Caroline Fonzo-Christe

Use of a systematic risk analysis method to improve safety in the production of paediatric parenteral nutrition solutions

Background: Until recently, the preparation of paediatric parenteral nutrition formulations in our institution included re-transcription and manual compounding of the mixture. Although no significant clinical problems have occurred, re-engineering of this high risk activity was undertaken to improve its safety. Several changes have been implemented including new prescription software, direct recording on a server, automatic printing of the labels, and creation of a file used to pilot a BAXA MM 12 automatic compounder. The objectives of this study were to compare the risks associated with the old and new processes, to quantify the improved safety with the new process, and to identify the major residual risks. Methods: A failure modes, effects, and criticality analysis (FMECA) was performed by a multidisciplinary team. A cause-effect diagram was built, the failure modes were defined, and the criticality index (CI) was determined for each of them on the basis of the likelihood of occurrence, the severity of the potential effect, and the detection probability. The CIs for each failure mode were compared for the old and new processes and the risk reduction was quantified. Results: The sum of the CIs of all 18 identified failure modes was 3415 for the old process and 1397 for the new (reduction of 59%). The new process reduced the CIs of the different failure modes by a mean factor of 7. The CI was smaller with the new process for 15 failure modes, unchanged for two, and slightly increased for one. The greatest reduction (by a factor of 36) concerned re-transcription errors, followed by readability problems (by a factor of 30) and chemical cross contamination (by a factor of 10). The most critical steps in the new process were labelling mistakes (CI 315, maximum 810), failure to detect a dosage or product mistake (CI 288), failure to detect a typing error during the prescription (CI 175), and microbial contamination (CI 126). Conclusions: Modification of the process resulted in a significant risk reduction as shown by risk analysis. Residual failure opportunities were also quantified, allowing additional actions to be taken to reduce the risk of labelling mistakes. This study illustrates the usefulness of prospective risk analysis methods in healthcare processes. More systematic use of risk analysis is needed to guide continuous safety improvement of high risk activities.

Subcutaneous administration of drugs in the elderly: survey of practice and systematic literature review.

Objectives and method: Survey of subcutaneous drug use and hypodermoclysis with a standardized questionnaire to 27 nursing teams and 52 physicians in a geriatric hospital department (404 beds). Evaluation of license status (CH, F, D and UK) and systematic literature review of 34 drugs used in the geriatric setting. Results: Subcutaneous route is used daily with drugs and fluids mostly for patients in palliative care (83%) or who are dehydrated (54%) when oral or IV administration is impossible (73%, 68% respectively). Morphine (98%), haloperidol (90%), furosemide (69%) and hydromorphone (56%) by bolus (36%) or slow injection over 5 min (82%) are the main drugs used and NaCl 0.9% (95%), and glucose 5%/NaCl 0.9% (31%) are commonly used for rehydration. Among the 34 drugs reviewed, only 13 (38%) are licensed for subcutaneous use in CH, UK, F or D, and only morphine (14 articles of 68) and rehydration (six articles) are evaluated in high level studies. Haloperidol and furosemide are used off-label and there are no well-designed studies supporting their subcutaneous use. Conclusion: There is a lack of information on drugs widely used by subcutaneous route in the elderly. In that context, physicians carry responsibility for the prescription.

Risk and pharmacoeconomic analyses of the injectable medication process in the paediatric and neonatal intensive care units

