines and Healthcare Products Regulatory Agency (2014a) Upadhyayula, S., Kambalapalli, M., & Harrison, C J (2007) Safety of Chlorhexidine solutions: Reminder of the risk of chemical burns anti-infective agents for skin preparation in premature infants in premature infants Retrieved from https://www.gov.uk/drug- Archives of Disease in Childhood, 92(7), 646–647 http://dx.doi safety-update/chlorhexidine-solutions-reminder-of-the-risk-of- org/10.1136/adc.2007.117002 chemical-burns-in-premature-infants UK Medicines and Healthcare Products Regulatory Agency (2014b) U.S Food and Drug Administration, Center for Drug Evaluation and Research (2012) 2% chlorhexidine gluconate Chlorhexidine solutions: Risk of chemical burn injury to skin in (CHG) premature infants Retrieved from http://www.mhra.gov.uk/ MedWatch/SafetyInformation/Safety-RelatedDrugLabelingChanges/ safetyinformation/drugsafetyupdate/con428307 ucm307387.htm JOGNN 2017; Vol 46, Issue cloth Retrieved from http://www.fda.gov/Safety/ 271 ... keeping medical charts, the NICU team can play an important role in helping to build the evidence base for chlorhexidine skin antisepsis in infants by routinely collecting, reporting and publishing... burns from unsafe infant warming methods but not from chlorhexidine products To act in the best interest of preterm infants and to reduce the cases of chlorhexidine- related burns, we suggest... Therefore, it 268 Avoiding Chlorhexidine Burns cautioned providers to administer the minimum amount of chlorhexidine solution required to avoid accumulation in skin folds or underneath an infant’s body