Developing Strategic Recommendations for Implementing Smart Pumps in Advanced Healthcare Systems to Improve Intravenous Medication Safety.

Avoidable harm associated with medication is a persistent problem in health systems and the use of preprogrammed infusion devices ('smart pumps') and data monitoring is seen as a core approach to mitigating and reducing the incidence of these harms. However, smart pumps are costly to procure, configure and maintain (in both human and financial terms) and are often poorly implemented. Variation in the manner in which medicines are prepared and used within complex modern healthcare systems exacerbates these challenges, and a strategic human-centred approach is needed to support their implementation. A symposium of 36 clinical and academic medication safety experts met virtually to discuss the current 'state of the art' and to propose strategic recommendations to support the implementation of medication administration technology to improve medication safety. The recommendations were that health systems (1) standardise infusion concentrations to facilitate the development of ready-to-administer formulations of frequently used medicines, and support 'out of the box' programming of infusion devices; (2) develop and implement drug libraries using human-centred approaches and the aforementioned standard concentrations, with a theoretical understanding of how devices are used in practice; (3) develop standardised metrics and outcomes to support the interpretation of data produced by infusion devices; (4) involve all stakeholders in the development of drug libraries and metrics to ensure broad understanding of the devices, their benefits and limitations; and (5) leverage input into device design, working with manufacturers and users. Using this strategic approach, it is then possible to envisage and plan real-world implementation studies using a uniform approach to quantify improvements in safety, efficiency and cost effectiveness.

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.

Potential Drug-Drug Interactions Among Critically Ill Pediatric Patients in a Tertiary Pulmonary Center.

Patients in the pediatric intensive care unit (PICU) are at increased risk of potential drug-drug interactions (pDDIs) because of the complexity of pharmacotherapy. The current study aimed to assess the rate, pattern, risk factors, and management of pDDIs in the PICU of an academic pulmonary hospital. A prospective observational study was conducted for 6 months. Pharmacotherapy data of PICU-admitted patients were evaluated by a clinical pharmacologist. Interacting drugs, reliability, mechanism, potential outcome, and clinical management of pDDIs were identified using the Lexi-Interact database. Logistic regression was applied to analyze the risk factors that could be associated with the interactions. One hundred and twenty-three medication profiles were evaluated during the study period. Diseases of the respiratory system were the main diagnoses among intensive care unit (ICU)-admitted patients (56.1%). A total of 38.6% of the patients exposed to at least 1 major and/or contraindicated interaction during ICU admission. Most pDDIs occurred through metabolic (35.4%) and additive (34.8%) mechanisms. The existence of pDDIs was significantly associated with the number of prescribed medications. Exposure to pDDIs is frequent in critically ill pediatric patients and related to the number of medications. Daily and close cooperation between clinicians and clinical pharmacologists is recommended to prevent harmful outcomes of DDIs.

Accuracy of enteral syringes with commonly prescribed paediatric liquid medicines.

OBJECTIVE: Oral syringes are the preferred method for delivering paediatric enteral drugs; however, little is known about factors affecting accuracy, particularly at volumes <5 mL. We investigated volumetric accuracy for enteral syringes, using commercially available liquid drug formulations with various physicochemical properties at clinically relevant volumes. DESIGN: In vitro experiment. INTERVENTIONS: Ten drugs were tested using two syringe brands (Baxa, Medicina) across a range of formulation volumes (0.05-5 mL) and syringe sizes (1-5 mL). Syringe weights (empty and filled) were converted into volume, using known formulation densities. Ten replications were performed for each drug/syringe/volume combination. MAIN OUTCOME MEASURES: Delivered volume accuracy was expressed as a percentage of intended volume, with the desired range being within ±10%. RESULTS: Baxa demonstrated a slight positive bias (excess average volumes delivered) at the smallest volumes for each syringe size, while Medicina had poorer precision (greater variability, analysis of variance-interactions all p<0.005). From these results, we identified the limit for volume accuracy for each syringe size and brand. Of note, the 1 mL syringe for both brands was inaccurate for delivering volumes ≤0.1 mL. The physicochemical properties of pH (range 2.82-7.45), surface tension (30.2-86.7 mN/m) and viscosity (2-299 mPaS) did not influence error in a discernible pattern. CONCLUSIONS: Dosing was inaccurate when small volumes were used across all syringe sizes and brands. These reflect volumes used in clinical practice. Administration error could potentially be reduced by (1) clinicians using syringes appropriate to dosing volumes and (2) manufacturers revising formulation concentrations for drugs.

Safe implementation of standard concentration infusions in paediatric intensive care.

