Safe and efficient practice of parenteral nutrition in neonates and children aged 0-18 years - The role of licensed multi-chamber bags.

Parenteral nutrition (PN) is recognized as a complex high-risk therapy. Its practice is highly variable and frequently suboptimal in pediatric patients. Optimizing care requires evidence, consensus-based guidelines, audits of practice, and standardized strategies. Several pediatric scientific organizations, expert panels, and authorities have recently recommended that standardized PN should generally be used over individualized PN in the majority of pediatric patients including very low birth weight premature infants. In addition, PN admixtures produced and validated by a suitably qualified institution are recommended over locally produced PN. Licensed multi chamber bags are standardized PN bags that comply with Good Manufacturing Practice and high-quality standards for the finished product in the frame of their full manufacturing license. The purpose of this article is to review the practical aspects of PN and the evidence for using such multi-chamber bags in pediatric patients. It highlights the safety characteristics and the limitations of the different PN practices and provides some guidance for ensuring safe and efficient therapy in pediatric patients.

Understanding the informal aspects of medication processes to maintain patient safety in hospitals: a sociotechnical ethnographic study in paediatric units.

Adverse drug events (ADEs) are common in hospitals, affecting one in six child in-patients. Medication processes are complex systems. This study aimed to explore the work-as-done of medication safety in three English paediatric units using direct observation and semi-structured interviews. We found that a combination of the physical environment, traditional work systems and team norms were among the systemic barriers to medicines safety. The layout of wards discouraged teamworking and reinforced professional boundaries. Workspaces were inadequate, and interruptions were uncontrollable. A less experienced workforce undertook prescribing and verification while more experienced nurses undertook administration. Guidelines were inadequate, with actors muddling through together. Formal controls against ADEs included checking (of prescriptions and administration) and barcode administration systems, but these did not integrate into workflows. Families played an important part in the safe administration of medication and provision of information about their children but were isolated from other parts of the system.

Formal medicines safety processes in paediatric units are disjointed and disconnected. This has led actors in the system (e.g. nursing and medical staff) to develop informal adaptations to increase resilience. There is a need to incorporate these adaptations into a systems-focussed consideration of safety processes, in order to properly inform the development of medication safety interventions.

For children admitted to hospital, what interventions improve medication safety on ward rounds? A systematic review.

OBJECTIVE: Every year, medication errors harm children in hospitals. Ward rounds are a unique opportunity to bring information together and plan management. There is a need to understand what strategies can improve medication safety on ward rounds. We systematically reviewed published interventions to improve prescribing and safety of medicines on ward rounds. DESIGN: Systematic review of randomised controlled trials and observational studies. SETTING: Studies examining inpatient ward rounds. PATIENTS: Children and young people aged between 0 and 18 years old. INTERVENTIONS: Any intervention or combination of interventions implemented that alters how paediatric ward rounds review inpatient medications. MAIN OUTCOME MEASURE: Primary outcome was improvement in medication safety on paediatric ward rounds. This included reduction in prescribing error rates, healthcare professionals' opinions on prescribing and improvement in documentation on ward rounds. RESULTS: Three studies were eligible for review. One examined the use of an acrostic, one the use of a checklist, and the other a use of a specific prescribing ward round involving a clinical pharmacist and doctor. None of the papers considered weight-based errors or demonstrated reductions in clinical harm. Reductions in prescribing errors were noted by the different interventions. CONCLUSIONS: There are limited data on interventions to improve medication safety in paediatric ward rounds, with all published data being small scale, either quality improvement or audits, and locally derived/delivered. Good-quality interventional or robust quality improvement studies are required to improve medication safety on ward rounds. PROSPERO REGISTRATION NUMBER: CRD42022340201.

Community pharmacy role in children's health in England: Experiences and opinions of parents and young people.

