Optimal dosing of cefotaxime and desacetylcefotaxime for critically ill paediatric patients. Can we use microsampling?

OBJECTIVES: To describe the population pharmacokinetics of cefotaxime and desacetylcefotaxime in critically ill paediatric patients and provide dosing recommendations. We also sought to evaluate the use of capillary microsampling to facilitate data-rich blood sampling. METHODS: Patients were recruited into a pharmacokinetic study, with cefotaxime and desacetylcefotaxime concentrations from plasma samples collected at 0, 0.5, 2, 4 and 6 h used to develop a population pharmacokinetic model using Pmetrics. Monte Carlo dosing simulations were tested using a range of estimated glomerular filtration rates (60, 100, 170 and 200 mL/min/1.73 m2) and body weights (4, 10, 15, 20 and 40 kg) to achieve pharmacokinetic/pharmacodynamic (PK/PD) targets, including 100% ƒT>MIC with an MIC breakpoint of 1 mg/L. RESULTS: Thirty-six patients (0.2-12 years) provided 160 conventional samples for inclusion in the model. The pharmacokinetics of cefotaxime and desacetylcefotaxime were best described using one-compartmental model with first-order elimination. The clearance and volume of distribution for cefotaxime were 12.8 L/h and 39.4 L, respectively. The clearance for desacetylcefotaxime was 10.5 L/h. Standard dosing of 50 mg/kg q6h was only able to achieve the PK/PD target of 100% ƒT>MIC in patients >10 kg and with impaired renal function or patients of 40 kg with normal renal function. CONCLUSIONS: Dosing recommendations support the use of extended or continuous infusion to achieve cefotaxime exposure suitable for bacterial killing in critically ill paediatric patients, including those with severe or deep-seated infection. An external validation of capillary microsampling demonstrated skin-prick sampling can facilitate data-rich pharmacokinetic studies.

Microsampling to support pharmacokinetic clinical studies in pediatrics.

BACKGROUND: Conventional sampling for pharmacokinetic clinical studies requires removal of large blood volumes from patients. This can result in a physiological/emotional burden for children. Microsampling to support pharmacokinetic clinical studies in pediatrics may reduce this burden. METHODS: Parents/guardians and bedside nurses completed a questionnaire describing their perception of the use of microsampling compared to conventional sampling to collect blood samples, based on their child's participation or their own role within a paired-sample pharmacokinetic clinical study. Responses were based on a seven-point Likert scale and were analyzed using frequency distributions. RESULTS: Fifty-one parents/guardians and seven bedside nurses completed a questionnaire. Parents/guardians (96%) and bedside nurses (100%) indicated that microsampling was highly acceptable and recommended as a method for collecting blood samples for pediatric patients. Responding to a question about the child indicating pain during the blood sampling procedure, 61% of parent/guardians reported no pain in their children, 14% remained neutral, and 26% reported that their child indicated pain; 71% of the bedside nurses slightly agreed that the children indicated pain. CONCLUSIONS: This study strongly suggests that parents/guardians and bedside nurses prefer microsampling to conventional sampling to conduct pediatric pharmacokinetic clinical studies. Employing microsampling may support increased participation by children in these studies. IMPACT: Pharmacokinetic clinical studies require the withdrawal of blood samples at multiple times during a dosing interval. This can result in a physiological or emotional burden, particularly for neonates or pediatric patients. Microsampling offers an important opportunity for pharmacokinetic clinical studies in vulnerable patient populations, where smaller sample volumes can be collected. However, microsampling is not commonly used in clinical studies. Understanding the perceptions of parents/guardians and bedside nurses about microsampling may ascertain if this technique offers an improvement to conventional blood sample collection to perform pharmacokinetic clinical studies for pediatric patients.

Real-time seizure detection in paediatric intensive care patients: the RESET child brain protocol.