OBJECTIVE To analyse safety risks in injectable medications. To assess the potential impact and pharmacoeconomic aspects of safety tools. DESIGN The injectable drug process was prospectively assessed using a failure modes, effects and criticality analysis. Criticality indexes were estimated based on their likelihood of occurrence, detection probability and potential severity. The impact of 10 safety tools on the criticality index was calculated and extrapolated to all drugs injected daily. Yearly costs for a reduction in criticality by 1 point (=1 quali) per day were estimated. SETTING Paediatric and neonatal intensive care units in a University Hospital. PARTICIPANTS Two paediatric nurses, a neonatologist, three hospital pharmacists. INTERVENTIONS Qualitative and quantitative risk assessment. MAIN OUTCOME MEASURES Failure modes, criticality indexes, cost-efficacy ratios. RESULTS Thirty-one failure modes identified, with the mean of their entire criticality indexes totalling 4540. The most critical failure mode was microbial contamination. The following gains were predicted: 1292 quali (46 500 per day by extrapolation) from ready-to-use syringes, 1201 (72 060) by employing a clinical pharmacist, 996 (59 780) from double check by nurses and 984 (59 040) with computerized physician order entry. The best cost-efficacy ratios were obtained for a clinical pharmacist (1 quali = 0.54 euros), double check (1 quali = 0.71 euros) and ready-to-use syringes (1 quali = 0.72 euros). Computerized physician order entry showed the worst cost-efficacy ratio due to a very high investment costs (1 quali = 22.47 euros). CONCLUSION Based on our risk and pharmacoeconomic analyses, clinical pharmacy and ready-to-use syringes appear as the most promising safety tools.

Compatibility of Intravenous Medications With Parenteral Nutrition In Vitro Evaluation

BACKGROUND AND AIM Hospitalized patients requiring parenteral nutrition (PN) often need to receive intravenous (IV) medications as well. Y-site administration is occasionally necessary, but physicochemical incompatibilities can occur between the medications and PN. The aim of the present study was to assess the physical compatibility between 25 frequently coadministered IV medications and a commercially available ready-to-use total PN. METHODS PN (NuTRIflex Lipid Special; B. Braun Medical AG, Sempach, Switzerland) and medications were mixed in 1:1 (v/v) proportions, and the stability was assessed at the time of mixing and after 1 and 4 hours. The stability of lipid emulsion was observed by microscopic investigation, visual inspection, dynamic laser light scattering, and laser light obscuration. The binary admixtures of PN (without lipid emulsion) and medications were used to detect discoloration, visibly detectable precipitates, and subvisual particles. RESULTS Two of 25 medications were incompatible with the lipid emulsion (serum albumin 20% and tropisetron), 2 showed signs of degradation (discoloration) over time (esomeprazole and pantoprazole), and 1 precipitated at high concentrations (5-fluorouracil). The other 20 medications were considered compatible when administered by Y-site. CONCLUSION The present study validated the compatibility of 1 commercially available PN and 20 medications. These results offer new solutions to support the implementation of complex therapeutic schemes in practice, when coadministration via Y-site cannot be avoided.

Long-term physico-chemical stability of standard parenteral nutritions for neonates ☆

BACKGROUND & AIMS Two ready-to-use parenteral nutritions (PN) have been developed, for the first days of life of the premature newborn, along with syringes of lipid emulsion with or without vitamins. Long-term physico-chemical stability for storage in wards was assessed. METHODS Physico-chemical stability of PN: visual inspection, particle size, pH, osmolarity measurement, amino acids, glucose, and electrolytes dosages. Physico-chemical stability of lipid emulsion: visual inspection, globule size, peroxide level and vitamins A, E, and C dosages. Stability was studied for 12 weeks on refrigerated (2-8 °C) and room temperature (30 ± 2 °C) samples. RESULTS No precipitation was detected in any PN. A brown coloration was observed in PN stored for four weeks at room temperature but not in the refrigerator. Concentrations of all the nutrients remained constant over the 12 week-study period. Phase separation of the lipid emulsion occurred after three weeks, but particle size complied with the USP limits for 12 weeks. Peroxide content increased only in the samples without vitamins at room temperature. Vitamins remained stable for one week under refrigeration. CONCLUSION The PN did not present a detectable change of the tested properties when refrigerated for 12 weeks. The lipid emulsion with vitamins is stable for one week when refrigerated.

