Systematic literature review on surgical site preparation in paediatric surgery.

BACKGROUND: Surgical site infections (SSIs) in children represent a common and serious postoperative complication. Surgical skin preparation is an essential preventive measure in every surgical procedure. The most commonly used antiseptic agents for surgical skin preparation are chlorhexidine gluconate and iodophors in alcohol-based solutions. In adult patients the use of chlorhexidine-containing antiseptic solutions for preoperative skin preparation has been advocated to reduce SSI rates. Our objective was to conduct a systematic literature review on use of antiseptic agents for surgical skin preparation in children less than 16 years of age. METHODS: A systematic review of MEDLINE, EMBASE, CINAHL and CENTRAL was performed using both MeSH and free text terms and using the relevant Cochrane filter to identify full text randomized trials (RCTs) and comparative observational studies. Interventions of interest were the choice of main agent in antiseptic solutions (chlorhexidine/povidone-iodine/alcohol) compared with each other or with other antiseptic agents. Primary outcome was the reported rate of surgical site infections. RESULTS: In total 8 studies were included in the review; 2 RCTs and 6 observational studies. Observational studies generally did not primarily investigate the association of different antiseptics with subsequent SSI. The identified randomised controlled trials included only 61 children in total, and were of low quality. Consequently, we did not conduct a formal meta-analysis. Since the publication of a comprehensive systematic review of perioperative measures for the prevention of SSI in 2016, no randomized controlled trials comparing antiseptic agents for surgical skin preparation in paediatric surgery have been conducted. CONCLUSION: Robust evidence on the optimal skin antisepsis to reduce SSIs in children is lacking. Direct extrapolation of effects from trials involving adults is not appropriate as physiologic characteristics and risk factors for SSIs differ between adults and children. It is therefore essential to conduct high quality RCT investigating interventions to identify optimal measures to reduce SSI rates in children. TRIAL REGISTRATION: Prospero registration ( CRD42020166193 ).

Extraction of diethylhexylphthalate by home total parenteral nutrition from polyvinyl chloride infusion lines commonly used in the home.

OBJECTIVES: Recently, our group detected that polyvinyl chloride (PVC) perfusion lines leach large amounts of the toxic plasticizer diethylhexylphthalate (DEHP) under conditions typical of intensive care units. In the present study, we investigated the extraction of DEHP from PVC connecting tubes that are commonly used for total parenteral nutrition (TPN) solutions. The aim of the study was to estimate the amount of DEHP to which children receiving home TPN are exposed for months and years. MATERIALS AND METHODS: 1000 mL of TPN, identical in constitution and amount to the home TPN of 1 of our patients, were perfused through 5 different connecting tube systems and collected in hexane-rinsed glass bottles. The concentration of DEHP in the TPN was analyzed before and after perfusion. RESULTS: Before perfusion of the lines, the solution had a DEHP concentration of 0.05 to 0.69 microg/mL (baseline value). After perfusion of the lines, the load of DEHP in the solution varied between 1.41 and 2.07 microg/mL. This TPN was established for children weighing 20 kg. The daily dosage is between 71 and 104 microg x kg(-1) x day(-1). TPN is administered at home for many months and years. The monthly charge of DEHP is between 42.3 and 62.1 mg. Children weighing 20 kg therefore receive a dosage between 2.1 and 3.1 mg x kg(-1) x month(-1). CONCLUSIONS: Diethylhexylphthalate and its metabolite monoethylhexylphthalate have been demonstrated to be carcinogenic, embryotoxic, hepatotoxic, pneumotoxic, and cardiotoxic and are known to disrupt endocrine pathways and liver detoxifying capacity in animals. They are suspected of having multiple effects in humans as well. The doses presented above should therefore be avoided in children receiving home TPN by the use of tubing systems that are completely free of DEHP. Such systems are available.

Extraction of the plasticizers diethylhexylphthalate and polyadipate from polyvinylchloride nasogastric tubes through gastric juice and feeding solution.

OBJECTIVES: Except for polyadipate, which is used as an alternative in polyvinylchloride (PVC) feeding tubes, diethylhexylphthalate (DEHP) is the plasticizer used almost exclusively in PVC medical products. A clear response to the chronic intake of DEHP has been shown in several organ systems from different species. In the present study, we compared the extraction of DEHP and polyadipate from PVC gastric tubes. METHODS: An in vivo setting was simulated. We used 5 cm of PVC nasogastric tubes containing DEHP or polyadipate, which were incubated with gastric juice for 1 week and a feeding solution for 4 weeks. The leakage of these plasticizers was measured daily in the gastric juice group and weekly in the feeding solution group. The amount of plasticizer extracted was compared between groups and days. RESULTS: In the feeding solution group, the extraction of DEHP ranged from 200 to 542 microg after 1 week and from 660 to 1700 microg after 4 weeks. The extraction of polyadipate was 10 times lower than that of DEHP. In the gastric juice group, extracted DEHP ranged from 635 to 1043 microg, whereas the extraction of polyadipate was 100 times lower. CONCLUSIONS: Within 1 week, the extraction of DEHP from a 5-cm PVC tube reaches up to 1 mg. Extrapolated, this represents an in vivo load of up to 4 mg. The load accumulated by a newborn in an intensive care unit can therefore easily reach several milligrams of DEHP per day. Polyadipate nasogastric tubes may therefore be an alternative and help to reduce the daily load of DEHP.

Diethylhexylphthalate extracted by typical newborn lipid emulsions from polyvinylchloride infusion systems causes significant changes in histology of rabbit liver.