INTRODUCTION: Approximately 20%-40% of comatose children with risk factors in intensive care have electrographic-only seizures; these go unrecognised due to the absence of continuous electroencephalography (EEG) monitoring (cEEG). Utility of cEEG with high-quality assessment is currently limited due to high-resource requirements. New software analysis tools are available to facilitate bedside cEEG assessment using quantitative EEG (QEEG) trends. The primary aim of this study is to describe accuracy of interpretation of QEEG trends by paediatric intensive care unit (PICU) nurses compared with cEEG assessment by neurologist (standard clinical care) in children at risk of seizures and status epilepticus utilising diagnostic test statistics. The secondary aims are to determine time to seizure detection for QEEG users compared with standard clinical care and describe impact of confounders on accuracy of seizure detection. METHODS AND ANALYSIS: This will be a single-centre, prospective observational cohort study evaluating a paediatric QEEG programme utilising the full 19 electrode set. The setting will be a 36-bed quaternary PICU with medical, cardiac and general surgical cases. cEEG studies in PICU patients identified as 'at risk of seizures' will be analysed. Trained bedside clinical nurses will interpret the QEEG. Seizure events will be marked as seizures if >3 QEEG criteria occur. Post-hoc dedicated neurologists, who remain blinded to the QEEG analysis, will interpret the cEEG. Determination of standard test characteristics will assess the primary hypothesis. To calculate 95% (CIs) around the sensitivity and specificity estimates with a CI width of 10%, the sample size needed for sensitivity is 80 patients assuming each EEG will have approximately 9 to 18 1-hour epochs. ETHICS AND DISSEMINATION: The study has received approval by the Children's Health Queensland Human Research Ethics Committee (HREC/19/QCHQ/58145). Results will be made available to the funders, critical care survivors and their caregivers, the relevant societies, and other researchers. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR) 12621001471875.

Development and validation of a UHPLC-MS/MS method to measure cefotaxime and metabolite desacetylcefotaxime in blood plasma: a pilot study suitable for capillary microsampling in critically ill children.

Critical illness has been shown to affect the pharmacokinetics of antibiotics, which can lead to ineffective antibiotic exposure and the potential emergence of resistant bacteria. The lack of studies describing antibiotic pharmacokinetics in critically ill children has led to significant off-label dosing. This is, in part, due to the ethical and physiological challenges of removing frequent, large-volume samples from children. Capillary microsampling facilitates the collection of small volumes of blood samples to conduct clinical pharmacokinetic studies. A sensitive, rapid, and accurate ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) bioanalytical method to measure cefotaxime and desacetylcefotaxime in 2.8 µL of plasma was developed and validated. Plasma samples were treated with acetonitrile and analytes were separated using a Kinetex C8 (100 × 2.1 mm) column. The chromatographic separation was established using a gradient method, with the mobile phases consisting of acetonitrile and ammonium acetate. An electrospray ionization source interface operated in a positive mode for the multiple reaction monitoring MS/MS analysis of cefotaxime, desacetylcefotaxime, and deuterated cefotaxime (internal standard). The bioanalytical method using microsample volumes met requirements for method validation for both analytes. Cefotaxime had precision within ± 7.3% and accuracy within ± 5% (concentration range of 0.5 to 500 mg/L). Desacetylcefotaxime had precision within ± 9.5% and accuracy within ± 3.5% (concentration range of 0.2 to 10 mg/L). The bioanalytical method was applied for the quantification of cefotaxime and its metabolite to 20 capillary microsamples collected at five time points in one dosing interval from five critically ill children.

The effectiveness of education in the recognition and management of deteriorating patients: A systematic review.

BACKGROUND: Survival from in-hospital cardiac arrest is poor. Clinical features, including abnormal vital signs, often indicate patient deterioration prior to severe adverse events. Early warning systems and rapid response teams are commonly used to assist the health profession in the identification and management of the deteriorating patient. Education programs are widely used in the implementation of these systems. The effectiveness of the education is unknown. AIM: The aims of this study were to identify: (i) the evidence supporting educational effectiveness in the recognition and management of the deteriorating patient and (ii) outcome measures used to evaluate educational effectiveness. METHODS: A mixed methods systematic review of the literature was conducted using studies published between 2002 and 2014. Included studies were assessed for quality and data were synthesized thematically, while original data are presented in tabular form. RESULTS: Twenty-three studies were included in the review. Most educational programs were found to be effective reporting significant positive impacts upon learners, patient outcomes and organisational systems. Outcome measures related to: i learners, for example knowledge and performance, ii systems, including activation and responses of rapid response teams, and iii patients, including patient length of stay and adverse events. All but one of the programs used blended teaching with >87% including medium to high fidelity simulation. In situ simulation was employed in two of the interventions. The median program time was eight hours. The longest program lasted 44h however one of the most educationally effective programs was based upon a 40min simulation program. CONCLUSION: Educational interventions designed to improve the recognition and management of patient deterioration can improve learner outcomes when they incorporate medium to high-fidelity simulation. High-fidelity simulation has demonstrated effectiveness when delivered in brief sessions lasting only forty minutes. In situ simulation has demonstrated sustained positive impact upon the real world implementation of rapid response systems. Outcome measures should include knowledge and skill developments but there are important benefits in understanding patient outcomes.