Maximizing Calcium and Phosphate Content in Neonatal Parenteral Nutrition Solutions Using Organic Calcium and Phosphate Salts

BACKGROUND The provision of high amounts of calcium and phosphate in parenteral nutrition (PN) solution for neonates is important for bone mass accretion. Because of the risk of calcium phosphate precipitation, a well-documented incompatibility for inorganic salts, the concentrations of these electrolytes in PN are generally limited to 5 mmol/L. The aim of this study was to assess the risk of precipitation of calcium phosphate when organic calcium and phosphate salts are used instead of inorganic salts. METHODS Precipitation curves were determined for inorganic and organic calcium and phosphate salts in a PN solution favorable to precipitation (low concentration of amino acids and glucose) using visual inspection and particle counts. RESULTS The use of organic phosphate salt was associated with a decreased risk of precipitation of calcium phosphate. No precipitation occurred up to a concentration of 50 mmol/L of calcium and phosphate. In contrast, organic calcium salt only slightly decreased the risk of precipitation. CONCLUSION Up to 50 mmol/L of organic calcium and phosphate salts can be safely mixed in PN, even in unstable conditions, making it possible to follow the current European recommendations for requirements in neonates.

Development of a standardised method to recommend protective measures to handle hazardous drugs in hospitals

Purpose Healthcare professionals frequently have to handle hazardous drugs in the hospital setting. Data on the inherent toxicity of drugs cannot be directly applied to occupational exposure. We developed a standardised method to evaluate occupational risks and to recommend protective measures. Methods Step 1: evaluation of chronic and acute toxicities and toxicity for reproduction. Step 2: toxicity weighting according to risk of exposure related to drug formulations. Step 3: definition of protective measures. Step 4: toxicity assessment of drugs used in our institution and comparison with hazardous drug lists published in the literature. Results The whole process resulted in a standardised evaluation algorithm. Risks of exposure were determined by a panel of experts to balance intrinsic toxicity of each drug formulation or administration route. Protective measures were recommended. 80 substances (109 drug formulations) were screened for toxicity. Centralisation of compounding in the pharmacy was recommended for 12/24 (50%) of intravenous liquids, 19/32 (60%) of intravenous powders and 7/26 (27%) tablets (crushing). We found a slightly different estimation of risk for only two products (prednisone and mycophenolate mofetil) compared with the literature lists (National Institute for Occupational and Safety in Health Alert and University Health System Consortium Consensus). Conclusions We developed a simple standardised method to generate a list of hazardous drugs in our hospital according to the risk of exposure. We determined reasonable protective measures that could be easily introduced into practice to protect healthcare workers.

Impact of clinical decision support guidelines on therapeutic drug monitoring of gentamicin in newborns.

Background: Our institutions gentamicin dosing and therapeutic drug monitoring (TDM) practices for newborns were suspected to be very heterogeneous. Once-daily dosing (ODD) or extended-interval dosing (EID) and trough concentration measurement were recommended. Clinical decision support guidelines were developed and implemented as clinical decision support in the computerized prescriber order entry system. Impact on dosing, TDM practices, and blood sampling were evaluated. Methods: A 1-year retrospective historically controlled study before (April 2008–March 2009) and after the implementation of guidelines (January 2010–December 2010) for newborns (<30 days of life) receiving gentamicin. Blood concentrations (% of peak concentrations sampled, % of patients with zero or one concentration sampled, % of trough concentrations ⩽1 mg/L) and dose regimen (ODD/EID) were compared between groups. Factors potentially associated with gentamicin concentration were analyzed (multivariate analysis). Results: One hundred thirty-two (postguidelines) versus 102 (preguidelines) patients were included (median gestational age: 34.3 versus 35.8 weeks, P > 0.05). After implementation of the guidelines, an ODD/EID regimen was almost exclusively used (97.7% versus 61.6%, P < 0.001), the percentage of peak concentrations (0.9% versus 17.2%, P < 0.001) and the number of blood samples per patient (87.1% having 0 or 1 concentration measured versus 48.0, P < 0.001) sharply reduced. A significantly higher percentage of trough concentrations were ⩽1 mg/L (68.5% versus 33.0%, P < 0.001). The probability of a trough concentration ⩽1 mg/L increased with an ODD/EID regimen (odds ratio, 7.23; 95% confidence interval: 3.48–15.0, P < 0.001) and in the postguidelines group (odds ratio, 2.02; 95% confidence interval: 1.01–4.02, P = 0.045). Conclusions: Guideline implementation generated a sharp reduction in blood sampling. Clinical benefits of better gentamicin dosing and TDM practices were evident. Cost-effectiveness and clinical benefit of reduced blood sampling should be evaluated.