Little is known about the reason behind the underutilisation of community pharmacy (CP) for children. This study explored the experiences, barriers and recommendations of parents/carers and young people regarding their use of CP services for children. Two-stage facilitated, structured, audio-recorded interviews were conducted at each of four CPs in London, England, between May and November 2019 [1 month in each CP]. Parents/carers or young persons (aged 16-18 years) who visited CP for a child-related matter were invited to participate. Interviews were transcribed verbatim. Data were analysed both quantitatively and qualitatively, using thematic analysis to identify themes. In total, 249 (58.2% of 428 eligible) customers agreed to participate and completed the two interviews. Out of these, 82.3% (205/249) reported positive experiences with the CP. The general practitioner (GP) was the preferred healthcare provider for minor ailments (44.6%,111/249), while 35.7% (89/249) would choose CP. Eighty-two participants (33%) visited an Emergency Department in the last 12 months, with 13.4% (11/82) of them visited for cold and cough reasons. Where a child was present with parents/carer (128/249), there was a low level of interaction between children and pharmacists (13.3%, 17/128). Lack of awareness about the CP services provided for children and privacy were among the barriers identified by participants. Advertising of CP services and creating a child-friendly environment were recommendations suggested by participants. The findings of this paper show that CP remains an underutilised health service for children by parents/carers and young persons. More work is needed to increase public awareness of the roles of CP in children's health and well-being.

The impact of the COVID-19 pandemic on antimicrobial prescribing at a specialist paediatric hospital: an observational study.

BACKGROUND: The COVID-19 pandemic has severely impacted healthcare delivery and there are growing concerns that the pandemic will accelerate antimicrobial resistance. OBJECTIVES: To evaluate the impact of the COVID-19 pandemic on antibiotic prescribing in a tertiary paediatric hospital in London, UK. METHODS: Data on patient characteristics and antimicrobial administration for inpatients treated between 29 April 2019 and Sunday 28 March 2021 were extracted from the electronic health record (EHR). Interrupted time series analysis was used to evaluate antibiotic days of therapy (DOT) and the proportion of prescribed antibiotics from the WHO 'Access' class. RESULTS: A total of 23 292 inpatient admissions were included. Prior to the pandemic there were an average 262 admissions per week compared with 212 during the pandemic period. Patient demographics were similar in the two periods but there was a shift in the specialities that patients had been admitted to. During the pandemic, there was a crude increase in antibiotic DOTs, from 801 weekly DOT before the pandemic to 846. The proportion of Access antibiotics decreased from 44% to 42%. However, after controlling for changes in patient characteristics, there was no evidence for the pandemic having an impact on antibiotic prescribing. CONCLUSIONS: The patient population in a specialist children's hospital was affected by the COVID-19 pandemic, but after adjusting for these changes there was no evidence that antibiotic prescribing was significantly affected by the pandemic. This highlights both the value of routine, high-quality EHR data and importance of appropriate statistical methods that can adjust for underlying changes to populations when evaluating impacts of the pandemic on healthcare.

Improving the experience of obtaining repeat complex paediatric prescriptions in the UK.

In the UK, medicines for chronic conditions in children and young people (CYP) are typically initiated within secondary or tertiary care, with responsibility for ongoing supply often then passed to the child's general practitioner (GP) and community pharmacist. The patient should then be reviewed in regular specialist clinics, with two-way communication for any changes in medications or clinical status undertaken between primary and secondary/tertiary care. This arrangement allows long-term medications to be obtained close to home.Although this is what parents expect, the reality is often messy, with families regularly needing to source some medicines from the GPs and others via hospitals or homecare services. In addition, these arrangements are not uniform, they vary across different areas of the UK and depend on individual GP or hospital prescriber acceptance. When neither primary, secondary or tertiary care accepts it is their responsibility to prescribe, or patients are under multiple specialists, families often feel left to navigate this complex and variable supply system themselves. Obtaining a prescription is only the start of the process for families as dispensing from a community pharmacy can also be challenging.In this article, we set out the barriers and potential solutions to this complex issue. We use the term specialist prescribers to include not only paediatricians but all other specialists looking after CYP including child and adolescent psychiatrists, ophthalmologists, dermatologists, surgeons, etc, as well as non-medical prescribers.