BACKGROUND: Looking for a candidate substance inducing hepatobiliary dysfunction under parenteral nutrition (PN) in newborns, we recently discovered that newborn infusions extract large amounts of the plasticizer diethylhexylphthalate (DEHP) from commonly used polyvinylchloride (PVC) infusion lines. This plasticizer is well known to be genotoxic and teratogenic in animals and to cause changes in various organs and enzyme systems even in humans. The aim of this study was to examine the effect of DEHP, extracted in the same way and in the same amount as in newborns, on livers of young rabbits. METHODS: Prepubertal rabbits received lipid emulsion through central IV lines continuously for 3 weeks either via PVC or polyethylene (PE) infusion systems. Livers were examined after 1 and 3 weeks by light and electron microscopy. RESULTS: By light microscopy, hydropic degeneration, single-cell necrosis, fibrosis, and bile duct proliferation were observed more in the PVC group. Electron microscopy revealed multiple nuclear changes, clusters and atypical forms of peroxisomes, proliferation of smooth endoplasmic reticulum, increased deposition of lipofuscin, and a mild perisinusoidal fibrosis only in the PVC group. These changes, which are generally regarded as reaction upon a toxic stimulus, could be exclusively attributed to DEHP. CONCLUSIONS: This investigation proved that DEHP produces toxin-like changes in livers of young rabbits in the same dose, duration, and method of administration as in newborn infants. For this reason, it is likely that DEHP is the substance that causes hepatobiliary dysfunction in newborns under PN. Possible modes of action of DEHP are proposed.

Leaching of plasticizers from polyvinylchloride perfusion lines by different lipid emulsions for premature infants under clinical conditions.

Plasticizers migrate from polyvinylchloride (PVC) infusion systems into lipid emulsions. The aim of this study was to investigate the leaching of different plasticizers from PVC perfusion lines by a selection of lipid emulsions under clinical conditions. Seven PVC perfusion lines with an equal length of 150cm and three internal diameters were perfused with three lipid emulsions: Intralipid® 20%, ClinOleic® 20% and SMOFlipid® 20%, mimicking clinical conditions. The concentrations of the plasticizers were measured directly in the emulsions by gas chromatography - mass spectrometry. Of the four plasticizers examined in this study, di (2-ethylhexyl) phthalate (DEHP) leached the most and was found, on average, at 46.5µg/ml in the emulsions - around one order of magnitude higher than the other plasticizers. This study demonstrates that the leaching of DEHP by lipid emulsions in conditions of total parenteral nutrition is many times higher than should be accepted and higher when compared to the other plasticizers. There was no significant difference in leaching of plasticizers in relation to the type of lipid emulsion. The influence of tube diameter on the leaching rate of plasticizers should be taken into account especially in particular exposed patients.

Kinetics of diethylhexyl-phthalate extraction From polyvinylchloride-infusion lines.

BACKGROUND: For infusion therapy, polyvinylchloride (PVC)-infusion lines are commonly used. In this study, we examined the temperature dependency and the dynamics of extraction in the time course of infusion. METHODS: PVC-infusion lines used on the newborn ICU were perfused with a typical 24-hour fat infusion. We collected the perfused solution and measured the concentration of DEHP. This procedure was carried out at 27 degrees C and 33 degrees C. In another experiment, we examined the extraction rate in the time course of a 24-hour infusion. The infusion was collected every 4 hours. RESULTS: We discovered that extraction of DEHP depends highly on the surrounding temperature. Whereas at 27 degrees C, the extraction of DEHP was 422.78 microg/mL, the leaching reached 540.78 microg/mL at 33 degrees C under otherwise identical conditions. This is important because the temperature on a newborn ICU is between 31 and 37 degrees C in an incubator. In the other experiment, we found out that the extraction rate rose from 25.44 microg/mL in the first 4 hours to 478.1 microg/mL after 24 hours. CONCLUSIONS: The result of this study is that the actual daily load of DEHP for a 2-kg newborn is 30% higher than measured before. The rate of extraction is dependent on the time of contact between solution and tubing. If PVC-infusion systems are used, solutions should be as cold as possible, and infusion time should be as short as possible.

Use of di(2-ethylhexyl)phthalate-containing infusion systems increases the risk for cholestasis.

INTRODUCTION: Most polyvinylchloride infusion systems are plasticized with up to 60% of di(2-ethylhexyl)phthalate (DEHP). DEHP is easily extracted from the tubing by total parenteral nutrition (TPN) solutions and has been shown to have toxic effects on various organ systems including the liver in animals and humans. A role was postulated for DEHP in the development of hepatobiliary dysfunction in premature and newborn infants receiving parenteral nutrition, and the incidence of cholestasis was investigated after changing from polyvinylchloride infusion systems to polyvinylchloride-free infusion systems. MATERIALS AND METHODS: Two 3-year periods from 1998 to 2004 were investigated retrospectively before and after changing from polyvinylchloride to polyvinylchloride-free infusion systems in our department. This resulted in 1 group of 30 patients treated with polyvinylchloride lines and a second group of 46 patients treated with polyvinylchloride-free lines. The 2 groups were examined for the incidence of cholestasis and other possible contributing factors. Statistics were performed by using SAS software (SAS Institute, Cary, NC). RESULTS: After changing infusion systems, the incidence of cholestasis dropped from 50% to 13%. Using DEHP-plasticized polyvinylchloride infusion systems for TPN increased the risk for cholestasis by a factor of 5.6. The use of polyvinylchloride lines correlated strongly with the development of TPN-associated cholestasis (P = .0004). CONCLUSIONS: Using DEHP-containing polyvinylchloride infusions systems contributes to the development of cholestasis. Therefore, the use of DEHP-free infusion systems for TPN is recommended, especially in premature and newborn infants.