Enhancing the management of deteriorating patients with Australian on line e-simulation software: Acceptability, transferability, and impact in Hong Kong.

International concerns relating to healthcare professionals' failure to rescue deteriorating patients exist. Web-based training programs have been developed and evaluated in Western settings but further testing is required before application in non-Western countries, as traditional modalities of learning may differ between cultures. We trialed an Australian English language online simulation program for the management of deteriorating patients, Feedback Incorporating Review and Simulation Techniques to Act on Clinical Trends (FIRST(2) ACTWeb), to test cultural acceptability, transferability, and educational impact. The study was designed as a quasi-experimental evaluation of the FIRST(2) ACTWeb program with final year nursing students from a Bachelor of Nursing program at the University of Hong Kong. Participants completed pre-course and post-course tests, three interactive scenarios, and program evaluations. The program was positively evaluated, with significant improvements in knowledge, skills, self-rating of performance, confidence, and competence. Outcomes were comparable to earlier evaluations with Australian students, demonstrating that an interactive simulation-based program of patient deterioration management has cultural and language acceptability and transferability across communities with significant educational impact.

The use and limits of eye-tracking in high-fidelity clinical scenarios: A pilot study.

AIM: To explore the potential of mobile eye-tracking to identify healthcare students' area of visual interest and its relationship to performance ratings. BACKGROUND: Eye-tracking identifies an individual's visual attention focus, and has been used as a training technique in medicine and in nursing. In this study participants wore a point of view (PoV) camera within a spectacle frame during simulation education experiences. METHODS: Thirty-nine final year nursing and paramedicine students individually participated in three 8 minute clinical simulations with debriefing using videoed eye-tracking recordings. Coloured dots on the video depicted the participant's pupil fixation on five targeted areas. Data extracted from the video camera were collated to report time spent on each target (their 'gaze'). RESULTS: The mean total gaze of expert designated targets in the environment for three 8 minute scenarios was 40-77%. Of 35 participants' focus on three main areas of interest, their priority was the patient's head (34%), the patient's trunk (24%) and their clinical assistant (5%), with significant differences between nursing and paramedic disciplines (P < 0.05). Objectively rated clinical performance improved significantly by the third scenario (P ≤ 0.001). Participants were positive regarding use of eye tracking during debriefing. CONCLUSIONS: Eye tracking has the potential to enhance debriefing and educational outcomes, although there are limitations to gaze capture in high fidelity environments and resource cost is high. Further study is warranted to enable better understanding of how expert clinicians achieve high levels of performance.

Distribution of health literacy strengths and weaknesses across socio-demographic groups: a cross-sectional survey using the Health Literacy Questionnaire (HLQ).

BACKGROUND: Recent advances in the measurement of health literacy allow description of a broad range of personal and social dimensions of the concept. Identifying differences in patterns of health literacy between population sub-groups will increase understanding of how health literacy contributes to health inequities and inform intervention development. The aim of this study was to use a multi-dimensional measurement tool to describe the health literacy of adults in urban and rural Victoria, Australia. METHODS: Data were collected from clients (n = 813) of 8 health and community care organisations, using the Health Literacy Questionnaire (HLQ). Demographic and health service data were also collected. Data were analysed using descriptive statistics. Effect sizes (ES) for standardised differences in means were used to describe the magnitude of difference between demographic sub-groups. RESULTS: Mean age of respondents was 72.1 (range 19-99) years. Females comprised 63% of the sample, 48% had not completed secondary education, and 96% reported at least one existing health condition. Small to large ES were seen for mean differences in HLQ scales between most demographic groups. Compared with participants who spoke English at home, those not speaking English at home had much lower scores for most HLQ scales including the scales 'Understanding health information well enough to know what to do' (ES -1.09 [95% confidence interval (CI) -1.33 to -0.84]), 'Ability to actively engage with healthcare providers' (ES -1.00 [95% CI -1.24, -0.75]), and 'Navigating the healthcare system' (ES -0.72 [95% CI -0.97, -0.48]). Similar patterns and ES were seen for participants born overseas compared with those born in Australia. Smaller ES were seen for sex, age group, private health insurance status, number of chronic conditions, and living alone. CONCLUSIONS: This study has revealed some large health literacy differences across nine domains of health literacy in adults using health services in Victoria. These findings provide insights into the relationship between health literacy and socioeconomic position in vulnerable groups and, given the focus of the HLQ, provide guidance for the development of equitable interventions.