Pharmacokinetic and pharmacodynamic evidence of adrenaline administered via auto-injector for anaphylactic reactions: A review of literature.

Anaphylaxis is a severe allergic reaction that can lead to death if not treated quickly. Adrenaline (epinephrine) is the first-line treatment for anaphylaxis and its prompt administration is vital to reduce mortality. Following a number of high-profile cases, serious concerns have been raised, both about the optimal dose of intramuscular adrenaline via an auto-injector and the correct needle length to ensure maximal penetration every time. To date, the public data are sparse on the pharmacokinetics-pharmacodynamics of adrenaline administered via an auto-injector. The limited available literature showed a huge variation in the plasma concentrations of adrenaline administered through an auto-injector, as well as variations in the auto-injector needle length. Hence, delivering an effective dose during an anaphylaxis remains a challenge for both patients and healthcare professionals. Collaborative work between pharmacokinetics-pharmacodynamics experts, clinical triallists and licence holders is imperative to address this gap in evidence so that we can improve outcomes of anaphylaxis. In addition, we advise inclusion of expertise of human factors in usability studies given the necessity of carer or self-administration in the uniquely stressful nature of anaphylaxis.

Recommendations for crushing Circadin® (melatonin) tablets for safe and reliable delivery via pediatric nasogastric tubes.

Melatonin is an important drug in pediatric medicine which often requires delivery through a narrow bore nasogastric tube (e.g. FR6; 1300 µm internal diameter) for patients that cannot swallow tablets. Although Circadin® 2 mg tablets are often crushed for nasogastric delivery, there is an absence of evidence for the effectiveness of different methods for producing powders that can be administered without risk of blocking nasogastric tubes. Our aim was to develop a robust protocol for crushing Circadin tablets and suspending the powder for safe administration via paediatric nasogastric tubes. Circadin tablets were crushed using four different tablet crushers. For comparison, a pestle and mortar and tablespoon were also used to crush tablets as these techniques are also used in clinical practice. The particle size of powders resulting from different crushing maneuvers was evaluated using sieve analysis, laser diffraction and image-based sizing methods. For all the tablet crushers, five operations produced powders with irregular-shaped individual particles less than 500 µm diameter. A protocol termed 'King's 5-5-5' was developed for tablet crushers: powder obtained after 5 crushes was suspended in 5 mL water and delivered through NG tubes with pre and post-administration flushing with 5 mL water. This protocol is simple, low cost, uses readily available materials and enables the safe and reliable delivery of melatonin to paediatric patients without the fear of blocking nasogastric tubes.

Establishing dose bands for commonly prescribed oral medications for children in the UK: Results of a Delphi study.

OBJECTIVE: To establish weight-based dose bands for commonly used oral medicines, given in liquid forms, for children in the UK that could be used for prescribing and administering accurate and safe drug doses. METHODS: A list of commonly prescribed, oral liquid medications was established from the medication dispensing database of four UK hospitals and a primary care database. The evidence base of currently used dose regimens for each drug was identified from paediatric reference books, summary of product characteristics and the literature. Then, weight-based dose bands were developed and a modified Delphi process was used to achieve healthcare professional consensus about the suggested dose bands for each drug. RESULTS: Forty-six experts in paediatric medicines participated in the Delphi process (mean years of experience 17.3 ± 9.4 [standard deviation]) and assessed 45 oral liquid drugs in total. Four categories of weight-based dose bands were established: drugs with two dose bands (17.8%, 8/45), drugs with three dose bands (64.4%, 29/45), drugs with four dose bands (15.6%, 7/45) and drugs with five dose bands (2.2%, 1/45). The 46 participants reached consensus on all the suggested dose bands for 53.3% (24/45) of the drugs. Consensus was reached in the first round of the Delphi process for 91.7% (22/24) of the drugs and after two rounds for two drugs. No agreement was achieved on any of the suggested dose bands for 26.7% (12/45) of the drugs. CONCLUSION: This study provides healthcare professionals with a set of recommended weight-based dose bands for commonly prescribed oral liquid drugs for children. These bands could establish the basis for change in clinical practice to reduce dosing errors and improve healthcare for children.