OBJECTIVE: To evaluate safety, following introduction of standard concentrations of morphine infusions in paediatric critical care. METHODS: Implementation: A multidisciplinary team was convened, and several workstreams designated, including derivation of concentrations, manufacturing, supply, prescribing, administration using smart pump technology, training and evaluation. Safety Evaluation: Retrieval of all existing data on medication errors linked to morphine use using our hospital incident reporting system and risk assessment of errors in relation to standard concentration implementation. KEY FINDINGS: The pilot identified several areas for improvement, stock control, reasons for reverting from standard to variable concentrations and sources of error. Improvements included the following: refining morphine concentrations and weight limits for bands, pump reprogramming and education. Long-term Safety: Over an 8-year period, 126 morphine-related incidents occurred (two-thirds in the 3 years around introduction). Of note, 67% (85/126) resulted in no patient harm; the remainder 33% resulted in low harm. Analysis of administration errors revealed that up to 70% could be eliminated by refining technology to include bar coding. These included the following: wrong syringe selection (24%), wrong pump mode (28%) and wrong patient weight inputted (18%). CONCLUSION: Introduction of standard infusions is safe and effective. We are exploring ways to further refine safety and extending to other drugs.

Standard concentration infusions in paediatric intensive care: the clinical approach.

The use of standard concentrations of intravenous infusions has been advocated by international organisations to increase intravenous medication safety in paediatric and neonatal critical care. However, there is no guidance on how to identify and implement these infusions leading to great interunit variability. OBJECTIVE: To identify the most appropriate clinical concentrations required by our paediatric intensive care unit (PICU) population with regard to accuracy of delivery and overall fluid allowance. METHODS: Firstly a matrix was used to balance the concentration, dose and infusion volume (weight range 1.5-50 kg). Results were further refined considering: patient fluid allowance based on fluid volume targets, infusion pump accuracy and challenging each infusion against clinical scenarios requiring administration of multiple drug infusions found in PICU. Consideration was given to the standard concentrations routinely used in adults, in order to assess whether alignment with paediatrics was possible for some of the concentrations proposed. Finally a risk assessment of the infusions was conducted using the NPSA 20 tool. KEY FINDINGS: Twenty-five drugs identified as the most commonly used intravenous infusions in the unit. For the majority of the medicines, three weight bands of standard concentrations were necessary to cover the children's weight ranges and kept within predefined fluid requirements and accuracy of delivery. CONCLUSIONS: This work shows a patient focused systematic approach for defining and evaluating standardised concentrations in intensive care children.

Levomepromazine for difficult sedation in pediatric intensive care.

Sedation and analgesia using opioids and benzodiazepines is frequently required in critically ill children to minimize pain and anxiety. In some patients, difficult sedation occurs when tolerance or unacceptable side effects limit the efficacy of conventional analgo-sedative treatment. We describe seven patients (age range 1 to 17 yr) where difficult sedation was successfully managed with enteral levomepromazine (LMZ). LMZ is a neuroleptic antipsychotic agent that exhibits potent analgo-sedative properties without respiratory depression, through non-opioid and non-benzodiazepine pathways. We describe its use in our pediatric intensive care unit to control agitation in patients with known behavioral disorders who frequently pose a significant sedation challenge. We also illustrate its successful use in cases of withdrawal syndrome and delirium, and discuss the association of fever and its distinction from neuroleptic malignant syndrome in two patients. LMZ should be considered as a useful sedative in critically ill children where difficult sedation occurs and conventional agents are exhausted.

Pediatric formulation issues identified in Paediatric Investigation Plans.

Since the European Paediatric Regulation was introduced in 2007, companies developing new medicinal products or new indications/routes of administration/pharmaceutical forms are obliged to present age-appropriate formulations for the pediatric population within a Paediatric Investigation Plan (PIP) to the European Medicines Agency. Our review highlights a number of discrepancies between what is proposed by applicants and what is considered acceptable by regulators, taking a sample of PIP applications assessed by a specialized Formulation Working Group (FWG) of the Paediatric Committee in 2009. This Working Group assessed 43% of the total number of validated PIP applications during that year. Ninety-two percent of the formulations assessed raised at least one issue, mainly relating to excipients, appropriateness of the route of administration or pharmaceutical form, dosing accuracy and patient's acceptability. A stronger focus on all these aspects, considering the targeted age range, the severity of the disease and the treatment duration, could streamline the development process.

Accuracy of the concentration of morphine infusions prepared for patients in a neonatal intensive care unit.