Developing situation awareness amongst nursing and paramedicine students utilizing eye tracking technology and video debriefing techniques: a proof of concept paper.

OBJECTIVE: The aims of this quasi-experimental before-and-after study were to first determine whether the use of eye tracking technology combined with video debriefing techniques has the potential to improve the quality of feedback and enhance situation awareness (SA) in simulated settings and second to determine students' satisfaction towards simulated learning. METHODS: Nursing and paramedicine students from three universities participated in three 8-minute simulation scenarios of acutely deteriorating patients. Eye tracking glasses video recorded the scenarios and tracked right eye movement. On completion, participants were questioned using the Situation Awareness Global Assessment Technique, completed the Satisfaction with Simulation Experience Scale (SSES), and provided textual feedback and received video-based verbal feedback. RESULTS: Participants lacked awareness of presenting medical conditions and patient environments and had poor recall of patient vital signs. Significant improvements in SA scores were demonstrated between the first and third scenarios (P = 0.04). Participants reported greater insight into their performance and were satisfied with simulated learning. CONCLUSIONS: Use of visual field review techniques appears to enhance the use of realistic simulated practice as a means of addressing significant performance deficits. Eye tracking and point of view recording techniques are feasible and with applicable debriefing techniques could enhance clinical and situated performance.

Managing patient deterioration: assessing teamwork and individual performance.

OBJECTIVE: To assess the ability of rural Australian nurse teams to manage deteriorating patients. METHODS: This quasi-experimental design used pre- and post-intervention assessments and observation to evaluate nurses' simulated clinical performance. Registered nurses (n=44) from two hospital wards completed a formative knowledge assessment and three team-based video recorded scenarios (Objective Structured Clinical Examinations (OSCE)). Trained patient actors simulated deteriorating patients. Skill performance and situation awareness were measured and team performance was rated using the Team Emergency Assessment Measure. RESULTS: Knowledge in relation to patient deterioration management varied (mean 63%, range 27-100%) with a median score of 64%. Younger nurses with a greater number of working hours scored the highest (p=0.001). OSCE performance was generally low with a mean performance of 54%, but performance was maintained despite the increasing complexity of the scenarios. Situation awareness was generally low (median 50%, mean 47%, range 17-83%, SD 14.03) with significantly higher levels in younger participants (r=-0.346, p=0.021). Teamwork ratings averaged 57% with significant associations between the subscales (Leadership, Teamwork and Task Management) (p<0.006), the global rating scale (p<0.001) and two of the OSCE measures (p<0.049). Feedback from participants following the programme indicated significant improvements in knowledge, confidence and competence (p<0.001). CONCLUSION: Despite a satisfactory knowledge base, the application of knowledge was low with notable performance deficits in these demanding and stressful situations. The identification and management of patient deterioration needs to be taught in professional development programmes incorporating high fidelity simulation techniques. The Team Emergency assessment tool proved to be a valid measure of team performance in patient deterioration scenarios.

Developing team based acute care scenarios: a rural hospital experience.

BACKGROUND: Health professionals work in teams in a variety of health care settings especially in medical emergency teams at times of crisis. However, Registered Nurses (RNs) rarely have the chance to partake in educational programs designed for teams of nurses to practice working together in life-threatening situations. Further RN's employed in rural setting have less opportunities for professional development than their city based counterparts. Simulated scenarios with a patient actor in a rural hospital have been utilised in this study to provide nurses with the opportunity to work as a team in the early recognition and management of patients with acute medical conditions. AIM: This discussion paper focuses on one aspect of a larger research project with the aim of describing the development of team based scenarios for a rural hospital setting, focusing on the detection and management of a deteriorating patient. METHODS: Three team based scenarios, the related assessments and feedback techniques are all described. CONCLUSION: Team based simulation provides a unique opportunity to assist registered nurses in rural settings in re-skilling or maintaining their emergency management skills.