Feasibility of developing children's Pill School within a UK hospital.

OBJECTIVE: We assessed the feasibility of introducing an intervention (children's Pill School-PS) within a UK hospital to provide swallowing training for children, identified the proportion of children who can be switched from oral liquid medicines to pills and assessed children/parents' opinions about the PS training. METHODS: 30 inpatient children (aged 3-18 years; taking oral liquid medicines; their liquid medications assessed suitable for switching to pills; can (and their parents) speak/understand English were included. Training sessions were delivered using hard sweets of different sizes. RESULTS: 87% (26) of children successfully learnt how to swallow pills after one training session (mean duration 14.5 min), and 92% (24) were discharged on pills. 75 prescribed oral liquid medications were deemed suitable for switching to pills. Of these, 89% (67) were switched successfully. CONCLUSION: Children as young as 3 years were successful in swallowing pills after training. Providing children PS training session within hospital is feasible and acceptable to children and their parents.

Cost-Consequences Analysis of Increased Utilization of Triple-Chamber-Bag Parenteral Nutrition in Preterm Neonates in Seven European Countries.

The safety of parenteral nutrition (PN) remains a concern in preterm neonates, impacting clinical outcomes and health-care-resource use and costs. This cost-consequence analysis assessed national-level impacts of a 10-percentage point increase in use of industry-prepared three-chamber bags (3CBs) on clinical outcomes, healthcare resources, and hospital budgets across seven European countries. A ten-percentage-point 3CB use-increase model was developed for Belgium, France, Germany, Italy, Portugal, Spain, and the UK. The cost-consequence analysis estimated the impact on compounding error harm and bloodstream infection (BSI) rates, staff time, and annual hospital budget. Of 265,000 (52%) preterm neonates, 133,000 (52%) were estimated to require PN. Baseline compounding methods were estimated as 43% pharmacy manual, 16% pharmacy automated, 22% ward, 9% outsourced, 3% industry provided non-3CBs, and 7% 3CBs. A modeled increased 3CB use would change these values to 39%, 15%, 18%, 9%, 3%, and 17%, respectively. Modeled consequences included -11.6% for harm due to compounding errors and -2.7% for BSIs. Labor time saved would equate to 41 specialized nurses, 29 senior pharmacists, 26 pharmacy assistants, and 22 senior pediatricians working full time. Budget impact would be a €8,960,601 (3.4%) fall from €260,329,814 to €251,369,212. Even a small increase in the use of 3CBs in preterm neonates could substantially improve neonatal clinical outcomes, and provide notable resource and cost savings to hospitals.

Evaluation of the practice of dose-rounding in paediatrics.

OBJECTIVES: To investigate the rounding of prescribed drug doses for paediatric administration. METHODS: A cross-sectional medication chart review was conducted at a UK paediatric hospital. Proposed administration dose volumes were calculated for prescribed doses using available manufactured liquids measured with oral and intravenous syringes. Resulting percentage deviations in doses administered were calculated. RESULTS: Of 2031 doses observed, 524 (25.8%) required rounding. The majority of which were for children aged 1-12 months. Twenty-seven rounded doses deviated from the prescribed dose by more than 10%. CONCLUSION: This study highlights the impact of dose-rounding in paediatrics and the need for standardisation.

Mapping the prevalence and nature of drug related problems among hospitalised children in the United Kingdom: a systematic review.