OBJECTIVE: To investigate the accuracy of morphine infusions prepared for neonates in relation to the label strength and to identify the differences in deviation between infusions made in neonatal intensive care unit (NICU) and those dispensed ready-to-use from pharmacy. METHODS: Unused portions of morphine solution for infusion were collected over a 6-weeks period and used to determine the concentration of the drug by high-performance liquid chromatography (HPLC). RESULTS: A total of 19.2% of infusions prepared by nurses in the ward and 7.8% prepared in the pharmacy were outside the limit required by the British Pharmacopoeia (±7.5%). Moreover, a deviation in concentration of more than 20% was found in ward-prepared infusions, although this was caused by volume discrepancies of less than 0.2 mL. The frequency and magnitude of deviations found in infusions prepared in pharmacy was lower than in those prepared by NICU. The latter showed significantly higher number of out-of-specification samples (p=0.015); however, deviations from intended concentration occurred in both settings. Significant differences between pharmacy and NICU for volumes of less than 0.5 mL or for less than 1 mL were not identified probably due to small sample size, but statistical data show a trend for differences. CONCLUSIONS: Current practice of preparation of infusions from strengths intended for older children and adults involves dilution of small volumes in a syringe and leads to inaccuracy in the final concentration of infusions for neonatal use. We propose the implementation of standard concentrations for this patient group to effectively eliminate these errors.

Pediatric clinical trials in Latin America and Guyana: present views of local practitioners and ways to embrace the future.

BACKGROUND: Global pediatric research has recently received increased attention by health professionals, and research and government institutions. Since the approval of the FDA Pediatric Exclusivity Provision and the EU Paediatric Regulation, pharmaceutical companies have begun to look to developing/transitional countries for international pediatric research collaboration as a way of facilitating the recruitment of patients to clinical trials. Among countries identified as being 'developing/transitional' some were in the North, Central, and South American regions. OBJECTIVE AND METHODS: The aim of this study was to ascertain views from local practitioners on awareness and understanding of pediatric clinical research and to clarify resources and training required by pediatricians engaging in such research in the North, Central, and South American regions. A brief survey was disseminated via Sociedad Iberoamericana de Neonatología (SIBEN) and several other randomly selected pediatric institutions. This survey provided information for a Paediatric Global Research meeting at WorldPharma 2010 (Copenhagen, Denmark). RESULTS: Pediatricians (n = 55) from seven countries in Latin America and Guyana replied to the survey. They appeared to be enthusiastic about embracing the opportunity to participate in meaningful research to improve treatment of children worldwide. However, some challenges remain to be addressed around good clinical practice in the conduct of trials, education, and training of professionals, and the availability and use of resources. CONCLUSION: The survey indicated a considerable depth of interest in the improvement of the pediatric clinical research environment in Latin America. There is some momentum toward the development of a Latin American network for the facilitation and supervision of pediatric clinical research.

The infancy of an international paediatric pharmacy network.

There are several pharmacy and clinical pharmacology organizations in which pediatrics is one of many special interest groups and a few whose focus is entirely pediatric drug therapy. Recently the foundation for the establishment of an International Network of Paediatric Pharmacists has been laid. This paper describes that network.

'Poppy seeds' in stomach aspirates: is oral omeprazole extemporaneous dispersion bioavailable?

We report the appearance of 'poppy seed'-like structures found in the aspirated stomach contents and faeces of a 3-month-old infant receiving an omeprazole liquid via nasogastric tube, prepared by dispersing an omeprazole tablet (10 mg MUPS(R)) in water. Electron microscopy and mass spectroscopy indicated that these particles were hollow, dark purple coloured spheres comprising undissolved omeprazole and its degradation products. These observations suggest rapid degradation of omeprazole in the acid stomach contents, with compromised absorption of active drug. Consequently, dispersion of omeprazole in water may be an inappropriate formulation in this setting.

Use of oral clonidine for sedation in ventilated paediatric intensive care patients.

OBJECTIVES: We aimed to document our experience with oral clonidine when used as a sedative in combination with intravenous morphine and lorazepam in a group of mechanically ventilated children with single-organ, respiratory failure. In particular, our objectives were to establish the relationship between oral dose, plasma concentration, and sedative effect, and second, to document the side-effect profile. DESIGN: Prospective, cohort study over a 72-h period. SETTING: Regional paediatric intensive care unit. PATIENTS AND PARTICIPANTS: Twenty-four children were enrolled (median age 3 months) of whom ten were excluded (six due to extubation before 72 h, three sedation failures, one protocol violation). MEASUREMENTS AND RESULTS: Plasma clonidine was measured using gas chromatography mass spectrometry, and sedation assessed using the COMFORT score. Using a dose of 3-5 microg/kg every 8 h, plasma concentrations appeared to plateau at approximately 41 h giving a mean value of 1.38 ng/ml (95% confidence interval 1.0-1.8). Adequate sedation was achieved during 82% (837/1022 h) of the study period; however, this decreased to 70.3% when analysed on an intention-to-treat basis. There was a concomitant overall decrease in the average hourly requirements for both morphine ( P = 0.02) and lorazepam ( P = 0.003). There were no documented episodes of bradycardia, hypotension or hyperglycaemia. CONCLUSIONS: Oral clonidine may be a safe and effective sedative in combination with morphine and lorazepam for young children with single-organ, respiratory failure. This agent may also exhibit opioid and benzodiazepine sparing effects in this patient group. A full pharmacokinetic study is warranted.