PIM-Check: development of an international prescription-screening checklist designed by a Delphi method for internal medicine patients

Objectives Potentially inappropriate medication (PIM) occurs frequently and is a well-known risk factor for adverse drug events, but its incidence is underestimated in internal medicine. The objective of this study was to develop an electronic prescription-screening checklist to assist residents and young healthcare professionals in PIM detection. Design Five-step study involving selection of medical domains, literature review and 17 semistructured interviews, a two-round Delphi survey, a forward/back-translation process and an electronic tool development. Setting 22 University and general hospitals from Canada, Belgium, France and Switzerland. Participants 40 physicians and 25 clinical pharmacists were involved in the study. Agreement with the checklist statements and their usefulness for healthcare professional training were evaluated using two 6-point Likert scales (ranging from 0 to 5). Primary and secondary outcome measures Agreement and usefulness ratings were defined as: >65% of the experts giving the statement a rating of 4 or 5, during the first Delphi-round and >75% during the second. Results 166 statements were generated during the first two steps. Mean agreement and usefulness ratings were 4.32/5 (95% CI 4.28 to 4.36) and 4.11/5 (4.07 to 4.15), respectively, during the first Delphi-round and 4.53/5 (4.51 to 4.56) and 4.36/5 (4.33 to 4.39) during the second (p<0.001). The final checklist includes 160 statements in 17 medical domains and 56 pathologies. An algorithm of approximately 31 000 lines was developed including comorbidities and medications variables to create the electronic tool. Conclusion PIM-Check is the first electronic prescription-screening checklist designed to detect PIM in internal medicine. It is intended to help young healthcare professionals in their clinical practice to detect PIM, to reduce medication errors and to improve patient safety.

Drug information leaflets improve parental knowledge of their child's treatment at paediatric emergency department discharge

Background Hospital discharge is a complex multidisciplinary process that can lead to non-compliance and drugs-related problems. Crucial issue for children is parental knowledge of discharge treatments, especially in the time-limited and stressful environment of an emergency department (ED). Objective To compare parental correct knowledge of treatment with and without supply of customised drug information leaflets for the 10 most commonly prescribed drugs. Method Inclusion criteria: paediatric patients (0–16 years) with French-speaking parents discharged from ED of the paediatric department of Geneva University Hospitals before (phase A) and after (phase B) intervention. Intervention Supply and brief comment of drug information leaflets focusing on specific information not available in official drugs information documents. Follow-up Semi-structured phone interview within 72 h after discharge to evaluate the percentage of parents with correct knowledge of dose, frequency, duration and indication of drugs. Multivariate analysis to identify factors associated with correct knowledge (phases A/B, drugs collection at usual pharmacy, drugs categories). Results 125 patients were included (phase A: 56; phase B: 69). Drug information leaflets were given to 63/69 ED patients (91%), covering 96/138 prescribed drugs (70%). Parental knowledge was significantly improved in phase B (dose: 62.3% to 89.1%; frequency: 57.9% to 85.5%; duration: 34.2% to 66.7%; indication: 70.2% to 94.9%; p<0.0001). Phase B and collection of drugs at usual pharmacy were significant factors associated with correct knowledge. Conclusions Drug information leaflets significantly improved treatment knowledge of French-speaking parents after paediatric ED discharge. Leaflets are now available online for general population.