BACKGROUND: Problems arising from medicines usage are recognised as a key patient safety issue. Children are a particular concern, given that they are more likely than adults to experience medication-related harm. While previous reviews have provided an estimate of prevalence in this population, these predate recent developments in the delivery of paediatric care. Hence, there is a need for an updated, focussed and critical review of the prevalence and nature of drug-related problems in hospitalised children in the UK, in order to support the development and targeting of interventions to improve medication safety. METHODS: Nine electronic databases (Medline, Embase, CINAHL, PsychInfo, IPA, Scopus, HMIC, BNI, The Cochrane library and clinical trial databases) were searched from January 1999 to April 2019. Studies were included if they were based in the UK, reported on the frequency of adverse drug reactions (ADRs), adverse drug events (ADEs) or medication errors (MEs) affecting hospitalised children. Quality appraisal of the studies was also conducted. RESULTS: In all, 26 studies were included. There were no studies which specifically reported prevalence of adverse drug events. Two adverse drug reaction studies reported a median prevalence of 25.6% of patients (IQR 21.8-29.9); 79.2% of reactions warranted withdrawal of medication. Sixteen studies reported on prescribing errors (median prevalence 6.5%; IQR 4.7-13.3); of which, the median rate of dose prescribing errors was 11.1% (IQR 2.9-13). Ten studies reported on administration errors with a median prevalence of 16.3% (IQR 6.4-23). Administration technique errors represented 53% (IQR 52.7-67.4) of these errors. Errors detected during medicines reconciliation at hospital admission affected 43% of patients, 23% (Range 20.1-46) of prescribed medication; 70.3% (Range 50-78) were classified as potentially harmful. Medication errors detected during reconciliation on discharge from hospital affected 33% of patients and 19.7% of medicines, with 22% considered potentially harmful. No studies examined the prevalence of monitoring or dispensing errors. CONCLUSIONS: Children are commonly affected by drug-related problems throughout their hospital journey. Given the high prevalence and risk of patient harm,, there is a need for a deeper theoretical understanding of paediatric medication systems to enable more effective interventions to be developed to improve patient safety.

GAPPS (Grading and Assessment of Pharmacokinetic-Pharmacodynamic Studies) a critical appraisal system for antimicrobial PKPD studies - development and application in pediatric antibiotic studies.

Introduction: There are limited data on optimal dosing of antibiotics in different age groups for neonates and children. Clinicians usually consult pediatric formularies or online databases for dose selection, but these have variable recommendations, are usually based on expert opinion and are not graded based on the existing pharmacokinetic-pharmacodynamic (PKPD) studies. We describe here a potential new tool that could be used to grade the strength of evidence emanating from PKPD studies.Areas covered: A scoring system was developed (GAPPS tool) to quantify the strength of each PK assessment and rate the studies quality in already published articles. GAPPS was evaluated by applying it to pediatric PKPD studies of antibiotics from the 2019 Essential Medicines List for children (EMLC), identified through a search of PubMed.Expert opinion: Evidence for most antibiotic dose selection decisions was generally weak, coming from individual PK studies and lacked PKPD modeling and simulations. However, the quality of evidence appears to have improved over the last two decades.Incorporating a formal grading system, such as GAPPS, into formulary development will provide a transparent tool to support decision-making in clinical practice and guideline development, and guide PKPD authors on study designs most likely to influence guidelines.

Pediatric pharmacokinetics of the antibiotics in the access and watch groups of the 2019 WHO model list of essential medicines for children: a systematic review.

Introduction: Pharmacokinetic-pharmacodynamic (PK-PD) studies of antibiotics in pediatrics are limited. Pediatric dosing regimens for many antimicrobial drugs have been historically derived from adult pharmacokinetic data. Most pediatric formularies and dosing guidelines globally are expert-based and provide no rationale for the recommended doses, leading to heterogeneous guidance.Areas covered: We systematically reviewed the current dosing for 28 antibiotics listed in the Access and Watch groups of the 2019 World Health Organization (WHO) Essential Medicines List for children (EMLc). PubMed and EMBASE were searched for all PK-PD and pharmacological studies in pediatrics up to May 2018. In total, 262 pediatric related articles were deemed eligible. The most studied drugs were those where therapeutic drug monitoring is routine (aminoglycosides, glycopeptides) and study reporting detail was variable, with only 60.0% using the PK-PD results in make dosing recommendations. Based on this evidence, dose recommendations for each antibiotic were made.Expert opinion: We provide an up-to-date review of the limited available evidence on pediatric dosing for the 28 commonly prescribed antibiotics in the 2019 WHO EMLc. We propose synthesized dosing recommendations for those antibiotics administered systemically for the treatment of serious infections. Further PK-PD studies in children, particularly with underlying conditions, are needed.

Impact of the e-prescribing system on the incidence and nature of drug-related problems in children in a Saudi hospital.

OBJECTIVES: To determine the impact of a computerised physician order entry (CPOE) system on the drug-related problems' (DRPs) incidence and characteristics in hospitalised children in a Saudi hospital, and to compare DRPs incidence pre-/post-CPOE implementation. METHODS: An observational study. DRPs were identified by pharmacists, reviewing children's (0-14 years) medical records on CPOE system, in paediatric wards and/or attending emergency department. DRPs preventability and severity were assessed. RESULTS: A total of 657 paediatric patients were included, with 235 (35.8%) experienced 328 DRPs, majority were preventable (99.7%, 327). Difference in DRP incidence pre- and post-CPOE implementation (44.8% versus 35.8%, P < 0.01) was significant. CONCLUSION: The CPOE system has significantly reduced DRPs incidence in children in the study hospital.

Standardised concentrations of morphine infusions for nurse/patient-controlled analgesia use in children.

BACKGROUND: Standardizing concentrations of intravenous infusions enables pre-preparation and is effective in improving patient safety by avoiding large deviations from the prescribed concentration that can occur when infusions are made individually in wards and theatres. The use of pre-prepared morphine standardized concentration infusions for paediatric nurse/patient-controlled analgesia (N/PCA) has not been previously investigated. We aimed to establish, implement and evaluate standardized concentrations of morphine in pre-filled syringes (PFS) for use in paediatric N/PCA. METHODS: Concentrations of morphine in PFS for N/PCA were identified that accommodated dosage variation across a 1-50 kg weight range. The use of infusions in PFS was implemented and evaluated using mixed methods involved direct observation of healthcare professionals (HCPs), focus groups and failure mode and effects analysis, a HCP survey and medication incident reports analysis. RESULTS: Standardized concentrations, 3 mg, 10 mg and 50 mg morphine in 50 mL sodium chloride 0.9%, delivered prescribed continuous and bolus doses using programmable smart pumps with variable infusion rates. During the implementation, 175 morphine pre-prepared infusions were administered to 157 children (9.4 ± 5.1 years) in theatres and wards. Time taken to set up a N/PCA was 3.7 ± 1.7 min, a reduction of one third compared with the previous system. The number of incidents associated with N/PCA infusions was reduced by 41.2%, and preparation errors were eliminated. HCPs reported using morphine PFS was an easier and safer system. CONCLUSION: A system using pre-prepared standardized concentrations of morphine for paediatric N/PCA was implemented successfully and sustainably.

Current practice of preparing morphine infusions for nurse/patient-controlled analgesia in a UK paediatric hospital: healthcare professionals' views and experiences.

OBJECTIVE: To explore the views and experiences of healthcare professionals (HCPs) regarding the preparation of morphine infusions for nurse/patient-controlled analgesia (N/PCA). METHODS: Three focus groups were conducted with HCPs (anaesthetists, nurses in theatres and wards) at one UK children's hospital. Focus groups were transcribed verbatim and content analysis was used to identify themes. RESULTS: A variety of approaches are used to prepare morphine infusions. A lack of appreciation of the excess volume present in morphine ampoules that nominally contain 1 or 2 mL was identified. Other sources of error were miscalculation, complexity of the multistep procedure, distractions and time pressure. Participants suggested that 'ready-to-use' prefilled syringes and preprogrammed syringe pumps would improve practice and minimise the risk of error. CONCLUSIONS: Risks associated with the preparation of infusions for paediatric N/PCA, in particular non-appreciation of the overage (excess volume) in morphine ampoules, raise concerns about the accuracy of current practices.